The hyperthermic effect of central cholecystokinin is mediated by the cyclooxygenase-2 pathway.

Cholecystokinin (CCK) increases core body temperature via CCK2 receptors when administered intracerebroventricularly (icv). The mechanisms of CCK-induced hyperthermia are unknown, and it is also unknown whether CCK contributes to the fever response to systemic inflammation. We studied the interaction between central CCK signaling and the cyclooxygenase (COX) pathway. Body temperature was measured in adult male Wistar rats pretreated with intraperitoneal infusion of the nonselective COX enzyme inhibitor metamizol (120 mg/kg) or a selective COX-2 inhibitor, meloxicam, or etoricoxib (10 mg/kg for both) and, 30 min later, treated with intracerebroventricular CCK (1.7 µg/kg). In separate experiments, CCK-induced neuronal activation (with and without COX inhibition) was studied in thermoregulation- and feeding-related nuclei with c-Fos immunohistochemistry. CCK increased body temperature by ∼0.4°C from 10 min postinfusion, which was attenuated by metamizol. CCK reduced the number of c-Fos-positive cells in the median preoptic area (by ∼70%) but increased it in the dorsal hypothalamic area and in the rostral raphe pallidus (by ∼50% in both); all these changes were completely blocked with metamizol. In contrast, CCK-induced satiety and neuronal activation in the ventromedial hypothalamus were not influenced by metamizol. CCK-induced hyperthermia was also completely blocked with both selective COX-2 inhibitors studied. Finally, the CCK2 receptor antagonist YM022 (10 µg/kg icv) attenuated the late phases of fever induced by bacterial lipopolysaccharide (10 µg/kg; intravenously). We conclude that centrally administered CCK causes hyperthermia through changes in the activity of "classical" thermoeffector pathways and that the activation of COX-2 is required for the development of this response.NEW & NOTEWORTHY An association between central cholecystokinin signaling and the cyclooxygenase-prostaglandin E pathway has been proposed but remained poorly understood. We show that the hyperthermic response to the central administration of cholecystokinin alters the neuronal activity within efferent thermoeffector pathways and that these effects are fully blocked by the inhibition of cyclooxygenase. We also show that the activation of cyclooxygenase-2 is required for the hyperthermic effect of cholecystokinin and that cholecystokinin is a modulator of endotoxin-induced fever.

Ginger (Zingiber officinale): An alternative for the prevention of postoperative nausea and vomiting. A meta-analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a distressing outcome related to surgeries. Traditionally, ginger has been used in the treatment of nausea and vomiting for thousands of years. Recently, several randomized, placebo-controlled clinical trials (RCTs) have been conducted to evaluate the efficacy of ginger in PONV. PURPOSE: To systematically evaluate the efficacy of ginger on postoperative nausea and vomiting (PONV) compared to placebo, based on RCTs. STUDY DESIGN: The meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched for relevant studies. Human, placebo-controlled clinical studies of patients undergoing any types of surgery, receiving pharmacological doses of ginger per os were included. Only clinical trials with explicit description of the ginger preparation used were analysed. No language or publication year restrictions was applied. RESULTS: Ten randomized trials including a total of 918 patients were pooled for the statistical analysis. The present meta-analysis supports that ginger has a significant effect on the severity of PONV based on visual analogue scale (VAS) results: in a fixed effects model the pooled standardized mean difference (SMD) was -0.247 (favouring ginger; [LL]: -0.455, [UL]: -0.040, p-value: 0.019). