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US 5643586 A Abstract Compositions for the topical treatment of sagging subcutaneous muscle and overlying cutaneous tissue contain catecholamines and/or related compounds in a dermatologically acceptable carrier. Examplary catecholamines include adrenaline, norepinepherine, dopamine and their precursors; catecholamine precursors such as tyrosine and phenylalanine are preferred. Preferred embodiments further contain at least one other ingredient that enhances neurotransmitter synthesis and/or skin penetration. In some embodiments, an acetylcholine precursor such as dimethylaminoethanol and/or a fatty acid ester of ascorbic acid are included in the formulation. In these and other embodiments, particularly those employing tyrosine and/or phenylalanine as a catecholamine precursor, other cofactors such as vitamin B.sub.6 and pantothenic acid or calcium pantothenate are included in the composition to enhance the action of the active ingredients. Other compounds that scavenge free radicals and antioxidants may also be added.
Claims(17) 1. A method for the topical treatment of subcutaneous muscle and overlying cutaneous tissue comprising topically applying to affected skin areas a composition comprising, as active ingredients:
(a) from about 0.25% to about 5% by weight of a catecholamine precursor selected from the group consisting of tyrosine, phenylalanine, and mixtures thereof, (b) an effective amount of ascorbyl palmitate, and (c) about 0.25% to about 5% by weight of dimethylaminoethanol, in a dermatologically acceptable carrier that penetrates the skin so that muscle tone in subcutaneous muscle tissue is increased. 2. A method according to claim 1 wherein the composition contains from about 1% to about 3% by weight tyrosine.
3. A method according to claim 1 wherein the composition further comprises a compound selected from the group consisting of pyridoxine, calcium pantothenate, pantothenic acid, and mixtures thereof.
4. A method for the topical treatment of aging subcutaneous muscle and overlying cutaneous tissue comprising topically applying to affected skin areas, in a dermatologically acceptable carrier that penetrates the skin, a composition comprising a catecholamine selected from the group consisting of dopamine, norepinephrine, epinephrine, dopa, serotonin, and mixtures thereof, or a catecholamine precursor selected from the group consisting of tyrosine, phenylalanine, and mixtures thereof, in amounts sufficient to increase muscle tone in the subcutaneous muscle tissue, wherein the composition further comprises a fat-soluble, saturated fatty acid ester of ascorbic acid selected from the group consisting of ascorbyl palmirate, ascorbyl laurate, ascorbyl myristate, ascorbyl stearate, and mixtures thereof, and about 0.25 to about 5% dimethylaminoethanol.
5. A method according to claim 4 wherein the fatty acid ester of ascorbic acid is ascorbyl palmitate.
6. A method according to claim 4 wherein the composition contains about 2% to about 3% by weight catecholamine precursor.
7. A method for the topical treatment of aging subcutaneous muscle and overlying cutaneous tissue comprising topically applying to affected skin areas a composition comprising an effective amount of a catecholamine selected from the group consisting of dopamine, norepinepherine, epinepherine, dopa, seratonin, and mixtures thereof, or a catecholamine-related compound selected from the group consisting of phenylalanine, tyramine, ephedrine, amphetamine, tetrahydrobiopterin, pyridoxine, and mixtures thereof, in a dermatologically acceptable carrier that penetrates the skin.
8. A method according to claim 7 wherein the composition contains from about 0.25% to about 5% by weight catecholamine or related compound.
9. A method according to claim 8 wherein the composition contains from about 2% to about 3% by weight catecholamine or related compound.
10. A method according to claim 7 comprising an effective amount of a catecholamine.
11. A method according to claim 7 wherein the catecholamine is dopa or the catecholamine-related compound is phenylalanine.
12. A method according to claim 11 wherein the composition further comprises a compound selected from the group consisting of pyridoxine, calcium pantothenate, pantothenic acid, and mixtures thereof.
13. A method according to claim 7 comprising an effective amount of a catecholamine-related compound.
14. A method according to claim 7 wherein the composition further comprises a fatty acid ester of ascorbic acid selected from the group consisting of ascorbyl palmitate, ascorbyl laurate, ascorbyl myristate, ascorbyl stearate, and mixtures thereof.
15. A method according to claim 14 wherein the fatty acid ester of ascorbic acid is ascorbyl palmirate.
16. A method according to claim 7 wherein the composition further comprises at least one antioxidant.
17. A method for the treatment of aging subcutaneous muscle tissue comprising topically applying to overlying affected skin areas a composition comprising an effective amount of tyrosine and 0.25 to 5% dimethylaminoethanol in a dermatologically acceptable carrier that penetrates the skin so that muscle tone in the subcutaneous muscle tissue is increased.
Description This invention is based upon the surprising finding that subcutaneous muscle tissue can be treated by the topical application of a catecholamine precursor such as tyrosine. Some preferred topical compositions also contain an acetylcholine precursor such as dimethylaminoethanol. Other substances that enhance neurotransmitter synthesis, particularly those that enhance acetylcholine synthesis, and additional antioxidants augment the efficacy of the topical composition. Substances that facilitate skin penetration also enhance the method. In accordance with the present invention, catecholamine or a catecholamine-related compound, in association with a dermatologically acceptable carrier in which the compound is dispersed or solubilized, is topically applied in effective amounts to skin areas which have been aged, or which are susceptible to age. As will be discussed in greater detail below, in preferred embodiments, an acetylcholine precursor such as dimethylaminoethanol and ascorbic acid or an ascorbic acid derivative such as a fatty acid ester, is applied in admixture with the catecholamine or catecholamine-related compound. By "catecholamine" is meant any one of a group of amines that act upon nerve cells as neurotransmitters or hormones. This group of similar compounds having a sympathomimetic action typically are molecules having an aromatic portion derived from catechol (2-hydroxyphenol) and an aliphic amine portion. Catecholamines include, but are not limited to, dopamine (5-hydroxytryptamine), norepinephrine (noradrenaline; 4-(2-amino-1-hydroxyethyl)-1,2-benzenediol), and epinephrine (adrenaline; 4-(1-hydroxy-2-(methylamino)ethyl)-1,2-benzenediol). As used herein, dopa (3,4-dihydroxyphenylalanine) and serotonin (5-hydroxytryptamine) are also included in this group. Catecholamine-related compounds include catecholamine precursors, catecholamine mimics, chemicals that augment the release of catecholamines, and mixtures of these with each other and with catecholamine. Catecholamine precursors include any in the synthetic pathway such as, for example, tyrosine, dopa, phenylalanine, and mixtures thereof. Catecholamine mimics include, but are not limited to, sympathomimetic amines that function similarly, augmenting, for example, the release of norepinepherine, such as tyramine, ephedrine, amphetamine, and mixtures thereof. Chemicals that augment the release of catecholamines specifically include those that augment release such as co-factors of enzymes in the metabolic pathway, e.g., tetrahydrobiopterin and pyridoxine, as well as inhibitors of enzymes that inactive catecholamines such as inhibitors of catechol-O-methyltransferase and monoamine oxidase. In preferred embodiments, the catecholamine-related compound is a catecholamine precursor such as tyrosine or phenylalanine or mixtures thereof. In these embodiments, cofactors such vitamin Be and pantothenate or pantothenic acid are typically employed to achieve a maximal metabolic effect. In some embodiments, an acetylcholine precursor is added to the composition; dimethylaminoethanol is used in one embodiment. Vitamin C may and/or a fatty acid ester of ascorbic acid such as ascorbyl palmirate are also added in some embodiments. Preferred compositions further contain at least one additional substance that directly or indirectly enhances neurotransmitter synthesis such as pyridoxine, calcium pantothenate, zinc, and mixtures of any of these, and another antioxidant such as vitamin E acetate or sorbate, tocotrienol, ascorbic acid, or mixtures of any of these. By the term "acetylcholine precursor" is meant any precursor in the biosynthetic pathway of acetylcholine, or related pathways. These include co-factors and precursors of acetylcholine, synthetic enzymes and precursors or enhancers of acetylCoA production. Acetylcholine precursors include, but are not limited to, dimethylaminoethanol, monoaminoethanol, choline, serine, and mixtures thereof. As used herein, "precursors" also include derivatives of precursors such as esters, e.g., acetic acid and para-chlorophenylacetic acid esters of dimethylaminoethanol or monoaminothanol, and the like. Folic acid and vitamin B.sub.12 augment acetylcholine synthesis in some embodiments. Other embodiments contain choline acetylase agonists and acetylcholinesterase inhibitors to augment acetylcholine synthesis. Dimethylaminoethanol is a preferred precursor. Catecholamines and/or catecholamine-related compounds are typically used in topical compositions with ascorbic acid (vitamin C) and/or an ascorbic acid derivative or precursor. Derivatives include, but are not limited to, salts such as the sodium or calcium salt of ascorbic acid, ascorbic acid anhydride and ascorbic acid esters, or mixtures of any of these. Fatty acid esters are preferred because these typically penetrate the skin more efficaciously than other derivatives. As used herein, the term "fatty acid esters of ascorbic acid" include any saturated or unsaturated fatty acid ester of ascorbic acid and mixtures of these esters. Because of their lack of susceptibility to oxidation and the development of off-odors in stored compositions, saturated fatty acid esters of ascorbic acid are especially preferred. These include, but are not limited to, ascorbyl palmitate, ascorbyl laurate, ascorbyl myristate, ascorbyl stearate, and mixtures thereof. Ascorbyl palmitate is employed in one embodiment. "Ascorbyl palmirate" includes the pure compound and esters enriched with ascorbyl palmirate such as those obtained by acylating ascorbic acid with fatty acids from feedstock oils or feedstock oil fractions containing primarily palmitic acid. The term includes preparations and liposomes