Pharmacokinetics of chloroquine: saliva and plasma levels relationship

The use of saliva levels as an alternative to plasma levels in monitoring chloroquine therapy was studied in five healthy volunteers. Subjects took two (250 mg) tablets of chloroquine diphosphate (300 mg chloroquine base) with 200 ml of water. Saliva and blood samples were collected at intervals over 6 days. Plasma was separated from blood samples after centrifugation while saliva samples were centrifuged to remove mucoid sediments. Both the plasma and saliva samples were analysed for chloroquine by a combination of thin-layer chromatography and spectrophotometry. Regression analysis was used to determine the correlation between saliva and plasma chloroquine levels. A significant correlation (r = 0.97, p less than 0.05) was observed between saliva and plasma levels of chloroquine. The saliva: plasma concentrations ratio was found to be 0.53. From the saliva: plasma relationship, the extent of chloroquine binding to plasma proteins was estimated to be 47%. The Cmax and AUC0-6 day values obtained from saliva data was about half those from plasma, while the Tmax obtained from both fluids remained the same. The saliva clearance rate (Cls/F) of chloroquine was about twice the plasma clearance rate (Cl/F). (Cls/F: 0.46 +/- 0.051/day/kg; 0.27 +/- 0.021/day/kg). However, the predicted Cl/F (0.27 +/- 0.031/day/kg) from saliva data was in agreement with Cl/F from plasma data. This was also true of the volume of distribution. The collection of saliva for measuring chloroquine levels provides a painless, non-invasive alternative to plasma sampling, and it is useful in predicting chloroquine pharmacokinetics.     

Effect of ranitidine on chloroquine disposition

Ten healthy, male volunteers (aged 19-27 yr; weight 62-67 kg) were randomly distributed into control and test groups of five subjects each in a controlled study on the effect of ranitidine on chloroquine disposition. The control group subjects received two tablets of chloroquine sulfate (300-mg base) only. The test group subjects received ranitidine 250 mg hs for four days prior to the administration of chloroquine sulfate and throughout the sample collection period. Blood samples (5 ml) were collected from the time of the chloroquine administration to the seventh day after drug administration. The samples were analyzed for chloroquine content by a combination of thin-layer chromatography and ultraviolet spectrophotometry. The Wilcoxon test at 0.05 significance level was used to compare the disposition parameters between control and test groups. Ranitidine therapy was associated with no significant alterations in chloroquine oral clearance rate, elimination rate constant, and apparent volume of distribution. Unlike cimetidine, ranitidine does not interact pharmacokinetically with chloroquine. Ranitidine, therefore, may be the H2-receptor antagonist of choice for ulcer patients receiving chloroquine.     

Transient synovitis of the hip in children: role of US

Transient synovitis of the hip remains a common diagnostic problem for the clinician. The physical signs are not pathognomonic of the condition, and the classic technical examinations are of little help. Therefore, the authors retrospectively studied the value of hip arthrosonography in 46 children with clinical symptoms suggesting pathologic hip conditions. In 20 of the 21 patients with a final diagnosis of transient synovitis, articular effusion was detected on ultrasound (US). Conventional radiography showed an increased medial joint space in only eight of these patients. Increased echogenicity of the articular fluid was found in both transient synovitis and septic arthritis. The high sensitivity of US in detecting intraarticular fluid was demonstrated by cadaver studies.     

Iron supplementation in female blood donors deferred by copper sulfate screening

Female blood donors with low hematocrit levels detected by copper sulfate screening were selected randomly to receive either 75 mg of iron per day, as ferrous gluconate, or a calcium phosphate placebo. Their ferritin, serum iron, total iron-binding capacity, zinc protoporphyrin, and hemoglobin values, as well as their suitability to donate blood, were determined initially (Visit 1) and at four follow-up visits (Visits 2-5). By the second visit, the serum ferritin and iron values of donors receiving iron supplementation differed significantly from those of donors receiving placebo. By the fifth visit, a less marked but significant increase in hemoglobin had occurred in the iron group, but not in the placebo group. At no time was there a significant difference between the groups' suitability to donate blood, with each group donating at almost half of their visits. The authors conclude that iron supplementation at this dose level in deferred female blood donors improves their iron status and hemoglobin levels, but does not significantly increase their suitability to donate blood as compared with the suitability of placebo-treated donors.     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.      

Correlates of HIV Knowledge and Sexual Risk Behaviors Among Female Military Personnel

Uniformed services personnel are at an increased risk of HIV infection. We examined the HIV/AIDS knowledge and sexual risk behaviors among female military personnel to determine the correlates of HIV risk behaviors in this population. The study used a cross-sectional design to examine HIV/AIDS knowledge and sexual risk behaviors in a sample of 346 females drawn from two military cantonments in Southwestern Nigeria. Data was collected between 2006 and 2008. Using bivariate analysis and multivariate logistic regression, HIV/AIDS knowledge and sexual behaviors were described in relation to socio-demographic characteristics of the participants. Multivariate logistic regression analysis revealed that level of education and knowing someone infected with HIV/AIDS were significant (P < 0.05) predictors of HIV knowledge in this sample. HIV prevention self-efficacy was significantly (P < 0.05) predicted by annual income and race/ethnicity. Condom use attitudes were also significantly (P < 0.05) associated with number of children, annual income, and number of sexual partners. Data indicates the importance of incorporating these predictor variables into intervention designs.     

Beliefs and social norms about codeine and promethazine hydrochloride cough syrup (CPHCS) use and addiction among multi-ethnic college students

In this study a qualitative approach is used to investigate relevant beliefs and norms concerning the consumption, initiation, and perceived addiction of codeine and promethazine hydrochloride cough syrup (CPHCS) among 61 college-age students who identified themselves as current CPHCS users. In general, a majority of students stated that doctors and pharmacists were the greatest facilitators of CPHCS acquisition. A majority of students believed that their friends felt codeine promethazine use was "normal" and "cool" among college students their age, and that reinforcing factors, such as peer pressure and curiosity, contributed to initial CPHCS use.     

Glucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells

Rheumatoid arthritis (RA), a chronic autoimmune form of inflammatory joint disease, progressively affects multiple joints with pathological changes in the synovia, cartilage, and bone. Numerous studies have suggested a critical role for glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) in the pathogenesis of autoimmune arthritis by modulating both innate and adaptive immune reactions, but the underlying mechanisms by which GITR activation promotes arthritic progression remain largely unclear. In this study, we found that collagen-induced arthritis mice treated with the ligand of GITR (GITRL) displayed an earlier onset of arthritis with a markedly increased severity of arthritic symptoms and joint damage, in which significantly increased Th17 cells in both spleen and draining lymph nodes were observed. Notably, results showed that a marked expansion of Th17 cells with increased RORγt mRNA expression was induced from na?ve CD4(+) T cells when cultured with GITRL. Consistently, normal mice that were treated with GITRL were found to display a substantial expansion of splenic Th17 cells. Furthermore, we detected elevated serum levels of GITRL in patients with RA, which were positively correlated with an increase in interleukin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells.