Suc Group Research Articles

The Elucidation of the Mechanism of Weight Gain and Glucose Tolerance Abnormalities Induced by Chlorpromazine

Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the role of adipocytokines secreted from adipocytes in the development of metabolic syndrome has received attention. The aim of this study was to investigate the effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose (Suc group), 15% sucrose and Cp at 7.5 mg/kg per day (Suc + Cp group), or Cp alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc + Cp groups were significantly higher than in the control (Cont) group. Fasting insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher than in the Cont group. The adiponectin level in the Suc group was significantly higher than in the Cont group, although the adiponectin level in the Suc + Cp group was not. Furthermore, the plasma tumor necrosis factor (TNF)-α level in the Suc + Cp group was significantly higher than in the Suc group. These data suggest that Cp inhibits the compensatory response of adiponectin with respect to obesity due to increased expression of plasma TNF-α level. Cp may exert more harmful effects on the glucose level and insulin resistance than on other factors, which may be one of the mechanisms responsible for the metabolic syndrome induced by antipsychotic agents.

A discriminative two-lever test of dizocilpine's ability to reinstate ethanol-seeking behavior

Because ethanol has N-methyl- d-aspartate (NMDA) antagonist effects, we tested whether dizocilpine, an NMDA antagonist, reinstates ethanol-seeking behavior. Rats were trained to lever-press for a 10% ethanol/2% sucrose (EtOH) or a 3% sucrose (Suc) solution using a two-lever (one lever active) procedure (FR2). After extinction, rats were injected with ethanol (0.5 g/kg). The EtOH group emitted more active than inactive lever presses and the Suc group showed minimal responding. Thus, ethanol reinstated ethanol-seeking behavior in a specific manner. In contrast, dizocilpine (0.175 mg/kg) increased responding on both levers in both groups suggesting a loss of discriminative control. Dizocilpine fails to reinstate ethanol-seeking behavior. These data also demonstrate the necessity of using a discriminative, two-lever test for drug reinstatement.

The effects of potassium on the rat middle cerebral artery

After traumatic brain injury, extracellular K + in brain can dramatically increase. We studied the effects of increased K + on the isolated pressurized rat middle cerebral artery (MCA). MCAs (200–250 μm OD) were isolated, cannulated with glass micropipettes, and pressurized. K + was increased in the extraluminal bath using three paradigms: (1) isotonic K + (K iso) where increases in K + were offset by decreases in Na +, (2) hypertonic K + (K hyper) where K + was increased without a concomitant adjustment of Na +, and (3) K suc, a solution using K iso but with the addition of sucrose to obtain a hypertonic solution. Increases in K + in the extraluminal bath produced significant dilations (approximately 20%) at 21 mM K + in all three groups (K iso, K hyper, and K suc). With the K hyper and K suc groups, the magnitude of the dilation diminished with further increases in K +. l-NAME (10 −5 M), an inhibitor of nitric oxide synthase, had no effect on the response of the K hyper and K suc groups at 21 mM but significantly enhanced constrictions of the MCAs above 40 mM K + compared to the control. The K iso group was not affected by l-NAME at any K + concentration and showed profound constrictions above 40 mM K +. We conclude that changes in the K + concentration and osmolality of the extracellular fluid may have profound effects on the cerebral vasculature.

COMPARISON OF ACID NEUTRALIZING AND NON-ACID NEUTRALIZING STRESS ULCER PROPHYLAXIS IN THERMALLY INJURED PATIENTS

We have compared the effectiveness of non-acid neutralizing stress ulcer prophylaxis (SUC) with sucralfate (n = 48) with that of acid neutralizing prophylaxis (AN) utilizing antacids and cimetidine (n = 48) in the prevention of stress ulcer bleeding and nosocomial pneumonia (PN) in thermally injured patients. In the subset of intubated patients, the incidence of PN was 17.8% and 42.8% in the AN and SUC groups, respectively (p < 0.05) despite a similar postburn time of onset of pneumonia. Ten patients in each group died. Three patients in the SUC group developed upper GI bleeding with one requiring gastrectomy. Bacterial colonization of the upper airway occurred in virtually all patients, whereas 83% (SUC) and 96% (AN) had colonization of gastric contents. Gram-negative colonization rates for the upper airway were not different (70%) whereas 48% of SUC patients compared with 60% of AN patients had gram-negative gastric colonization. In conclusion, SUC therapy was efficacious in the prevention of stress ulcer bleeding but did not alter the rate of bacterial colonization of the airway or gastric contents, and was associated with a higher incidence of nosocomial pneumonia in intubated patients.