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Heme oxygenase (HO) activity in liver homogenates. Samples were obtained from sham animals and those that underwent trauma and hemorrhage (T-H) at 5 hours after resuscitation. The enzyme activity was determined as described in the "Determination of HO Activity" subsection of the "Methods" section. Data are presented as mean ± SEM for 6 or 7 animals per group. For T-H males and females, P<.05 compared with shams. For T-H females, P<.05 compared with T-H males.
Heme oxygenase inducible 1 (HO1) and constitutive (HO2) isoforms of expression in liver homogenates. A, Representative Western blot of HO1. B, Quantitation of relative HO1 levels. C, Representative Western blot of HO2. D, Quantitation of relative HO2 levels. Samples were obtained from sham males, sham proestrus females, male animals who underwent trauma and hemorrhage (T-H), and proestrus T-H females 5 hours after resuscitation. Data are presented as mean ± SEM for 6 or 7 animals per group. For HO1 expression in T-H males and females, P<.05 compared with sham animals. For HO1 expression in T-H females, P<.05 compared with males.
Effects of trauma and hemorrhage (T-H) on changes in portal pressure in response to the vehicle or tin protoporphyrin IX (SnPP). Measurements were performed 5 hours after resuscitation. Data are presented as mean ± SEM for 6 or 7 animals per group. For T-H males and females who received SnPP, P<.05 compared with sham animals. For females who received the vehicle, P<.05 compared with T-H males.
Effect of trauma and hemorrhage (T-H) on changes in bile production in response to the vehicle or tin protoporphyrin IX (SnPP). Measurements were performed 5 hours after resuscitation. Data are presented as mean ± SEM for 6 or 7 animals per group. For T-H males who received the vehicle or SnPP, P<.05 compared with sham males. For T-H females who received SnPP, P<.05 compared with T-H males in the same group.
Effect of trauma and hemorrhage (T-H) on changes in plasma alanine transaminase (ALT) levels in response to the vehicle or tin protoporphyrin IX (SnPP). Plasma samples were collected 5 hours after resuscitation. Data are presented as mean ± SEM for 6 or 7 animals per group. For T-H males or females who received the vehicle or SnPP, P<.05 compared with sham animals. For T-H females who received the vehicle, P<.05 compared with males in the same group. For T-H females who received SnPP, P<.05 compared with T-H females who received the vehicle.
Toth B, Yokoyama Y, Kuebler JF, Schwacha MG, Rue LW, Bland KI, Chaudry IH. Sex Differences in Hepatic Heme Oxygenase Expression and Activity Following Trauma and Hemorrhagic Shock. Arch Surg. 2003;138(12):1375-1382. doi:10.1001/archsurg.138.12.1375
© 2017
Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock.
Prospective controlled animal study.
A university laboratory.
Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 × the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity.
Main Outcome Measures
Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation.
Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage.
Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide.
TRAUMA WITH accompanying blood loss is the leading cause of death among young adults.1- 3 Hemorrhagic shock decreases organ perfusion, resulting in organ and immune dysfunction.1 Several studies have suggested that carbon monoxide (CO) may participate in the maintenance of organ perfusion4 and thus produce beneficial effects following trauma and hemorrhage.5 The endogenous source of CO (which acts as a vasodilator agent via the activation of guanylate cyclase6) is the heme oxygenase (HO) enzyme, which catalyzes the degradation of heme to biliverdin. Three isoforms of HO have been identified: HO1, the inducible isoform, and HO2 and HO3, the constitutive isoforms.7 The heme oxygenase inducible isoform is considered a heat shock protein (HSP) and is also identified as HSP-32.8 The HSPs protect the cellular machinery of many organs from a wide variety of insults and stresses, such as ischemia and oxidative stress.9,10 Studies have shown that the maintenance of hepatic microcirculation is essential following low-flow conditions to maintain liver function.11 Data indicate that the HO pathway, and specifically HO1, may contribute to the attenuation of hemorrhagic shock and the subsequently impaired circulation of the liver via the generation of CO.6 However, in the male animal model, HO1 fails to fully eliminate the deleterious effects of trauma and hemorrhage.
Clinical and laboratory studies have shown that sex differences exist in liver function following adverse circulatory conditions.12- 15 Studies indicate that male sex steroids have deleterious effects and female sex steroids produce beneficial effects on hepatic function following circulatory stress.16- 18 Testosterone receptor blockade after trauma and hemorrhage has been shown to improve hepatic function in male animals.19 Alternatively, administration of 17β-estradiol improved cardiac and hepatic functions in male animals after trauma and hemorrhagic shock.20 In addition, Jarrar et al16 have shown that proestrus female rats have normal organ function 24 hours after trauma and hemorrhage, whereas males show marked depression in cardiovascular and hepatocellular functions. Estradiol levels are highest during the proestrus stage of the estrus cycle, a stage in which females are protected against the deleterious effects of trauma and hemorrhage. Furthermore, it has been shown that estrogens are protective during other adverse circulatory conditions such as ischemia or inflammation.21 We hypothesized that the elevated estrogen levels in proestrus females compared with males increase HO activity following trauma and hemorrhage and thus produce salutary effects on organ blood flow. The aim of our study, therefore, was to determine whether there is any difference in HO expression and activity in males vs proestrus females following soft tissue trauma and hemorrhagic shock.
Adult male (275 to 300-g) and female (250 to 275-g) Sprague-Dawley rats (Charles River Laboratories, Wilmington, Mass) were used in this study. All experiments were performed in adherence to the National Institutes of Health guidelines for the use of experimental animals and were approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham.
A nonheparinized model of trauma and hemorrhage in the rat, as previously described, was used in this study.22 Age- and cycle-matched female and age-matched male Sprague-Dawley rats were fasted overnight before the experiment but were allowed water ad libitum. The female rats were in the proestrus state of the estrus cycle, as determined by daily examination of the vaginal smears.23 The proestrus stage was defined as the period when both leukocytes and nucleated epithelial cells were present in approximately equal numbers. Experiments were performed after at least 1 complete estrus cycle had been documented. To minimize the effects of circadian rhythms, vaginal smears were obtained between 7 AM and 9 AM, and the hemorrhage procedure began between 9 AM and 10 AM. The rats were anesthetized by isoflurane (Minrad Inc, Bethlehem, Pa) inhalation before the induction of soft tissue trauma (5-cm midline laparotomy). The abdomen was closed in layers, and catheters were placed in both femoral arteries and the right femoral vein (PE-50 polyethylene tubing; Becton, Dickinson and Company, Sparks, Md). The wounds were bathed with 1% lidocaine hydrochloride (Elkins-Sinn, Cherry Hill, NJ) throughout the surgical procedure to minimize postoperative pain. The rats were then allowed to awaken, after which they were bled to a mean arterial blood pressure of 35 mm Hg within 10 minutes. Rapid bleeding places the animals in a depressed state of sensibility, thereby minimizing stress. The point at which the animals could no longer maintain a mean arterial blood pressure of 35 mm Hg without the infusion of fluid was defined as the maximum bleed-out volume. The rats were maintained at this pressure until 40% of the shed blood was returned in the form of Ringer lactate solution. The animals were resuscitated with 4 × the volume of withdrawn blood using Ringer lactate solution for 60 minutes. Following resuscitation the catheters were removed, vessels were ligated, and skin incisions were closed with sutures.