containing the compound. The amount of the catecholamine and/or catechol-amine-related compound necessary to bring about the therapeutic treatment of subcutaneous muscle and overlying skin is not fixed per se, and necessarily is dependent upon the severity and extent of the aged tissue, the efficacy of the carrier in skin penetration, the particular catecholamine or related compound employed and additional antioxidants and agents affecting neurotransmitter synthesis such as acetylcholinie precursors employed, and the concentrations of these ingredients in the formulation put together in association with a dermatologically acceptable carrier that penetrates the skin. Preferred embodiments employ active ingredients in amounts effective to achieve a clinically perceptable increase in subcutaneous muscle tone by topical application of the composition. Agents that enhance skin penetration are employed in amounts effective to deliver active ingredients to subcutaneous muscle tissue. Typical embodiments contain from about 0.1% to 10% by weight, more narrowly from about 0.25% to about 7%, even more narrowly, from about 3% to 5%, catecholamine or related compound. Where the carrier functions well as a skin penetrant, lower amounts of active compound are included in the formulation. Some embodiments thus contain from about 0.25% to about 3% active compound. Other embodiments contain higher amounts, e.g., from about 1% to about 7% active compound. Many embodiments contain from about 3% to 5% active compound. Compositions of the invention are applied in admixture with a dermatologically acceptable carrier or vehicle (e.g., as a lotion, cream, ointment, soap, or the like). Topical application is facilitated and, in some cases, additional therapeutic effects are provided as might be brought about, e.g., by moisturizing of the affected skin areas and by enhancing penetration of active ingredients. When a carrier is employed, it is necessary that the carrier be inert in the sense of not bringing about a deactivation of active ingredients, and in the sense of not bringing about any adverse effect on the skin to which it is applied. Preferred carriers function well in skin penetration or augment the effect of other ingredients that enhance penetration so that active compound is delivered to subcutaneous muscle tissue. Suitable carriers include water, alcohols, oils and the like, chosen for their ability to dissolve or disperse the active ingredients at concentrations of active ingredients most suitable for use in the therapeutic treatment. Generally, even low concentrations of active ingredients in a carrier will be suitable, requiring only that more frequent topical application be resorted to. As a practical matter, however, to avoid the need for repeated application, it is desirable that the topically applied composition (e.g., catecholamine and/or related compounds in association with other ingredients in a carrier) be formulated to contain at least about 0.25% by weight, more preferably at least about 1% by weight, and most preferably at least about 2% by weight, of the catecholamine or related compound. In one embodiment, the composition contains from about from about 1 to about 5 weight %, more narrowly from about 2% to about 3%, tyrosine or phenylalanine, or mixtures thereof; from about 0.25 to about 2 weight %, more narrowly from about 0.5% to about 1%, vitamin B.sub.6, and from about 1 to about 10 weight %, more narrowly from about 2% to about 8%, vitamin C. Carriers are chosen which solubilize or disperse the active ingredients at such concentrations, and penetrate the skin to deliver them to subcutaneous muscle tissue. Preferred compositions of the invention contain at least one additional substance that enhances neurotransmitter synthesis such as an acetylcholine precursor, pyridoxine, folic acids vitamin B.sub.12, calcium pantothenate, pantothenic acid, zinc, and mixtures of any of these, and another antioxidant such as vitamin E, vitamin E acetate, vitamin E sorbate, vitamin E succinate, tocotrienol, ascorbic acid, or mixtures of any of these. The formulation can also contain additional ingredients such as membrane stabilizers. In some embodiments, the compositions contain tocotrienols or derivatives thereof for enhanced therapeutic or prophylactic treatment as described in U.S. Pat. No. 5,376,361 to Petricone (which is hereby incorporated herein in its entirety by reference). These are particularly advantageous because tocotrienols are oily so that they physically contributes to the lubrication and soothing of affected skin areas. Reductive agents such as α-hydroxy acids can, optionally, be utilized with the tocotrienols for a means for yet further enhancing the efficacy of the compositions. Glycolic acid is preferred in one embodiment. As used herein, the term "tocotrienol" encompasses tocopherols bearing unsaturated tails, including, but not limited to, naturally occurring α-, β-, γ-, and δ- tocotrienols, desmethyl-tocotrienol, didesmethyl-tocotrienol, their synthetic counterparts, their counterparts having methylated or demethylated chroman rings, stabilized derivatives such as those having the phenolic hydroxyl functionality acylated with an organic acid to form an ester such as acetates and succinates, and mixtures thereof. The term also includes tocotrienol-enriched fractions and tocotrienol-enriched vitamin E preparations. Where tocotrienols are employed, the amount of tocotrienol or one or more derivatives thereof (hereinafter referred to collectively as tocotrienol for ease of reference) necessary to bring about enhanced prevention and/or therapeutic skin treatment in conjunction with catecholamines and/or catecholamine-related compounds (and optionally other ingredients described above) is not fixed per se, and necessarily is dependent upon the identity and form of tocotrienol employed, the concentration of tocotrienol when employed as a tocotrienol-enriched vitamin E preparation and/or with a carrier, the amount and type of other ingredients, the user's skin type, and, where present, the severity and extent of the patient's pathological skin condition. Many embodiments contain from about 0.025% to 0.25% tocotrienol. While the carrier for the catecholamines and/or related compounds, and optionally, other ingredients (such as acetylcholine precursors and/or fatty acid esters of ascorbic acid) can consist of a relatively simple solvent or dispersant such as water or oils, it is generally preferred that the carrier be one which aids in percutaneous delivery and penetration of the active ingredients into lipid layers and subcutaneous muscle tissue. Moreover, the composition preferably is one that is conducive to topical application, and particularly one that can be applied so as to localize the application. Many such compositions are known in the art, and can take the form of lotions, creams, gels or even solid compositions (e.g., stick-form preparations). Typical compositions include lotions containing water and/or alcohols and emollients such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties. These same general ingredients can be formulated into a cream rather than a lotion, or into gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophillic colloids. Such compositions are referred to herein as dermatologically acceptable carriers. Most preferred for skin are those carriers which are fat-soluble, i.e., those which can effectively penetrate skin layers and deliver the active ingredients to the lipid-rich layers of the skin and to subcutaneous muscle tissue. Generally, the composition is topically applied to the affected skin areas in a predetermined or as-needed regimen to bring about improvement, it generally being the case that gradual improvement is noted with each successive application. Insofar as has been determined based upon clinical studies to date, no adverse side effects are encountered. When tyrosine is applied to skin in a dermatologically acceptable carrier, there is clinically visible increased muscle tone. In an assessment of the efficacy of a composition of the invention, an aqueous suspension made up of approximately 7% by weight ascorbyl palmirate, 3% dimethylaminoethanol, 2% by weight vitamin E acetate, 1/2% by weight of vitamin B.sub.6 (pyridoxine), 1% by weight zinc sulfate (weighed as zinc), 1% by weight calcium pantothenate, and 2% by weight tyrosine is applied to facial skin. Within 3 to 5 minutes of application, the facial skin becomes more taut. A reduction of nasolabial folds is observed, as well as a general tightening of the face in the periorbital region and the forehead. This effect lasts for approximately 24 hours, and, when the formulation is reapplied on a daily basis, after about a month, there apears to be a marked shortening of muscle tissue resulting in a more youthful appearance. The formulation can also be placed on the pectoralis area and in the area of breast tissue, resulting in an uplifted look to that area. It can also be applied to the faces of myasthenia gravis patients to improve their appearance. While not wishing to be bound to any theory, by providing catecholamine-related compounds, muscle tone is increased and the resultant shortening of muscles lifts tissue on the face, chest, or other areas where the composition is applied. It is believed that the presence of catecholamines or catecholamine-related compounds, particularly catecholamine precursors, as well as other compounds involved in catecholamine production and neurotransmitter synthesis, such as vitamin C, vitamin B.sub.6 (pyridoxine), calcium pantothenate or pantothenic acid, and zinc, appears to help boost levels of acetylcholine in the neuromuscular junction, resulting in increased muscle tone, particularly where nerve synapses interact with involuntary muscles. This increased muscle tone causes a slight shortening of the muscle, and over a period of time, the muscle actually does become shorter. A shorter muscle results in a lifting of overlying skin, with the cosmetic appearance of a diminishment of sagging. Catecholamines have also been implicated in glyco-genolygic effects that are particularly evident in muscle tissue. As disclosed in U.S. Pat. Nos. 4,647,453 and 4,772,591 to Meisner, a combination of precursors of norepinephrine, ascorbic acid, and an anti-inflammatory have been suggested to have efficacy in the treatment for tissue degenerative inflammatory disease and wound healing. The treatment was not formulated for skin penetration, however. Schinitsky and Meisner further suggested a diminution of fine wrinkling when a combination of tyrosine and water-soluble zinc salt were applied to the skin, but the composition also did not penetrate the skin and caused irritation in some subjects (U.S. Pat. No. 4,938,969). In addition, where additional preferred ingredients discussed above are employed, treatment in accordance with the present invention helps prevent