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Multilayered controlled-release solid pharmaceutical composition in tablet form suitable for oral administration comprising at least two layers containing active material in association with excipients and additives. One layer of the tablet releases a portion of the drug quickly while the other layer and optionally further layers release portions of the drug more gradually.
1. A solid pharmaceutical composition for oral administration, comprising:
at least one first layer consisting essentially of a first active material and a disintegrating or superdisintegrating compound which is a cross-linked polyvinylpyrrolidone, sodium carboxy methylcellulose, carboxymethyl starch, potassium methacrylate--divinylbenzene copolymer, a polyvinylalcohol, a starch, a microcrystalline cellulose, a dextrin, beta cyclodextrin, and mixtures thereof; and
at least one second layer located on said first layer containing a portion of said first active material or a second active material and an excipient or adjuvant selected from the group consisting of hydroxypropylmethylcellulose of molecular weight 1,000 to 4,000,000, hydroxypropylcellulose of molecular weight from 2,000 to 2,000,000, a carboxyvinylpolymer, a polyvinylalcohol, a glucan, a scleroglucan, a mannan, a xanthan, alginic acid, methylcellulose and a polymethylcellulose;
said active material in said first layer being released upon administration to a host at a rate faster than the rate of release of said active material in said second layer.
2. A pharmaceutical composition according to claim 1, wherein said disintegrating or superdistintegrating compound is present in an amount of 10 to 90% by weight of said first layer.
3. A pharmaceutical composition according to claim 2, wherein said disintegrating or superdisintegrating compound is present in an mount of 20 to 70% by weight of said first layer.
4. A pharmaceutical composition according to claim 1, wherein said said first layer further comprises an adjuvant selected from the group consisting of starch, pregelled starch, calcium phosphate, mannitol, lactose, sucrose, glucose, sorbitol and microcrystalline cellalose, a binding agent, a lubricant and an antiadhering compound.
5. A pharmaceutical composition according to claim 4, wherein said binding agent is selected from the group consisting of gelatin, polyvinylpyrrolidone, methyl cellalose, starch water, ethylcellulose, gum arabic and tragacanth gum.
6. A pharmaceutical composition according to claim 4, wherein said lubricants and antiadhering compounds are selected from the group consisting of magnesium stearate, stearic acid, colloidal silica, glyceryl monostearate, a polyoxyethyleneglycol of 400 to 50000 number average molecular weight, hydrogenated castor oil, waxes and a glyceride.
7. A pharmaceutical composition according to claim 1, wherein said first layer includes an effervescent agent capable of causing rapid disintegration of said first layer when said composition comes into contact with an aqueous environment.
8. A pharmaceutical composition according to claim 7, wherein said aqueous environment is gastric juice.
9. A pharmaceutical composition according to claim 7 wherein said first layer includes a compound that can produce effervescence in an acid environment selected from the group consisting of alkali metal carbonates, alkaline-earth metal carbonates, sodium bicarbonate and glycine sodium carbonate.
10. A pharmaceutical composition according to claim 7, where said first layer includes a compound that can produce effervescence and disintegration of said first layer independently of pH selected from the group consisting of citric add, tartaric acid and fumaric add.
11. A pharmaceutical composition according to claim 7, wherein said effervescent agent capable of producing effervescence is present in an amount of 3 to 40% by weight of said first layer.
12. A pharmaceutical composition according to claims 1, and further comprising a second and a third layer including a same or different active material together with a disintegrating or superdisintegrating compound which is a cross-linked polyvinylpyrrolidone, sodium carboxy methylcellulose, carboxymethyl starch, potassium methacrylate--divinylbenzene copolymer, a polyvinylalcohol, a starch, a microcrystalline cellulose, a dextrin, beta cyclodextrin, and mixtures thereof, and excipients and adjuvants.
13. A pharmaceutical composition according to claim 12, wherein said disintegrating or superdisintegrating compound in said second and third layer is present in each layer in an amount of 5 to 90% by weight of the said layer.
14. A pharmaceutical composition according to claim 1, wherein said adjuvant contained in said at least one second layer is selected from the group consisting of polyvinylpyrrolidone, methylcellulose, starch water, ethylcellulose, arabic gum and tragacanth gum.
15. A pharmaceutical composition according to claim 1, wherein said adjuvant of said at least one second layer is selected from the group consisting of glyceryl monostearate, semi-synthetic glycerides, glyceryl palmitostearate, glyceryl behenate, microcrystalline cellulose, sodium carboxymethylcellulose, magnesium stearate, stearic acid, sodium stearate, talc, sodium benzoate, boric acid and colloidal silica.
16. A pharmaceutical composition according to claim 1, wherein said adjuvant of said at least one second layer is selected from the group consisting of hydrogenated castor oil, fatty acids, waxes, glycerides and polyoxyethyleneglycol with a molecular weight of from 400 to 60,000.
17. A pharmaceutical composition according to claim 1, wherein said active material is selected from the group consisting of steroidol anti-inflammatories non-steroidal anti-inflammatories (NSAID1), sleeping substances, tranquilizers, active substances for preventing anginous and hypertensive attacks, antihistamines and antiasthmatic drugs, and combinations thereof.
18. A pharmaceutical composition according to claim 17, wherein said anti-inflammatory is selected from the group consisting of diclofenac sodium, indomethacin, ibuprofen, ibuprofen lysine salt, ketoprofen, diflunisal, piroxicam, naproxen and flurbiprofen.
19. A pharmaceutical composition according to claim 17, wherein said sleeping substance or tranquilizer is selected from the group consisting of diazepam, nitrazepam, fluorozepam, oxazepam and chlorodiazepoxide.
20. A pharmaceutical composition according to claim 17, wherein said antianginous and antihypertensive active material is selected from the group consisting of diltiazem, trapidil, verapamil, urapidil and benziodarone dipyridamole.
21. A pharmaceutical composition according to claim 17, wherein said antihistaminic or antiasthmatic material is selected from the group consisting of ephedrine, terfenadine, theophylline, chloropheniramine and termutiline.
22. A pharmaceutical composition according to claim 1, wherein said first layer has a thickness from 0.5 to 5 mm and contains from 1 to 90% by weight of active material.
23. A pharmaceutical composition according to claim 1, wherein said second layer has a thickness of from 0.1 to 6.0 mm and contains from 1 to 90% by weight of active material and from 10 to 90% by weight of said excipient or adjuvant.
24. A pharmaceutical composition according to claim 1, wherein said second layer contains a portion of the same active material as present in said first layer.
25. A pharmaceutical composition according to claim 1, wherein an active material different from that present in said first layer is present in said second layer.
26. A pharmaceutical composition according to claim 1, wherein a third layer is present and contains an active material and an adjuvant as defined in claim 1.
This application is a 35USC371 of PCT/EP94/01050 filed Apr. 2, 1994.
The present invention relates to novel pharmaceutical forms for oral administration capable of releasing active substances at controlled and differentiated rate. It is well known that the pharmaceutical forms for the oral administration are the overwhelming majority of the pharmaceutical market for numerous and diversified reasons which, in the case of tablets, are mainly determined in that they guarantee precise dosage, excellent stability of carried active materials and easy administration. In the last twenty years, of great importance has been the achievement of more and more sophisticated and diversified pharmaceutical forms, with the purpose of simplifying the posological scheme and obtaining greater patient's compliance. Such so called modified or controlled release pharmaceutical forms were aimed at, in the majority of cases, releasing the active material carried therein at constant rate in time, following a release kinetics defined as being of zero order.
In some cases it was also possible to highlight that, to a drug release at a constant "in vitro" rate, corresponded a more regular trend of plasmatic levels obtainable consequently to the administration to the patient.
If, in theory, such approach could have been correct so far as some drugs are concerned, in practice it has been noticed that, in many cases, the pharmacokinetics and pharmacodynamics of the active material in biological liquids are influenced and sometimes strictly determined by chronobiological rhythms. Furthermore, the developments of systems able to release the active material at constant rate has brought about the designing and therapeutical utilization of dosage forms more and more sophisticated that required the use of always new polymeric substances with specific properties from the technological and productive point of view. However, such polymeric materials, which are normally biocompatible are, not always biodegradable as well, and this implies that residues of these polymeric materials employed in creating grid therapeutic systems could remain in the organism and, above all, by repeated administration, cause unwanted accumulation phenomena.
In this respect, the setting in of now and then serious and, in some cases, lethal side effects occurred following the administration of the so called OROS system osmotic pump disclosed in the U.S. Pat. No. 4,160,020, 1979.
In the majority of cases, the slowing down of the active material release is obtained by utilizing gellable hydrophilic polymers capable of swelling in contact with water and/or aqueous fluids, thereby forming a gelled layer. From these systems the active material is in general released according to Fickiam type kinetics, A number of studies and research work have been carried out in the past and also recently aiming at the modulation of the release rate of active principles. This research was originated for therapeutic reasons (for instance the achievement of determined hematic and bioavailability levels of the drug) and because of practical problems related to the timing of the drug administration. Generally these studies to proposals consisting in two layer tablets, prevailingly of concentric type, and capable of a fast release of the active principle whereas the other was formulated so as to provide a slow or delayed releasing of the drug.
In some cases (WO-A-9305769 and EP-A-0384514) the outer layer is that with slow release, whereas the inner one (thus accessible only when the outer layer has fulfilled its function) is of the fast release type.
In other cases (U.S. Pat. No. 2,993,836 and U.S. Pat. No. 2,887,438) the delayed release layer forms the core of the tablet, whereas the outer coating layer is formulated for a fast or instantaneous release of a portion of the active principle.
