Irit Gil-ad, PhD, Blana Shtaif, MSc, Rina Eshet, PhD, Rachel Maayan, PhD, Moshe Rehavi, PhD and Abraham Weizman, MD
Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.
Objectives: To compare the effect of the two neurohormones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).
Methods: Cell viability and cell proliferation were determined with the neutral red and 3H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.
Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased 3H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of 3H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respectively, vs. control 2.54%).
Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.
Gabriel Kenet, MD, Joram Wardi, MD, Yona Avni, MD, Hussein Aeed, PhD, Haim Shirin, MD, Liliana Zaidel, MD, Rami Hershkovitz, MD and Rafael Bruck, MD
Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hypnotic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.
Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.
Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.
Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalidomide) than the control group (iodoacetamide only). Histologically, colonic inflammation in the treated group was markedly decreased.
Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.
by Allan I. Bloom, MD, Talia Sasson, MD, Anthony Verstandig, MD, Yehuda G. Wolf, MD, Haim Anner, MD, Yakov Berlatzky, MD, Inna Akopnick, MD, Chaim Lotan, MD, Richard Lederman, MD and Pinchas D. Lebensart, MD
David S. Blondheim, MD, Orna Blondheim, MD and S.H. Blondheim, MD
Background: Fasting is required by the Jewish and Islamic religions, and may sometimes be necessary for nonreligious reasons as well. Very little empiric data are available on the effect of 24 hours of food and water deprivation.
Objectives: To compare the effects of the dietary composition of different pre-fast meals on subjective discomfort and various other parameters of a 24 hour food and water fast.
Methods: Thirteen volunteers of both genders participated in a non-randomized crossover study. Each consumed three different equicaloric pre-fast meals in which the main source of calories was protein (49% of calories), carbohydrate (86%), or fat (69%). Weight, heart rate, blood pressure, blood and urine were tested before and after 24 hours of fasting, and the subjective evaluations of the discomfort during the three fasts were compared.
Results: After the protein-rich meal greater discomfort and more side effects were reported. Weight and blood pressure decreased at the end of the fasts that followed each of the three meals heart rate increased after the high fat and carbohydrate meals but not after the protein meal. The main laboratory findings were a 40% increase in blood urea nitrogen and higher urine osmolarity after the protein-rich meal than after the other meals.
Conclusion: A protein-poor pre-fast meal is likely to be followed by easier fasting.
Slomo Vinker, MD, Boris Kaplan, MD, Sasson Nakar, MD, Gita Samuels, MD, Gidon Shapira, MD and Eliezer Kitai, MD
Background: Urinary incontinence in older women is common. Its characteristics and impact on quality of life is not well established since these women are usually reluctant to tell their healthcare providers about the problem.
Objective: To determine the characteristics of urinary incontinence in women and the manner in which it affects patients quality of life.
Methods: Twenty family physicians were requested to distribute a questionnaire to the first 25 consecutive women aged 30 to 75 years who visited their clinic for any reason. The questionnaire covered general health issues, symptoms of urinary incontinence, and quality of life.
Results: A total of 418 women, mean age 50.0 ± 11.8 years, completed the questionnaire (84% response rate). Of these, 148 (36%) reported having episodes of urinary incontinence. Urinary incontinence was found to be associated with older age, menopause, obesity and coexisting chronic disorders. Sixty percent of the women with urinary incontinence found it to be a disturbing symptom, and 44% reported that it had a detrimental effect on their quality of life. Only 32% of the affected women had sought medical advice, half of them from their family physician. Treatment was recommended to 66% of those who sought help, and in about two-thirds of these it brought some measure of relief.
Conclusions: Urinary incontinence is a common complaint among women attending primary care clinics, but it does not receive appropriate attention, Though it often adversely affects quality of life, only a small proportion of women seek medical advice. Family physicians should raise the issue as a part of the routine general health check-up.