free radical damage to skin and helps reverse cell membrane damage by application of free radical scavengers and quenchers. It is important to have free radical scavengers in the cell membrane that protect the target site and have a greater affinity for free radicals than the target tissue. As a free radical scavenger or neutralizer, ascorbyl palmirate, because of its palmitic fatty acid side chain, intersperses in membranes more effectively, and therefore provides better protection for cell membranes during free radical attack. Substances that stabilize membranes or increase endogenous glutathione production further prevent free radical damage to the cell and membrane structures. In membranes, vitamin E also provides protection from free radical damage. Moreover, fatty acid esters of ascorbic acid such as ascorbyl palmirate aid or accelerate collagen synthesis, so as to remedy the depeleted collagen observed in aging. By virtue of its fat solubility, fatty acid esters of ascorbic acid enhance percutaneous delivery of catecholamine precursors and related compounds as well as acetylcholine precursors such as dimethylaminoethanol if they are part of the formulation. Again, while not wishing to be bound to any theory, the special efficacy of methods of the invention may in part be due to the multiple functions catecholamines play in the system. In addition to the fact that the compounds facilitate acetylcholine release, they serve also as penetration enhancers, which help absorption of other active ingredients in embodiments where these are included in the compositions applied to the skin. Catecholamines and related compounds also act as antioxidants. In the practice of the invention, they exert this activity interspersed within lipid-rich membranes, areas that other topical compositions typically do not reach. The application of free radical scavengers and topical antiflammatories with substances that cause a shortening of muscles, produces increased tone, provides a composition that enhances the appearance of the skin, and results in a smoother, tighter, and more youthful appearance for aging persons and patients afflicted with conditions that cause sagging faces such as myasthenia gravis. Acetylcholine receptors are found on human epidermal keratinocytes. When these are occupied, they can affect keratinocyte growth, resulting in a more youthful appearance, enhancing the effects of compositions of the invention because they increase acetylcholine production. Having described the invention with reference to particular compositions, theories of effectiveness, and the like, it will be apparent to those of skill in the art that it is not intended that the invention be limited by such illustrative embodiments or mechanisms, and that modifications can be made without departing from the scope or spirit of the invention, as defined by the appended claims. It is intended that all modifications and variations be included within the scope of the invention. The claims are meant to cover the claimed components and steps in any arrangement or sequence which is effective to meet the objectives intended for the invention, unless the context specifically indicates the contrary. This invention relates primarily to the treatment of subcutaneous muscles and overlying skin, particularly for faces that have developed prominent lines such as the nasolabial folds, hanging of tissue from the mandibular region, and increased sagging of tissue around the eyes and other areas observed in aging and in other conditions such as myasthenia gravis. In addition, sagging pectoralis muscles result in sagging of the chest and breast. The invention concerns compositions and methods of treating subcutaneous muscles and the overlying epidermis to ameliorate these changes, and improve the external appearance. With age, subcutaneous muscles lengthen and give a sagging appearance to the skin because underlying muscle is looser. Current treatments of placid skin and muscles from aging typically involve plastic surgery. The plastic surgeon cuts the skin and muscle and then pulls it taut, reducing some of the tissue and discarding it, then suturing it so that the facial, chest and/or buttocks muscles remain tight. The external appearance of aging individuals is particularly affected by subcutaneous changes in skeletal muscle tissue. When muscles are at rest, a certain amount of tautness usually remains. The residual degree of contraction in skeletal muscles is called muscle tone. In aging individuals, the degree of contraction relaxes, and is particularly obvious in the face. In order for a muscle to contract, a message is sent from the brain to the spinal cord, and then from the spinal cord to the skeletal muscles. This is accomplished by an action potential which travels down the axon of the nerve. The nerve ends at an area called the synaptic knob, and this action potential causes the synaptic knob to release small diffusible chemical neurotransmitters into the synaptic cleft. The synaptic knob is rich in tiny vesicles containing neurotransmitters, and these vesicles are rich in acetylcholine in knobs innervating muscles. Acetylcholine is released into the synaptic cleft, and then meets the muscle at an invagination called the synaptic gutter. This acetylcholine then finds receptors on the muscle surface, which causes the muscle to become permeable to sodium ions, which result in membrane potential increases in the local area of the end plate, about 75 millivolts, creating a local potential called the end plate potential. This causes the muscle to contract. Once this contraction takes place, the remaining acetylcholine in the cleft is destroyed by an enzyme called cholinesterase. The choline is reabsorbed by the pre-synaptic knob to be used again to synthesize acetylcholine. Thus, it is at this neuromuscular junction where acetylcholine causes its effect. The synaptic knobs have the capability of continually synthesizing new transmitter substance. This occurs mainly in the cytoplasm of the synaptic knobs, and then it is absorbed into tiny vesicles and stored as needed. It can be seen that neurotransmission at neuromuscular junctions is a complicated process affected by many factors including the biosynthesis of the neurotransmitter, storage of the neurotransmitter, release of the neurotransmitter, interaction of the neurotransmitter with receptors on effector cells, and termination of neurotransmitter activity by reuptake and/or metabolic processes. The process is further complicated by the interactions among neurotramsmitters in the sympathetic and parasympathetic nervous systems. As described above, cholinergic neurons act at the myoneural junction and cause skeletal muscle contraction through the action of chemical mediators such as acetylcholine at synapses in the parasympathetic nervous system. In the sympathetic (autonomic) nervous system, adrenergic neurons employ other neurotransmitters at smooth muscle junctions, e.g., norepinephrine, epinephrine, dopamine, and serotonin. Norepinephrine is a mediator of activity at most postganglionic sympathetic endings in the autonomic nervous system. Neurotransmitters of the adrenergic neurons enhance neurotransmitters at the myoneural junction, e.g., acetylcholine release. Thus, epinephrine, an adrenergic catecholamine, can affect muscle contraction by enhancing the release and effects of acetylcholine at the myoneural junction. The principal catecholamines found in the body, norephinephrine, epinephrine, and dopamine, are formed by hydroxylation and decarboxylation of the amino acids phenylalanine and tyrosine. Tyrosine is transported into adrenergic nerve endings by a concentrating mechanism. It is converted to dopa by hydroxylation and then decarboxylated to dopamine (3,4-dihydroxyphenylethylamine) in the cytoplasm of the neurons by tyrosine hydroxylase and dopa decarboxylase, respectively. The dopamine then enters the granulated vesicles from which it is converted to norepinephrine (noradrenaline) by dopamine β-hydroxylase. L-dopa is the isomer involved, and it is the Lisomer of norepinephrine that is produced. The rate-limiting step in synthesis is the conversion of tyrosine to dopa. Tyrosine hydroxylase which catalyzes this step is subject to feedback inhibition by dopamine and norepinephrine, thus providing internal control of the synthetic process. The co-factor for tyrosine hydroxylase is tetrahydrobiopterine, which is converted to dihydrobiopterine when tyrosine is converted to dopa. Norepinepherine is synthesized in nerve endings but can also be resorbed by nerve endings after systemic secretion. This active uptake mechanism is characteristic of adrenergic neurons. It is also known that circulating norepinephrine and epinephrine (adrenaline, methylated norepinephrine) within the body are incorporated in small amounts by adrenergic neurons in the autonomic nervous system. Thus, adrenergic neurons differ from cholenergic neurons in the ability to uptake a complete molecule. Acetylcholine is not taken up to any appreciable degree, but the choline that is formed by the action of acetyl cholinesterase is taken up and recycled. The aging process results in damage to presynaptic knobs, and therefore fewer neurotransmitters become available to a muscle for contraction. Receptor sites on muscle also deteriorate, and are unable to respond to the levels of acetylcholine present. Muscle tone maintained by nerve fibers releasing acetylcholine to small areas of muscle decreases, so that an appearance of sagging is observed. In addition to changes in subcutaneous muscle tissue, the overlying epidermis thins and the skin appendages atrophy with age. Hair becomes sparse and sebaceous secretions decrease, with consequent susceptibility to dryness, chapping, and fissuring. The dermis diminishes with loss of elastic and collagen fibers. Typical treatment of sun-damaged and aged skin consists primarily of applications of various creams, lotions and gels to add moisture to the skin, as well as various acid peels to retexture the skin. Cell age is due in part to free radical damage, which takes place mostly within the cell membrane. The cell membrane is most susceptible to attack by free radicals because of its dense molecular structure largely comprising lipids and lipoproteins, which are easily oxidized by reactive oxygen species. In the epidermis, reactive oxygen species, such as singlet oxygen, the superoxide anion, and hydroxyl radicals, and other free radicals are generated in normal metabolism, as well as through ultraviolet sun exposure, other forms of radiation, other environmental factors such as pollution or exposure to chemicals in the home or workplace, and the like. In addition, free radicals can activate chemical mediators of inflammation, particularly where arachadonic acid is released, which is then oxidized via two predominant pathways to produce either prostaglandins or