According to further proposals two layer tablets have been disclosed in which the composition of the slow release layer was taken into consideration.
For instance in U.S. Pat. No. 2,951,792 the slow release layer consists of lipidic matrix formed by fatty alcohols or acids or more generally fatty derivatives. Besides the features relating to the formulation, particular attention is paid to the tablet size and to the extension of the area from which the release takes place.
In the two layer tablet disclosed in GB-A-2123291, the fast release part has a conventional composition, whereas that with slow release must contain at least one surface active ingredient.
Moreover the release delaying agent consists of a mixture of cellulose derivatives and of a slow solubilizing agent for the polymer mixture (particularly PEG). EP-A-63266 discloses a two layer composition (a fast release and a slow release layer) wherein exclusively sodium alginate is used as the release delaying agent. However the prior proposals were not satisfactory for several reasons, whereby it is still of interest the problem of the therapeutical cases wherein the administration (as acute or symptomatic treatment) of a first therapeutically effective dose of an active material is required, whereas in a following step the slow or at a lower rate administration of a maintenance dose of the same or different drug is necessary. These therapeutic needs obviously require complicated posological schemes that are not always correctly adhered to by the patient, especially if outpatient subjects are involved; it is well known in fact that non-compliance with posological schemes is directly proportional to the complexity and number of the daily required of recommended administrations.
In the case, for example, of rheumatic diseases, particularly for the night time pain treatment, it would be better to have the availability of pharmaceutical forms capable of a fast release of a dose of the drug for the so called acute treatment, whilst a second quantity should be slowly released, in order to maintain for a more prolonged period of time a plasmatic level sufficiently high and therapeutically effective. That is, during this second step the release of the active substance should occur at a rate comparable to that of the drug elimination (due to either the metabolism or normal biological elimination processes).
The main object of the present invention is to solve the above explained problems and drawbacks, keeping unchanged the oral administration form by means of tablets. A more specific object of the present invention is a novel pharmaceutical form containing one or more active substances that can be released with different release kinetics and, namely, that such pharmaceutical form be designed and realized to meet the specific therapeutic requirements of particular pathological situations as those quoted in the introduction. The new form is in fact intended mainly of the administration of one or more drugs, one of which must act immediately, while a hematic level or a therapeutic activity for a more prolonged period of time is required for the second active substance (or for a portion of the same active substance).
These objects are achieved with the pharmaceutical form of the invention, which consists of a solid form having at least two layers of which:
at least a first layer contains an active material, carried with usual excipients and additives, that are able to promote the compressibility of the mass, in which the active material is distributed, such as to guarantee an immediate release of the active material, and
at least a second layer, superimposed upon the first one which, carries a portion of the same active material of said first layer or a second active material, the formulation of said second layer involving the use of excipients and adjuvants which can adjust the releasing rate of the active material at a definitely differentiated rate in comparison with that of the above mentioned first layer.
The novel formulation in accordance with the present invention allows, the use of well-established production technologies and to obtain the possibility of administering one or more active materials that are released by the pharmaceutical formulation with differentiated releasing rates.
The designed and realised system, as better pointed out by the examples supporting the present application, is intended for the administration of:
1- One drug only, released at different rates: one quantity immediately and a quantity within a prolonged and/or programmable period of time.
2- Two drugs, one of which is immediately released and the second one within a more prolonged period of time.
3- Association of two drugs, of which one quantity (drug 1+drug 2) is immediately released and one quantity (of both) over a prolonged period of time.
4- Three drugs, one of which is released fast, a second one which is released at a "in vitro" programmable speed in a longer period of time, and a the third one, that is released in an even more prolonged period of time.
The invention will now be described in more detail with reference to the accompanying drawings, in which
FIG. 1 shows an embodiment of the invention with two layers a and b;
FIG. 2 shows an embodiment with three layers a, b and c;
FIGS. 3-5 are graphs showing percentage release profiles;
FIGS. 6 is a graph showing plasma levels as a function of time.
In preparing the different layers, besides the active material and depending on its solubility characteristics in water and/or aqueous liquids, polymeric materials capable of adjusting (slow down and/or accelerate) the active material release are also employed.
Among these substances of particular importance as regards the release rate are the so-called disintegrating and superdisintegrating polymers. Exhaustive information about these polymers are contained in the paper by Shangrow R, et el. Pharmaceutical Technology, October 1980, which is, incorporated herein by reference.
With regard to active materials sparingly soluble in water, particular adjuvants to facilitate a rapid solubilization can be used, such as cyclodextrins, superdisintegrators, etc., as reported in the book "Techniques of solubilization of drugs" by S. H. Yalkowsky Ed. M. Dekker, New York 1985, and in the Italian patent application No. 21091 A/90 of Jul. 20, 1990.
Active materials for the prevention of anginous attacks and hypertensive attacks, such as:
trapidil, diltiazem, verapamil, urapidil, or anti-inflammatory non steroidal (NSAID) or steroidal drugs: trapidil (7-diethylamino-5-methyl-1,2,4-triazol 1,5-a!pyrimidine), diltiazem hydrochloride (cis-(+)-3-acetoxy-5-(2-dimethylaminoethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benz othiazepin-4(5H)-one hydrochloride), verapamil hydrochloride (5- N-(3,4-dimetheoxyphenethyl)-N-methylamino!-2-(3,4-dimethoxyphenyl)-2-isopropylv aleronitrile hydrochloride), Urapidil hydrochloride (6- 3-(4-o-methoxyphenylpiperazin-1-yl)propylamino!-1,3-dimethylpyrimidine-2,4(1H,3H)-dione hydrochloride)or non steroidal antiinflammatory drugs (NSSAID) or steroidal diclofenac sodium (sodium 2-(2,6-dichloroanilino)phenyl!acetate), indomethacin ( 1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl!acetic acid), ibuprofen lysine salt (2-(4-isobutylphenyl)propionic acid compounded with L-2,6-diaminohexanoic acid acetate), ketoprofen (2-(3-benzoylphenyl)propionic acid), diflusinal (-(2,4-difluorophenyl)salicylic acid), piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-caboxamide 1,1-dioxide), naproxen (+)-2-(6-methoxy-2-naphtyl)propionic acid), flurbiprofen (2-(2-fluorobiphenyl-4-yl)propionic acid) or sleeping substances and tranquillizers, such as diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one), nitrazepam (1,3-dihydro-7-nistro-5-phenyl-1,4-benzodiazepin-2-one) or antihistaminic and/or antiasthmatic drugs, such as ephedrine ((1R,2S)-2-methylamino-1-phenylpropan-1-ol hemihydrate), terfenadine (1-(4-tert-butylphenyl)-4- 4-(α-hydroxybenzhydryl)piperidino!butan-1-ol), teophhylline (3,7-dihydro-1,3-dimethylpurine-2,6(1H)-dione), chlorpheniramine ((�)-3-(4-chloro-phenyl)-NN-dimethyl-3-(2-pyridyl)propylamine hydrogen maleate) can be carried in the described pharmaceutical form.
As polymeric substances for the preparation of said for fast release layer of the active material, cross-linked polyvinylpyrrolidone, microcrystalline cellulose and cellulose derivatives, cross-linked sodium carboxymethylcellulose, carboxymethylstarch, potassium methacrylate-divinylbenzene copolymer, polyvinylalcohols, starches, starch derivatives, beta cyclodextrin and dextrin derivatives in general may be for example employed. Said polymeric substances make up from 10% to 90% of the layer's weight.
In said first layer other adjuvant substances may further find utilization, consisting of the so called effervescent mixtures, namely that can rapidly disintegrate the tablet or, in the specific case, the layer when it comes in contact with aqueous liquids and, preferably, with gastric juice.
These substances include the carbonates and bicarbonates of sodium and of other alkali metals or earth-alkali metals, the glycine sodium carbonate and other pharmaceutically acceptable salts, capable of producing effervescence in an acid environment.
Depending on the pH of the medium where the rapid disintegration of the compacted product should occur, further substances such as citric, tartaric, fumaric acids that can produce the effervescence and the rapid disintegration of the compacted product may find use in the formulation.
In the preparation of the slow release second layer, adjuvants may be used such as natural and/or synthetic polymeric materials belonging to the class of the so called hydrophilic gellable polymers, capable of slowing down the active material release from said layer.
The polymeric materials for the preparation of the slow release second layer may be selected in the class that includes hydroxypropylmethylcellulose of a molecular weight of between 1,000 and 4,000,000, hydroxypropylcellulose of a molecular weight of between from 2,000 to 2,000,000, carboxyvinylpolymers, polyvinyl alcohols, glucans, scleroglucans, mannans, xanthans, carboxymethylcellulose and its derivatives, methylcellulose and, in general, cellulose derivatives.
Of all the mentioned polymers various types are commercially available, characterized by different chemical, physical, solubility and gelling properties, in particular concerning hydroxypropylmethylcellulose, various types of different molecular weight (1,000 to 4,000,000) and different substitution degree can be employed.
Said hydroxypropylmethylcellulose types exhibit different characteristics, being prevailingly erodible or prevailingly gellable as a function of the viscosity in the polymeric chain. According to the solubility of the active material and of the hydration and/or erosion properties of the polymeric substance, different release and "in vitro" programmable rates could be achieved by suitable tests.
Said polymeric substances might be present in a percentage of 5 to 90% based on the total weight of said second layer but, preferably, from 50 to 85%.
