Israel Medical Association Journal

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic

Background: Dyslipidemia and obesity serve as risk factors for the development of atherosclerotic cardiovascular disease. Fasting is sometimes recommended for treating these conditions. This study was undertaken to try to resolve conflicting results reported in the literature.

Objectives: To study the effect of fasting (0 calories, with free intake of fluids) for 3-5 days on plasma concentration of triglyceride, cholesterol and apolipoprotein B.

Methods: Physicians, about to begin a hunger strike, were divided into four groups: normolipidemic non-obese men (group 1), two moderately obese men and two men with type IV hyperlipidemia (group 2), healthy non-obese women (group 3), and healthy non-obese women on oral contraceptives (group 4). Adherence to fasting was monitored daily by detailed interviews, loss of weight, drop in plasma glucose, presence of ketonuria, progressive rise in serum creatinine and uric acid, and decrease in plasma pH. We monitored their serum glucose, electrolytes, liver function, lipids, lipoproteins and apolipoprotein B on days 0, 3, and 5.

Results: Physicians who adhered to complete fasting lost more than 1.5% of their body weight after 3 days of fasting (n=12), and more than 3.2% at 5 days (n=5). All non-obese normolipidemic males and females (groups 1 and 3) showed an increase in plasma triglyceride (by 28-162%) and very low density lipoprotein cholesterol (by 22-316%) after 3 days of fasting. The obese and hyperlipidemic men (group 2) showed a decrease of 17-63% in their VLDL cholesterol, and the women on oral contraceptives (group 4) showed a 20% decrease in their plasma triglyceride on day 3. Low density lipoprotein cholesterol increased by 13% in group 2, decreased by 7.3% in group 4, and remained unchanged in group 1 and 3. Apolipoprotein B level correlated well with LDL cholesterol in all groups. High density lipoprotein cholesterol changes were inconsistent.

Conclusions: These results help to explain and reconcile previous published reports. The metabolic background of the individual together with the amount of energy consumed affect the behavior of plasma lipids and lipoproteins levels during fasting.

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VLDL= very low density lipoprotein

LDL= low density lipoprotein
 

Background: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery.

Objectives: To evaluate if these factors have improved in recent years.

Methods: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98.

Results: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%.

Conclusions: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.
 

Background: The pathogenesis of neurological symptoms, the most common extraintestinal complication ofchildhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role.

Objectives: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R.

Methods: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate.

Results: In our animal model of Shigella related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection.

Conclusions: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.
 

Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.

Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.

Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.

At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.

Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.

Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

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TPN= total parenteral nutrition