Sham animals underwent the same groin dissection, which included ligation of the femoral artery and vein; however, neither trauma and hemorrhage nor resuscitation was carried out. All animals were returned to their cages and were allowed food and water ad libitum until death. The animals were killed 5 hours after resuscitation. The time point for death was selected on the basis of HO1 expression following trauma and hemorrhage, as described by Bauer at al.4
We determined HO activity in liver homogenates by measuring the amount of bilirubin formed in a 2-step enzymatic reaction, as described by Maines and Kappas24 and Wang et al.25 Liver tissue samples were homogenized in 10mM of phosphate-buffered saline (pH, 7.2) containing protease inhibitors (Complete; Roche, Basel, Switzerland). The homogenates were centrifuged at 10 000g for 15 minutes at 4°C. The supernatant was further centrifuged at 105 000g for 1 hour at 4°C. The resulting pellet was resuspended in phosphate-buffered saline with protease inhibitors. Protein content was determined using a protein assay kit (Bio-Rad Laboratories, Hercules, Calif). The solution mixture was prepared containing 0.5 mL of microsomal protein (6-9 mg/mL), 200 µL of a 105 000g-centrifuged supernatant fraction of the rat liver (10 mg/mL of protein) as a source for biliverdin reductase, a nicotinamide adenine dinucleotide phosphate (NADPH)–generating system (0.8mM of β-NADPH, 0.8mM of glucose 6-phosphate, 1.5 U of glucose-6-phosphate dehydrogenase, and 2mM of magnesium chloride), and 20 µL of 2.5mM of heme solution. The final volume was adjusted to 1.5 mL with 0.1M of phosphate-buffered saline. Reagent blanks were prepared in a similar way but without the addition of the NADPH-generating system. Samples were prepared on ice and then incubated in the dark at 37°C with agitation for 60 minutes. Bilirubin content was measured spectrophotometrically at 460 nm and 530 nm; HO activity was expressed as nanometers of bilirubin per 60 minutes per milligram of protein.
Liver samples were homogenized in 10 vol of cell lysis buffer (phosphate-buffered saline; pH, 7.2) containing 50mM of sodium fluoride, 100mM of tetrasodium pyrophosphate, 2.5mM of sodium orthovanadate, 50mM of phenylmethylsulphonyl fluoride, 1M of dithiothreitol, and protease inhibitors (Roche). The lysate was clarified by centrifugation at 12 000g for 10 minutes, the clear supernatant was collected, and the total soluble protein content was determined (Bio-Rad Laboratories). Samples were stored at −80°C until analysis. Electrophoresis was performed on precast 4% to 10% polyacrylamide gels (Bis-Tris; Bio-Rad Laboratories) in 3-(N-morpholino) propanesulfonic acid (Sigma, St Louis, Mo) running buffer containing sodium dodecyl sulfate (Novex, San Diego, Calif) for 50 minutes at 200 V. Each lane was loaded with 40 µg of protein. Western blot transfer to nitrocellulose membranes (Novex) was carried out for 60 minutes at 37 V. The membrane was incubated with polyclonal rabbit antirat HO1/HSP32 primary antibody (1:1000) or polyclonal rabbit antirat HO2 primary antibody (1:500; Stress Gen Biotechnologies Corp, Sidney, British Columbia) overnight at 4°C. Unbound primary antibody was removed by washing the membrane with Tris-buffered saline plus 0.5% polysorbate 20 (TBST) (Bio-Rad Laboratories). Horseradish peroxidase–conjugated goat antirabbit antibodies were used as a secondary antibody (1:10000) for 1 hour. After repeated washings of the membrane with TBST, the detection of the conjugate was performed with an enhanced chemiluminescent reaction. Densitometric analysis of the images was performed (ChemiImager 5500; Alpha Inotech, San Leandro, Calif). The intensity of the positive control band on each blot was arbitrarily set at 100 densitometric units.
To block HO activity, a second set of animals was treated with tin protoporphyrin IX (SnPP) (50 µmol/kg of body weight, subcutaneously) at the beginning of resuscitation. The portal pressure measurements were performed according to Baveja et al26 with modifications. Five hours after resuscitation, the carotid artery was cannulated and the cannula was connected to a pressure transducer. A laparotomy was performed, after which the intestines were covered with wet gauze to minimize evaporative loss during the measurements. The portal vein was identified and exposed. The common bile duct was cannulated with polyethylene-10 tubing (Becton, Dickinson and Company), and the bile flow was measured in preweighted tubes for 10 minutes. A polyethylene-10 catheter filled with saline was inserted into the portal vein without compromising the flow. The catheter was connected to a low-pressure analyzer (Digi-Med, Louisville, Ky) to monitor the portal pressure. The pressure transducers were calibrated and zeroed against a column of fluid open to the atmosphere at the level of the cannula tips.
Five hours after resuscitation, blood samples were obtained and placed in microcentrifuge tubes. After centrifugation, plasma samples were separated, immediately frozen, and stored at –80°C until assayed. Hepatocyte injury was determined by measuring levels of alanine transaminase (ALT) using a commercially available colorimetric reaction kit according to the manufacturer's instructions (Sigma, Ronkonkoma, NY).
Data are presented as mean ± SEM. Statistical differences between groups were determined by analysis of variance followed by the Newman-Keuls post hoc test or t test, and differences were considered significant if P<.05.
Trauma and hemorrhagic shock increased HO activity in the livers of both male and female animals as compared with sham animals (Figure 1). The trauma and hemorrhage–induced increase in HO activity was significantly greater (P<.05) in proestrus females than in males. To determine which isoform of the HO enzyme was responsible for the observed increase in activity, liver homogenates were analyzed for HO1 and HO2 protein using Western blot analysis. No significant differences were observed in HO1 expression in livers from male and female sham animals (Figure 2A and B). Trauma and hemorrhage induced significantly greater (P<.05) HO1 expression in proestrus females than in males. In contrast, HO2 expression and protein levels remained constant: neither trauma and hemorrhage nor sex influenced its expression (Figure 2C and D).
In normal conditions, there was no difference in portal pressure between males and females. Trauma and hemorrhage elevated portal pressure in vehicle-treated males; however, the differences were not significant when compared with sham animals. In contrast, vehicle-treated females exhibited significantly lower pressure compared with males following trauma and hemorrhage (Figure 3). Blockade of HO activity with SnPP did not affect portal pressure in sham animals; however, trauma and hemorrhage and SnPP increased the portal pressure significantly (P<.05) in both males and proestrus females.
Following sham operation, neither sex nor blockade of HO suppressed bile production. Trauma and hemorrhage significantly decreased bile flow in males, whereas bile flow was maintained in proestrus females (Figure 4). In addition, SnPP did not alter the suppressed bile production in males following trauma and hemorrhage; however, SnPP significantly (P<.05) decreased bile production in proestrus females following trauma and hemorrhage (Figure 4).
Mean arterial blood pressure was not significantly different at the beginning of the experiment or at the time point of euthanasia in sham animals. Furthermore, SnPP treatment did not significantly alter the pressure in either group. Although there was a significant decrease in mean arterial blood pressure 5 hours after trauma and hemorrhage and resuscitation, neither sex nor SnPP affected it (Table 1).
In sham animals, neither sex nor blockade of HO altered ALT activity (Figure 5). Trauma and hemorrhage significantly increased ALT activity in males (P<.05) but not in proestrus females. However, SnPP treatment further increased ALT activity in males and also increased activity in proestrus females following trauma and hemorrhage (Figure 5).
Recent studies have suggested that CO generated via the HO may act as a vasodilator in the liver following trauma and hemorrhagic shock.6,27 Studies have also shown that hemorrhagic shock and resuscitation can induce the expression of HO1 (the inducible isoform) in the liver of male animals,6 whereas levels of HO2 (constitutive HO) are unchanged in such conditions.4 Our study shows a difference in magnitude of the increased expression pattern of HO1 in the liver of male and proestrus female rats following trauma and hemorrhage: HO activity (which reflects the combined activity of HO1 and HO2) in proestrus females was significantly higher compared with males following trauma and hemorrhage, which correlated with elevated HO1 protein expression in proestrus females. The markedly elevated HO1 activity and expression correlated with decreased liver tissue damage (lower ALT level) and maintained hepatocellular function (unaltered bile flow and lower portal pressure) in proestrus females following trauma and hemorrhage.