leukotrines. The body contains an endogenous antioxidant defense system made up of antioxidants such as vitamin E, vitamin C, superoxide dismutase, and glutathione. When metabolism increases or the body is subjected to other stress such as extreme exercise, radiation (ionizing and non-ionizing), or chemicals, the endogenous antioxidant systems are overwhelmed, and free radical damage takes place. Over the years, the cell membrane continually receives damage from reactive oxygen species and other free radicals, resulting in cross-linkage or cleavage of proteins and lipoproteins, and oxidation of membrane lipids and lipoproteins. Damage to the cell membrane can result in myriad changes including loss of cell permeability, increased intercellular ionic concentration, and decreased cellular capacity to excrete or detoxify waste products. As the intercellular ionic concentration of potassium increases, colloid density increases and m-RNA and protein synthesis are hampered, resulting in decreased cellular repair. Some cells become so dehydrated they cannot function at all. In aging, the regularity of tissue structure is lost, and individual cells enlarge, but the total number of cells decreases approximately 30%. Intercellular collagen and elastin increases. The proportion of soluble collagen decreases, and there may be increased crosslinking between long-chain collagen macromolecules. Elastin loses its discrete structure and elasticity and has an increased calcium content. Sunlight exposure wreaks far greater destruction on the skin than time itself, and intensifies and augments the aging process. Free radical damage to the surface of the skin from sun exposure is manifested as lines, mottling, discoloration, precancers and cancers. Aging of both skin and other tissues is, in part, the result of constant free radical damage to cell membranes, leading to decreased cell function. This results in accumulation of waste products in the cells, such as lipofuscin; increase in the potassium content of the cells, which results in dehydration of the cells; and decreased production of messenger RNA and proteins. The combination of sagging subcutaneous muscles and aging skin contributes to the overall cosmetic changes typically observed in aging, such as wrinkling, which involves the transition of a formerly smooth skin surface to one that appears unevenly shrunk and/or contracted, and the effects of gravity on the aging skin overlying the muscle tissue. It would be desirable to reverse or diminish these effects without cosmetic surgery, and to treat other conditions exhibiting sagging facial muscles such as myasthenia gravis. It is an object of this invention to provide a method for treating sagging subcutaneous muscle and overlying skin. It is another and more specific object of the invention to provide a topical composition and method for shortening subcutaneous muscles, resulting in a lift in tissue on the face, chest or other area of application, while at the same time improving the overall condition of the skin. These and other objects are accomplished by the present invention, which provides a method for the topical treatment of subcutnaeous muscle and overlying cutaneous tissue. The method comprises applying to affected skin areas a formulation containing an effective amount of catecholamines, catecholamine precursors, catecholamine mimics, chemicals that augment the release of catecolamines, or mixtures thereof, in a dermatologically acceptable carrier. Active compounds are applied in amounts sufficient to increase subcutaneous muscle tone. Catecholamines include epinephrine, norepinephrine, dopa, and serotonin; catecholamine precursors include tyrosine and phenylalanine; and catecholamine mimics include tyramine, ephedrine and amphetamine. Catecholamine precursors are particularly preferred. Preferred embodiments further include at least one compound that enchances neurotrnsmitter synthesis and/or one compound that enhances skin penetration. In some embodiments, for example, an acetylcholine precursor such as dimethylaminoethanol is included in the formulation with the catecholamine or related compound. In these and other embodiments, ascorbic acid or an ascorbic acid derivative such as a fatty acid ester can be included in the topical composition; ascorbyl palmitate is particularly preferred. Preferred embodiments also contain whatever cofactors augment the effect of the active ingredient. For example, in embodiments employing tyrosine, phenylalanine, or a mixture of these, pyridoxine (vitamin B.sub.6) and calcium pantothenate or pantothenic acid (or mixtures of these) are typically employed. Antixodiants such as vitamin E acetate or sorbate, tocotrienol, ascorbic acid, or mixtures of any of these may be included in the formulation. In one embodiment, the composition contains from about from about 1% to about 5% by weight, more narrowly from about 2% to about 3%, tyrosine or phenylalanine, or mixtures thereof and ingredients that facilitate the metabolic activity of these catecholamine precursors, namely, from about 0.25 to about 2 weight %, more narrowly from about 0.5% to about 1%, vitamin B.sub.6, and from about 1 to about 10 weight %, more narrowly from about 2% to about 8%, vitamin C. As summarized above, this embodiment preferably further contains ascorbyl palmitate and at least one other ingredient that enhances neurotransmitter synthesis and/or skin penetration. This is a continuation-in-part of U.S. application Ser. No. 08/435,944, filed Apr. 27, 1995, which issued as U.S. Pat. No. 5,554,647 on Sep. 10, 1996 (which is hereby incorporated herein in its entirety by reference). Patent Citations
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Thematic focus: Understanding WASH sector monitoring
Updated - Friday 08 February 2013
As water and sanitation coverage expands, the need to know the status of systems and services becomes more critical. Governments are increasingly realising the importance of good monitoring information at multiple levels to ensure that services are sustainable and investments are not wasted. Development partners adapt their monitoring indicators to make their interventions more sustainable. The number of initiatives to strengthen WASH service delivery monitoring is growing. New tools are being developed and international indicators are being refined. The Monitoring Sustainable WASH Service Delivery Symposium 2013 will provide a global platform for sharing these initiatives, tools, indicators and experiences.
Read more about the programme set-up, or return to the symposium pages here.


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Jack Katz on 'The First Kingdom'
Titan Reprinting Visionary Graphic Novel
Published: 07/14/2013, Last Updated: 07/15/2013 08:32am
After a career in comics and comic strips during which he met and worked with many of the greats of the Golden Age, Jack Katz turned to teaching only to be lured back to the world of comics after seeing the freedom of expression enjoyed by the Underground comics artists in the 1960s and 1970s. Katz was one of the first to explore epic length comic book storytelling with The First Kingdom, which he began in the 1970s and finished in the 1980s. First published in installments in an oversize comic book format by Bud Plant, the entire First Kingdom saga is being reprinted by Titan Books with the first two volumes due out this year. Katz graciously took time off from his latest project to talk with ICv2 about the strange genesis of The First Kingdom and his second career, which began at age 45, as a visionary graphic novelist.
You had worked in commercial comics for two decades, more or less; then you went to teaching. What made you decide to do
The First Kingdom
and did you have any models or role models for such an epic project?
Well let me explain the paradigm to you. Here's what the deal is. I spoke to Alex (Raymond) and I spoke to Hal Foster and I said why not a visual novel? And they said, "Oh Jack, nothing like that is ever going come to pass." And I said, but look, you put your stuff together like in a book, and he said "it's not the same thing." I had the idea, but the question is, how do I go about it?
Suddenly, here I am, I'm doing some teaching and boom, then it happened. The undergrounds. What the heck? Why not take a chance? The inspiration for
The First Kingdom
came to me in a dream when I was just three years old. Most of my major works owe their genesis to dreams I had as a kid. All the costuming from
The First Kingdom
comes from these dreams.
So I made up the first seven pages, and I showed them to the people at Comix and Comics (I think the only one alive now is Bud Plant). And they said well, we'll do it. They figured it'd be one shot book. When they took a look at the size, they said, nobody uses a size like this, it's like an old
magazine--you know, long and up and down, and I said this is the only way I can give the figure work the opportunity for them to display themselves.
Well in the beginning it was very primitive. I don't know, have you ever seen the early
First Kingdom?
Yes, actually.
You have copies?
No. I worked for a distributor and we distributed it. So I looked at it.
Well I just want you to tell you something about that. The original, first sets are $1000, $1500--I can't afford that! I'm telling you, this is what happens. Somebody just bought one of my old paintings for $16,000 bucks. It was on eBay, it was gobbled up immediately. There are people who know who I am.
I saw some of the later issues that Bud Plant was publishing in the 80s.
Yeah... Bud did not have a budget for advertising. But they gave me the chance to do
The First Kingdom
the way I wanted it to be done. No editing. It was just an extraordinary opportunity. Finally I could do the
And I started it at the age of 45.
Now I want to bring up a point. All of these people, they were "oh you're 45, you're over the hill!" I'm 85 now! I'm ready to take on
Beyond the Beyond
! And for heaven's sake, you know, if you climbed Mt. Everest one time, it's not a snap the second.
Before I started drawing
The First Kingdom
, the whole darn thing was already written. And believe me, you have to have a shooting script, no matter what anybody says. And I wrote it out, 768 pages. Actually it was well over 1000, 100 pages that I had to melt down, you know, on the cutting room floor.
So I started
The First Kingdom
, and by book 2 all four partners, including Bud, were getting very antsy and "I don't know about this," but there was a magazine then called
Rocket Blast
Comic Collector
, or
] and they gave
The First Kingdom
a rave, which put forward the possibility that maybe I had something as valid in its own way as the undergrounds.
And then I did two books a year, and it took much longer to be produced because Bud never had the kind of funding that was necessary. So finally I did a portfolio, also, for
The First Kingdom
that went out.
