Effect of purinergic agonists and antagonists on insulin secretion from INS-1 cells (insulinoma cell line) and rat pancreatic islets

Verspohl EJ, Johannwille B, Waheed A, Neye H

The effects of purinergic agonists on insulin release are controversial in the literature. In our studies (mainly using INS-1 cells, but also using rat pancreatic islets), ATP had a dual effect on insulin release depending on the ATP concentration: increasing insulin release (EC50 0.0032 mM) and inhibiting insulin release (EC50 0.32 mM) at both 5.6 and 8.3 mM glucose. This is compatible with the view that either two different receptors are involved, or the cells desensitize and (or) the effect of an inhibitory degradation product such as adenosine (ectonucleotidase effect) emerges. The same dual effects of ATP on insulin release were obtained using rat pancreatic islets instead of INS-1 cells. ADPbS, which is less degradable than ATP and rather specific for P2Y1 receptors, had a dual effect on insulin release at 8.3 mM glucose: stimulatory (EC50 0.02 mM) and inhibitory (EC50 0.32 mM). The effective-ness of this compound indicates the possible involvement of a P2Y1 receptor. 2-Methylthio-ATP exhibited an insulinotropic effect at very high concentrations (EC50 15 mM at 8.3 mM glucose). This indicated that distinct P2X or the P2Y1 receptor may be involved in these insulin-secreting cells. UTP increased insulin release (EC50 2 mM) very weakly, indicating that a P2U receptor (P2X3 or possibly a P2Y2 or P2Y4) are not likely to be involved. Suramin (50 mM) antagonized the insulinotropic effect of ATP (0.01 mM) and UTP (0.32 mM). Since suramin is not selective, the data indicated that various P2X and P2Y receptors may be involved. PPADS (100 mM), a P2X and P2Y1,4,6 receptor antagonist, was ineffective using either low or high concentrations of ATP and ADPbS, which combined with the suramin data hints at a P2Y receptor effect of the compounds. Adenosine inhibited insulin release in a concentration-dependent manner. DPCPX (100 mM), an adenosine (A1) receptor antagonist, inhibited the inhibitory effects of both adenosine and of high concentrations of ATP. Adenosine deaminase (1 U/mL) abolished the inhibitory effect of high ATP concentrations, indicating the involvement of the degradation product adenosine. Repetitive addition of ATP did not desensitize the stimulatory effect of ATP. U-73122 (2 mM), a PLC inhibitor, abolished the ATP effect at low concentrations. The data indicate that ATP at low concentrations is effective via P2Y receptors and the PLC-system and not via P2X receptors; it inhibits insulin release at high concentrations by being metabolized to adenosine.

Can. J. Physiol. Pharmacol./Rev. Can. Physiol. Pharmacol.2002;80(6):5628

Suicide on the Indian subcontinent

Khan MM

The Indian subcontinent comprises eight countries (India, Pakistan, Bangladesh, Nepal, Sri Lanka, Afghanistan, Bhutan, and the Maldives) and a collective population of more than 1.3 billion people. 10% of the world's suicides (more than 100,000 people) take place in just three of these countries, viz. India, Sri Lanka, and Pakistan. There is very little information on suicides from the other four countries. Some differences from suicides in Western countries include the high use of organophosphate insecticides, larger numbers of married women, fewer elderly subjects, and interpersonal relationship problems and life events as important causative factors. There is need for more and better information regarding suicide in the countries of the Indian subcontinent. In particular, studies must address culture-specific risk factors associated with suicide in these countries. The prevention of this important public health problem in an area of the world with myriad socio-economic problems, meager resources, and stigmatization of mental illness poses a formidable challenge to mental health professionals, policy makers, and governments of these countries.

Crisis 2002;23(3):104-7

Pills, injections and audiotapes: reaching couples in Pakistan

Collumbien M, Douthwaite M

An innovative social marketing intervention in Pakistan distributes audiocassettes via chemist shops and Lady Health Visitors (LHVs) to reach women in a segregated society with accurate information on hormonal contraceptives. Operations research was done to assess the utility of the cassette in knowledge dissemination and adoption of hormonal use. In total 187 structured questionnaires were completed with couples who had obtained a cassette. Listeners were significantly more knowledgeable than non-listeners about correct use of hormonals (OR = 8.6 for women and OR = 12.7 for men). Hormonal use increased from 12% to 25%. LHVs also organized discussion groups for women, and attending such a chat group was the strongest predictor for adoption of pills and injectables (OR = 4.15). Equivalent male groups are suggested to reach apprehensive men. By providing accurate information to urban couples and by acquiring a knowledgeable critical mass of satisfied users, the cassette could be a powerful catalyst to further contraceptive diffusion.

J Biosoc Sci 2003 Jan;35(1):41-58

Epidemic of hepatitis E in a military unit in Abbottabad, Pakistan

Bryan JP, Iqbal M, Tsarev S, Malik IA, Duncan JF, Ahmed A, et al

An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease), but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to be 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development.

Am J Trop Med Hyg 2002 Dec;67(6):662-8

Hematological changes in cement mill workers

Meo SA, Azeem MA, Arian SA, Subhan MM

OBJECTIVE: Considering the hazards of exposure to cement dust, this study incorporated basic haematological parameters, erythrocyte sedimentation rate and the total leukocyte count. The idea was to identify a simple, readily available and cost effective screening test that could help in identifying the presence of disease, its severity, or both in cement mill workers potentially related to their work place. METHODS: This study was carried out in the Department of Physiology, Faculty of Health and Medical Sciences, Hamdard University, Karachi and the University of Karachi, Pakistan, during the time frame 1999-2000. In this study a group of 50, apparently healthy volunteers male cement mill workers were randomly selected with ages ranging from 20-60 years. They were matched with another group of 50, control healthy male subjects in terms of age, height, weight and socioeconomic status. Both groups met with exclusion criteria as per standard. The total leukocyte count was performed on an auto analyzer, (Symex-K-1000 CP-Analyzer, Japan) and the erythrocyte sedimentation rate was measured by Westergren tube method. Results were compared in a mean, and on the basis of, period of exposure in a cement mill. RESULTS: In the present study, the mean values of erythrocyte sedimentation rate (p<0.05) and total leukocyte count (p<0.02) significantly increased, but the parameters do not revealing statistically significant differences between 2 groups on the basis of duration of exposure in a cement mill. CONCLUSION: This study has shown that exposure to cement dust causes increased mean values of total leukocyte count and erythrocyte sedimentation rate. However, this change is not related to the duration of exposure in a cement mill.

Saudi Med J 2002 Nov;23(11):1386-9

Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital.

Babar N, Alam M, Ali SS, Ansari A, Atiq M, Awais A et al.

OBJECTIVE: To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital. SUBJECTS AND METHODS: A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa. RESULTS: A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%. CONCLUSION: Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour.

J Pak Med Assoc 2002 Jun;52(6):272-6.