Conceptual and methodologic challenges of assessing the short-term efficacy of Guggulu in obesity: data emergent from a naturalistic clinical trial

An open comparative trial was conducted in 58 adult obese patients (Body Mass Index > or = 25 kg/square metre). Group I (n = 27), non-drug, was advised diet (1200-1600 cals) and a brisk walk for 30 minutes. Group II, in addition, received Guggulu (Medohar) 1.5-3 gms/day for 30 days. Mean difference in weight loss between Guggulu and non-drug group was 0.32 kg (ns) on day 15 and 0.58 kg on day 30 (ns). The mean weight reduction in patients (> 90 kgs) was 1.92 kg (ns) and 2.25 kg (ns) higher in Guggulu group. All patients weighing > 90 kg lost weight in Guggulu group whilst 3 in non-drug group did not lose weight. Guggulu was tolerated well. The data from this pilot study suggest a synergistic diet-Guggulu interaction over 30 days in patients weighing > 90 kgs which needs to be confirmed in a large placebo controlled study.     

Fatal renal failure as the first manifestation of sarcoidosis diagnosed on necropsy in a young man: a case report

Renal involvement as the first manifestation of sarcoidosis is rare and has never been reported in India. This report describes a 35 year old man who was admitted to the emergency department with a clinical diagnosis of acute on chronic renal failure, secondary to obstructive uropathy. Postmortem examination unexpectedly revealed disseminated sarcoidosis.     

Analysis of immune responses against T- and B-cell epitopes from Plasmodium falciparum liver-stage antigen 1 in rodent malaria models and malaria-exposed human subjects in India

Liver-stage antigen 1 (LSA-1) is a potential vaccine candidate against preerythrocytic stages of malaria. We report here the immunogenicity of linear synthetic constructs delineated as T(H)-cell determinants from the nonrepeat regions of Plasmodium falciparum LSA-1 in murine models and human subjects from areas where malaria is endemic in Rajasthan State, India. Seven peptide constructs (LS1.1 to LS1.7) corresponding to predicted T-cell sites from both the N- and C-terminal regions and peptide LS1R from a repeat region of PfLSA-1 were synthesized to analyze the cellular immune responses. These linear peptides were also tested for humoral responses in order to determine if there were any overlapping B-cell epitopes in the predicted T-cell sites. Most peptides induced cellular responses in peptide-immunized BALB/c and C57BL/6 mice as measured by proliferation and cytokine analysis. Cross-reactive T-cell recognition of P. falciparum-based peptides in Plasmodium berghei-immune animals was evaluated, but only one peptide, LS1.2 (amino acids 1742 to 1760) triggered T-cell proliferation and interleukin-2 and gamma interferon secretion in P. berghei-immune splenocytes of BALB/c and C57BL/6 mice as well as in Thamnomys gazellae (natural host of P. berghei ANKA). In an enzyme-linked immunosorbent assay with the peptides, only one peptide, LS1.1, was recognized by anti-P. berghei liver-stage serum. Three peptides (LS1. 1, LS1.2, and LS1.3) of the eight peptides tested in this study were recognized by a relatively large percentage of P. falciparum-exposed human subjects; the reactivities ranged from approximately 45% for LS1.3 to approximately 60% for LS1.1 and LS1.2. Interestingly, all of the eight putative T-cell determinants were also recognized by the sera collected from malaria patients, although the response was variable in nature. These T(H)- and B-cell epitopes may be of potential value for preerythrocytic antigen-based malaria subunit vaccine formulations.     

Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.     

Identification of epididymis-specific antigens using neonatal tolerization

PROBLEM: Conventional immunization using whole sperm containing multiple antigens as the immunogen followed by hybridoma technology usually gives antibodies to antigens invariably of testicular origin, probably because of the strong immunogenic nature of these antigens. Therefore, an alternate approach of neonatal tolerization or subtractive immunization has been utilized to raise antibodies specific to epididymis by suppressing immune response to testicular antigens. METHOD OF STUDY: Neonatal mice were tolerized with testicular sperm proteins on days 0 and 5. These animals were then immunized with epididymal sperm proteins on day 21, followed by two boosters at biweekly intervals. Sera from these mice were used to localize epididymis-specific antigens. RESULTS: Sera from mice that were tolerized to testicular sperm proteins and later immunized with epididymal sperm proteins reacted only with epididymal proteins. CONCLUSION: The results of this study demonstrate that neonatal tolerization with testicular sperm proteins, followed by immunization with epididymal sperm proteins, enhances the production of antibodies to proteins exclusively of epididymal origin.     

