Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat

ABSTRACT: BACKGROUND: Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R. METHODS: Male Sprague--Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p.) to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg) of des-Arg9-Bradykinin (BK) and Sar-[D-Phe8]des-Arg9-BK (B1R agonists) or BK (B2R agonist). The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR) and B1R was localized by confocal microscopy. RESULTS: B1R agonists (0.1 to 5 mg/kg) showed transient (5- to 30-minute) and dose-dependent increases of rectal temperature (+1.5[degree sign]C) in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612), cyclooxygenase-2 (COX-2) (niflumic acid) and nitric oxide synthase (NOS) (L-NAME), and after vagal ligation. In contrast, COX-1 inhibition (indomethacin) had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers. CONCLUSION: B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2) and nitric oxide.     

Diabetic pregnancy: outpatient follow-up in a Brazilian University Hospital

In this study we assessed neonatal complications of diabetic in 50 pregnant women at a University Hospital during 2001-2002: 13 (26%) with type 1 diabetes (DM1), 16 with DM2, and 21 (42%) with gestational DM (GDM). The mean outpatient follow-up was at 16.3+/-8 wk for patients with DM1, 22.9+/-7.5 wk for DM2, and 26.0+/-8.9 wk for GDM. Mean HbA1c, fasting and 2-h post-prandial glycemia on first attendance were respectively: 6.1+/-1,1% (RV: 2.6-6.2%), 132+/-39 mg/dL and 190+/-54 mg/dL. 22 patients were on insulin and 15 were on oral antidiabetic agents (OA) at first evaluation. OA were taken on conception and during the first pregnancy trimester and no malformations were seen in the children. Their metabolic profile was similar to other pregnant women. Caesarean section was needed in 54.5% of deliveries. Complications: 56.1% were macrosomic babies, with a mean fetal weight of 3.48+/-0.73 Kg, with no differences according to treatment (insulin vs. OA). We conclude that diabetic pregnant women begin their prenatal care at a later period, often taking OA that are not officially advised to be used during pregnancy and are not in a regular metabolic control. As a result, they have macrosomic infants. Even though we have found no complications related to the OA use during pregnancy, we should not encourage their use until more safety studies are available.     

Nutritional status and serum zinc and selenium levels in Iranian HIV infected individuals

Background  

Human immunodeficiency virus infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and increased catabolism. Trace elements such as zinc and selenium have major role in maintaining a healthy immune system. This study was designed to evaluate the nutritional status of Iranian subjects who were newly diagnosed with human immunodeficiency virus infection and to compare serum level of zinc and selenium in these patients with those of the sex and aged match healthy subjects.     

Effect of different swallow time intervals on the nutcracker esophagus

OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis. METHODS: Eight patients with NE (seven women, 1 man, mean age 50 yr) and eight age- and sex-matched normal volunteers (seven women, 1 man, mean age 48 yr) underwent a special protocol using three-channel (3, 8, and 16 cm above the lower esophageal sphincter) solid state esophageal manometry to evaluate deglutitive inhibition. Ten pairs of 5 ml of wet swallows were given at each of five different time intervals (30, 20, 15, 10, and 5 s). Pairs of swallows were spaced by 30 s, and different time intervals were spaced by 1 min. Tracings were recorded using a computer program and blindly automatically analyzed for both amplitude and duration of the contraction separately for the first and second swallow of each pair. Presence of deglutitive inhibition or muscle refractoriness was assessed according to interactions between the first and second swallow of the pair. Results were found abnormal when larger than the mean percent variation of the second and first swallow calculated for the 30-s interval, considered as baseline for each participant. Statistics included paired and nonpaired nonparametrical comparisons as appropriate. RESULTS: The median amplitude for the NE was 202 mm Hg (range 186-376) and for the controls was 118 mm Hg (range 64-167) (p = 0.0002). The median duration in the NE group was 5.1 s (range 4-9.3) versus 4.1 (range 3.3-5.0) for the controls (p = 0.02). The percent variation in duration (p = 0.31), amplitude (p = 0.42), and propagation velocity of the peristaltic waves (p = 0.69) did not differ between the control and NE groups. Peristalsis frequency dropped at the 5-s interval for both studied groups (p = 0.84). CONCLUSION: Central and local inhibitory mechanisms induced by closely timed swallows are preserved in the NE and do not explain the mechanism of the high amplitude and long duration contractions.