And by the way, if you look at Book 1, you will see Yoda before his time. You think I'm kidding?
And then there's that... green guy flying around on that dragon, you know like in
. I have concrete evidence as to the fact that the last time I did
was in 1985. And all of those creatures are in all throughout
The First Kingdom
books, so what are you going to do? I'll never forget this.
But you did a great job of creating a different world, with different plants and creatures.
That's what I did with the
. I just want to bring up one more point. Did you ever hear of the movie
The Red Shoes
? Do you remember what he said to that composer who had his work stolen? He said "isn't it more tragic to steal than to be stolen from?" And I've always felt very comfortable about that. Because not only, so many of the artists, of the writers, have been taking from me, and it's fine because it's just comics to me. I... Yes, I've read 90% of
and it's the same stuff, and by the way, there's not one original story that he wrote. Everything was about an incident that happened in the past. And also, he was very careful not to rock the boat, because Elizabeth came from a certain family (the Tudors) who came after the Plantagenets? And stuff like that. Elizabeth came from the Tudor line, so that's why he defamed Richard the III. Richard III was not a cripple, he was lancer. And all lancers, their right arms were lower than left arms because of the shield was on that side. Well I don't blame Shakespeare. He had to deal with the powers that be. He was trying to save his ass. Well, we all do that, but not me.
When did you finish
The First Kingdom
The last book was 1986, that's Book 24. After that, there was a big lull until I did
. I never thought I'd go back into the field but now I'm involved with
Beyond the Beyond.
I almost thought I'd leave it in manuscript form, but apparently I'll be able to pick up, and my art is just as strong as it ever was, If not better.
the Kingdom
started, I worked on it in earnest. But I had to take out a lot of stuff, which later became a part of
The Space Explorers Club
. There's another thing here. In
The Space Explorers Club,
I let out a little hint as to the most innocent part of
Beyond the Beyond.
And I said two people, a man and a woman, who have the unity of purpose, and perfect pitch. ...can meld together, become raw energy and go through the infinite-verse and try to break out of the seal around it, because there are a number of infinite-verses- universe, multiverse... and I said the infinite-verse has had us become so developed to this point so that the damage that was done, they could start to repair the damage, or go beyond it- to go to
Beyond the Beyond.
This is in
Space Explorers Club.
Which I hope you get a copy of that. It's a good book. It's drawn a little simpler (I mean the anatomy) than
The First Kingdom.
Is Titan going to publish The
Space Explorers Club
Yes, that's going to come right after they finish with
The First Kingdom
. They are publishing that in four parts,
The Birth of Tundran
is available now with
The Galaxy Hunters
coming in December,
in March of 2014,
in June of 2014, then
The Space Explorers Club
in September of 2014, and
in December of 2014.
By the way, I want you to remember the word "Migration."
To me there are three instincts. So the first instinct is to survive. The second instinct is the instinct to replicate, whether we like it or not. You want to call it love, I don't care WHAT you call it, "the magic made in heaven," whatever. The third instinct is a very interesting one. It's dormant in most people, and it's latent in others. And that's the instinct to migrate. Now there's a major instinct. We all have it. It has nothing to do with "maybe we were all birds;" it is something else entirely.
As I've said, in
Beyond the Beyond
I talk about the re-creation, the bastardized re-creation that basically explains why everything we have is a makeshift. This is why pencils have erasers, because we make mistakes. This is why we age. This is why everything ages. This is why every system goes through the same situation. And I also explained in the nature of time in a different way than the scientist do, and I love my scientist friends but they cling so. It's tribalism. They live in beehives. We have a scientific beehive, we have a spiritual beehive, we have an industrial beehive, we have an economic beehive, and this... they fight with each other, they have wars. On the other hand they protect each other from without. It's like the defensive mechanism of the skin or whatever that protects us from the GMOs and the pesticides as and the conditioners they put in the foodstuffs.
OK so the
The First Kingdom
itself, if you want to look at just what revolves around that, I thought that it was pretty complete within itself and it was also preparing the way for
The Space Explorers Club
, which I know you'll enjoy. The work was a little simpler, but the drawing is just as fine if not better. In fact a number of people have said to me, the drawing of
was superior to
The First Kingdom
, and in some ways it is, it's more human, and of course, the last book is weird. It kind of puts the cap on it, but it also leaves open the opportunity for
Beyond the Beyond
. Because I'm only 85, you know; I start a new series.
Editor's Note: Jack Katz will be promoting the new edition of The First Kingdom at the San Diego Comic-Con; Jack Katz will be at the Titan Comics panel 'Launching at SDCC and Beyond!' on Friday July 19, 12:00PM, room 32AB and will be signing advance copies of The First Kingdom Vol 1: The Birth of Tundran on the Friday as well at 3:00PM, Autograph Alley AA07.
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WHITE WASHED HEART SHAPED PICNIC BASKET FOR 2 (Item #W81909)
This White Washed Heart Shaped Picnic Basket is designed with the most romantic couples in mind. The rattan and bamboo in a white wash finish paired with its unique shape helps it stand out among the rest. This basket also features folding rattan handles, a fully lined white quilted cotton interior and all the amenities for a picnic for 2. Basket comes complete with the following: 2 white 9" melamine plates; 2 hand-blown 8oz wine glasses; 1 wooden 6x6" cutting board; 2 stainless steel forks, knives, spoons; 2 white 100% cotton 14x14" napkins with eyelet edges; 1 stainless steel waiter-style corkscrew with wooden handle; 1 salt and pepper shaker set; 1 plastic food storage container; 1 stainless steel cheese knife with wooden handle; 1 white 100% cotton 44x44" tablecloth with eyelet edging. Color: white. Dimensions: 17.5" x 15" x 10". *Extra $10 shipping.


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Topic: William Babcock
All Content
Letters to the Editor
Readers write about the cost of cleaner cars, why mandatory public service would be a good thing for the US, and how the people of Russia and the US can help their countries' relations.
01/29/2009 12:00 am -
Opinion Obama can instill civic responsibility – through a mandatory Youth Corps
The times call for a regeneration, not just a feel-good tweak.
01/26/2009 12:00 am


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Whiteleaf Business Centre Buckingham Industrial Park Buckingham MK18 1TFUnited Kingdom Tel.+44 (0)1296 715228Northern Office: Allendale Forge Studios, Market Square, Allendale NE47 9BD, United Kingdom
Founded in 1985, Peter Muir Public Relations (pmpr) is a marketing communications consultancy located in central England. pmpr implements a network of consultant professionals to provide a range of marketing support functions meeting the needs of a diverse client base Enjoy your stay with pmpr online. If we can be of help to your business, please contact us now.
pmpr is a founder member of Strategy Hub
Home | About | Services | Sector expertise | Client News | Contact


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Saturday, March 02, 2013Wisconsin
Should show this one as a 4 star in difficulty! Easy enuf to find, following the footprints in the snow. But from there it gets difficult fast! A long skinny pair of fingers, instead of the fat cold ones I had, would have made retrieving this faster than the 10 minutes that it took! ;-( But neat hide anyway. TFTC!
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Red Hat JBoss Middleware
Accelerate Automate Integrate Red Hat JBoss BPM Suite Red Hat JBoss Developer Studio Portfolio Edition Web Framework Kit Application Platform Web Server Data Grid Portal Fuse Red Hat JBoss A-MQ BRMS Red Hat JBoss Fuse Service Works JBoss Operations Network JBoss Community or JBoss enterprise Red Hat JBoss Data Virtualization -
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United States, January 31, 2000SAP solutions on Red Hat shipped to more than 100 customers; R/3 on Red Hat now generally available
Red Hat, a leading provider of open source software, service and information, have announced that SAP R/3, a major component of mySAP.com, is now generally available on the Red Hat Linux operating system and has already been shipped to more than 100 customers. The huge growth in customer demand and industry support prompted Red Hat to partner SAP (the leading provider of inter-enterprise software solutions) to deliver productive solutions on Linux.
Red Hat and SAP have been working together to build an extended version of the award winning Red Hat Linux 6.1. The Kernel, glibc and the installer have been improved to fit the needs of an enterprise server and for use with Sap R/3. In this partnership with Red Hat, SAP will deliver additional mySAP.com components including the Business Information Warehouse and Business-to-Business Procurement, on Linux, in the first half of 2000.
mySAP.com provides an open collaborative business environment of personalized solutions on demand. This equips enterprises with the efficiency, ease-of-use and inter-enterprise collaboration they need to take full advantage of the Internet economy.
Commenting on the partnership, Colin Tenwick Vice President Red Hat, Europe, Middle East and Africa said, "The SAP partnership is yet another seal of approval for Red Hat Linux. SAP is aware of the increasing consumer demand for Linux based systems and has chosen the expertise of Red Hat to operate them. With the award winning Red Hat version 6.1, SAP has the perfect operating system to extend their Internet business solutions."
