Effect of gender specific anthropometric characteristics on lung function in young competitive triathletes from Malaysia.

BACKGROUND: Anthropometric and lung function characteristics of triathletes are important for the implementation of individual specific training and recovery recommendations. However, limited data are available for these parameters in triathletes. Hence, the aim of this study was to characterize and examine the gender differences of lung function and anthropometry parameters in competitive triathletes from Malaysia. METHODS: Body composition assessment and lung function tests were performed on sixteen competitive triathletes (nine male and seven female). The subject's body composition profile including muscle mass (kg), fat free mass (kg), and percent body fat was measured using a bio-impedance segmental body composition analyzer. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured by Quark PFT2 spirometer. RESULTS: The anthropometric measurements revealed that male triathletes were significantly taller than female triathletes and had significantly more protein and skeletal muscle mass. The female triathletes, however, had significantly higher percent body fat. Male triathletes had statistically significant higher FVC and FEV1 than female triathletes. Both the male and female triathletes showed a positive correlation between height, fat free mass and the lung function markers FVC and FEV1. This association was not seen with Body Mass Index (BMI) in female triathletes. CONCLUSIONS: The data from our study shows that anthropometric parameters are directly linked to lung function of a triathlete. We also found the relationship between BMI and lung function to be gender specific in triathletes and is dependent on the body protein and fat content. Hence, body composition characterization is essential and provides valuable information for developing individual specific training modules.

The dopamine D3 receptor antagonist, SR 21502, facilitates extinction of cocaine conditioned place preference.

BACKGROUND: Pharmacotherapeutic agents that could facilitate extinction of cocaine cues would be useful in the treatment of cocaine addiction. We tested whether SR 21502, a selective dopamine (DA) D3 receptor antagonist, can facilitate extinction of cocaine conditioned place preference (CPP) in rats. METHODS: In experiment 1, cocaine (10mg/kg) CPP was first established and then extinguished. During the extinction phase the rats were injected with SR 21502 and placed in the previously cocaine-paired compartment for four sessions and vehicle in the other compartment on four alternating sessions. The rats were then tested again for cocaine CPP. In experiment 2, different groups of rats were trained to associate SR 21502 with one compartment and saline with the other. RESULTS: In experiment 1, the animals spent significantly more time in the cocaine-paired compartment after cocaine conditioning than they did before conditioning. Subsequently, the animals treated with SR 21502 during the extinction phase spent significantly less time in the cocaine-paired compartment than the vehicle group. In experiment 2, animals conditioned with SR 21502 preferred neither side of the CPP apparatus, indicating that SR 21502 produced no effects of its own. CONCLUSIONS: These findings suggest that treatment with SR 21502, a DA D3 receptor antagonist, in the presence of cocaine cues can facilitate extinction of cocaine CPP and further suggest that this compound might be an effective cocaine addiction treatment.

Crystal structure of 3-methyl-2,6-bis-(4-methyl-1,3-thia-zol-5-yl)piperidin-4-one.

In the title compound, C14H17N3OS2, the central piperidinone ring adopts a chair conformation and the thia-zole rings are inclined to its mean plane by 80.16 (12) and 67.15 (12)°. The O atom and methyl group C atom deviate significantly from the mean plane of the central piperidinone ring, by 0.8138 (2) and 0.3175 (2) Å, respectively. The dihedral angle between the thia-zole rings is 51.88 (13)°. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming zigzag C(10) chains running parallel to [001].

The novel dopamine D3 receptor antagonist, SR 21502, reduces cocaine conditioned place preference in rats.