Consistent with previous studies, we demonstrated increased expression of HO1 in male rats following trauma and hemorrhagic shock.5 It has been shown that endogenous CO has protective effects following trauma and hemorrhage in male animals.6 However, that study used a less severe trauma-and-hemorrhage model compared with ours. Despite the doubled HO1 activity in males following trauma and hemorrhage, no protective effects of HO1 were observed in males. However, the markedly increased activity found in proestrus females improved liver function, and blockade of HO with SnPP abolished these protective effects following trauma and hemorrhage. Thus, the higher levels of HO1 in proestrus females compared with males following trauma and hemorrhage were effective in protecting the host in those conditions.
Multiple organ failure following adverse circulatory conditions is caused by several factors, including decreased microcirculation, cardiovascular function, and immunological responsiveness.1 Several studies have supported the concept that maintenance of hepatic circulation following trauma and hemorrhage, specifically the microcirculation in low-flow conditions, is essential in preventing hepatocellular dysfunction.5,27,28 Recent findings from our laboratory as well as others have shown that sex and sex hormones can influence the response to adverse circulatory effects such as trauma and hemorrhagic shock.1 Female rats in the proestrus stage of their estrus cycle and estradiol-treated males have maintained cardiovascular and hepatocellular functions compared with untreated males following trauma and hemorrhage.16,20 These experimental results suggest that female sex steroids such as 17β-estradiol are responsible for the observed beneficial effects following trauma and hemorrhage.
In contrast, it appears that physiological levels of male sex steroids are responsible for producing the depressed organ function following trauma and hemorrhage in males. Studies have also demonstrated that implantation of testosterone-releasing pellets in female mice resulted in decreased levels of 17β-estradiol and markedly depressed immune function, whereas vehicle-treated proestrus females maintained immune function following trauma and hemorrhage.3 These findings suggest that the ratio of androgen to estrogen influences immune and cardiovascular function following trauma and hemorrhage. Besides improved cardiovascular function, hepatocellular function is also maintained in proestrus females after trauma and hemorrhage and in males following estradiol treatment, as determined by the indocyanine green clearance technique.16,29 Harada et al13 have shown that ovarian 17β-estradiol could prevent mortality caused by liver ischemia and reperfusion injury in mice. This beneficial effect was blocked by ovariectomy or administration of a selective estrogen antagonist in female mice. Furthermore, Eckhoff et al30 have shown that estradiol administration significantly reduced injury after ischemic reperfusion to the liver; this effect was mainly receptor mediated and was associated with increased serum nitric oxide levels, decreased levels of tumor necrosis factor α, and a decreased number of neutrophils in liver biopsy specimens. Our recent study17 has shown that estradiol administration following trauma and hemorrhage improves splanchnic perfusion even after the induction of sepsis.
Estradiol is the predominant circulating sex hormone in females. It has been demonstrated that female rodents have the highest circulating estradiol levels in their proestrus phase compared with the other phases.31 The peak level of estradiol is reached in the morning hours, followed by a gradual decrease. On the basis of the observed salutary effects of estradiol on the proestrus state of the female animals following trauma and hemorrhage,13,16,20,29,32 we used proestrus female and male animals in our studies.
Previous results from our laboratory have shown that whereas cardiac output, heart performance parameters, and hepatocellular function are significantly depressed in male animals following trauma and hemorrhage, these functions are maintained or even enhanced in proestrus females in those conditions.16,19,33 In contrast, ovariectomized females with decreased levels of 17β-estradiol have significantly reduced hepatocellular function and increased ALT activity following trauma and hemorrhage.34 Furthermore, Jarrar et al29 have shown that depressed cardiovascular and hepatocellular functions were restored in animals receiving 17β-estradiol following trauma and hemorrhage. These results collectively indicate that cardiovascular and immunological functions are maintained in proestrus females but not in ovariectomized females, males, or females in the nonproestrus stages of the estrus cycle following trauma and hemorrhagic shock. Therefore, male animals served as controls for proestrus females in this study. Further studies are required to determine the possible differences in HO1 expression in female animals in the different stages of the estrus cycle in such conditions.
Although the HO pathway was originally described in connection with the degradation of the heme molecule to biliverdin,35 recent findings have suggested that HO may be an important vasoactive effector through the formation of CO, activation of guanylate cyclase, and subsequently increased formation of cyclic guanosine monophosphate.36 It has been shown that HO1 has cytoprotective effects following hepatic ischemic reperfusion injury via the generation of CO.37 Furthermore, Suematsu et al38 have shown that CO can function as an endogenous modulator of vascular perfusion in the liver in an isolated perfusion model. Hepatic stellate cells, or Ito cells, have been identified as liver-specific pericytes influencing sinusoidal tone and liver circulation.39 In normal conditions, HO2 is constitutively present in Ito cells. Nevertheless, in our study, the blockade of HO with SnPP in sham animals did not alter portal pressure or bile production, indicating the low importance of HO in maintaining the liver microcirculation in normal conditions.
Because the expression of HO1 reaches its maximum around 5 hours after resuscitation in male animals following trauma and hemorrhage,4,5 we selected this time point for our study. Furthermore, studies indicate the importance of maintaining liver circulation in the early phase of circulatory disturbances following trauma and hemorrhage.6,40 Additional studies are required to determine the exact time course of HO expression following trauma and hemorrhage in proestrus females and to clarify whether different estradiol concentrations (baseline estradiol levels in other phases of the estrus cycle) or those of other female sex hormones (eg, progesterone or prolactin) have any salutary effects on HO1 expression.
Nitric oxide is another gaseous mediator that acts as a vasodilator through the activation of soluble guanylate cyclase.41 In normal conditions, minimal nitric oxide–mediated vasodilation is observed42; however, increased nitric oxide activity has been described after endotoxic shock.43 Although increased inducible nitric oxide synthase activity occurs in vascular hyporeactivity states such as trauma and hemorrhage, Nishida et al42 and Wang et al44 showed reduced nitric oxide release from aortic rings following trauma and hemorrhage and resuscitation. Thus, the role of endothelium-derived relaxing factor (nitric oxide) remains unclear in the regulation of systemic vascular tone and hepatic sinusoidal circulation following trauma and hemorrhage.
In the liver, Kupffer cells are the only cell population expressing HO1 constitutively. Bauer at al4 have shown that HO is increased in male rats following trauma and hemorrhage. Our findings extend these results by showing that the induction of HO activity following trauma and hemorrhage is significantly greater in proestrus females than in males. Moreover, HO1 is the isoform responsible for the observed increase in enzyme activity. Blockade of HO with SnPP showed that in normal conditions, the HO-CO system has little effect on the macrocirculation of the liver. In contrast, trauma and hemorrhage resulted in elevated portal pressure in males but not in proestrus females. Treatment with SnPP attenuated this sex-specific difference and increased the portal pressure in both males and females. The observed sex-specific differences suggest that CO is protective against hepatic circulatory disturbances6 and that the increased induction of HO in females may be partly responsible for the better-preserved hepatocellular function in proestrus females compared with males following trauma and hemorrhage.16
Our study focused on the circulatory aspects of the HO system and CO. However, other potential mechanisms might be responsible for the observed effects. Besides its vasoactive properties, CO possesses functional and immunomodulatory properties such as anti-inflammatory effects.45 Furthermore, CO and HO1 have been shown to modulate various cellular functions such as cytokine production,46 cell proliferation,47,48 and apoptosis.49 In addition, it has been shown that the induction of HO1 may protect the cell against oxidative injury by producing biliverdin (an antioxidant).50 Biliverdin and bilirubin, considered harmful substances in vivo, have been shown to scavenge reactive oxygen species following ischemic reperfusion injury51 and endotoxin administration.52 Further studies are needed to determine whether there are any additional effects of CO, biliverdin, and bilirubin following trauma and hemorrhagic shock.
Recent studies using immunohistochemistry techniques have demonstrated that the distribution of the HO enzyme has distinct topographic patterns: HO1, the inducible form, was observed only in Kupffer cells; HO2, the constitutive isoform, was distributed in the parenchymal cells (but not in the Kupffer cells) in normal conditions.53 In contrast, neither of the 2 isoforms was detectable in hepatic stellate cells or sinusoidal endothelial cells.50 Hemorrhagic shock led to a different cell type–specific expression pattern of HO1. A marked up-regulation was detected with immunohistochemistry in parenchymal and sinusoidal lining cells as well as in periportal hepatocytes and sinusoidal lining cells in the periportal region.4 However, such studies have been performed only in male animals. Additional studies are needed to determine the localization and possible differences in HO1 expression in proestrus female rats following trauma and hemorrhagic shock.
The perturbation of hepatic circulation (microcirculation and macrocirculation) and the resulting decrease in energy charge following trauma and hemorrhage6 and SnPP treatment are associated with decreased total bile production, an indicator of hepatic secretory function. Although the observed decrease was moderate in female rats, males exhibited significantly depressed bile flow following trauma and hemorrhage. These findings may indicate that the protective effects of CO are manifested not only by preventing tissue damage but also by maintaining hepatocellular function in proestrus females.
In summary, our study provides evidence that female sex hormones influence the expression of HO1 following trauma and hemorrhagic shock. Thus, the higher level of HO1 and the generated CO in proestrus females may help to preserve portal pressure and secretory function (bile flow) after trauma and hemorrhage. These results lead us to conclude that the HO-CO pathway may be partly responsible for the previously observed attenuation of hepatocellular damage following trauma and hemorrhage in proestrus females.
Trauma and hemorrhagic shock with accompanying multiple organ failure is the major cause of morbidity in patients 39 years and younger. Several experimental and epidemiological studies have shown that female animals tolerate the consequences of trauma better than males. Although some epidemiological data do not support sex-related effects on outcome following trauma, those studies do not take into account the hormonal status of the women. In contrast, experimental studies show that the high levels of 17β-estradiol in the proestrus state are essential to observe the beneficial effects. This could explain the difference between the experimental and clinical studies. Future clinical studies should include the hormonal status of women. In this study, we attempted to find a possible explanation that could help to clarify the mechanism of salutary effects observed in proestrus females following trauma and hemorrhage. We examined liver activity and expression of the HO system in male and proestrus female rats following trauma and hemorrhage. The results demonstrate that the expression of HO1 is twice as high in proestrus females as in males and that this is associated with decreased portal pressure, normal bile production, and decreased ALT levels in proestrus females following trauma and hemorrhage. Because the cycle stops after trauma and the precise menstrual cycle of women who undergo trauma may not be known, administration of a single dose of estradiol in women and particularly in postmenopausal women following trauma would be expected to prevent the elevation of portal pressure, maintain normal bile production, and decrease hepatic injury in those conditions.
Corresponding author and reprints: Irshad H. Chaudry, PhD, Center for Surgical Research, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall, Room G094, Birmingham, AL 35294-0019 (e-mail: Irshad.Chaudry@ ccc.uab.edu).
Accepted for publication July 12, 2003.


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THe bestselling African American stories in the horror genre, just in time for Halloween!
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Dark Corner Publishing is pleased to present THE DARKNESS TO COME–the author's original version of his novel published in July 2008 as DON'T EVER TELL–available now exactly as the author intended.What if everything you knew about the love of your life was a lie?Atlanta graphic designer Joshua Moore was one of those nice guys who always seemed to finish last, especially when it came to love. But all that changed when he met sweet, smart, almost magically perceptive Rachel. In less than a year they marry, and soon she announces that she is pregnant with their first child. The future is full of promise–but Joshua cannot escape his growing suspicion that Rachel is hiding something from him, something about a terrifying man from her past . . .Formerly a successful attorney in Chicago, Dexter Bates spent four long years in prison thinking about the woman who betrayed him. He emerges free with one chilling purpose: to hunt her down. Brilliant and cunning, with a capacity for ruthless violence, he's also acquired a frightening talent that aids his mission of vengeance–and makes him virtually unstoppable . . . When Rachel vanishes suddenly, leaving behind only a cryptic letter, Joshua realizes that everything he believed about her was a lie–everything except her love for him. He vows to find out the truth about her past, to protect her, their unborn child, and their future. His search brings him face-to-face with the cold-blooded, inhumanly powerful Dexter . . . and the darkness that may consume all that he cherishes . . . A gripping exploration of commitment, love, and hope in the face of insurmountable odds, this is award-winning author Brandon Massey at his thrilling best.
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René Rodriguez Soriano: An all-sweeping book, magical, transparent and evocative, sown with reflections and signals, so much as lightning, so much as light that, after reading it, no reader goes back to be the same.Horacio Semeraro: Syncretism effect for a great narrative.Thousands of stories and novels deal with mirrors. To write about them is a challenge to originality. Otilia Umaga the mulatto girl from Martinique -short novel, winner of the Juan Rulfo Prize 2008- totally deserves that distinction for its subtle sensuousness and the atmosphere achieved, A Brazilian woman and a Dutchman, who owns an inn at Senegal, play the leading roles in a particular encounter. Over this background they will tell their story. But it will be a revealing mirror that through its transhumant becoming shows us another leading couple of the novel in a far away time:A Belgian slave dealer –married to a Spanish woman from Seville- and a mixed race –mulatto- girl from Martinique, who enters the scene late, but with decisive participation. With a narrative as exotic as it is attractive, the author leads us to a mixture of Eden and Purgatory. The treatment of the passions and human behaviour in a torrid and sensuous climate coexists with the freshness and originality of her prose. Towards the end the features of magical realism –so dear to Juan Rulfo- get stronger, in an unexpected and fascinating spectacular encounter. The breaking-up of the temporal fields, the natural narration of unconventional or fantastic deeds, as also the meticulous description of characters in the real plane; coexist eclectically with Afro-American mythical elements, ghosts and catholic nuns. But it is Barugel's prose, precise and erotic, that sinks the reader in that scenery with Senegalese drums rhythm and strong temperaments, achieving a syncretist effect in this surprising novel.Lidia Barugel was born in Buenos Aires, Argentina.She published Amores de vidrio (2007) and Contrapalabra (ilustrated poem, 2010)Otilia Umaga, la mulata de Martinica, obtained the Juan Rulfo Prize,sponsored by:Radio France InternationaleInstituto CervantesInstituto de México en ParísCasa de América Latina Colegio de EspañaThe newspaper Le Monde DiplomatiqueEmail: email@example.com Ilustratión: "Woman", Digital drawing by Lidia Barugel
- My Soul to Keep by Tananarive Due
(Harper Voyager, 2011-11-15, Kindle Edition)
When Jessica marries David, he is everything she wants in a family man: brilliant, attentive, ever youthful. Yet she still feels something about him is just out of reach. Soon, as people close to Jessica begin to meet violent, mysterious deaths, David makes an unimaginable confession: More than 400 years ago, he and other members of an Ethiopian sect traded their humanity so they would never die, a secret he must protect at any cost. Now, his immortal brethren have decided David must return and leave his family in Miami. Instead, David vows to invoke a forbidden ritual to keep Jessica and his daughter with him forever. Harrowing, engrossing and skillfully rendered, My Soul to Keep traps Jessica between the desperation of immortals who want to rob her of her life and a husband who wants to rob her of her soul. With deft plotting and an unforgettable climax, this tour de force reminiscent of early Anne Rice will win Due a new legion of fans.
- Never Dead by Jumata Emill Jones
(STJ Publishing, 2011-03-28, Kindle Edition)
THE PERFECT COUPLE?Emerson McGee has spent most of his life living with a secret, and the first-year law student's menacing struggle with his sexuality is only the half of it. His wife, Danielle, has her own scars of adolescent heartache—which she thinly veils behind her façade as an upper-middle class princess. The newlywed's cookie-cutter marriage is abruptly interrupted when they make a reluctant move into the quaint house Emerson inherited from his deceased grandmother. Unbeknownst to them, there's already something else living there: A malevolent entity hell-bent on exposing its connection to Emerson and the tragic secret they share.A GHOST'S STORYWhile a mysterious narrator recounts the details of his abject life, the McGee's vengeful poltergeist pulls Danielle deeper into a mystery that has haunted an impoverished ghetto in South Baton Rouge—aptly called "'Da Bottom"—for nearly a decade, and spills into the provocative world of New Orleans hoodoo. Before its final scare, Never Dead concludes with a bloody twist the McGees never saw coming.
- Serving Monster by Jervey Tervalon
(Jervey Tervalon Books, 2011-04-02, Kindle Edition)
Serving Monster is the story of Gibson, the personal chef of an immensely talented, but deeply strange icon of popular culture, Monster Stiles. While working for Monster, Gibson realizes that not all is what it seems at the Lair, Monster's isolated and beautiful retreat. At great cost to himself, what Gibson discovers at the heart of the Lair, will reveal more about the startling truth of Monster than anyone could ever imagine.
- Deadlier by the Dozen, an Urban Fantasy (Dark Encounters) by Marcia Colette
(Dusk Till Dawn Books, 2011-09-09, Kindle Edition)
Dark Encounters, Book #2The more the scarier.Put up for adoption at seven-years old, history teacher Mackenzie Lawson has spent the last twenty years dreaming of meeting her family again. However, her hopes to rekindle old memories and find closure have hit one hell of a snag. A hundred-year-old curse placed upon her relatives has begun, unleashing a dozen of her doppelgangers who want her dead. Their purpose is to infiltrate her family and kill everyone in sight. To exact revenge for a wrong that happened more than a century ago. Mackenzie must find a way to get rid of her psychotic doubles or risk having them go after her loved ones. However, each doppelganger kill causes her blood pressure to skyrocket to dangerous levels. This and more attract the attention of a mysterious mutant with patchwork skin who volunteers his services, but leaves out the part about it being his job to destroy the source of the doppelgangers starting with her. Mackenzie needs to figure out where his loyalties lie before DEADLIER BY THE DOZEN becomes deadlier by thirteen.
- The Exorsistah: X Restored by Claudia Mair Burney
(Pocket Star, 2011-05-31, Mass Market Paperback)
God finally gave X what she asked for. If only he would teach her how to use it. After three years and more creepy demons than she'd care to recall, Emme Vaughn has finally found her mama. Only the reunion doesn't go as X expected. It's not easy adapting to a new life in New Orleans, with a mother who was possessed by the devil until recently and a stepfather she didn't know existed. Especially when a mysterious stranger, her stepfather's charming and handsome protégé Jean-Paul, drives a wedge between Emme and Francis. Is the enigmatic outsider trying to replace her man? Or does he have a more sinister plan— one she couldn't have imagined? Haunted by a mysterious ghost and threatened by a demon in her mama's house, X gets ready to rumble. She dons God's armor to face the evil force that has hunted her all her life, but first she must cast aside the little girl act and draw strength from all the celestial and worldly friends who have guided her this far. Once and for all, the devil has it coming . . . Exorsistah style.
- The Vampire and The Vegan, Book I: Food by Merlene Alicia Vassall
(Technical Assistance & Support Consultants, 2011-01-01, Paperback)
Pearl, a temptress vampire living in Washington, DC, discovers that the blood of her next would-be victim, Salaam, lacks that certain something she craves – necromantic energy that comes from eating meat. Yet he may offer her something that she needs even more… Through fast-paced prose peppered with surprises, The Vampire and The Vegan explores the complex relationship between a carnivore and her food.
- The Spider Inside Her, an Urban Fantasy (Dark Encounters) by Marcia Colette
(Dusk Till Dawn Books, 2011-06-26, Kindle Edition)
It's in her nature.As the manager of a domestic abuse shelter, Loréal Ingram is making half the salary she's used to, behind on her mortgage, and has lost faith in being an advocate for victims after three die on her watch. When a job offer lands in her lap, she wants to take it…until a curse changes her into a humanoid spider. But that's not the worst of it. She's forced to share her mind and body with an insect spirit who thrives on death.The arachnid, her Mr. Hyde-like personality, is fueled by vengeance, and the handler who should be managing her kills sucks at his job. One abuser after another dies and the trail leads to Loréal. She learns that the handler has botched the curse and unleashed The Spider Inside Her upon wrongdoers. If she doesn't find a way to lift the curse soon, the arachnid will take complete control of her body and kill anyone who crosses her path, including her boyfriend.
- Best Black Vampire Story by Donna Monday
(2011-03-23, Kindle Edition)
Rochelle Prescott is adrift. After experiencing the tragic loss of her fiancé, Everett, she decides to take a trip through upstate New York—hoping to find a little solace for her bruised soul. Tired and hungry, she pulls into the town of Venice Springs. A local directs her to what seems like a charming, old-fashioned bed and breakfast inn. However, as Rochelle is about to find out, the Sleepy Trail Inn offers more than cozy comfort for weary travelers.Every guest is a potential meal for the black vampires who own this quaint old place. In spite of her best efforts, the unsuspecting Rochelle finds herself falling under the spell of the handsome Darius Champion. Will her love for the master vampire lure her into the world of the immortals forever?Darius Champion has lived his life to the fullest. During his 200 plus years of walking the earth, he has satisfied his every whim and lust. Having grown weary of the fast life, he settles down in upstate New York. Yet, there's a place deep down in his heart that yearns for true love and companionship. While he is master of his home and the town of Venice Springs, there is one thing he's not in control of—his heart. Will his blind love for one woman cause him to lose everything he cherishes—including his life?BEST BLACK VAMPIRE STORY is much more than a vampire romance, you'll be drawn into a world of love, lust and terrifying power, where vampires have taken over an entire town against its will. All of the intriguing action leads up to a final clash between vamps and townies where one group must win over the other or perish.NOTE: This book was originally published under the title of THE BEST BLACK VAMPIRE STORY YOU'VE EVER READ (paperback).Want more great stories? Click on the author name above to see more titles.
- HOWL: A Short Story by Christian Slade
(, 2011-05-31, Kindle Edition)
Short Story; 10,000 Words.Zandeleigh's father moves her to West Africa for a summer mining contract. She's expected to grow and bring her experiences back home with her before her Senior year of high school.Her first night in the village she sees a young boy attacked by a great, black enraged beast; a Drill.Some mysterious disease drove the animal mad, and soon the locals are beginning to act strangely lethargic. Worse still, the symptoms are spreading quickly. It isn't long until Zandeleigh witnesses horrors like she'd never imagined before.Includes a 2 chapter preview of upcoming novel EDEN, a bizarre and compelling tale of horror.
- Hollowstone by Dennis Upkins
(Parker Publishing Inc, 2011-06-06, Kindle Edition)
Life for Noah Scott changes drastically when he is accepted to Hollowstone Academy, one of the most prestigious boarding schools in the country set in the mountains of Eastern Tennessee. Within the hallowed halls of the illustrious school, Noah soon discovers that the world of the privileged is rife with social hierarchies, politics, depravity and corruption. It is also there that Noah meets his roommate and best friend, the charming and enigmatic Caleb Warner. Tragedy soon strikes when Cal is brutally murdered in a hold-up. But when Noah is haunted by Cal's ghost, he soon discovers that the random act of violence was in fact a premeditated one. Determined to uncover the truth and find Cal's killer, Noah soon finds that the school and its patrons have more than their share of secrets. Secrets they are willing to preserve at any cost. Through a series of prophetic dreams and visions, Noah also quickly learns that greater supernatural forces are at play. In a race against time, Noah must solve Cal's murder and uncover the truth before he's the killer's next victim.

