The Effectiveness of Respondent Driven Sampling for Recruiting Males Who have Sex with Males in Dhaka,Bangladesh

This paper evaluates the effectiveness of respondent driven sampling (RDS) to sample males who have sex with males (MSM) in Dhaka, Bangladesh. A major objective for conducting this survey was to determine whether RDS can be a viable sampling method for future routine serologic and behavioral surveillance of MSM as well as other socially networked, hard to reach populations in Bangladesh. We assessed the feasibility of RDS (survey duration; MSM social network properties; number and types of initial recruits) to recruit a diverse group of MSM, the efficacy of an innovative technique (systematic coupon reduction) to manage the implementation and completion of the RDS recruitment process and reasons why MSM participated or did not participate. The findings provide useful information for improving RDS field techniques and demonstrate that RDS is an effective sampling method for recruiting diverse groups of MSM to participate in HIV related serologic and behavioral surveys in Dhaka.     

Evaluation of the Clearance of a Sublingual Buprenorphine Spray in the Beagle Dog Using Gamma Scintigraphy

Purpose The aim of this study was to evaluate clearance from the buccal cavity and pharmacokinetic profiles of a sublingual spray formulation in the dog, to assist in interpretation of future pharmacokinetic studies. Methods Radiolabelled buprenorphine in a spray formulation (400 μg/100 μl in 30% ethanol) was administered sublingually to four beagle dogs, and the residence in the oral cavity was determined using gamma scintigraphy. Pharmacokinetic sampling was performed to facilitate correlation of location of dose with significant pharmacokinetic events. Results Scintigraphic imaging revealed that clearance of the formulation from the oral cavity was rapid, with a mean T _50% clearance of 0.86 ± 0.46 min, and T _80% clearance of 2.75 ± 1.52 min. In comparison, absorption of buprenorphine was relatively slow, with a T _max of 0.56 ± 0.13 h. Good buccal absorption despite short residence time can be explained by lipophilicity of buprenorphine enabling rapid sequestration into the oral mucosa, prior to diffusion and absorption directly into systemic circulation. Conclusion This study demonstrated rapid clearance of a sublingual solution from the canine oral cavity, with T _50% similar to results previously reported in man, providing initial confidence in using a conscious dog model to achieve representative residence times for a sublingual solution.     

Effect of acute unilateral renal denervation on renal hemodynamics in spontaneously hypertensive rats

1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation. 2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg(-1) i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II. 3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats. 4 The data obtained in denervated rats suggested an enhanced sensitivity of the alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT(1) and alpha(1)-adrenoceptor subtypes.     

Evaluation of Antinociceptive Activity of Methanol Extract from Cleome rutidosperma in Mice

Objective Cleome rutidosperma (Capparidaceae), commonly known as “Fringed Spider Flower”, is a medicinal plant found in Southeast Asia. C. rutidosperma is used in folk medicine for diuretic, laxative, analgesic, anti-inflammatory, antipyretic, antimicrobial, anti-oxidant, hypoglycemic, and anthelmintic activities. We have evaluated the anti-nociceptive properties of methanol extract from C. rutidosperma (MECR) in vivo. Methods Thermal method (hot plate test and tail flick test) was induced to judge the anti-inflammatory effect and couple of chemical method also used (formalin induced licking test; writhing test carried by acetic acid) to evaluate analgesic effect. Both of these tests were made over animal models, like mice and rats. Two different doses (100 and 200 mg/kg) were used for each case of test, while morphine sulphate (5mg/kg, ip) was used as reference drug. Results MECR demonstrated the significantly anti-nociceptive activity in the analgesic and anti-inflammatory tests by reducing nociception in mice models (P < 0.001). In the hot-plate and tail-flick tests, MECR significantly elongated the time to response to the thermal stimuli (100 and 200 mg/kg with P < 0.05, 0.001). The remarkable increase in the latency was observed at 90 and 120 min. In acetic acid-induced writhing test and formalin induced licking test for anti-inflammatory activity, MECR at 100 and 200 mg/kg doses exhibited significant (P < 0.001) reduction of writhing and licking response. Conclusion The anti-inflammatory and analgesic effects of C. rutidosperma propose that this effect may be a result of both peripheral and central mechanisms. Further study is required to ensure the proper mechanism of action as well as the active ingredient.     

Identification of the alpha1L-adrenoceptor in rat cerebral cortex and possible relationship between alpha1L- and alpha1A-adrenoceptors