Research has shown that dopamine (DA) D3 receptors play a crucial role in cocaine addiction. Recently, there has been a strong focus on the development of DA D3 receptor antagonists as potential pharmacological treatments for cocaine addiction. We investigated the ability of a novel selective D3 receptor antagonist SR 21502 to block the expression of cocaine-induced conditioned place preference (CPP) in rats. CPP was determined using a two-chamber apparatus. All of the animals had free access to both chambers on day 1, followed by 4 alternating conditioning days of cocaine injection (paired chamber) and 4 alternating non-conditioning days with saline (non-paired chamber). On the test day, animals were systemically treated with 0, 3.75, 7.5 or 15mg/kg of SR 21502, 10min prior to being placed in the CPP apparatus, and the time spent in each chamber was recorded for 15min. The amount of time spent in the cocaine-paired chamber on the test and pre-exposure days was analyzed. Vehicle-treated animals spent significantly more time in the cocaine-paired side during the test than during the pre-exposure session, indicating a cocaine CPP. SR 21502 produced a dose-related significant reduction in the time spent in the cocaine-paired side compared to vehicle. The DA D3 receptor antagonist SR 21502 blocks the rat's preference for the cocaine-paired chamber, thereby attenuating the rewarding effect of the cocaine cues. This suggests that this compound may be an effective pharmacological treatment against cocaine addiction.

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

RATIONALE: There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. OBJECTIVE: We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. METHODS: In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. RESULTS: SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. CONCLUSIONS: SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

3,5-Dimethyl-1-{2-[(5-methyl-1,3,4-thia-diazol-2-yl)sulfan-yl]acet-yl}-2,6-diphenylpiperidin-4-one.

In the title compound, C24H25N3O2S2, the piperidine ring adopts a distorted boat conformation. The phenyl rings subtend angles of 75.6 (1)° and 86.3 (1)° with the mean plane of the piperidine ring. In the crystal, mol-ecules are linked through a network C-H⋯N hydrogen bonds, forming zigzag chains along [100]. The thia-diazol ring methyl group is disordered over two positions with an occupancy ratio of 0.69 (4):0.31 (4).

3-Isopropyl-1-{2-[(1-methyl-1H-tetra-zol-5-yl)sulfan-yl]acet-yl}-2,6-di-phenyl-piperidin-4-one hemihydrate.

In the title compound, C24H27N5O2S·0.5H2O, the piperidine ring adopts a distorted boat conformation. The phenyl rings subtend dihedral angles of 69.7 (1) and 88.7 (1)° with the best plane through the piperidine moiety. In the crystal, symmetry-related mol-ecules are linked through a network of C-H⋯O and C-H⋯N inter-actions, the former connecting them into zigzag chains along the c-axis direction and the latter forming an R (2) 2(4)motif. The dimer formation (C-H⋯N) and the repetition of symmetry-related molecules (C-H⋯O) along the b-axis direction stabilize the packing mode. The water mol-ecule is located on a twofold rotation axis.

N'-[(E)-2-Chloro-benzyl-idene]-2-[(1,3,4-thia-diazol-2-yl)sulfan-yl]acetohydrazide.

In the title compound, C(11)H(9)ClN(4)OS(2), the thia-diazole and chloro-phenyl rings are oriented at an angle of 43.1 (1)°. The sum of the bond angles around the amide N atom (359.8°) of the acetohydrazide group is in accordance with a model of sp(2) hybridization. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. Weak C-H⋯π inter-actions also occur.

Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function.

We have employed a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) approach to predict the biochemical activity for inhibitors of T. cruzi dihydrofolate reductase-thymidylate synthase (DHFR-TS). Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state (DHFR domain) were used to validate and refine docking poses of ligands that constitute likely active conformations. Structural information from these complexes formed the basis for the structure-based alignment used as input for the QSAR study. Contrary to indirect ligand-based approaches the strategy described here employs a direct receptor-based approach. The goal is to generate a library of selective lead inhibitors for further development as antiparasitic agents. 3D-QSAR models were obtained for T. cruzi DHFR-TS (30 inhibitors in learning set) and human DHFR (36 inhibitors in learning set) that show a very good agreement between experimental and predicted enzyme inhibition data. For crossvalidation of the QSAR model(s), we have used the 10% leave-one-out method. The derived 3D-QSAR models were tested against a few selected compounds (a small test set of six inhibitors for each enzyme) with known activity, which were not part of the learning set, and the quality of prediction of the initial 3D-QSAR models demonstrated that such studies are feasible. Further refinement of the models through integration of additional activity data and optimization of reliable docking poses is expected to lead to an improved predictive ability.

Programs to facilitate tuberculosis drug discovery: the tuberculosis antimicrobial acquisition and coordinating facility.