subset: commoncrawl


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Auguste Casimir-Perier
Auguste Victor Laurent Casimir-Perier (20 August 1811, Paris – 6 June 1876) was a French diplomat and political leader. He was the son of Casimir Pierre Perier and the father of President Jean Casimir-Perier.
He entered the diplomatic service, being attached successively to the London, Brussels and St Petersburg embassies and in 1843 became minister plenipotentiary at Hanover.
In 1846 he resigned from the service to enter the legislature as deputy for the département of Seine, a constituency which he exchanged for another one in the département of Aube after the Revolution of 1848.
On the establishment of the Second Empire he retired temporarily from public life, and devoted himself to economic questions of which he published a series of works, notably Les Finances et la politique (1863), dealing with the interaction of political institutions and finance. He contested Grenoble unsuccessfully in 1863 against the imperial candidate, Casimir Royer; and failed again for Aube in 1869.
In 1871 he was returned by three départements to the National Assembly, and elected to sit for Aube. He was minister of the interior for a few months from 11 October 1871 to 6 February 1872, and his retirement deprived Thiers of one of the strongest elements in his cabinet. He also joined the short-lived ministry of May 1873 (18 to 25 May). He consistently opposed all efforts in the direction of a monarchical restoration, but on the definite constitution of the republic became a life senator, declining Mac-Mahon's invitation to form the first cabinet under the new constitution. He died in Paris.
|This article does not cite any sources. (June 2009) (Learn how and when to remove this template message)
|This French diplomat-related article is a stub. You can help Wikipedia by expanding it.
- 1811 births
- 1876 deaths
- Politicians from Paris
- Orléanists
- French republicans
- French interior ministers
- Members of the Chamber of Deputies of the July Monarchy
- Members of the National Legislative Assembly of the French Second Republic
- Members of the National Assembly (1871)
- French Life Senators
- 19th-century French diplomats
- French diplomat stubs


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Pet Odor Eliminator is formulated using natural mixed ingredients. In a granular form. this product is good in absorption, neutralization and removal of odor. It does not "mask" up the odor with a fragrance, but removes them.
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+91-11-45679615Post Your Requirement
Description :
Srinagar has a long history, dating back at least to the 3rd century BC,[citation needed] and has been known by different names. The city is said to have been founded by the King Pravarasena II over 2,000 years ago, named it Parvasenpur.[citation needed] The city was then a part of the Maurya Empire, one of the largest empires of the Indian subcontinent.[citation needed] Ashoka introduced Buddhism to the Kashmir valley, and the adjoining regions around the city became a centre of Buddhism.[citation needed] In the 1st century, the region was under the control of Kushans, based out of modern Pakistan and Afghanistan. Several rulers of this dynasty strengthened the Buddhist tradition.[citation needed] Vikramaditya (of Ujjain) and his successors probably ruled the regions just before the city fell to the control of the Huns-a nomadic tribe from central Asia in the 6th century, and Mihirkula was the most dreaded ruler of the city and the valley.[citation needed].
Srinagar became the capital of Kashmir around 960 CE.[6] Some of the notable independent rulers were Lalit Aditya, Avantivarman who named his city Avantipora and Sangrama Deva.
Description :
Sonamarg gives rise to The Three Sisters (Kashmir). In its vicinity lies the great Himalayan glaciers of Kashmir Valley namely Kolhoi Glacier and Machoi Glacier with some peaks of above 5000 meters: Sirbal Peak, Kolhoi Peak, Amarnath Peak and Machoi Peak. Sonamarg an alpine valley is situated at the bank of Nallah Sindh, 87 km north-east from Srinagar, it is a popular tourist destination, nestled with in the imposing Himalayan peaks.[1] It lies at an altitude of 2800 metres above sea level. The drive to Sonamarg is though yet another spectacular facet of country side in Kashmir, this time its the Nallah Sindh, the largest tributary of the Jehlum River in the valley of Kashmir. It is upwards of sixty miles long valley and deep rock-girt gorge to open grassy meadow land and village-dotted slopes.
Description :
Gulmarg a heartland of winter sports in India is easily accessible from Srinagar international airport (SXR) in less than 2 hours by a private car or coach. CNN International has rated Gulmarg as Asia's seventh best ski destination. The resort also hosts one of the highest cable cars (Gondola) in the world reaching 3980 m. The summers are just as busy with temperatures ranging from 25' - 30' C. Gulmarg attracts outdoor sports fanatics with its world class golfing, trekking, mountain biking, horse riding and fishing.
Description :
Pahalgam is a town and a Municipal committee in Anantnag district in India's northernmost state of Jammu and Kashmir. It is a popular tourist destination, and every year, many tourists visit Pahalgam. This world famous hill station is 45 km. from the District Head Quarter at Anantnag and located on the banks of river Lidder at an altitude of 7200 ft. from sea level. Pahalgam is one among the five tehsils of Anantnag district and tehsil head quarters are located in the main town of Pahalgam. It was once a tourist attraction and a favourite place for shooting of Bollywood films,[1] and is still a health resort. Besides tourist huts, several hotels in private sector have come up here and these hotels provide modern facilities to their guests. A number of treks in this region also begin from Pahalgam, as the 35 km trail traverses through pinewoods to the spectacular Kolahoi Glacier.
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Jennifer Aniston, recently voted as the Hottest Woman Of All Time by Men's Health magazine, spends a staggering amount of money every year on beauty treatments. And the Friends star admits that she has an obsession with keeping the years at bay. In an interview for a magazine, Jennifer Aniston has admitted that she likes reading online about skin, products and lasers in her spare time.
Jennifer says, "I'd love to be a dermatologist. I'd be so obsessive about it. I'm fascinated by skin, products and lasers. I go on the internet and read all about it. I call it laser porn."
Aniston gives her views on beauty by saying, "You know what makes me feel old? When I see girls who are twenty-something or the new crop of actresses and think, 'Aren't we kind of the same age?' You lose perspective". However, Jen, who is in a relationship with actor Justin Theroux, admits she still doesn't feel that she's 43.
When asked what the worst misconception people have about her is, she said, "There are so many. I would say the triangle with my ex-husband - and that there's a feud. It's a headline that won't go away - a story that has nothing to do with reality."


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Ninjago Fans Wiki is a community about Ninjago that allows Ninjago fans to:
- Make Characters
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- Chatcom
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Of course,we DO NOT like vandilism.We also try to keep the wiki drama-free.
- No sharing private info(but First Name).Doing so will get you a Infinite ban.
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- Ask before making catagory page or before editing a Important Page.
- NEVER edit Navigation or background.
- No editing Main Page.This will ban you for 1 year.2nd Time will ban you forever.
- No vandiling.
- No romance.Doing so will block you are the person who you are in love with.
So,what are you waiting for?JOIN NOW!


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Group Booking Terms and Conditions
Because you are making a Group Booking, there are additional Terms and Conditions that apply. Please read them and click 'I Accept' below to continue with your booking
General Group Booking Terms
By making a group reservation through Hostelworld.com you agree to the following terms and conditions as set by Hostelworld.com and as set by the hostel in question.
- In order to make a group reservation on Hostelworld.com it is necessary to pay a deposit. The balance is due directly to the hostel according to their payment conditions.
- The booking deposit is non-refundable.
- Please note that any cancellations must be notified directly to the hostel at least 24 hours in advance of your scheduled arrival date, unless otherwise stated in the hostel's conditions.
- Hostelworld.com are not responsible for changes or amendments to your reservation once it has been processed. All correspondence with regard to changes to your booking need to be dealt with directly with the hostel.