To provide end-to-end support for SAP solutions based on Red Hat and so ensure customer success, SAP is working with leading hardware partners like Hewlett Packard, IBM, Siemens and Compaq, service organisations and database suppliers. Red Hat and the Open Source Community joined forces with the SAP LinuxLab to implement Red Hat 6.1 Enterprise Version 1.0 that includes a special label, "Certified by SAP LinuxLab." Critical enterprise enhancements in this version of Linux include full native language support that make Linux suitable for multi-national, mission critical applications.
More information about mySAP.com on Red Hat is available online at http://www.redhat.com/products/rhl_packages.html
About Red Hat, Inc.
Founded in 1994, Red Hat is a leader in the development of Linux-based operating system software (OS) and services. Based in Durham, N.C., Red Hat builds the most accessible and advanced server OS available anywhere with technical innovations such as RPM and the disk druid installation tool. Red Hat Linux is available for Intel, Compaq Alpha and Sun SPARC platforms. Red Hat Linux available directly from the company and through Red Hat?s partner, distributor and reseller programs, which include top PC and server manufacturers like Dell, IBM and Hewlett-Packard.
Red Hat Linux was named InfoWorld?s Product of the Year for four years in a row, was given a productivity accolade in Software Development's Jolt Awards, was named an environment/desktop finalist in the Ziff-Davis European Excellence Awards, won the editor's choice awards from the Linux Journal and Australian Personal Computing magazines, and won the "Just Plain Cool" award from Australian Personal Computing magazine.
At March?s LinuxWorld Expo, more than 8,000 members of the Linux community voted Red Hat a "LinuxWorld Favorite". Red Hat Linux recently won a Product Excellence award from Software Development Magazine.
LINUX is a trademark of Linus Torvalds. RED HAT is a registered trademark of Red Hat, Inc. UNIX is a registered trademark of The Open Group. All other names and trademarks are the property of their respective owners.


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This quilt is going to be raffled off during our 2014 Run4Rescue event. It was donated by Susan Wynne (our current CARE board President). If you would like to purchase a raffle ticket please contact Peggy (254) 631-6937. Tickets are $1.00 each. All proceeds will be used to provide for our animals needs.
Our multi-talented, overworked, tireless volunteers Leslie Clements and "KSTV-FM The Mighty 93″ DJ Justin McClure have started a new website showcasing the animals available at CARE, the City of Dublin Animal Shelter and the Erath County Humane Society. Here is the link to THE ANIMAL ARK.
Come join us April 12th 2014 in Gordon Texas for the 2nd Annual Run for the Rescue 5k/10k and family fun run. Runners can enjoy the clean crisp country air while they take in the beautiful scenery of Gordon Texas. The run course will take you through historic downtown Gordon and includes the beautiful surroundings of a pecan orchard. All ages are welcome as well as your leashed furry family members. For more information about the race please email firstname.lastname@example.com.
Here is a link to the online signup. http://www.racedayeventservices.com/
OR: here is a direct link to our printable RUN4RESCUE entry form, if you prefer not to fill it out online. Please print as many as you need and distribute them freely. ENTRY FORM. Printed forms are also available at the Gordon Community Library and the Country Dollar Store in Strawn.
We just received 200 goodie bags from the CONTAINER STORE for our RUN. We thank them for their support. Please support those who support us. It's time to put away those weird unused Christmas gifts from Aunt Pearl and your cousin with one tooth. Well, they've got just the right storage containers to put them in. We still need more sponsors and volunteers for this event. Also if you have a couple of hundred things we could put in these bags, please contact us. We need free give away items of all sorts. Please give us a call. Here is a link to THE CONTAINER STORE.
Millsap Vet is the Gold sponsor for our RUN4RESCUE event. Please support them. They support us all the time with our animal needs. This is indeed an amazing, talented, tireless group of dedicated animal lovers. We could not continue our efforts without them. These are very special people and dear to our hearts. Large or small, they do it all.
C.A.R.E.'s mission is to alleviate animal suffering by aiding abandoned, abused and neglected animals; reducing overpopulation and disease; and assisting responsible pet owners in meeting the needs of their own companion animals. We are their voice!
Please visit our Facebook page to find out more. Facebook is your voice, feel free to post. Also our PetFinder page for all of our animals currently ready for adoption.
Feel free to shoot me an email if you have any questions, comments, additions, requests, etc. Check back often, WE ARE ROCKING!!! The website email address is firstname.lastname@example.com.
Remember, it is against the law to dump or abandon an animal. Know the law regarding animal cruelty.
Low Cost Spay/Neuter Program!
Contact C.A.R.E. about our low cost spay/neuter program to see if you qualify and to arrange for the service. See more
We still Need Volunteers! Anyone interested in helping animals, whether you want to "poop scoop," walk dogs, foster animals, help at adoption events, or make phone calls on our behalf… WE NEED YOU! Please call us at (254) 631-6937.
Donations or Adoption Fees (Same Pay Now Button)


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November 30, 2012 at 09:45 AM EST
Investors Eye Fiscal Cliff as Markets Edge Higher
The markets opened slightly higher as negotiators in Washington continued working on a budget deal. The Dow edged up 19 points to 13,040 while Nasdaq slipped 2 points to 3009.
Shares of Ulta Salon (Nasdaq: ULTA) rose after the beauty retail chain posted higher 3rd quarter revenues and profits. Analysts promptly upgraded the stock. Tellabs (Nasdaq: TLAB) named a new CEO and declared a special cash dividend of $1 a share. Shares of Christopher & Banks (NYSE: CBK) surged after the women's clothing retailer posted a 3rd quarter profit on higher same-store sales. On the downside Yum! Brands (NYSE: YUM) lowered its earnings outlook for the next year citing weak sales growth in China for the fast food chain. VeriSign (Nasdaq: VRSN) agreed to certain limitations for the pricing of domain names in an agreement with ICANN. Shares of Zynga (Nasdaq: ZNGA) fell after the online gaming company lost preferential treatment in its relationship with Facebook (NYSE: FB). In the broad market, advancing issues outpaced decliners by a margin of 5 to 4 on the NYSE and on Nasdaq. The Russell 2000 which tracks small cap stocks rose rose a fraction to 823.
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A collection of news and information related to Pennsylvania published by this site and its partners.
Top Pennsylvania Articles
Displaying items 34-44
August's best political comedy
McManus: Obama's clarity gap
Jonah Goldberg: Talk about a meltdown
Weekly remarks: GOP's Dean Heller sees regs killing jobs; Obama 9/11 should bring unity
Story | Aug 27, 2011 | 4:35 AMRepublican Dean Heller says Obama administration policies hurt job creation; Democrat Obama hopes national unity flourishes around 10th anniversary of 9/11.... -
Obama and Lincoln: trash-talking, Civil War-era style
Story | Aug 18, 2011 | 9:36 PMAfter President Obama remarked on how comments about him compared to those directed at Abraham Lincoln, we take a look at some historical trash talk.... -
The Sunday Brunch: In Redistricting, It's Give A Little To Get A Little.
Story | Aug 21, 2011 | 4:22 PMFor political junkies, the once-a-decade redrawing of Pennsylvania's legislative district lines is a board- game geek's paradise: It's "Risk," "Stratego" and "Battleship" all rolled into one, with the balance of power for the next 10 years as the prize.... -
Report: Corbett To Name Bill Ryan As Gaming Board Chairman.
Story | Aug 19, 2011 | 4:22 PMFrom The AP: "A top official at the state attorney general's office is expected to be named by Gov. Tom Corbett to become the new chairman of the Pennsylvania Gaming Control Board, two people familiar with the matter told The...... -
ADHD is on the rise
Story | Aug 19, 2011 | 4:23 PMIf you find that your son is inattentive, impulsive or just "hyper," perhaps he has Attention Deficit Hyperactivity Disorder. If so, he's not alone. ADHD is one of the most commonly diagnosed mental health disorders and is increasing in prevalence,... -
Local Army vets to participate in Sept. 11 memorial ride for charity
Story | Aug 17, 2011 | 4:34 PMArmy veterans Brian Smith and Lynn Bigelow are about to embark on the ride of their lives. Next month, the two AthletiCo physical therapy employees …... -
Top Highways Not to Drive on Empty
Blog | Aug 16, 2011 | 4:32 PMEver drive your car on or near empty, hoping the next highway exit has a gas station with cheaper prices, or maybe one that accepts your rewards card? Or it's next to your preferred fast-food joint? We have a list...... -
Lawmaker Apologizes for "Womenfolk" Remark, Sticks By Criticism of Drillers.
Story | Aug 17, 2011 | 4:22 PMA Lancaster lawmaker apologized this morning for remarks he made Tuesday claiming that that the the impact of Pennsylvania's burgeoning natural gas industry includes the spread of sexually transmitted diseases "amongst the womenfolk." Speaking to...


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Digmen1 - 8:31 pm on Jun 29, 2010 (gmt 0)
I have XP, did not get Vista, due to it being bloated and offering no major advantages.
But I am just setting up a new machine and I bought 7.
I like it so far. I can't wait to use the snap to windows feature that will allow me to have two windows side by side easily on my 24inch screen. (a bit like Windows 3.11 did)


text: 19. COLLEGE SENIOR. FRUSTRATED SINGER :)) ❤ I am very loyal. You can really count on me. You can tell me secrets, your fears, your ultimate crush and your most inconsiderate teacher. I am placid, and I don't really care what other people may think of me. I am very much open and welcome to changes. I simply enjoy life!