There is a real need to discover new drugs that are active on drug-resistant tuberculosis (TB), and for drugs that will shorten the time of therapy. Large pharmaceutical companies have traditionally led the quest for discovering and developing new antiinfective agents but this is not the case when it comes to diseases like tuberculosis that primarily occur in resource restricted countries. Throughout the world many research groups are actively engaged in the scientific discovery of new TB drugs. Unfortunately, most research laboratories do not have the necessary safety facilities or resources for all facets of TB drug discovery. The Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) was established in order to make comprehensive testing services available at no cost to research laboratories with an interest in discovering new TB drugs. The TAACF is a consortium of contracts managed and funded by the National Institute of Allergy and Infectious Diseases (National Institutes of Health, Bethesda, MD) as a resource to support preclinical drug discovery and development. The core of the TAACF is the Southern Research Institute, Birmingham, AL, which supports compound acquisition, storage, medicinal chemistry, and high throughput assays. Other collaborating groups provide biological data on antimycobacterial activity and cytotoxicity, preliminary in vivo toxicity, oral bioavailability and efficacy in animal models, specialty testing (such as activity against non-replicating persistent bacteria), and assistance in technology transfer for developing comprehensive promotional packages and facilitating partnerships with pharmaceutical companies for drug development. The TAACF program and recent progress that has been publicly disclosed by suppliers is reviewed. There are many aspects promising of the program that will not be discussed due to confidentially.

Cefoxitin resistance mediated by loss of a porin in clinical strains of Klebsiella pneumoniae and Escherichia coli.

PURPOSE: Porins are outer membrane protein (OMP) that form water filled channels that permit the diffusion of small hydrophilic solutes like beta-lactam antibiotics across the outer membrane. Two major porins that facilitate diffusion of antimicrobials have been described in Klebsiella spp. and Escherichia coli. The present study was carried out to examine the role of porins among Extended Spectrum beta-Lactamase (ESBL) and AmpC beta-Lactamase positive strains of Klebsiella spp. and E.coli. METHODS: Preparation of OMP from phenotypically characterized clinical isolates K.pneumoniae and E.coli and the separation of the proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were performed as per a previously described procedure. RESULTS: OMP analysis revealed that cefoxitin and ceftazidime resistance was mediated by loss of a porin Omp K35 in the isolates of K.pneumoniae and E.coli. CONCLUSIONS: Loss of porin mediated resistance mechanism against cefoxitin was observed among the multidrug resistant K.pneumoniae and E.coli.

Detection of Enterocytozoon bieneusi (Microsporidia) by polymerase chain reaction (PCR) using species-specific primer in stool samples of HIV patients.

BACKGROUND & OBJECTIVE: Microsporidia are obligate intracellular parasites causing infections predominantly in immunocompromised patients. Enterocytozoon bieneusi is the most important microsporidian causing chronic diarrhoea in AIDS patients. The current method used for diagnosing the microsporidia spores is based on light microscopy using stained smears, which do not differentiate spores at species level. The present study was undertaken to detect microsporidia and confirm at species level (E. bieneusi) by PCR from stool samples of HIV positive patients. METHODS: During September 2002 to April 2003, stool samples from 153 HIV-positive patients (with chronic diarrhoea n = 105; without diarrhoea n=48) were collected and examined microscopically for microsporidia spores using modified Weber's chromotrope stain. Stool samples were subjected to PCR assay using species-specific primer EBIEFI/EBIER1, which amplifies small subunit ribosomal RNA (SSU rRNA) of this microsporidian RESULTS: A total of 10 HIV positive patients with chronic diarrhoea were positive for microsporidia by microscopic analysis and confirmed as Enterocytozoon bieneusi by PCR. No false positive results were observed. A diagnostic DNA fragment of 607 bp of the unique SSU rRNA was amplified from all samples infected with E. bieneusi. INTERPRETATION & CONCLUSION: The study revealed that polymerase chain reaction is a useful tool for accurate species identification of microsporidia in stool samples, which serves the benefit of treatment to the patients.

Electron microscopy identification of microsporidia (Enterocytozoon bieneusi) and Cyclospora cayetanensis from stool samples of HIV infected patients.