- Cancellations for reservations must be made directly with the hostel and must conform with the individual hostels cancellation policy (see below)
- It is your responsibility to pay the balance of your accommodation cost to the hostel in accordance with their payment conditions (see below). Failure to do so may result in your reservation being cancelled by the hostel.
- Individual hostels may have special booking conditions relating to group stays, please read the hostel booking conditions carefully before making your reservation.
Hostel Specific Terms & Conditions
The remainder of the amount due will be charged to your credit card ???? Should numbers or room selection change, the per person deposit times the number of people who actually travelled will be deducted from the total accommodation charge levvied by the hostel.
The following group types are not accepted by this hostel: Holiday with Friends, Junior / Primary School, High / Secondary School, College / University, Business Trip, Stag/Hen/Bachelor Party, Sports Group, Cultural Group If you have misrepresented the type of group you are booking for, your booking may be cancelled by the hostel.
Any cancellations resulting from agreement to these terms and conditions under false pretences will result in loss of deposit.
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" My stay at this hostel was far better than any other hostel I stayed at in Egypt. The staff was so so so kind. No hassle, only the best prices you could ask for a tour around West Bank or hot air balloon, or whatever you'd like. The Luxor temple is walking distance, the train station is walking distance, bus station is walking distance, great food and markets... walking distance. Hassan is the best there is. Thank you oasis for a perfect time in luxor. "- Anonymous
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Lincoln Collection
The Wolf Hollow Mission Trestle Table is Amish handcrafted with a rustic Mission look! This authentic Amish table comes with recessed leg levelers and a 1" solid wood top. Please call to speak to one of our Amish furniture specialists with questions on our Amish dining room furniture.
© Copyrights 2003 - 2017 DutchCrafters All rights reserved.


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16 - 27 Final
Brees, Saints get rebound win over BucsNov 7, 2011 - 12:05 AM
Brees passed for 258 yards and two touchdowns Sunday, and the New Orleans Saints rushed for 195 yards to defeat the Tampa Bay Buccaneers for only the second time in their last five meetings, 27-16.
Throwing touchdown passes to Lance Moore and Darren Sproles in the first two quarters, Brees led the Saints (6-3) to a 17-3 halftime lead and was 27- of-36 in the game.
He has a touchdown pass in 36 straight games, tying Brett Favre for second place on the all-time NFL list, and also extended his NFL record to 29 games in a row with at least 20 completions.
"This is a pretty critical time," said Brees. "It's a time when teams separate themselves from the rest of the league and we want to be one of those teams."
Josh Freeman, who had won his previous two starts against the Saints, threw a five-yard touchdown pass to Kellen Winslow with 5:33 remaining in the game, but Brees scrambled for 20 yards on 3rd-and-4 and New Orleans sealed the win with John Kasay's second field goal of the day.
Before Winslow's touchdown, the Bucs (4-4) got all of their points on three Connor Barth field goals.
"We're 4-4 and right in the hunt, but we made the same mistakes today that have been killing us all season," said Tampa Bay coach Raheem Morris, whose team was penalized nine times for 80 yards.
"Foolish penalties, those are the ones that absolutely kill you."
Chris Ivory, Pierre Thomas and Sproles led the potent New Orleans rushing attack, with Thomas scoring on a nine-yard run in the third quarter.
The Saints were blindsided last week by the lowly Rams, who got their first win of the season over the NFC South leaders one week after New Orleans had routed the Colts, 62-7, to set a franchise record for points.
But they have won two of three now since losing to Tampa Bay, 26-20, on the road last month.
"We did a lot of things well. It wasn't perfect, but I thought we were physical. I thought we played with the energy we look for," said Saints head coach Sean Payton.
The Bucs, who were coming off a bye after losing to the Bears in London two weeks ago, had a four-game division winning streak snapped and fell to 1-3 in their last four games overall.
LeGarrette Blount rushed 13 times for 72 yards in the loss, but also punched a Saints player in the head early in the third quarter for a penalty that forced the Bucs to settle for a field goal after Ronde Barber intercepted Brees.
Kasay clanked a 42-yard field goal off the upright on New Orleans' first possession of the game, but the Saints stopped Tampa Bay on a 4th-and-1 and scored five plays later when Brees found Moore in the left side of the end zone on a three-yard fade pass to tie Favre.
The 66-yard drive was sparked by Sproles' bruising 35-yard run on first down and his 15-yard catch on the next play.
Thomas had a 33-yard run on the next Saints possession and Sproles took a pass 21 yards down the right side for a TD and 14-0 lead in the second quarter.
Barth kicked a 40-yard field goal with 1:39 left in the first half. Dezmon Briscoe had a 46-yard catch on the first play of the 53-yard drive and it took four Saints to tackle him after he cut in from the right sideline.
But Brees was 6-for-7 on a rushed 76-yard drive, spiking the ball with one second left to set up Kasay's 21-yard field goal for a 17-3 halftime lead.
He was intercepted by Barber on the fifth play from scrimmage in the second half, but the Bucs settled for Barth's 48-yard field goal after Blount's 15- yard penalty for hitting a Saints player in the head with an open hand.
Brees went 6-for-7 on the ensuing drive and Thomas busted through the line on 1st-and-goal for a nine-yard touchdown run to make it 24-6 Saints. The Bucs went on a 15-play drive after that, but again looked to Barth for a 25-yarder.
Earlier, Saints cornerback Tracy Porter was carted off the field after injuring his neck on a low tackle on the second play from scrimmage. Porter was placed on a stretcher with his head stabilized after hitting Buccaneers wide receiver Mike Williams in the legs to break up a slant pass.
The Saints said he was transported to a local hospital and checked out OK neurologically.
"The information back on Tracy has been good news," said Payton. "It was good to come in here after that game and find out he was dong pretty good."
Game Notes
Favre had TD passes in 36 straight games for the Packers from 2002-04, while Colts legend Johnny Unitas holds the record at 47 games from 1956-60...New Orleans leads the all-time series, 23-17...Sproles has three receiving TDs this season and six overall, including a punt return. He ran for 42 yards, Ivory rushed for 67 and Thomas 66...New Orleans was 5-for-10 on third downs.
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Buccaneers 16, Saints 27 FinalNov 29 12:26 AM
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Buccaneers 16, Saints 27 FinalNov 20 3:16 PM
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Buccaneers 16, Saints 27 FinalNov 7 12:55 PM
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Buccaneers 16, Saints 27 FinalNov 7 12:39 AM
Nov 6 4:18 PM
End of Regulation
Nov 6 4:18 PM
- New Orleans Field Goal - 34-yarder by John Kasay.
Buccaneers 16, Saints 27 4th - 1:17Nov 6 4:10 PM
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Buccaneers 16, Saints 24 4th - 1:46Nov 6 4:05 PM
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Buccaneers 16, Saints 24 4th - 4:04Nov 6 3:56 PM
- Connor Barth extra point is good.
Buccaneers 16, Saints 24 4th - 5:33Nov 6 3:48 PM
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Buccaneers 16, Saints 24 4th - 5:33Nov 6 3:48 PM
- Tampa Bay Touchdown - Josh Freeman pass to Kellen Winslow for 5 yards.
Buccaneers 15, Saints 24 4th - 5:33Nov 6 3:48 PM
4th Quarter - 11:08
Buccaneers 9, Saints 24 4th - 11:08Nov 6 3:34 PM
End of 3rd
Nov 6 3:20 PM
- John Kasay extra point is good.
Buccaneers 6, Saints 24 3rd - 3:11Nov 6 3:11 PM
- New Orleans Touchdown - Pierre Thomas rushed right for 9 yards.
Buccaneers 6, Saints 23 3rd - 3:11Nov 6 3:10 PM
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Buccaneers 6, Saints 23 3rd - 3:11Nov 6 3:10 PM
- Tampa Bay Field Goal - 48-yarder by Connor Barth.