Finally, excipients usually employed in the pharmaceutical technics can find application, such as mannitol, lactose, magnesium stearate, colloidal silica and others like glyceril monostearate, hydrogenated castor oil, waxes, mono-, bi- and tri-substituted glycerides.
Onto said finished tablets, a film of polymeric gastroresistant and enterosoluble material may be further applied, in order to allow the activation of the system only after the tablet has reached the duodenal-intestinal tract.
Pharmaceutical systems of this latter type might find use to make tablets specifically designed and intended to release the active material in the last part of the intestinal tract, namely at the colon level.
Cellulose acetophthalate, cellulose acetopropionate, cellulose trimellitate, acrylic and methacrylic polymers and copolymers, having different molecular weight and solubility depending on different pH values, may be used as polymeric materials for realizing gastroresistant systems.
Said gastroresistant and enterosoluble materials can be also utilized associated with retardant polymers.
Said gastroresistant and enterosoluble materials can be also utilized in combination with retardant polymers.
The pharmaceutical forms of the present invention allow therapeutic results and quite impredictable advantages to be reached as will be confirmed by experimental tests carried out both "in vitro" and "in vivo".
Referring for sake of description simplicity to the case wherein only one active material is administered either in the immediate release form or in that of programmed release, the pharmaceutical form of the present invention is likely to achieve the following results:
1) The immediate release of an amount of active material such as to set a plasmatic concentration equal to the minimum threshold needed for a symptomatic or active treatment; If, in the pharmaceutical forms for oral use with immediate release, a peak or maximum is reached in a time relatively closed to the administration arriving at a plasmatic concentration greater than the minimum required for a symptomatic therapeutic effect, this also means that with the new pharmaceutical form of the present invention the administered dosage is lower as compared to that usually estimated for the acute treatment.
Considering also that many of the drugs involved in the present invention, as for example the anti-inflammatory active principles, often exhibit high toxicity and are gastrodetrimental the important advantage thus achieved is clearly evident.
The slow or retarded release of the same active material starts when a plasmatic concentration, higher than that which can be achieved with the only slow release form is already secured, whereby higher plasma levels are obtained than those which can be achieved with only the slow release form, the time being the same from the beginning of the treatment.
Another aspect adds to such therapeutically important results, namely that the pharmaceutical form of the present invention is prepared by means of production technologies consolidated in the practice and presently used, whereby are directly applicable on industrial scale.
The following examples describe, by way of illustration and by no limitation whatsoever, the preparation of the pharmaceutical forms according to the invention.
Two-layered tablet, containing 200 mg trapidil, one layer of which contains 50 mg for a fast release and the second slow release layer with additional 150 mg trapidil.
1-a Preparation of the granulate forming the first fast release layer, comprising as active material 50 mg trapidil.
______________________________________Trapidil (B.15910100) 50.0 mgLactose (C. Erba, Milan, I) 25.0 mgStarch maize (C. Erba, Milan, I) 15.0 mgPolyvinylpyrrolidone (Plasdone K29-32, 1.0 mgGaf Corp., Wayne, NY USA)Carboxymethylstarch (Explotab, Edward 10.0 mgMendell Co. Inc. Carmel, NY USA)Magnesium stearate (C. Erba, Milan, I) 2.0 mgTalc (C. Erba, Milan, I) 3.0 mgTotal 106.0 mg______________________________________
Trapidil, lactose and maize starch are mixed and wetted with a 10% polyvinylpyrrolidone solution in ethanol, followed by sieving on a 25 mesh sieve, drying so produced the granulate in an oven up to constant weight and sieving again on the same sieve. Carboxymethyl starch, magnesium stearate and talc are added, mixing thereafter in Turbula for 15 minutes.
A granulate (granulate A) is in this way made, showing good flow and compacting properties. The granulate undergoes the compression step as hereinafter described.
1-b Preparation of the granulate used to prepare the second layer containing 150 mg slow release trapidil
______________________________________Trapidil (B.15910100) 150.0 mgMannitol (C. Erba, Milan, I) 85.0 mgHydroxypropylmethylcellulose (Methocel K 4 M, 45.0 mgColocorn Orpinton UK)Polyvinylpyrrolidone (Plasdone K29-32, 7.5 mgGaf Corp., Wayne, NY, USA)Magnesium stearate (C. Erba, Milan, I) 1.5 mgColloidal silica (Syloid 244,Grace GmbH, Worms D) 1.5 mgTotal 290.5 mg______________________________________
Trapidil, mannitol and hydroxypropylmethylcellulose are mixed and wetted with a 10% ethanol solution of pyrrolidone.
After sieving on a 25 mesh sieve, so produced the granulate is dried in an oven at 40� C. up to constant weight and sieved again on the same sieve. The magnesium stearate and colloidal silice are added and mixed in Turbula for 10 minutes. With this procedure a granulate (granulate B) is obtained with good flow and compacting properties. The granulate undergoes the compression step as hereinafter described.
1-c Preparation of finished systems (by compression)
A Layer Press rotative compression machine (Manesty Liverpool U.K.) is, used to prepare tablets as shown in FIG. 1b; this machine as known by those skilled in the art, consist of a rotative compression mechanism equipped with two or three loading stations and thus able to make two or three layered tablets. In the specific case, the machine is assembled and set to produce two layered tablets. The machine for this purpose is equipped with oblong (capsule-type) punches of 16�16 min. The first loading hopper is filled with the granulate described at point 1-a (granulate A), while the second one is filled with the granulate described at point 1-b (granulate B). The First loading station is adjusted so as to provide layers of 106 mg granulate (equal to 50 mg active material) while the second loading station is adjusted so as to provide an amount of granulate B (slow release active material) of 290,5 mg equal to 150 mg active material.
By operating as previously illustrated, two-layered tablets, are produced weighing on average 396.5 mg which totally contain 200 mg trapidil. Said finished systems are subjected to the dissolution test as hereunder specified.
1-d Dissolution test
To evaluate the releasing features of the finished (two-layered) systems, the basket apparatus 1 (described in USP XXII) is utilized, operating at 100 r.p.m. and using as a dissolution fluid 1000 ml of deionized water at 37� C. The active material release is monitored by U.V. spectrophotometric determination at 299 nm, with an automatic system of sampling and quantitative determination, and with an automatic data processing program(Spectrocomp 602, Advanced Products-Milano) The test results are listed in Table 1
TABLE 1______________________________________Time (min) % released trapidil______________________________________15 27,030 37,560 45,3120 57,7240 75,5360 100,6______________________________________
It clearly appears that 25% of the 200 mg of the carried active material (first amount) is fast released in 15 minutes, whereas the second amount is released in about 6 hrs.
The data reported in Table I have been transferred in the FIG. 3 graph: to help in a comparison, FIGS. 4 and 5 report the graphs obtainable with the same dissolution test procedure, referred respectively only to the fast release form of 50 mg active material (that is of the trapidil itself) and only to the slow release form of 150 mg active material.
FIG. 6 shows the same release curves in just one graph, and it is easy to appreciate that, with the pharmaceutical form of the present invention, (curve a) an initial peak clearly higher than that attainable with the only form of retarded release is achieved, making it sufficient to add in the immediate release pharmaceutical form an active material concentration sufficient just to exceed the minimum threshold at which an immediate effect or, in other words of symptomatic treatment is attained to achieve the desired result.
In other words, from FIG. 6 it can be immediately appreciated that in the immediate release form (curve b) the 100% level of the active material release is quickly reached (within 15 minutes) and this makes to estimate that such a drug's quantity might be similarly absorbed attaining effective plasmatic concentrations. Likewise, in the case of administering the only one form of slow or retarded release (curve c), the total release occurs after a very long time, and therefore, a release level "in vivo" sufficient to produce a therapeutic effect will also be reached after a longer time.
Thus before the present invention, the therapeutical choice had to be made between adopting a symptomatic or shock therapy and a treating and maintaining therapy without, or at least with a poor symptomatic effect.
With the pharmaceutical form of the present invention comprising the two dosages of the immediate release and slow release forms respectively, as it is easy to verify from the corresponding curve (c) of FIG. 6, the release is about twice as much as that of the only slow release form, and is high enough to produce an immediate symptomatic effect.
Once this initial function is completed, the release takes place in the same way as with the slow release form, which consequently affect the release of the immediate release form.
An experimental confirmation of the previous "in vitro" tests has been obtained by carrying out the "in vivo" treatment in well being volunteers at the following dosages (and by plotting in FIG. 6 the corresponding plasmatic levels as a function of time):
(i) Fast release pharmaceutical form containing 100 mg of trapidil (curve b of FIG. 6) and
(ii) Slow release pharmaceutical form containing 200 mg of trapidil (curve c of FIG. 6) and
(iii) Pharmaceutical form according to the presente invention containing 200 mg of trapidil wherein the 25% of the active material dose was present as a fast release amount, and the remaining 75% was present as a slow release amount (curve a of FIG. 6).
The numerical data of the aforementioned plasmatic levels are listed in Table 1A which follows.
TABLE IA______________________________________Time Fast system 100 mg Slow system Fast/Slow system(hours) (ng/ml) 200 mg (ng/ml) 200 mg (ng/ml)______________________________________0.5 1015 482 17671 1969 762 27242 1464 1638 32053 1046 1479 28554 575 2058 28136 239 466 18158 76 421 130112 11 14 44024 8 0 0______________________________________
From Table 1A and FIG. 6 it can be immediately appreciated as the pharmaceutical form of the present invention makes it possible to reach the above mentioned therapeutic advantages, namely the effect of the symptomatic treatment (obviously by adjusting in a suitable manner the dosage of the fast release portion and that of ensuring that the slow release Form will maintain its effect.
