Ribavirin-induced hemolytic anemia is one cause for cessation of combination therapy with alpha interferon 2b and ribavirin for hepatitis C infection. Determining cellular ribavirin levels in blood, including the levels of its phosphorylated metabolites, might be useful for predicting ribavirin-induced anemia, because the metabolites accumulate in erythrocytes. We simplified an assay method developed previously to make it suitable for routine monitoring of cellular ribavirin. Whole blood diluted with a sixfold volume of ice-cold distilled water was subjected to acid phosphatase digestion to convert phosphorylated ribavirin metabolites to free ribavirin. The resulting mixture, spiked with an internal standard, was treated by phenyl boronic acid column extraction, followed by reverse-phase high-performance liquid chromatography analysis. The calibration curve for ribavirin levels in whole blood was linear at concentrations of 5.3 to 1,024 M (r 2 ؍ 0.9999). Validation coefficients of variation for intra-and interday assays were 2.9 to 5.8% and 4.3 to 8.3%, respectively. We tested this method by monitoring blood ribavirin concentrations in two hepatitis C patients receiving alpha interferon 2b-plusribavirin combination therapy.Ribavirin, a guanosine analog broad-spectrum antiviral agent, is used for hepatitis C virus (HCV) elimination in combination with alpha interferon 2b (2, 3, 13). Polyethyleneglycolalpha interferon 2a combined with oral ribavirin also brings substantial benefit to HCV patients (12,14). Despite the strong beneficial effects of these combination therapies in severe HCV infection, loss of hemoglobin occurs in a substantial population of HCV patients. Progressive loss of hemoglobin leads to anemia, which is counteracted by reducing the ribavirin dose or prematurely discontinuing the combination therapy (1,5,12). Current studies suggest that the excessive accumulation of ribavirin in erythrocytes is responsible for the anemia (8, 11). Once incorporated into erythrocytes, ribavirin is converted into phosphorylated metabolites by intracellular phosphorylation (9). The phosphorylated metabolites decrease intracellular ATP levels, resulting in the reduction of erythrocyte integrity, which is followed by extravascular hemolysis via the reticuloendothelial system (4). It should therefore be possible to predict the occurrence of ribavirin-induced anemia by determining the ribavirin concentrations in blood cells and plasma.A high-performance liquid chromatography (HPLC) method was previously developed to determine ribavirin levels in order to assess the disposition of ribavirin in erythrocytes (7). Since phosphorylated metabolites are the main form of intracellular ribavirin (7, 8), whole-blood samples were treated with acid phosphatase prior to column extraction and analysis. However, the dephosphorylation procedure used in a previous study (7) was too tedious to use for routine monitoring of cellular ribavirin. In the present study, we simplified the dephosphorylation procedure. The modified method was ...
Eating disorders are common psychiatric disorders in young women. The aim of the present study was to evaluate the gastric electrical acitivity of patients with eating disorders and its relation to their symptoms. The electrogastrography (EGG) was performed before and after a water load test for outpatients with eating disorders ( n = 36; 14 anorexia nervosa, 14 bulimia nervosa, eight eating disorder not otherwise specified) and healthy women ( n = 19). A structured interview (Eating Disorder Examination) was used to assess clinical symptoms. The percentage of normal gastric myoelectrical power was significantly smaller in the eating disorder patients (44.5% vs 74.2%; P < 0.05), while the percentage of bradygastric power was significantly greater, both before and after the water load test compared with the control subjects (30.4% vs 10.4%; P < 0.05). In addition, moderate correlation was found between the duration of illness and the percentage of bradygastria ( P < 0.05). In conclusion, it is suggested that longstanding abnormal eating in patients with eating disorders may induce disturbances to gastric motor function, resulting in their abnormal, eatingrelated behavior, and form a symptomatic vicious circle. The EGG may be a promising method for determining the pathophysiology of eating disorders and for developing effective therapeutic approaches.
Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves' ophthalmopathy in culture. Acta Endocrinol 1992;126:541-52. ISSN 0001-5598 serum albumin (BSA) from Daiichi Pure Chemicals Co., Ltd.; insulin-like growth factor-1 (IGF-1) from Kabigen AB; platelet-derived growth factor (PDGF) from R&D System Inc.; hondroitin sulfate AC and ABC lyase from Seikagaku-kogyo, Tokyo. Sephadex G-50,
A three-year-old white-handed gibbon ( Hylobates lar ) was tested in terms of her ability to follow experimenter-given directional cues in an object-choice task. Four conditions were run: the experimenter baited one of two cups and then gave one of the following four directional cues: (a) pointing at the baited cup from a short distance (5 cm); (b) pointing at the target from a long distance (20 cm); (c) orienting body, head, and eyes toward the baited cup; and (d) orienting eyes only toward the baited cup. A young gibbon was able to use all of the experimenter-given cues to obtain hidden food rewards. Several possible reasons for the gibbon's superior performance in comparison to other primates reported in the existing literature were discussed.
ABSTRACT. The effects of male and female sex hormones on the protective capacity of Wistar rats against infection with Strongyloides venezuelensis were investigated. Male rats were more susceptible than females in terms of worm recovery from the lungs. Orchidectomy of male animals significantly reduced the plasma testosterone concentration and increased host resistance to the migratory stages of S. venezuelensis larvae. In contrast, ovariectomy of female animals significantly decreased host resistance in association with a significant reduction of estrogen levels. To examine the direct effect of sex hormones, exogenous testosterone and estrogen were implanted into animals. Susceptibility significantly increased or decreased in ovariectomized females given testosterone or estrogen, respectively. These results suggest that male and female sex hormones are important in the down-and up-regulation of host resistance against S. venezuelensis in Wistar rats. KEY WORDS: estrogen, sex difference, Strongyloides venezuelensis, testosterone, Wistar rat.J. Vet. Med. Sci. 64(6): 457-461, 2002 Interest in host sex and host hormones, that influence parasitic infection, dates back to the early 1940's, and the influence of hormones was first widely reviewed by Solomon [27]. However, many of the hypotheses and theories proposed still remain to be moot. Sex differences are usually attributed to either ecological (sociological in humans) or physiological causes, the latter usually being hormonal in origin [37]. Testosterone has immunosuppressive properties [9,10,15,37]. The prevalence and intensity of parasitic infections are greater in males of many mammalian species than in females [5, 14, 17, 19-21, 30, 36], especially in abnormal hosts with a primary infection, but not always in normal hosts.Our most recent study [24] demonstrated a significant sex difference in the susceptibility of sexually mature Wistar rats (Rattus norvegicus) to infection with S. venezuelensis. As reported [23], the strain of S. venezuelensis used in our studies was originally isolated from wild R. norvegicus in Okinawa Prefecture, Japan [11], indicating that laboratory rats including the Wistar strain are within the same group of natural/normal hosts for S. venezuelensis.Since sex differences in susceptibility to a parasite are rare in a normal host, the present study examines whether host sex hormones affect the susceptibility of Wistar rats to infection with S. venezuelensis. MATERIALS AND METHODS Animals:Wistar rats (R. norvegicus) at 4 weeks of age were purchased from Seac Yoshitomi, Ltd. (Fukuoka, Japan). These rats were housed in clean metal cages and fed with a standard diet and tap water ad libitum in an air-conditioned room (23 ± 1°C), under conventional conditions with a 12:12 hr light/dark cycle. They received human care as outlined in the "Guide for the Care and Use of Laboratory Animals" by The Faculty of Agriculture, Miyazaki University.Parasitological techniques: A strain of S. venezuelensis was originally isolated from wild brown rats (R...
The objective of this study is to examine psychological/psychopathological characteristics of eating disorders and their subtypes through a combined administration of questionnaires and projective tests. ) were clearly differentiated from the controls, both by the questionnaires and the projective tests. Compared with the controls, ANBP/BNP showed more problematic profiles across the three questionnaires, drew smaller and poorer trees in TDT to a more left location on the drawing paper, and gave fewer positive, and more negative responses in SCT. In contrast, few significant differences were found between anorexia nervosa -restricting type (ANR) and the controls, and between ANBP and BNP. As a trend, however, ANR was consistently located between the controls and ANBP/BNP across the whole questionnaires and projective tests.
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