Microsporidia (Enterocytozoon bieneusi) and Cyclospora cayetanensis have been reported worldwide causing diarrhoea in AIDS patients. Stool samples from HIV infected patients were subjected to routine examination for parasites, followed by special staining techniques to detect microsporidia and Cyclospora cayetanensis. Confirmed positive cases of these parasites were further processed for electron microscopy identity of the parasites and characteristic details. Scanning and transmission electron microscopy showed better morphological and structural details of the parasites.

Rotavirus infection among infants and young children in Chennai, South India.

BACKGROUND: Group A rotavirus has been recognized as the major etiologic agent of childhood gastroenteritis in infants and young children worldwide. Rapid progress towards the development of an efficacious rotavirus vaccine has warranted extensive epidemiological studies on rotavirus serotypes that cause severe disease in developing and developed countries and to monitor the emergence of newer and unusual strains in different geographical settings that could represent variants not covered by existing vaccines. METHODS: In this study, we determined the prevalence of rotavirus infection and characterised group A rotavirus in stool samples by using monoclonal antibody (MAb) based ELISA and polyacrylamide gel electrophoresis (PAGE). Stool samples were collected from 745 children of 0-3 years of age presenting to the hospital with acute diarrhea between March 1995 and August 1999. These were assayed for antigenic (group, subgroup, serotype) and genomic (viral RNA profile and VP7 and VP4 genotype) characterization by ELISA and PAGE. RESULTS: Out of 745 stool samples analysed 168 were found to be positive for rotavirus. Among these 118 could be assigned a subgroup (SG), serotype and electropherotype (E-type). The study has evidenced the predominant occurrence of strains with short E-type, SGI and serotype G2 in 66.1% of the samples. The presence of strains representing 10 different E-types and mixed genotype specificities with G2 P[4,8] and G1-G2 P[4,8] has documented the prevailing high genomic diversity of rotaviruses in this geographical area. CONCLUSION: This study has described the predominant strains of rotavirus in south India. There is a need for further detailed studies on the molecular characterization of rotaviruses which would have important implications in vaccine evaluation programmes.

AmpC beta-lactamase producing multidrug resistant strains of Klebsiella spp. & Escherichia coli isolated from children under five in Chennai.

BACKGROUND & OBJECTIVES: AmpC beta-lactamases are Group I cephalosporinases that confer resistance to a wide variety of beta-lactam drugs. Plasmid mediated AmpC beta-lactamases has been discovered most frequently in isolates of Klebsiella pneumoniae, K. oxytoca, Salmonella, Proteus mirabilis and Escherichia coli. The present study was undertaken to study the occurrence of multidrug resistant and AmpC beta-lactamase producing Klebsiella spp. and Escherichia coli in children less than five years of age as this age group is very susceptible to intestinal and extraintestinal infections. METHODS: A total of 116 isolates of Klebsiella species and 32 isolates of Esch. coli were tested for resistance to cephamycin such as cefoxitin, third generation cephalosporin (3GC) antibiotics (ceftazidime, cefotaxime, ceftriaxone), ampicillin, amikacin, cephaloridine, cefuroxime, co-trimoxazole, gentamycin, imipenem and tetracycline by disc diffusion method. Isolates found resistant to cefoxitin were tested for the production of AmpC beta-lactamases by three dimensional extract method. Transconjugation experiments were done to study the transfer of drug resistance and AmpC beta lactamase production from AmpC producing Klebsiella and Esch. coli isolates to a recipient Esch. coli strain (K12 J62-2). RESULTS: Twenty eight isolates (24.1%) of Klebsiella spp. and 12 (37.5%) of Esch. coli were found to be AmpC beta-lactamase producers; 66.6 per cent and 81 per cent of Klebsiella and Esch. coli isolates respectively showed resistance to all the 3GCs. All the strains were found to be sensitive to imipenem. Eighty four (72%) of Klebsiella isolates and 20 (62.5%) of Esch. coli were found to be resistant to cefoxitin. Transfer of cefoxitin resistance to the recipient strain was observed in all the AmpC producing strains of Klebsiella spp. Of the 12 AmpC producing strains of Esch. coli, only 4 (33.3%) showed the transfer of cefoxitin resistance to the recipient strain. INTERPRETATION & CONCLUSION: This study has shown the occurrence of AmpC beta-lactamase producing Klebsiella and Esch. coli strains in children in Chennai. Since AmpC beta-lactamase production is frequently accompanied by multiresistance to antibiotics, therapeutic options become limited resulting a need for new measures for the management of Klebsiella and Esch. coli infections. Also failure to identify AmpC beta-lactamase producers may lead to inappropriate antimicrobial treatment and may result in increased mortality. Detecting plasmid mediated AmpC beta-lactamase producing strains is technically difficult and the phenotypic tests for AmpC detection are not well defined. If an investigational AmpC beta-lactamase inhibitor was made available for diagnostic testing, it could be useful in combination with a suitable cephamycin to confirm AmpC production.