In addition the symptomatic effect is obtained with a lower dosage of active principle (obviously calculated so as to exceed the threshold over which the acute effect is attained), with the clear advantages in terms of lower toxicity or, in the case of anti-inflammatory non-steroidal drugs (FANS), lower gastrolesiveness besides a minor quantity administered to the patient.
--Two--layered tablet containing 400 mg of 4-methoxy-N3-(3-pyrimidilmethyl)1,3-benzenedicarboxamide (compound hereinafter indicated with G619), of which one layer contains 200 mg of active material for a fast release and in a second layer there are 200 additional mg of G619 for slow release.
2-a Preparation of the granulate forming the first fast release layer, containing 200 mg of G619 as active material.
______________________________________G 619 (Farma resa batch n. 89043 200.00 mgMaize starch 75.00 mgMannitol 25.00 mgPolyvinylpirrolidone (10% in ethanol) 6.25 mgCarboxymethylstarch (Explotab) 10.00 mgMagnesium stearate (C. Erba) 3.75 mgColloidal. Silica (Syloid 244) 0.75 mgTotal 320.75 mg______________________________________
2-b Preparation of the granulated used for preparing the second slow release layer wherein 200 mg of G619 are contained.
______________________________________G 619 (Farma resa batch N. 89043) 200.0 mgMannitol (C. Erba, Milan, I) 50.0 mgHydroxypropylmethylcellulose (Methocel K 4 M, 30.0 mgColorcon, Orpington UK)Hydroxypropylmethylcellulose (Methocel E 5, 30.0 mgColorcon, Orpington UK)Polyvinylpirrolidone (Plasdone K29-32, 13.0 mgGaf Corp, Wayne NY USA)Magnesium Stearate (C. Erba, Milan, I) 2.5 mgColloidal Silica (Syloid 244, Grace GmbH, 0.5 mgWorms, D)Total 326.0 mg______________________________________
Both these layers are prepared as per Example 1.
2-c Preparation of the finished systems (by compression)
The same rotative compression machine, equipped with oblong (capsule-type) punches of 19�9 mm, as described in Example 1, is used to prepare the tablets. The first loading hopper is filled with the granulate described at point 2-a (granulate A), while the second one is filled with the granulate described in 2-b (granulate B). The first loading station is adjusted in order to provide layers of 320,75 mg of granulate (equal to 200 mg active material), while the second loading station is adjusted so as to provide an amount of granulate B (with slow active material release) of 326.0 mg equal to 200 mg active material.
By operating as previously illustrated, two-layered tablets with an average weight of 646,75 mg, totally containing 400 mg of G619, are produced.
Said finished systems are subjected to the dissolution test as hereunder specified. 2-d Dissolution test
To evaluate the releasing features of the finished (two-layered) systems, the 2 paddle apparatus (as per USPXXII) is used, operating at 100 r.p.m. and with 1000 ml at 37� C. of deionized water used as a dissolution fluid. The active material release is monitored by U.V. spectrophotometric determination at 251 nm, with an automatic system of sampling and dosage, as well as with an automatic data processing program (Spectracomp 602, Advanced Products Milano).
The results of the tests carried out are listed in Table II.
TABLE II______________________________________Time (min) % Released G619______________________________________15 53,030 58,560 65,0120 78,2180 90,3240 98,5360 100,4______________________________________
It is evident that of the 400 mg of the carried active material, 50% (first amount) is fast released, in 15 minutes, whereas the second amount is released in about 4-6 hours.
Two layer tablet containing 800 mg of ibuprofen, one fast release layer containing 250 mg of active principle and the other slow release layer containing 550 mg of ibuprofen.
3-a Preparation of the granulate forming the first fast release layer containing as the active principle 250 mg of ibuprofen.
______________________________________Ibuprofen (CFM B. 2235/18/87) 250.00 mgMaize starch (USP grade, C. Erba, Milan, I) 74.63 mgDye (Nacarat Red E 120) 0.25 mgMethylcellulose (BDH, Poole, UK) 1.25 mgSodium laurylsulfate (C. Erba, Mllan, I) 0.75 mgCarboxymethylstarch (USP grade) 18.75 mgCrosslinked polyvinylpyrrolidone 7.50 mg(Polyplasdone XL, ISP, Wayne, US)Magnesium stearate (C. Erba, Milan, I) 3.37 mgTotal 356.50 mg______________________________________
The manufacturing process comprises the preparation of a granulate obtained by admixing, in a sigma mixer (Erweka model type K 5, Frankfuert a.M., D) the proper amounts of active principle and 50 mg of maize starch; the homogeneous powder mixture is wetted with a 1.3% (w/v) aqueous solution of methylcellulose in which the sodium laurylsulfate and the dye have been previously dissolved; the homogeneously moistened mass is forced through a 25 mesh (710 um) grid leading to a regular granulate which is dried in an air circulation oven at 40�-45� C. The granulate, after drying to constant weight, is placed into a powder mixer (Turbula mod.T2A, Bachofen, Basel, CH), added with the crosslinked polyvinylpyrrolidone, the remaining 24.63 mg of maize starch and the carboxymethylstarch and admixed for 20 minutes. Then the magnesium stearate is added and the admixing is continued for further 20 minutes. The granulate, lubricated and analyzed for the content of active principle, is subjected to the hereinafter described compression phase.
3-b Preparation of the granulate used for the second slow release layer containing 550 mg of ibuprofen.
______________________________________Ibuprofen (CFM B. 2235/18/87) 550.0 mgHydroxypropylmethylcellulose 183.3 mg(Methocel K4K Colorcon, Orpington UK)Mannitol (C. Erba, Milan, I) 110.0 mgPolyvinylpyrrolidone (Plasdone 18.3 mgK 29 ISP, Wayne, NY USA)Talc (C. Erba, Milan, I) 16.5 mgMagnesium stearate (C. Erba, Milan, I) 3.7 mgColloidal silica (Syloid 244, 0.9 mgGrace GmbH, Worms D)Total 882.7 mg______________________________________
A granulate is preparaed by admixing in a sigma nixer (Erweka model type K5) the proper amounts of ibuprofen, mannitol and hydroxypropylmethylcellulose (Methocel K4M, apparent viscosity 4,000 cP); the homogeneous powder mixture is wetted with a 10% (w/v) alcoholic solution of polyvinylpyrrolidone and the homogeneously wetted mass is forced through a 25 mesh grid leading to a regular granulate which is dried in an air circulation oven at 40�-45� C. The granulate, dried to constant weight, is placed in a powder mixer (Turbula model T2A) and added with talc, magnesium stearate and colloidal silica, and admixed for 20 minutes. The granulate is then compressed as hereinafter described.
3-c Preparation of the finished systems (by compression)
For the preparation of the tablets the same rotating compression machine and the same operating conditions as in the previous examples are used, so as to obtain two layer tablets.
The resulting tablets have an avenge weight of 1239.2 mg containing on the whole 800 mg of ibuprofen, which are subjected to the dissolution test as hereinafter specified.
3-d Dissolution test
In order to assess the realeasing behaviour of the tablets the 2 paddle apparatus is used (USP XXII) adjusted for a vessel of 5 liters capacity in order to maintaining the sink conditions, the test being carried out at 100 r.p.m. and using as the dissolution fluid 5 l of simulated intestinal fluid (USP XXII), without enzymes at 37� C. The release of the active principle is monitored by U.V. spectrophotometric measurement at 223 nm, using an automatic sampling and reading system (Spectracomp 602 of Advanced Products, Milano, I).
The results of the test are reported in the following table III
TABLE III______________________________________time (h) Released % (total)______________________________________0.5 31.32 37.04 42.98 52.912 66.216 78.520 88.024 99.1______________________________________
It is thus seen that from the tablets the fast release of the first amount of drug (about 31% of the total) is obtained within 30 minutes, whereas in the second phase, definitely differentiated from the first one, the drug is released under controlled rate in about 24 hours.
The foregoing examples refer to pharmaceutical forms containing only one active material divided within two layers.
It is understood that is also possible and foreseen within the scope of the present invention to produce, with the above mentioned procedures, three-layered pharmaceutical forms, that is with delayed release of the same active material but adjusted at different rates from one layer to another.
Similarly, the third layer might instead include another active material for supplementing, at a certain point of the treatment, the therapeutic effect of the first active material, already released in fast and/or slow released form as well.
So far the realisation of the aforementioned pharmaceutical forms is concerned, these are made with the galenical technics already cited, and by employing the adjuvants and carriers well known by themselves in the technical field.
It should be finally noted that the previous list of the active materials which can be used in the pharmaceutical forms of the present invention is not intended as a limit since, as it is evident, the invention is extended to all the active materials, for which is foreseen or foreseable either the fast release administration for a systemic therapeutic effect or the slow release administration for a treatment of maintaining or prolonging the main therapeutical effect.
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In Excel 2010: Pivot Tables in Depth, author Curt Frye provides comprehensive, hands-on tutorials on Excel PivotTables, including more advanced techniques such as using macros and the new PowerPivot add-in. The course shows how to connect and consolidate data sources to power PivotTables, sort and filter records, display data in a PivotChart, print tables and charts, and also introduces the DAX language for performing advanced summaries in PowerPivot. Exercise files are included with the course.
Most of the time when you sort PivotTable data you can use the standard methods to sort the values in alphabetical or numeric order. There will be times though when you might want to define a custom list of values and sort a PivotTable using those values. For example, if your company has stores in four regions, north, south, east, and west, and you want the regions to show in that order, instead of alphabetical order, you can create a custom list and use that list to sort your fields' values. So for this example, I have a PivotTable with sales data for four regions, east north, south, and west, but I want to have them sorted into the order north, south, east and west, instead of alphabetical order like they are now.
To do that we can create a custom list. So click the File tab on the Ribbon to display the Backstage view, and then click Options to display the Excel Options dialog box, and then on the Advanced page scroll down, which I'll do using my mouse with scroll wheel, and then under the General heading, click the Edit Custom List button. Doing so displays the Custom Lists dialog box. Now you can create your list and in this case we will do it by typing it in.
So here in the List Entries bo, we can type North, then press Enter. Each item needs to be on its own line, and we have South, Enter, East, Enter, and West. So all the entries look to be correct and spelled correctly so I can click OK. And then click OK again to close the Excel Options dialog box. And now I can sort the field values based on the new list that I have just created.
Now to sort by row labels, in this case, the regions, into north-south-east-west order, just click any cell that contains one of those labels, in this case East is already selected, and then on the Options contextual tab of the Ribbon, click the Sort button to display the Sort dialog box, and then select the ascending A to Z option by, and then make sure that the region field is selected, and then click the More options button. In the More Sort Options dialog box, clear the Sort Automatically checkbox here at the top, and then under First key sort order click the down arrow and select list that you want to use, in this case North, South, East and West, and then click OK.
Then back in the Region dialog box click OK again, and when you do Excel applies the sort using your custom list. Custom lists help you arrange your PivotTable data to emphasize the elements you feel are most important, making sorting a more powerful and useful tool than ever before.
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Power Metal
Power Metal is a generally up-beat metal genre consisting of fast guitar hooks and catchy tunes, often associated with neo-classical metal and progressive metal, and occasionally glam metal. The earliest influences of power metal are traced back to 1976 when the musical group Rainbow(led by Ronnie James Dio) released the track, "Stargazer". The track is widely considered the first power metal song. The genre achieved widespread popularity through Helloween's 'Keeper of the Seven Keys' albums. Helloween, with artists Blind Guardian and Stratovarius, are considered the pioneers of the genre.
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Posted 04/06/2013 05:33:15 EDT
Sad that this is a newsworthy item in the 21st Century.
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Just in case anyone thinks that a new Pope means the Vatican is changing, think again.
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Just found out our neighborhood in Cambridge is called Neighborhood Nine. Who knew?
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Are you suggesting married couples stop having sex? How absurd. Birth control can fail, you know. It happened to me and it's happened to millions of women like me. I carried the baby to term because a more »
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So sorry about Otis, Elizabeth. We lost a beloved dog last Christmas and her absence made the house feel so empty. You don't realize how much space dogs take up: nails clicking on the floor, sighs and more »
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My house in No Cambridge (build on fill) was shaking so hard that there were loud creaking sounds.
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Havi B3 Pro 1
"My first quality IEM purchase was the Hifiman RE-400 when they first came out. I was used to low end Skullcandy sets at the time, and I really wanted to see what "reference sound" sounded like for a reasonable price of under $100. At the time, I felt anything above that price was absurd for me to purchase. From the first listen, the RE-400 showed me what quality sounded like. I was..." --bhazard
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Another goal of innovation achieved by Essepi! The EP-10 PLUS has already been tested and stumentalmente "on stage" by Stevan Martinovic (noise) and directly on the stage by the "Stadium". The most important innovation is the exclusive three-way system: technology mixed with a dynamic woofer and midrange - tweeter balanced armature allows us to provide a product with great...


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Three Rivers Press | Apr 03, 2013
| 222 Pages
Three Rivers Press
| Apr 03, 2013
| 222 Pages
The latest scientific reports show vitamin E as an effective shield against heart disease, cancer, and problems associated with aging. In this important new book, Ruth Winter presents the fascinating history and current scientific excitement about this inexpensive, vital, and formerly unappreciated vitamin. -How the antioxidant effects of vitamin E work to protect the body against disease and aging-How vitamin E helps to build muscle and strengthen the heart-The beneficial effects of vitamin E on the skin-The documented effects of vitamin E for preventing impotence and maintaining fertility-The best ways to incorporate vitamin E into your diet Here is everything you need to know about vitamin E and how medical science has documented its use for maintaining health and vitality.
RUTH WINTER, M.S., is an award-winning author of thirty-seven books. She has contributed to Good Housekeeping, Harper's Bazaar, Self, and Vogue, and has also appeared on many TV programs, including Good Morning America and Today. She runs an informational website… More about Ruth Winter
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No student has been fatally shot in a Chicago public school since 1992. The last two fatal shootings occurred in high schools on Chicago's South Side during a 10-day period from November 10 to 20, 1992. A youth accidentally shot himself at school in the first incident. The second incident that is the focus of this study resulted in the death of one 15-year-old boy, the serious wounding of a second youth, and the shooting of a third youth in the foot. The youth who was killed, Delondyn Lawson, was identified in the first front page news stories (November 20, 1992), while the shooter and other two victims were not.
The initial stories came on Friday, the day after the Thursday shooting. They reported the shooting as a response to a skirmish about a gambling debt. The gambling involved a dice game earlier in the week in a school washroom. The shooter was described as having "fired a handgun about four times randomly toward the skirmish." Two unidentified suspects were reportedly arrested, and it was noted that metal detectors at the school were not functioning on the day of the shooting because they were being used on randomly chosen days to minimize cost and disruption.
The next day, Saturday, the story was again on page one and the headline read, "Even Safety of Schools Shattered, Student Slain, 2 Others Wounded in Hallway at Tilden" (November 21, 1992). The story was built around the victim's mother, Linda Lawson, who asked, "What was I supposed to do with a 15-year-old? I drove him there in the morning, and I was there at 2:02 p.m. to pick him up. What else can you do? You have to send them to school." The story noted that Delondyn Lawson had been fatally shot in the back, and two other youths were injured.
Joseph White was identified in this story as the alleged shooter and as a 15-year-old freshman at Tilden now charged in adult court with first degree murder. He had fled the school pursued by other youths and a security guard and hid under a nearby back porch before being found and arrested. The story again mentioned the dice game and now briefly the possibility of gang involvement. Delondyn Lawson was described as a "great dancer and funny," a boy who liked football and video games and who was trying to stay away from gangs.
This second story also marked the entry of Mayor Richard Daley into the matter. The mayor responded to the random use of metal detectors, which was defended by the police and schools. "They have to realize you have to run them every day," the mayor insisted, "because if we run them in the federal building and in the state criminal justice system, you can't get [guns] in there." The mayor asked, "What's more important? Children are more important than anybody else in society. And that shooting, the death of a young child, directly affects everyone." The mother of a


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35 year old man | Canton, OH, USA | Seeking women 23-39 within 100 miles of Cambridge, OH
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Aaannndddd I'm back. First off, please be real. Please have your stuff together and know what you want. If its just the bedroom stuff there is a whole separate website for that. If you are looking for a relationship Great! But please dont still be involved with someone else. In the immortal words of the famous youtube lady "aint nobody got time for that". Now Lets see... what can I say about me? I guess first off my name is Krs. I'm 33 years old. I'm from Casper Wyoming and I just moved here a couple months ago. I'm a pretty easy going person and I dream of a drama free existence (not gonna happen I know but hey... LOL)so if you are a drama magnet please stay away from me. I don't like people that are wishy washy or play games. I've had plenty of that childish crap already and am really not in a place where I am willing to deal with it. I hold tight to my beliefs and will respect yours as long as you respect mine. My kids are my world and NOTHING will ever ever change that. I enjoy life and have found that the key is not to find someone that makes you happy. the key is find happiness first and then find someone to share it with. I am looking for someone that knows what they want out of life and isn't afraid to go get it. I have been told that I am too ambitious but I have goals in life and I will reach them no matter how much blood sweat and tears it takes to get there. I don't like drama, stupid people, hypocrisy, prejudice, mushrooms, or the Oakland Raiders. Think that pretty much gets the basics covered... If our paths cross I'm sure we will have ample opportunity to learn more of each other. Feel free to drop me a line and say Hi sometime.
Camping , Coffee and conversation , Cooking , Dining out , Fishing/Hunting , Music and concerts , Exploring new areas , Playing sports , Travel/Sightseeing , Watching sports , Wine tasting
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I exercise 3-4 times per week.
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I listen to all kinds of music but mostly country. I enjoy cooking and am the self proclaimed king of the grill lol. If you havent tried my tequilla lime ribs you dont know what you are missing!!
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Product Details
BedXTender HD™ Bed Extender by AMP Research®. Multiple designs of bed extenders are available whether you prefer a cage with the maximum amount of room, one designed for use with tonneau covers, or one that's custom-designed for carrying motorcycles. Aluminum tubing provides light weight and high strength that won't corrode, and a choice of powder coat finishes prevents chips and scratches. Replacement brackets and latch pegs are available, as well as custom brackets for irregularly-shaped pickup walls.