Buccaneers 6, Saints 17 3rd - 9:29Nov 6 2:57 PM
Nov 6 2:33 PM
- Tampa Bay Field Goal - 40-yarder by Connor Barth.
Buccaneers 3, Saints 14 2nd - 1:39Nov 6 2:25 PM
- John Kasay extra point is good.
Buccaneers 0, Saints 14 2nd - 8:34Nov 6 1:59 PM
- New Orleans Touchdown - Drew Brees pass to Darren Sproles for 21 yards.
Buccaneers 0, Saints 13 2nd - 8:34Nov 6 1:59 PM
End of 1st
Nov 6 1:46 PM
- John Kasay extra point is good.
Buccaneers 0, Saints 7 1st - 2:27Nov 6 1:39 PM
- New Orleans Touchdown - Drew Brees pass to Lance Moore for 3 yards.
Buccaneers 0, Saints 6 1st - 2:27Nov 6 1:39 PM
1st Quarter - 15:00
Nov 6 1:04 PM
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rootsThomas Added 5 roots
Buccaneers vs. SaintsNov 6 12:52 PM
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rootsTúlio Paschoalin Leão Added 5 roots
Buccaneers vs. SaintsNov 6 11:45 AM
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rootsGaston Jordan Added 5 roots
Buccaneers vs. SaintsNov 6 10:59 AM
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rootsYung Stunna Added 5 roots
Buccaneers vs. SaintsNov 5 7:35 PM
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rootsGREGnKY Added 5 roots
Buccaneers vs. SaintsNov 4 6:21 PM
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rootsqwertyui Added 5 roots
Buccaneers vs. SaintsOct 31 7:26 PM
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rootsRUWTbot Added 13 roots
Buccaneers vs. SaintsJul 7 6:02 AM
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text:
Home :: PHP SCRIPTS :: Shopping-Carts :: Furniture Store - Readymade Online Furniture Shopping Website Customized Script
All Features of ZeeStores Powered by PHP and MySQL technology (PHP Script).
Added: Export Import Tool, Price Slider
Browse the Microsite for all Details and demo.
Color Schemes and Live Customizer.
Customizable Backgrounds and more additional design options.
Fully Responsive design - works perfectly for Mobile, Iphone, Tablets and Smart Phones Automatically.
Disclaimer: Every effort has been made to accurately represent our product and it's potential. Any claims made of actual earnings do not apply to the average purchaser and are not intended to represent or guarantee that anyone will achieve the same or similar results. Each individual's success depends on his or her background, dedication, desire and motivation. As with any business endeavor, there is an inherent risk of loss of capital and there is no guarantee that you will earn any money. This script is a GPL Script and provided with full unencoded source codes and hence carries no support and warranty except installation. We are charging a fee for customization, design, handling, translations and bug fixes.
This means you can White label The Entire PHP Script / Software and Sell as your own.
In that case, you have to provide support for your own clients.
You get full unencrypted open source codes of the script. You modify it or white label it under your own brand name and keep 100% of the sales/profits.


text:
Beautiful view from the panoramic window/balcony. The room was very clean and lovely. The staff was accomodating and friendly. The turn-down service and breakfast delivered directly to the room was a nice touch.
- Official Description (provided by the hotel):
- The inviting Monterey Bay Inn sits high above the tides at its magnificent site on the Monterey Bay National Marine Sanctuary. Your private balcony provides a ringside seat to the ever-changing show-the delightful wonders of one of the world's richest marine regions. The Inn's 49 rooms, most with stunning ocean views, include a balcony, mini-refrigerator, king size bed, flat screen TV, Keurig coffee maker, CD and DVD player, usb charging ports, bath robes, hair dryer, and wireless internet connection. Two outdoor hot tubs, and a fire pit on the terrace complement your stay, as does the convenient parking. Complimentary continental breakfast is delivered to your room each morning. ... more less
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- Also Known As:
- Monterey Bay Hotel Monterey


text:
Towers of Midnight Book Tour, Joseph-Beth Booksellers, Cincinnati, OH 3 November 2010Edit
Report by Maji
Couple of notes from last night:
Only real questions specific to the book were about the WOT Encyclopedia which Harriet said will be released 12 months after AMoL.
Confirmed Asmosdean's killer will be revealed in this book (but we knew that already). Someone asked if he would let them know what page and Brandon laughed and said he's not making it that easy.
One question I wrote down when somenoe asked was:
"Will we see Demandred in the book?"
Brandon: *Big Smile* "What do you mean? You saw Demandred all the time! He's shows up all the time!"
Revised Question: "Will we find who Demandred's alter-ego is?"
Brandon: "I'm gonna have to RAFO that one."
I have some pictures but I'm at work and will have to do that later.
URL for report: http://www.theoryland.com/vbulletin/showthread.php?p=122265#poststop


text:
- Overview
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Reminiscent of They Might Be Giants both in their music style, a bizarre folk/pop hybrid, and their loyal grassroots support, this US trio, originally known as Gus, formed in 1992. The members, Adam Gardner (vocals/guitar), Brian Rosenworcel (percussion) and Ryan Miller (vocals/guitar), met while studying at Tufts University in Boston. The unusual line-up, incorporating two acoustic guitars and Rosenworcels bongos, attracted a dedicated live following in the Boston area. They collaborated with local independent producer Mike Denneen on April 1994s Parachute, which was released by Aware Records. The surprising commercial success of this album and the follow-up, Goldfly, owed much to the dedication of their fans, who traded live tapes on the Internet and some of whom worked as unpaid reps for the band. Guster received a further boost when they were named Best Live Act at the Boston Music Awards in 1997. They then signed a major-label recording contract...
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text: Rachel Thompson won the 2011 First Book Competition by the Writer's Studio at Simon Fraser University for her poetry book, Galaxy (Anvil Press 2011). She was born in Manitoba and went to the University of Winnipeg where she majored in English and International Development Studies. She now lives in Vancouver, B.C.


text:
What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
How do a make a conditional date based on a business dateAsked by gregseares on January 09, 2016 at 07:02 PM
I'm building a form that capture some information from bartenders at my restaurant, and sometimes they will submit it after midnight, at the end of their shift. So I'd like to calculate the "business date" regardless of whether it's before or after midnight. For instance, if they submit the form at 11pm on 1/9/16, then the business date will be 1/9/16. But if they submit it after midnight - say, at 1am on 1/10/16, it will still set the business date as 1/9/16. I tried to set this up with conidtional logic but I couldn't figure it out. I think I need to have a date field and a time field (the latter set to 24 hour format), and then my output field will be called "business date", which will be the current date if it's before midnight and the current date minus 1 if it's after midnight. And then I realize there needs to be a cutoff time so that people who submit on the next business day, say at noon on 1/10/16, don't have the logic change the date to the previous day. I think a good cutoff time would be 6am. So I think the logic will be something like, "if (current time) is between midnight and 6am THEN business date = (current date)-1" - I just can't figure out the right way to do this via the jotform logic
JotForm Support
Thank you for contacting us.
Yes, you can make that condition in your form, I cloned it and I can see you are capturing the current day, the current time and then as I understand, you need to subtract the current day with -1 after passed some hour.
I tried to do it, as you explained and I can see it's working.
First set the current date :
Then add an Update/Calculate field conditions as the one in the image below :
You can add a Before statement as there is not a between option, I set the time to 11:00 , however as you are using 24 hours format, after the midnight will be 23:00.
Take a look to my cloned form here : https://form.jotform.com/60094571095962
Do let us know if it's what you were looking for.
Perfect! Thanks so much Kevin. Got it, case closed. Cheers!
JotForm Support
On behalf of my colleague, you are most welcome. Feel free to contact us again if you have any other concerns. Regards.