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Our desire at Brown Funeral Home and Crematory is to provide you with quality and service that you won't find anywhere else. Our goal is simple: To serve Citrus County and surrounding areas with quality, professionalism, and integrity that...
Moore Obituaries
It was reported on December 20th, 2013 that David L Taylor died in Moore, South Carolina. Taylor was 63 years old and was born in Clinton, IL. Send flowers to share your condolences and honor David L's life.
It was reported on January 23rd, 2013 that Charles Edward "Chuck" Cagle died in Moore, South Carolina. Cagle was 79 years old and was born in Bristol, TN. Send flowers to share your condolences and honor Charles Edward "Chuck"'s life.
It was reported on January 23rd, 2013 that Charles Edward "Chuck" Cagle died in Moore, South Carolina. Cagle was 79 years old and was born in Bristol, TN. Send flowers to share your condolences and honor Charles Edward "Chuck"'s life.
It was reported on June 14th, 2011 that Viola Dolores Chase (Robinson) died in Moore, South Carolina. Ms. Chase was 88 years old and was born in Blakesburg, IA. Send flowers to share your condolences and honor Viola Dolores's life.
Moore Funeral Home News
College Football Sunday Rewind: Post-Alabama eliminated edition
Forget for a moment Kellen Moore's monster 507 yards passing in a 42 ... What an embarrassing performance by South Carolina, losing at home 41-20 to Arkansas one week before the Gamecocks and Gators decide the SEC East title. I figured South Carolina would ...
Gamecocks honor 'the Voice'
A funeral will be held at 2 p.m. Tuesday ... Sanders 2-4, Lattimore 1-10, Triglia 1-10, Maddox 1-8, D..Moore 1-4. BRETT FLASHNICK/ASSOCIATED PRESS Arkansas' Knile Davis goes over the South Carolina defensive line to score a touchdown late in the third ...
Lois E. Galasso, 47, of Conshohocken
Born in Beaufort, SC, on April 26, 1963, she was a self ... Donovan Malantonio, Schwenksville. Her funeral service will be held on Friday, Nov. 5, 2010, at 10:30 a.m. from the Moore & Snear Funeral Home, 300 Fayette St., Conshohocken, with Rev. Scott Roth ...
Passing game won't change with Bray as starter
They'll only throw it to Justin (Hunter) and Denarius (Moore)." Jones, though ... Stone, who is being groomed as UT's center for the future, was held out of the South Carolina game because Dooley was apprehensive about Stone's chemistry with the quarterbacks.
Funeral - Wikipedia, the free encyclopedia
A funeral is a ceremony for celebrating, sanctifying, or remembering the life of a deceased person. Funerary customs comprise the complex of beliefs and ...
Funeral (album) - Wikipedia, the free encyclopedia
Funeral is the debut full-length album by Canadian indie rock band Arcade Fire, released on September 14, 2004 in North America by Merge Records and on ...
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funeral-homes.net offers you a way to find a funeral home shop in Moore, South Carolina SC or anywhere you wish. We locate funeral homes in all cities ...
Moore Embalmers | Embalmers in Moore, SC - YP.COM
Find embalmers & Embalmers in Moore, SC. Read business reviews, find driving directions, and more. embalmers on YP.COM.
Moore Funeral Planning in South Carolina - Pre-Plan now ...
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Moore, South Carolina SC Funeral Homes | Gilbert Guide
Find a Funeral Home inMoore, South Carolina SC to provide the caring burial and ceremonial services your family deserves.


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Shock and Burn
Electrical safety demands compliance and more
August 2, 2011
The Bureau of Labor Statistics recorded more than 18,000 injuries involving electrical shock or electrical burn between 2003 and 2009, and 1,573 electrical fatalities.
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Safety analytics - the future is now
September 1, 2010
Safety analytics is an emerging science that is helping to drive improvements not only in workforce safety and health programs, but also in overall business performance.
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Groosham Grange : Sent to Groosham Grange as a last resort by his frustrated parents, thirteen-year-old David Eliot quickly discovers that his new boarding school is very peculiar. New pupils are made to sign their names in blood . . . the French teacher cancels classes on days there's a full moon . . . there are chilling secrets hidden in the assistant headmaster's office. What's the meaning of the black rings everyone wears? Where do the other pupils vanish to at night? Suddenly, his biggest problem isn't staying in school -it's getting out alive.
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Children Fiction | Horror & Ghost Stories |


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The same concerned nurse who had lovingly stood by my side during the ultrasound begged me to please stop using the word "kill." I didn't. I couldn't. To me that's exactly what it was. Tell me how I as a mother would go about "selecting" which beating heart to snuff out as if it were just a candle. Please don't think I am judging all of the women who are faced with this horrible decision. I can only answer for myself, and "as for me and my house, we will serve the Lord."
Jon, even at the risk of losing me and raising Mady and Cara on his own, unconditionally agreed with me. Who would live and who would die was not a decision that rested in our human hands. My doctor, visibly shaken, stood and pounded his fists on his desk for emphasis. He declared that it would be a long, arduous, uphill battle that he was strongly urging me not to fight. I realized that I had become a fertility doctor's worst nightmare, and dawn was a long way off. See how the Gosselins are doing today |


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Napster launches DRM-free MP3 store
By Charles Starrett
Contributing Editor
Published: Tuesday, May 20, 2008
News Categories: Digital Media
Napster has launched the world's biggest DRM-free MP3 download store with a catalog of more than 6 million songs. Most of the songs available on the store sell for $0.99 each, with most albums selling for $9.95. "We're now moving from under the DRM cloud," said Chris Gorog, Napster chief executive. "Now consumers can use Napster with any device." The move makes Napster the latest high-profile DRM-free music download store to have the blessing of the major labels, which Reuters says have been hoping to use the services to lessen Apple's dominant position in the industry. Despite the success of the download-to-own model, Napster will still support its subscription service, which it believes will grow as people become more aware of it. Said Gorog, "We believe ultimately that consumers will be moving to an unlimited music model."
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The record labels just love sticking it to Apple, don't they? The only DRM-free music that the iTunes Store is able to offer is from EMI and independent labels.
Posted by Galley in Greenville, SC on May 20, 2008 at 6:21 AM (PST)
The irony of all of this is that it's not likely to have nearly as big of an impact as might be expected.
There have been legal DRM-free alternatives to the iTunes Store for years in the form of physical CDs, and of course the less legal DRM-free alternatives in the form of P2P sites.
People who have traditionally demanded high quality DRM-free music probably weren't heavy iTunes Store customers to begin with, so while the Napster and Amazon services are likely to attract new customers from other sources, I'm not sure they're going to take very many away from iTunes.
The average iTunes Store customer either isn't overly concerned about DRM (in the very least is willing to trade it off for the convenience factor), or they don't really understand what DRM is. Either way, for these types of users the advent of these DRM-free services isn't going to make much difference.
The subscription model and pricing model might have more of an impact (Amazon is selling some tracks for $0.89, for instance), but is that enough to make the average iTunes Store customer change their buying habits?
Posted by Jesse Hollington in Toronto on May 20, 2008 at 7:37 AM (PST)
I was under the impression that the DRM is there because the labels want it not Apple.
And aren't the prices on iTunes partially dictated by the labels too?
Personally I think its better to get a hard copy, rip at 256 VBR with something that uses LAME then store the original as a backup.
But what do I know, I'm just a music lover
Posted by Greg on May 20, 2008 at 12:17 PM (PST)
Correct, and that's rather the point… The labels are willing to give DRM-free music to Apple's competitors in the hope that it will topple the iTunes Store's dominant position.
The assumption is that most people would rather have DRM-free music than music with DRM, and therefore by ensuring that all of Apple's competitors are able to offer better-quality, DRM-free music, Apple will lose its dominant position in the online music industry and the recording industry will therefore regain control.
IMHO, this inexpensive, higher-quality DRM-free music is most definitely not an altruistic move on the part of the recording industry—it's merely a desperate attempt to topple the iTunes Store's dominant position by offering more attractive alternatives. Since the largest DAP consumer base out there is made up of iPods, which will only play either Apple's FairPlay DRM or NO DRM, the labels really have no choice but to provide their music without DRM.
Of course, it's a nice benefit for the consumer in the meantime, but I can't help but wonder if the DRM-free model really fits into the RIAA's long-term agenda….
Posted by Jesse Hollington in Toronto on May 20, 2008 at 2:21 PM (PST)
You make some good points Jesse.
I have friends at work who have brought thousands of pounds worth of music from iTunes between them and have no idea of the restrictions attached to it. And when the one guys hard drive crashed the panic it caused was unbelievable.
Like you say there always has been DRM free music in various forms available and there always will be no matter what the longer term aims of the music industry are. the sooner they stop treating consumers like idiots the better.
I'd personally like to see prices dropped by at least half of what they are now. I have a fairly fixed amount of money to spend on music as I imagine do most other people. If prices were lower I'd spend the same but it would be spread over more artists. Basically I'd try stuff I wouldn't have brought otherwise, new talent would be encouraged and rewarded instead of the top 10% of artists making 90% of the sales.