- Aircraft-grade aluminum tubing provides high strength, light weight, and resistance to corrosion
- Upright vertical pieces made from glass-reinforced nylon composite are durable yet flexible to provide cushioning and structural support
- Bed extender width is adjusted for a perfect fit on your truck using the upright vertical pieces
- Great for short-bed pickup trucks
- Bed Extender cage is easily removable from your truck to double as a seat or bench while at a tailgate party
- Creates a fenced-off proximity inside your bed when tailgate is up, then flips over to extend your walled storage area by 2 feet when the tailgate is down
- Comes with two attached hold-down straps for securing the bed extender in place when the tailgate is down
- Max Bed Extenders are shaped to provide the largest amount of corralled space to secure cargo and gear
- Sport Extenders provide extra clearance needed for tonneau cover rails
- Moto Extender cage shape is tailored for motorcycle hauling
- Durable powder coat (available in multiple colors) provides a hard outer finish that is resistant to chips, scratches, and the elements
- Replacement "Quick Latch" mounting brackets and latch pegs for hold-down straps are available
- Custom L-shaped brackets are available for irregularly-shaped pickup walls
- 3-year/36,000-mile manufacturer warranty
- Manufactured in the United States
AMP Research invented the BedXTender in the late 1990s, and has since perfected it to the current form you see here today. Keep it inside your bed with the tailgate up to create a two-foot fenced in area when heavier cargo needs to be separated from smaller items that can be damaged. When it's time to carry longer items that won't fit inside the bed, simply lower the tailgate and flip the BedXTender over to extend your usable carrying area by two additional feet. Vertical cross pieces provide structural support for the horizontal bars, and are designed to be both durable and shock-absorbing.
AMP Research offers three different bed extender designs. The Max Bed Extender is U-shaped to provide the largest amount of corralled space, the Sport Extender provides extra clearance needed for tonneau cover rails, and the Moto Extender cage taper is designed specifically with motorcycle hauling in mind. Replacement "Quick Latch" mounting brackets and latch pegs for hold-down straps are available, and custom L-shaped secondary brackets are available to offset pickup bed walls with irregular indentations or pockets.
All bed extenders feature three horizontal aluminum bars which span the entire width to effectively prevent smaller, lower-height items from sliding through in between. Whether you've got grocery bags, electronic equipment, mulch bags, or large items such as motorcycles or ATVs, you'll truly maximize your truck's carrying ability with any AMP Research Bed Extender. Installation is easy - after drilling a series of three template-guided holes on both sides of your bed, install the bracket pieces that hold your bed extender cage. Aircraft-grade aluminum ensures a minimum of weight is added to your vehicle, and a choice of durable powder coat finishes provides a surface that's extremely resistant to chips, scratches, and the elements. AMP Research builds all components in the United States and backs them with a 3-year / 36,000 mile warranty against failure due to manufacturing defects.209.00 245.00
Founded in 1980 in southern California, AMP Research came together with a wealth of engineering talent drawn from company founder Horst Leitner and others who were previously involved in motorcycle racing and engineering. During the 1980s and 1990s, AMP Research pioneered the first 4-stroke engines for off-road motocross bikes as well as other suspension and chain torque advancements for bicycles and motorcycles. Hauling dirt bikes to racing events in the back of their pickup trucks, company engineers rigged up temporary bed extenders to keep chairs and other items from sliding out on the road when tailgates were down. What they did worked so well, AMP Research patented the idea and introduced it for 1998 - quickly becoming a supplier to vehicle manufacturers that offered the bed extenders as factory equipment. During the following decade, AMP Research pioneered power retracting running boards and has become a featured supplier to major automakers who use them as well. AMP Research is ISO 9001:2008 certified for best business practices in manufacturing and customer satisfaction, and their range of high-quality products is widely respected throughout the industry. CARiD is proud to offer the best values on the full AMP Research lineup of power retracting running boards, step pads, bed extenders, and all individual replacement parts at prices that can't be beat.Product Reviews (13)
Every Customer can leave a review about our service and the product that was purchased. In order to leave your review for your new product, please follow the link in the email you receive after completing your purchase. You can rate appearance, ease of installation, price/value and product quality.AMP Research® - BedXTender HD™ Bed ExtenderAverage Rating: 4.7 of 5APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITYShow Next 10 Shop Now(4.3)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2011 Dodge Ram | Posted by Jeffrey | (Florence, KY)
Nothing better than to now open tailgate and there is something there to holds stuff close to the tailgate. No more climbing in the truck to get your items that have slid all over your truck. Great for making your bed bigger for those big jobs. Made of good material and very easy to put together. I'd also get the other brackets as well better for locking in place and removing from truck. Good price for what your getting.Was this review helpful for you? YesNoShare this review:(4.5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITYCare And Fast2009 Ford Ranger | Posted by Mohammad | (Dubai, AA)
The extender came in very good condition and handled with care. The joints were so useful. Thanks a lot.Was this review helpful for you? YesNoShare this review:(5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITYBedXTender| Posted by Earl | (Kitchener, ON)
Nice looking product. Easy to install.Was this review helpful for you? YesNoShare this review:(4.8)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY1983 Ford Ranger | Posted by Lorenzo | (Oshawa, ON)
Took 20 minutes to install and works great.Was this review helpful for you? YesNoShare this review:(4.5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2013 Toyota Tacoma | Posted by garry | (Westbury, NY)
Easy installation, durable materials,Was this review helpful for you? YesNoShare this review:(5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITYGreat Part2013 GMC Canyon | Posted by Andrew | (Mission, TX)
This device makes removing the extender so easy.Was this review helpful for you? YesNoShare this review:(5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2013 Toyota Tacoma | Posted by Andrew | (Mission, TX)
Easy installation and really fits great.Was this review helpful for you? YesNoShare this review:(4.8)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2013 Chevy Colorado | Posted by David | (Leominster, MA)
BedXTender was easy to install and works great.Was this review helpful for you? YesNoShare this review:(5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2013 Toyota Tundra | Posted by Yunier | (Key Largo, FL)
This product is very durable. Looks great and is extremely easy to install. Definitely recommend it!Was this review helpful for you? YesNoShare this review:(5)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2013 Toyota Tacoma | Posted by Cynthia | (Tolleson, AZ)
Very nice piece. Pretty easy to install, only took me about an hour. Looks very nice and appears to be well made. I like the black powder coat finish... It looks sharp. And while I wondered at the $200 price, it is still cheaper than Toyota OEM, and I like the look of this extender better than Toyota's stock one.Was this review helpful for you? YesNoShare this review:
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Product Reviews (13)
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Children usually
progress in a natural, predictable sequence from one developmental milestone to
the next. Children who are 12 to 24 months of age make gains in five major
areas: physical growth, cognitive abilities, emotional and social development,
language skills, and sensory and motor development.
Although most children reach milestones, such as walking
and talking, by a specific age, it is important to remember that development
happens at an individual pace. Also, many children tend to make progress in one
area, such as talking, while another skill, such as walking, levels off. If
your child has a slight delay in an area, it does not always mean there is a
problem. But be sure to talk to your doctor anytime you have a concern.
12 months (1 year) of age many children are walking without help or by
holding onto furniture ("cruising"). Most children will have a few teeth and
like to put almost anything in their mouths that they can. And many children
will say a few words and practice a lot of sounds. Your child may like to
"flirt" with you and other caregivers.
18 months of age—look out!—most children are walking with ease and anything
within reach is fair game. Your child may like to press buttons, move handles,
and turn knobs. You may notice your child pretending to "feed" a toy or a
similar act that he or she sees. Most children understand 10 times as many
words as they can say, including the names of some people, body parts, and
objects. Many children can often point to an object in a book when
24 months (2 years) of age most children feel excited, confused, and scared
about their emerging independence.
Temper tantrums may start happening regularly.
Children may start thinking in more complex ways, such as recalling events that
happened days earlier. A child's make-believe world gets bigger as he or she
may have play "events" rather than just one act. For example, he or she may
pretend to be a mommy or daddy and care for a baby by changing a stuffed
animal's diaper and feeding it a bottle. Most children say at least 50 words
and use two-word phrases. Not only can most toddlers walk, but they also can
run—and go up and down stairs.
Until age 2, a child born prematurely (3 or more weeks early) will have growth
and development milestones adjusted based on
gestational age. To figure out your baby's adjusted
(corrected) age, doctors subtract the number of weeks your baby was born early
from his or her current age. For example, the corrected age of a 17-month-old
baby who was born premature at 30 weeks is between 14 and 15 months.
Last Revised:
July 19, 2012
Healthwise Staff
Medical Review:
Susan C. Kim, MD - Pediatrics & Louis Pellegrino, MD - Developmental Pediatrics
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How this information was developed to help you make better health decisions
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You can now invite anyone to meet at your favorite Starbucks.
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23 year old woman | Cedar Creek, TX, USA | Seeking men 22-31 within 50 miles
Live life to the fullest
I was born and raised in Austin. I have a little girl who is my world. I am currently a full time student but will be finishing my degree this summer with my last two classes. My major is human resources management. I am out going and love the country. I have my own horse which I can't wait to finish classes and start riding her again. I am one who always pushes to do better no madder what is going on. I am looking for someone who has a good career path, loves sports just about as much as I do, and loves to make someone smile. I'm not so picky because I have always thought that you can't find the right person without meeting them and talking to them. I do have my little girl and she will always come first. I am not looking for a baby daddy for her as she has her own father.
Cooking , Dining out , Hobbies and crafts , Movies/Videos , Music and concerts , Exploring new areas , Nightclubs/Dancing , Travel/Sightseeing , Watching sports
Aerobics, Baseball, Bowling, Dancing, Football, Swimming, Walking / Hiking
I exercise 3-4 times per week.