Biochemical characteristics, serogroups, and virulence factors of Aeromonas species isolated from cases of diarrhoea and domestic water samples in Chennai.

PURPOSE: The objective of the present study was to delineate the differences between the clinical and environmental Aeromonas species with respect to their biochemical characteristics, serogrouping and virulence factors, in order to find a phenotypic marker of enteropathogenicity. METHODS: A total of 55 Aeromonas spp. inclusive of 19 isolates from cases of diarrhoea, and 36 from water samples comprising, 10 isolates of A. hydrophila, 21 isolates each of A. sobria, and A. caviae, two isolates of A. jandaei and one isolate of A. veronii were subjected to analysis of their biochemical characteristics, serogrouping, and virulence factors. RESULTS: Among the differences recorded in the biochemical characteristics in the three major species, the most striking characteristic was fermentation of lactose, which was observed in all the 11 A. caviae isolates recovered from water samples. None of the 10 clinical isolates of A. caviae tested fermented lactose. The clinical Aeromonas isolates belonged to seven typable serogroups, O:13, O:14, O:16, O:21, O:27, O:32 and O:35. The environmental isolates belonged to eight different serogroups, such as, O:3, O:11, O:14, O:16, O:18, O:28, O:64 and O:78 and were predominated by serotypes O:18 and O:64. Among the virulence factors tested, 89% of the environmental isolates produced b haemolysin, while only 62.3% of clinical isolates were able to do so. There was no significant difference between the clinical and environmental aeromonads with respect to their enterotoxigenicity in suckling mice in vivo, cytotoxicity in vitro in Vero cell monolayers, and ability to produce siderophores. CONCLUSION: Efforts to delineate the differences between the clinical and environmental Aeromonas spp. did not reveal significant difference between them. However, difference was observed with respect to their ability to produce b haemolysin, wherein, higher percentage of environmental isolates was haemolytic. The results also suggest that all the haemolytic environmental isolates need not be enteropathogenic. Further, serogroups O:18 and O:64 may not be involved in aeromonal diarrhoea in children in this geographic region.

Extended spectrum beta lactamase (ESBL) mediated resistance to third generation cephalosporins among Klebsiella pneumoniae in Chennai.

PURPOSE: To examine the incidence of extended spectrum b lactamase (ESbL) producing strains and multidrug resistant strains of Klebsiella pneumoniae isolated from children between 0-5 years of age. METHODS: Multidrug resistance and ESbL production was studied in a total of 120 isolates of Klebsiella pneumoniae obtained from patients aged 0-5 years. RESULTS: 95% of the isolates showed resistance or decreased susceptibility to at least one of the three third generation cephalosporins [3GC (ceftazidime, cefotaxime, ceftriaxone)] used for the study. 87% of the isolates showed resistance to all the three 3GC antibiotics and this resistance to all the three 3GC was found to coexist with resistance to other antibiotics. All the isolates were found sensitive to the antibiotic imipenem. ESbL production was detected in 8 strains of Klebsiella pneumoniae. The ESbL activity could be experimentally transferred to recipient E. coli (K12 J62-2). Resistance to b-lactam antibiotics was co-transferred with resistance to gentamicin. CONCLUSIONS: This study has shown the incidence of ESbL producing Klebsiella pneumoniae strains among children in Chennai. Tests for the detection of ESbL producing Klebsiella strains should be carried out in all diagnostic centers routinely and the therapeutic use of all the 3GC should be avoided against Klebsiella strains that appear resistant to any third generation antibiotic.

Intestinal parasitic infection in HIV infected patients with diarrhoea in Chennai.

PURPOSE: To determine the prevalence of intestinal parasites in HIV patients with and without diarrhoea in Chennai. METHODS: A total of 150 stool samples, 41 - acute diarrhoea, 59 - chronic diarrhoea and 50 control samples without diarrhoea were collected and examined for enteric parasites by microscopy. RESULTS: Enteric parasites were detected in 39% patients with diarrhoea compared to 14% in patients without diarrhoea. Isospora belli was found in 18.6% (11/59) of chronic diarrhoea and 7.3% (3/41) in acute diarrhoea (P > 0.2). Cryptosporidium was detected in 7 cases each in acute and chronic diarrhoea, which was statistically insignificant as compared to the control group (P> 0.05). Microsporidia and Cyclospora cayetanensis associated diarrhoea were detected in only one chronic case each 1/59 (1.69 %). CONCLUSIONS: Isospora belli appeared to be a predominant parasite associated with diarrhoea among HIV patients. Detection rate of Microsporidia and Cyclospora was found to be very low.

Role of coccidian parasites in causation of diarrhoea in HIV infected patients in Chennai.

BACKGROUND & OBJECTIVES: Diarrhoea is one of the major problems of HIV positive patients. A coproparasitological study was carried out to assess the role of coccidian parasites in the causation of diarrhoea in HIV infected patients in Chennai. METHODS: During May 2000 to January 2001, 152 stool samples from HIV seropositive individuals (43 with acute diarrhoea, 59 with chronic diarrhoea, 50 without diarrhoea) and 50 normal individuals without diarrhoea were examined for enteric coccidian and other intestinal parasites by microscopy and special staining methods. RESULTS: A total of 52 enteric parasites, 15 from patients with acute diarrhoea and 24 from patients with chronic diarrhoea, 7 from patients infected with HIV without diarrhoea and 6 from normal individuals without diarrhoea were detected from 49 patients. Isospora belli was detected in 14 of 102 (13.7%) patients with acute and chronic diarrhoea. The association with diarrhoea among HIV positive individuals was significant (P < 0.001). Cryptosporidium was detected in 7 patients each with acute and chronic diarrhoea and 4 patients with HIV infection without diarrhoea, its association with diarrhoea among HIV patients was found to be not significant in the present study. Cyclospora and Microsporidia each were detected in only one HIV positive patient with chronic diarrhoea. INTERPRETATION & CONCLUSION: The study revealed that the coccidian parasites are one of the important etiologic agents of diarrhoea (P < 0.001) especially of chronic diarrhoea among HIV positive patients. Isospora belli was found to be a frequent enteric parasite associated with diarrhoea among HIV positive patients in Chennai.

SoRI 9409, a non-peptide opioid mu receptor agonist/delta receptor antagonist, fails to stimulate [35S]-GTP-gamma-S binding at cloned opioid receptors.

Recent work suggests that opioids which combine mu agonist and delta antagonist activity may be non-addicting antinociceptive agents. SoRI 9409 (5'-(4-Chlorophenyl)-17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5alpha-epoxypyrido-[2',3':6,7]morphinan) is a naltrexone-derived non-peptide ligand which demonstrates partial mu and kappa agonist activity and antagonist activity at delta receptors. Chronic administration of SoRI 9409 to mice failed to produce tolerance to its antinociceptive effect and SoRI 9409 produced less withdrawal signs than naloxone in acute and chronic morphine dependence models. To further characterize SoRI 9409 we determined its effects in the guanosine 5'-O-(3-[35S]thio)-triphosphate binding assay. SoRI 9409 demonstrated no agonist activity at cloned mu delta, or kappa receptors. Other experiments demonstrated that SoRI 9409 was a potent and selective delta antagonist (K(i) = 0.08 nM) which acted also as an antagonist at mu and kappa receptors. Its profile of activity resembled that of naltrindole (NTI). Viewed collectively, the in vitro data reported here predict that SoRI 9409 should be a mu antagonist in vivo, which is not observed. Resolving these discrepant findings will require additional research.