BACKGROUND AND PURPOSE: In addition to alpha1A, alpha1B and alpha1D-adrenoceptors (ARs), putative alpha1L-ARs with a low affinity for prazosin have been proposed. The purpose of the present study was to identify the alpha1A-AR and clarify its pharmacological profile using a radioligand binding assay. EXPERIMENTAL APPROACH: Binding experiments with [3H]-silodosin and [3H]-prazosin were performed in intact tissue segments and crude membrane preparations of rat cerebral cortex. Intact tissue binding assays were also conducted in rat tail artery. KEY RESULTS: [3H]-silodosin at subnanomolar concentrations specifically bound to intact tissue segments and membrane preparations of rat cerebral cortex at the same density (approximately 150 fmol mg(-1) total tissue protein). The binding sites in intact segments consisted of alpha1A and alpha1L-ARs that had different affinities for prazosin, while the binding sites in membranes showed an alpha1A-AR-like profile having single high affinity for prazosin. [3H]-prazosin also bound at subnanomolar concentrations to alpha1A and alpha1B-ARs but not alpha1L-ARs in cerebral cortex; the binding densities being approximately 200 and 290 fmol mg(-1) protein in the segments and the membranes, respectively. In the segments of tail artery, [3H]-silodosin only recognized alpha1A-ARs, whereas [3H]-prazosin bound to alpha1A and alpha1B-ARs. CONCLUSIONS AND IMPLICATIONS: The present study clearly reveals the presence of alpha1L-ARs as a pharmacologically distinct entity from alpha1A and alpha1B-ARs in intact tissue segments of rat cerebral cortex but not tail artery. However, the alpha1L-ARs disappeared after tissue homogenization, suggesting their decomposition and/or their pharmacological profile changes to that of alpha1A-ARs.     

Different affinities of native alpha1B-adrenoceptors for ketanserin between intact tissue segments and membrane preparations

The pharmacological profiles of alpha1-adrenoceptors for ketanserin, prazosin, silodosin, and BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione dihydrochloride) were examined under different assay conditions. Among the tested antagonists and alpha1-adrenoceptors subtypes, ketanserin showed significantly lower affinity for the alpha1B-adrenoceptor subtype in intact tissue sampled from the rat tail artery, thoracic aorta, and cerebral cortex (functional pKB and binding pKi were approximately 6), than in cerebral cortex membrane preparations or whole cell and membrane preparations of alpha1B-adrenoceptor transfected human embryonic kidney 293T (HEK 293T) cells (pKi was approximately 8). In these tissues and cells, however, ketanserin showed a similar affinity (pKi = approximately 8) for alpha1A- and alpha1D-adrenoceptors even though the assays were conducted under different conditions. In contrast, the affinities of alpha1A-, alpha1B-, and alpha1D-adrenoceptors for prazosin, silodosin, and BMY 7378 did not significantly change under different assay conditions and in different tissues. The present study reveals that the pharmacological profiles of native alpha 1B-adrenoceptors for ketanserin is strongly influenced by the assay conditions and suggest that antagonist affinity is not necessarily constant.     

Intraperitoneal glycerol induces oxidative stress in rat kidney

1. Glycerol has been used for the treatment of intracranial hypertension, cerebral oedema and glaucoma. Experimentally, intramuscular administration of hypertonic glycerol solution is used to produce acute renal failure. In this model, glycerol causes rhabdomyolysis and myoglobinuria, resulting in the development of renal injury. The pathogenesis is thought to involve vascular congestion, the formation of casts and oxidative stress. However, the effect of glycerol itself independent of rhabdomyolysis has not been investigated. Therefore, the aim of the present study was to investigate the effects of i.p. glycerol on some biochemical and oxidative stress parameters in the kidney of young rats. 2. Rats received 10 mL/kg, i.p., hypertonic glycerol solution (50% v/v) or saline (NaCl 0.85 g%) followed by 24 h water deprivation. Twenty-four hours after the administration of glycerol, rats were killed. Creatinine levels and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in the plasma. In addition, CK, pyruvate kinase and LDH activity and oxidative stress parameters (free radical formation, lipid peroxidation and protein carbonylation) were measured in renal tissue. 3. Glycerol did not alter plasma CK activity and increased plasma creatinine levels, suggesting renal insufficiency and the absence of rhabdomyolysis. Renal CK and pyruvate kinase activity was decreased, suggesting diminution of energy homeostasis in the kidney. Plasma and renal LDH activity was decreased, whereas the formation of free radicals, lipid peroxidation and protein carbonylation were increased, suggesting oxidative stress. 4. These results are similar to those described after the intramuscular administration of glycerol. Therefore, it is possible that glycerol may provoke renal lesions by mechanisms other than those induced by rhabdomyolysis.     

Impaired dendritic cell function resulting from chronic undernutrition disrupts the antigen-specific immune response in mice

We examined whether antigen-specific immune responses are lower in mice with protein energy malnutrition (PEM mice) compared with nourished (control) mice. The mechanisms underlying reduced antigen-specific immune responses of PEM mice were evaluated through analysis of the functional capacities of antigen-presenting dendritic cells (DC). PEM mice were produced by subjecting male C57BL/6 mice for 52 wk to a daily food intake equivalent to 70% of the mean amount consumed by the control mice that consumed food ad libitum. PEM mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) at 52 wk and humoral and cellular immune responses to HBsAg were evaluated at 58 wk. Lymphoproliferative assays were performed to assess the functional capacities of lymphocytes and DC. After 52 wk of food restriction, PEM mice had a 49% lower body weight than controls, almost no subcutaneous fat, severe muscle wasting, and atrophied spleen. All control mice developed antibodies to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen as a result of immunization with the hepatitis B vaccine. PEM mice, however, were almost unresponsive to immunization with the hepatitis B vaccine. In PEM mice, the numbers of spleen DC, the T lymphocyte stimulatory capacities of DC, and their production of IL-12p70 and IFN-gamma was less than those of control mice (P < 0.05). We suggest that chronic undernutrition disrupts antigen-specific immune responses and that this disruption can be attributed at least in part to reduced frequencies and impaired functions of DC.