I have Dogs, Horses
I like Fish
i love to go to Hawaii, and vegas. favorite local hot spot is the piano bar on 6th
Park University, Parkville, MO
my favorite music is country, i hardly get to watch tv but when i do love Duck Dynasty, i love home cooked meals, anything cooked on the grill is best.
for fun i love sports. anything with nascar, football, or baseball i enjoy. i like to spend time out with my horse as much as i can.
Being a full time student I don't have a lot of time to read books. The last one I read was 50 Shades of Grey. I would love to have time to read Chris Kyle - American Sniper
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'3" (160cms)
|3'0" (91cms) to 8'11" (271cms)
|Body type:
|Slender, About average, Athletic and toned, A few extra pounds
|No preference
|Dark brown
|No preference
|No Way
|No Way
|Social Drinker
|Social Drinker, Moderately
|Other profession
|No preference
medical billing
|$35,001 to $50,000
|$50,001 to $75,000, $75,001 to $100,000, $100,001 to $150,000, $150,001+
|No preference
|Have kids:
|Yes, and they live at home (1)
|Yes, and they sometimes live at home, No, Yes, and they live away from home, Yes, and they live at home
|Wants kids:
|White / Caucasian
|White / Caucasian
|I'll tell you later
|Christian / Catholic, Christian / Protestant, Spiritual but not religious, Christian / Other
|Some college
|High school, Some college, Associates degree, Bachelors degree
I am currently finishing my degree in Human Resources


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PLATTSBURGH - The State University of New York at Plattsburgh will host its annual Spring Kick-Off Classic outdoor soccer tournament Saturday, April 9, and Sunday, April 10 at the Plattsburgh State Field House Soccer Complex on Rugar Street. The tournament will have four age groups - U12 boys, U12 girls, U14 girls, and a combined group of U16/U18 girls.
For more information or to register a team, contact Karen Waterbury at 564-4141 or e-mail karen.waterbury@plattsburgh-.edu.
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Planning a 2-3 day trip in South Eastern Arizona. What are your thoughts?
Hey everyone! After having lived in Arizona my entire life, I have never spent very much time in this part of the state. With that said, I was thinking it was about time that I planned a trip to tour through this part of the state and see the highlights. After panning around Google maps for a bit, I have come up with the itinerary below. Anyone think I'm missing anything? By the way, I plan on bringing the wife along so the vineyards are there for her as she would really enjoy that.
Anyone who wants to jump in and give their 2 cents would be much appreciated. :freaky
Southeast Arizona Motorcycle Ride Idea:
<!--[if gte mso 9]><xml> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings> </xml><![endif]-->
Go to Mexico.
There's nothing to see here:
Please keep out:
You sold me! Looks like a cool place to go :evil
Edit: By the way, what road is in that bottom picture? The one with the slab in it?
I take it by the quietness that this might not be the most visited place on the map.
I'm still keeping my fingers crossed that someone will post on this with some good spots to visit. :nod
FR143 from Patagonia to Amado is a tough ride if you are doing it double. It is a rough 2 track in places but very beautiful. I would also go up the road to the observatory that is East of Amado (sorry can't remember name) as this is a fun and twisty road that is pretty well graded. Should be a nice time of year for this. Of course you can always go to Tombstone while you are in the Chiricauhua Mon area also. Then there is the great Portal to Chir Nat Mon road that is really fun and beautiful also and stops you just short of entering NM. Also a little rough and rocky in places but very twisty and up/down. Enjoy your ride .
Thanks for the feed back. I went and found the roads you are talking about on the map. Looks like a great addition to what I was thinking of. I didn't even know there was an observatory on top of what looks to be Mount Hopkins. I might have to check that out. Thanks again.
Hell, when are you leaving? Would love to join if I'm in town.
Looks like a great route, are you looking for another couple to join you at the wineries.....just sayin' !
I think you are skipping the best road in arizona... 191 between Alpine and Clifton
Garden Canyon might not work for ya
Unfortunately you won't be able to go over Garden Canyon Road like you were hoping, it is locked off by Fort Huachuca. Another option is to go over Montezuma Pass via Coronado Memorial Raod off HWY92, then west on Montezuma Canyon road . That is a pretty cool ride up and over the mountain and across the San Rafael Valley. If you stop just past the Coronado National Memorial Visitor's Center, there is a short hike (.5 mi) up to a cave that you can go down into that is pretty cool, just bring some flashlights. That road will take you all the way over to Nogales if your interested also. Any problems and just wave down one of the friendly BP vehicles along the way and they can point you to some more interesting places close by. :drif
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Buy Tickets The Shortest Day
Show From Series
Monday, April 22
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The Shortest Day
December 21, 2012
Free event! Join Film Society and the Centre National de la Cinematographie for a selection of French short films that will screen around the world on the shortest day of the year! Read more »


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North County crime blotter
From police and sheriff's reports.
CARLSBAD: A 49-year-old man was arrested at 10:13 a.m. March 28 on Circulo Adorno on suspicion of domestic battery.
CARLSBAD: A 34-year-old was arrested at 11:57 p.m. March 28 on Rising Glen Way on charges of inflicting corporal injury on a spouse.
CARLSBAD: An 18-year-old man was arrested at 7:54 p.m. March 25 on Jefferson Street on charges of possessing concentrated cannabis.
CARLSBAD: An 18-year-old student at Carlsbad Village Academy was arrested at 5:17 p.m. March 26 on Walnut Avenue on suspicion of possessing a dirk or dagger, among other charges. His bail was set at $25,000.
CARLSBAD: A 50-year-old man was arrested at 6:28 p.m. March 27 on Caminito Estrada on charges of battery with injury.
CARLSBAD: A 29-year-old man and a 25-year-old woman were arrested around 10:30 p.m. March 26 on State Street on suspicion of conspiracy.
DEL MAR: A juvenile was arrested for vandalizing city property and possessing spray paint and marijuana on Camino Del Mar at 27th street, 4:27 p.m. March 27.
DEL MAR: An 18-year-old man was arrested after burglarizing a vehicle on Stratford Court between 2:45 and 2:48 a.m. March 26. Deputies recovered the $165 in electronics he stole from the car.
DEL MAR: A 53-year-old man suffered major injuries after fighting another 53-year-old male transient at 12:50 p.m. March 25 on 14th street.
ENCINITAS: A 43-year-old man was arrested for making verbal gang/terrorist threats to three women, 5 p.m. March 29 on Second Street.
ENCINITAS: A 23-year-old woman was arrested for battery against a police officer after a domestic dispute, 2:15 a.m. March 31 on Leucadia Boulevard at North Vulcan Avenue.
ENCINITAS: A shoplifter stole a $15 bottle of liquor from Rite Aid on Santa Fe Drive, 8:26 p.m. March 31.
ENCINITAS: A 24-year-old man was arrested for presenting a counterfeit money or checks at a Wells Fargo branch on El Camino Real, 1:04 p.m. March 29.
ENCINITAS: A 65-year-old man was arrested on suspicion of driving under the influence, 2:46 p.m. March 29 on Village Park Way at Park Dale Lane.
ENCINITAS: A 37-year-old man was arrested on suspicion of assaulting a 47-year-old man with a deadly weapon at 8:20 p.m. March 29 on Village Wood Road.
ENCINITAS: A thief stole a $699 bicycle and $45 in miscellaneous items from REI on Leucadia Boulevard, 7:45 p.m. March 28.
ENCINITAS: A 46-year-old woman was arrested on suspicion of public drunkenness at 7:03 p.m. March 25 on North Vulcan Avenue.
ENCINITAS: A 61-year-old woman was arrested on suspicion of public drunkenness at 8:31 p.m. March 25 on El Camino Real. ESCONDIDO: Two juveniles were cited for truancy at 9:23 a.m. March 24 in the 1100 block of South Citrus Avenue.
ESCONDIDO: A burglary was reported at 10:31 a.m. March 24 at Five Star Market on West Ninth Ave.
ESCONDIDO: Four juveniles were cited for possession of alcohol at 1:19 p.m. March 25 in the 1400 block of West Ninth Avenue.
ESCONDIDO: A hit-and-run was reported at 9:49 p.m. March 25 in the 300 block of West Valley Parkway.


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Hostelworld "meet the world" by Lucky Generals
Rating: 5.0
By Matt Williams, campaignlive.co.uk, Monday, 30 March 2009 03:15PM
The ad has been called "an attack against Christian symbols", after it was published in the Lebanese newspaper Al Mostakbal last week.
Samsung had not commissioned FP7 to create any ad campaigns, and argued that the agency had only created the spot in order to pick up some honours at the recent Dubai Lynx Awards.
Sunny Hwang, the president of Samsung Electronics Levant, said: "At no time was Samsung Electronics aware of these advertisements and the company has not approved or commissioned FP7 to create any advertising campaigns.
"Samsung has the utmost respect for all cultures and religions and would never produce or approve the use of such culturally insensitive advertisements."
At the award ceremony, FP7 picked up two golds and a silver for its Samsung work, as well as winning the agency of the year title.
The agency is now being investigated by the event's organisers, and is expected to be stripped of its honours.
Phillip Thomas, the chief executive of Cannes Lions, the organiser of the Dubai Lynx Awards, said: "It appears in this case that FP7 Doha has knowingly tried to mislead ourselves and our jury regarding work they claimed to have created on behalf of Samsung Electronics, which in reality the client had never seen or approved."
FP7, which is part of Interpublic Group and has an affiliation with McCann Worldgroup, is expected to hear its fate on Tuesday.
This article was first published on campaignlive.co.uk
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Rating: 5.0
Agency: Grey London
Rating: 5.0


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Photo by Marcus Nilsson
YIELD: Makes 8 servings
ACTIVE TIME: 15 minutes
TOTAL TIME: 15 minutes
Purée chiles, garlic, lime juice, fish sauce, oil, and palm sugar in a blender until smooth.
Toss mangoes, shallots, peanuts, cilantro, mint, dried shrimp, if using, sesame seeds, and dressing in a large bowl; season with salt.
DO AHEAD: Dressing can be made 1 day ahead. Cover and chill.


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Official: Gunmen knew ICE agents were law officers
MEXICO CITY Gunmen who shot up an SUV carrying two U.S. Immigration and Customs Enforcement agents, killing one, knew they were attacking law enforcement officers, according to U.S. officials.
But details of the attack that emerged Wednesday indicate the two agents were not targeted ahead of time, rather stopped in the wrong place at the wrong time in a blue Suburban - a vehicle coveted by drug cartels.
Special Agent Jaime Zapata, 32, died and a second agent, Victor Avila, was wounded Tuesday when they were attacked after being stopped on a four-lane federal highway in northern Mexico.
They were returning to Mexico City from a meeting with other U.S. personnel in the state of San Luis Potosi, according to an ICE statement, which also said the Mexican government does not authorize U.S. law enforcement personnel to carry weapons.
Some reports said the two were stopped at a roadblock, while others said they were run off the road by other vehicles.
Texas Congressman Michael McCaul, who was briefed on the incident as chairman of the Homeland Security Oversight and Investigations Subcommittee, the gunmen opened fire after the agents identified themselves as U.S. diplomats.
An U.S. law enforcement official told The Associated Press that the gunmen made comments before they fired indicating they knew who their targets were. The official was not authorized to discuss the case publicly.
"This was an intentional ambush against two United States federal agents," McCaul said in a statement. "This tragic event is a game changer. The United States will not tolerate acts of violence against its citizens or law enforcement and I believe we must respond forcefully."
U.S. Homeland Security Secretary Janet Napolitano and Attorney General Eric Holder announced a joint task force led by the FBI to help Mexico find the killers.
The State Department also expressed confidence in the ability of President Felipe Calderon's government to pursue the case.
"The Calderon government has stepped forward very courageously in recent years. They are, with the United States' help, taking aggressive action against the perpetrators of this kind of violence," State Department spokesman P.J. Crowley told reporters in Washington.
Zapata and Avila, both assigned to the ICE attache office in Mexico City, were attacked in an area where violence is on the rise from drug cartels fighting for territory. Avila was shot twice in the leg and has been discharged from the hospital, according to an ICE statement Wednesday.
Al Pena, a senior ICE official until he retired in December, said the agents arranged to meet Monterrey-based ICE agents midway between Mexico City and Monterrey to pick up equipment. They were returning south to Mexico City when attacked. He didn't know what equipment the ICE agents exchanged.
Pena, who was the Homeland Security attache in Mexico City in 2008 and 2009, said the ICE office in Mexico works on many issues - from training customs investigators to investigating drug and human trafficking, gun running and money laundering.
Avila "was working on many, many issues," said Pena, who knows him well. "There's not much specialization when you have an office that small."


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Nigel de Jong sweated his way through the hardest game of his career last night - and he was not even playing.
De Jong was a helpless spectator in Cape Town, having been ruled out of the Netherlands' 2010 FIFA World Cup™ semi-final with Uruguay through suspension. Thankfully for the Manchester City star, the Dutch emerged triumphant thanks to second-half goals from Wesley Sneijder and Arjen Robben, and he can now look forward to the game of his life at Soccer City on Sunday.
But the chances are, no matter how the contest works out, De Jong will not expend as much energy as he did last night. "That was the hardest game I have ever been involved in," said De Jong. "I am more tired than all the other guys in the dressing room put together.
That was the hardest game I have ever been involved in. I am more tired than all the other guys in the dressing room put together.
"I was so nervous. I was missing the semi-final of the World Cup because I had picked up two yellow cards. It just made it a very stressful night. But the guys did a terrific job. They made it possible for me to play in a World Cup Final."
The Netherlands have never won the FIFA World Cup, losing both their previous final appearances - in 1974 and 1978. Indeed, last night represented their ninth major tournament semi-final and so far their reward stands at one single triumph, at the UEFA European Championship in 1988.
It has often been suggested Holland are the best team never to have won the most prestigious tournament the game has to offer. That assessment is one De Jong agrees with. "That is right, but it is not a problem," he said. "The energy we get from it is positive, not negative.
"Those teams in the past put Holland on the map. But that was 32 years ago. This is a new generation. We cannot go into the game with any memories of the past. This is our squad and our time. With all due respect, they had theirs."
It is debatable whether any of the current Dutch generation compare with Johan Cruyff, legendary leader of the 'Total Football' team that were denied glory by West Germany 36 years ago. Yet in Sneijder they have a midfield schemer who will surely be crowned world footballer of the year should Holland be crowned champions on Sunday night, given he has also won the treble with Inter Milan, including that famous UEFA Champions League final victory over Bayern Munich.
Little wonder Manchester United, among many others, are casting admiring glances in Sneijder's direction, although Sir Alex Ferguson knows the asking price has continued to rise with each of the five goals the midfielder has scored in this competition.
Although there have been more talented Dutch squads in the past three decades, the difference this time appears to be the harmony achieved by coach Bert van Marwijk, something to which De Jong can testify. "We have a good spirit," he said. "We always play the best football we can and we are together as one.
"You can see that in the way we perform. Even yesterday we had some difficult times but we stick together, and we always have the quality to score goals."


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Find the perfect hotel in Nymburk using our hotel guide provided below. Search for the cheapest discounted hotel and motel rates in or near Nymburk, Czech Republic for your upcoming personal or group travel. We show the best Nymburk motel and hotel rooms. Browse the Nymburk area hotels to find the perfect lodging! Please use the provided map of the Nymburk hotels.The Nymburk center is about 24 miles from O2 Arena and 24 miles from Sazka Arena.
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Latest News
Late For Work Permission Slip
Frustrated with all the road construction in La Crosse? Is your boss angry because the congestion is making you late for work? Then print off this handy permission slip and hand it your boss, compliments of WIZM!
LaCrosse Talk
Information about and from LaCrosse Talk
Mark Meier's (Marc Meiner's) "Lifepod"
WI's Do Not Call List or call (866) 966-2255
MN's Do Not Call List or call (800) 921-4110
Federal Do Not Call List or call (888) 382-1222
Scammers Still At It
Crooks are still calling people's homes and are posing as state workers trying to get your personal information.
Consumer official Sandy Chalmers say the imposters will claim they're from
Medicare or an insurance firm and they'll ask for personal information like
Social Security or bank account numbers. Chalmers say reputable firms won't do
that and you should never give personal information over the phone until you're
the one making the contact, and you know who you re dealing
No Leads In Winona Arsons
The tips have came in, but still no leads towards a rash of arsons in Winona. Police there are still asking for the public's help in solving three suspected arson fires that occurred in the same general location within six weeks back in November and December.
Full Referendum Ballot for La Crosse Voters in Spring
They're just advisory referendums. But they're already causing a rift among La Crosse city council members. The council has approved sending advisory measures to the spring ballot regarding billboards and city council size. City councilman Jim Bloedorn is upset the issues got pushed through the approval process so quickly
A binding referendum on hiring a city administrator will also be on the city ballot for April. Next month, the council will decide whether the mayor's salary gets cut in half if the administrator is approved by voters.
Another Veto Override from La Crosse Council
No difference this year so
Wrecks Galore In Coulee Region
Winter weather has finally hit leading to several accidents in Onalaska. The Onalaska Police Department has worked 7 accidents between midnight and 4:00 p.m. today.
An injury accident occurred this afternoon at the intersection of 8th & Redwood in Onalaska. A vehicle travelling East on Redwood could not stop for the yield sign due to the road conditions and struck a vehicle going North on 8th Street. One person was transported from the scene to a local hospital.
Police remind you to please drive safe and allow for additional stopping distances.


text:
Littlewood, R; (2001) Caribbean Immigration to Britain: Mental Health of the Migrant and their British Born Families. In: Yilmaz, Y and Weiss, MG and Riecher-Rassler, A, (eds.) Transcultural Psychiatry: Challenges of Diagnostical Treatment. (81 - 102). Karger: Basle.
Full text not available from this repository.
|Book chapter
|Caribbean Immigration to Britain: Mental Health of the Migrant and their British Born Families
|BRITAIN, Caribbean, CHALLENGE, families, family, health, immigration, mental health, MENTAL-HEALTH, psychiatry, transcultural psychiatry, treatment, health, transfer, BORN, BRITAIN, British
|UCL classification:
|UCL > School of Arts and Social Sciences > Faculty of Social and Historical Sciences > Anthropology
Archive Staff Only: edit this record


text:
8 historic sites under review for national listing
Posted: July 27, 2014 at 4:15 a.m.
Two North Little Rock houses are among eight properties in Arkansas to be considered for nomination to the National Register of Historic Places by the Arkansas Historic Preservation Program's State Review Board on Aug. 6, program Director Frances McSwain announced.
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A former Bryant alderman, who is suing the city for the second time over a ditch in his lawn, is looking to settle the suit for $30,000 and for the city to fix his property... Read »