Noninvasive Measurement of Acceleration at the Knee Joint in Patients with Rheumatoid Arthritis and Spondyloarthropathy of the Knee

Spondyloarthropathy represents a group of joint diseases with a tendency to reactive new bone formation. Spondyloarthropathy includes Reiter's syndrome, ankylosing spondylitis, and the arthropathy of inflammatory diseases (ulcerative colitis and Crohn's disease). Usually, an extensive investigation is required to distinguish spondyloarthropathy of the knee joint from rheumatoid arthritis. Recently, Reddy et al. (Ann. Biomed. Eng. 23:78–84, 1995) have developed the accelerometry technique to characterize various types of arthritis. The question remains if noninvasive acceleration measurements can be used to distinguish between spondyloarthropathy and rheumatoid arthritis. An ultraminiature accelerometer was placed on the patella, and the subject was asked to rhythmically rotate the knee from 90 flexion to full extension. Results have shown that the mean power of acceleration signal in the range of 100–500 Hz is significantly different (p < 0.05) for spondyloarthropathy patients when compared to rheumatoid arthritis patients. The noninvasive accelerometry technique represents a potential tool for characterization of spondyloarthropathy patients. © 2001 Biomedical Engineering Society. PAC01: 8719St, 8719Xx, 0630Gv     

Prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service

The purpose of this study was to determine the prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service. One hundred patients were administered the Executive Interview (EXIT25), the Executive Clock Drawing Task (CLOX), and the Mini-Mental State Examination at admission and discharge. Fifty-two percent of the patients at admission and 56% at discharge had scores indicating impairment on at least one measure of executive function. Median scores on every measure improved during hospitalization. Older patients and those with a cardiac or gastrointestinal disorder were more likely to have executive impairment. The prevalence of executive impairment on general medicine services is high. Although improvement in executive function occurs during hospitalization, many patients remained impaired.     

Sodium channel blocking actions of the kappa-opioid receptor agonist U50,488 contribute to its visceral antinociceptive effects

The goal of the present study was to determine whether the kappa-opioid receptor agonist (ORA) U50,488 attenuates behavioral and primary afferent nerve responses to noxious colorectal distension (CRD) by sodium channel blockade. We tested the analgesic kappa-ORA (+/-)-trans U50,488, its enantiomers (-)-trans (1S,2S)-U50,488 and non kappa-ORA (+)-trans (1R,2R)-U50,488, and/or its diastereomer (-)-cis (1S,2R)-U50,488 for their ability to attenuate visceromotor and pelvic nerve afferent fiber responses to noxious CRD in vivo and voltage-activated sodium current in colon sensory neurons in vitro. In unanesthetized rats, subcutaneous administration of U50,488, (1S,2S)-U50,488, and (1R,2R)-U50,488 attenuated the behavioral visceromotor response to noxious CRD; the rank order of potency was: (1S,2S)-U50,488 > U50,488 angle quotation mark, right (1R,2R)-U50,488. U50,488 and its stereoisomers also inhibited responses of decentralized pelvic nerve afferent fibers to noxious CRD in a dose-dependent manner. Cumulative doses of 16 mg/kg of (1S,2S)-U50,488, (1S,2R)-U50,488, and (1R,2R)-U50,488 reduced responses to a mean 29, 30, and 47% of control, respectively. The mean inhibitory doses of these drugs were not different (range: 6.6-10.8 mg/kg). Sodium channel blockers mexiletine and carbamazepine mimicked the effect of U50,488. In contrast, the kappa-ORAs dynorphin (1-13) and ICI 204,488 were ineffective in attenuating pelvic nerve activity. Perfusion of (1S,2S)-U50,488, (1S,2R)-U50,488, or (1R,2R)-U50,488 on colon sensory neurons in vitro decreased voltage-activated sodium currents. This inhibition by U50,488 and its stereoisomers was not opioid receptor-mediated because it could not be reversed by the opioid receptor antagonist naloxone and was also not a G protein-mediated effect. The results reported here suggest that the visceral antinociceptive effects of U50,488 and its stereoisomers are contributed to by their peripheral sodium channel blocking actions.