Home taping didn't kill music, we're in a new era now so why not embrace the changes and move forward instead of constantly trying to fight a losing battle.
Posted by Greg on May 20, 2008 at 11:54 PM (PST)
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Canceled plans won't be resurrected in Colorado
Colorado is joining about a dozen other states that are not requiring health insurance companies to revive canceled health plans.
Colorado is joining about a dozen other states that are not requiring health insurance companies to revive canceled health plans.
No one mentioned cancellation notices. And no one expressed concerns about costs. Instead, at a sparsely attended public meeting about health insurance issues Tuesday evening, potential customers wanted to know if they could skip filling out Colorado's complex Medicaid application.
Health exchange board members on Monday pressed for immediate improvements to Colorado's mandatory Medicaid application, but state officials, who contend that Colorado is a "shining example" among the states, refused to promise that a full slate of short-term fixes will be completed before Dec. 15.
Colorado has no quick fix for a seemingly endless Medicaid application that health exchange board members believe is driving away customers and decreasing the number of people buying health insurance through Colorado's new multi-million dollar health exchange.
In Choosing Wisely, physicians across the spectrum of medical specialties nationwide have created lists of procedures, tests and drug treatments that deserve second thoughts before doctors order them or patients accept them.
A report by Health Policy Solutions
By Diane Carman
Colorado once again laid claim to being the fittest of the 50 states in 2010 with an obesity rate of 19.1 percent – well below the national figure of 34 percent. When the statistics were released last summer, the chorus of self-congratulations could be heard from the Cherry Creek trail to the top of Mount Bierstadt.
Behind those numbers lurks the specter of a far different future for the state, however. Childhood obesity here appears to be out of control.
Lisa Piscopo, vice president of research for the Colorado Children's Campaign, crunched the latest numbers from the National Survey of Children's Health and found that childhood obesity in Colorado increased 23 percent between 2003 and 2007 – the second-fastest rate of increase in the nation behind Nevada.
"We went from fourth or fifth least obese (among children) to 23rd in two or three years," said James O. Hill, executive director of the Anschutz Health and Wellness Center and a professor of pediatrics at the University of Colorado School of Medicine. "This presents a call to action."
The threat posed by runaway increases in childhood obesity is daunting.
"One of the things we hear over and over is that we're raising the first generation of kids who are going to die before their parents," said Hill. "I don't believe that."
Instead, he said, "What's going to happen is that they're going to live 30, 40 or 50 years with debilitating chronic diseases. What happens to adults, we're beginning to see starting in children. We have 13-year-olds with (Type 2) diabetes, 20-year-olds with cardiovascular disease. Now we've got very good drugs and procedures to keep people alive, but they're going to live the majority of their lives with debilitating chronic diseases, and for many people that's a lot scarier than dying early."
For policymakers determined to cut health care costs, that prospect is scary, too. The estimated cost of obesity-related health care in 2009 was $147 billion. If the rate of obesity continues to increase unchecked, those costs will be harder to contain.
• Schools test anti-obesity programs
• Treatment options few for overweight kids
It's one reason why local and national foundations have focused so much of their attention – and their resources – on addressing the challenges of childhood obesity.
In one of the most ambitious nationwide initiatives, the Robert Wood Johnson Foundation announced in 2007 that it would commit $500 million – or more – toward reversing the rate of childhood obesity in the United States by 2015.
Laura Leviton, senior advisor for evaluation at RWJF, said that the emphasis is on prevention.
"For kids who are already overweight, adolescents would have to do something on the order of reducing their intake by 1,000 calories a day or getting that much more exercise. That's a serious issue," she said. "But think about how little might be required to prevent kids from becoming obese."
Leviton said researchers estimate that American children and adolescents on average consume 110 to 165 calories more than they need for growth and activity every day. "That's the equivalent of a can of soda."
Over a year, that relatively slight bit of daily overeating amounts to more than 15 extra pounds. In five years, a pattern of lifelong obesity often has been set.
So reducing intake by 165 calories or increasing activity by 30 to 60 minutes a day across the population seems like a reasonably achievable goal.
"What could you do?," she said. "Maybe bring recess back to schools that don't have it or require that kids not be excused from physical education classes. There are curricula out there for really active physical education classes that are not punitive."
That's not to say it will be easy. Nothing about reversing the obesity epidemic is easy.
"To do that is going to be very tough," said Hill.
"Do fast-food ads play a role? I don't know. It's logical to think they might. It's the same thing about high-fructose corn syrup," Hill said. "Who knows?
"All these things play a role. Where we err is in thinking that addressing any one of those things is going to solve the problem. If we start tomorrow and have no high-fructose corn syrup in anything, it wouldn't solve the problem.
"The challenge we face," he said, "is there are so many things that contribute to childhood obesity, we have to stop thinking about fixing one or two things and look at the whole problem."
Research on the problem is voluminous and breathtakingly frank. Among the findings:
Beyond all those influences, Hill said one overriding fact remains: "More and more people are choosing to be obese rather than doing what it takes to not be obese. It comes down to motivation."
It's one more reason that advocates are focusing on children; there's still time to influence how that choice is made. "We talk about 'little things for little people,'" said Leviton.
The little things include changing taste preferences by serving more baked foods instead of fried foods in school cafeterias; removing sweetened beverages from school vending machines – or removing vending machines altogether; restoring recess; supporting active before- and after-school programs; and offering cooking classes, nutrition programs or other changes in the curriculum that support healthy lifestyles.
Beyond schools, Leviton said, a sea change is needed in communities nationwide.
A 2009 report by the Centers for Disease Control recommended 24 wide-ranging public-policy strategies for communities to help address the nation's obesity epidemic. They range from improving the availability of healthier food choices in public venues and limiting advertisements of less healthy foods in public buildings to encouraging physical education in schools, improving access to recreation facilities and enhancing urban services to encourage walking, cycling and outdoor play.
The Campaign to End Obesity also has called for changes in federal policy to identify obesity as a disease, which would enable patients to negotiate for health coverage for treatment and prevention programs.
In Colorado, lawmkers are pursuing a handful of anti-obesity initiatives.
Last year, the food exemption from sales taxes was eliminated for candy and soda despite relentless lobbying from the soft-drink and grocery industries. Pepsico alone spent a reported $8.6 million in the last quarter of 2009 and the first quarter of 2010 lobbying against soft-drink taxes and other anti-obesity initiatives nationwide.
This session, House Bill 1069 has been introduced calling for public schools to provide at least 150 minutes of activity per week for elementary school children.
Across the country, public policy strategies mimicking the successful anti-tobacco campaigns have begun to take root in the anti-obesity movement, calling for nutritional labeling in restaurants, targeting taxes on certain foods and mobilizing public education campaigns.
While Hill doesn't object to the various legislative attempts to address the problem, he cautions that one or two targeted strategies can't begin to produce the results the state needs.
"One of the problems in this field is it's like the rest of politics in the U.S. We debate at the extremes," he said. "We have people who believe that the government should regulate all this, and tax bad food, and mandate this and that. And on the other hand, people say it's personal responsibility.
"There's some truth on both sides. I don't think we're going to solve this problem with the government telling you what to eat. Alternatively, if we leave it to the individual, it's going to continue like it is."
Hill believes we have to "figure out how to create a better environment so people make better choices."
Colorado, he said, is poised to take the lead in this field. "We're one of the top places in the country with more than 100 researchers doing obesity research, everything from cell biology and clinical studies to community studies.
"I'm very positive Colorado will be the first state ever to show a reduction in obesity rates."
In an attempt to innovate in this arena, Hill said the Health and Wellness Center, Children's Hospital and two school districts – Cherry Creek and Aurora — are working on a long-range project to design a model school district for the nation using a wide variety of strategies and measuring outcomes to determine what approaches offer the greatest chance for success.
"It's a very exciting project," he said. "We look at the science and look at what we can implement. We're taking a very long-term approach."
One of the keys, he said, is looking at the entire population at the schools – teachers, administrators and students. "We're implementing some exciting workplace wellness programs.
"But it's hard," he said. "It's going to be a long, long road if we're going to turn this obesity epidemic around."
For older articles visit our Health Archive.
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Work experience
The first 200 words of this essay...
The government insists upon every fourth year student completing a one week work experience. This is to give the pupils a taste of what working will be like when they leave school. Many of them will do this after having sat their standard grade exams, so it is very beneficial for those students in particular. I have recently completed my work experience at Glaxo SmithKline Beechams. I found my placement mainly by myself, although Mr Cook, the teacher in charge or work experience aided me in contacting them. In the following paragraph I shall give some basic factual information concerning my work experience.
I was working at Glaxo SmithKline Beechams, Irvine Plantation. It is a pharmaceuticals' plantation which makes the main ingredients in medicines such as Clavuanate, which in an antibiotic and Paroxetine, which is an anti-depressant. I was there from 2nd - 4th December. My working hours were from 08:30 - 16:30, however on the initial day I did not start until 09:00. The company had been preparing for my arrival. Transport to Beechams is awful. There are no buses or trains, consequently the only way to travel there is by car.
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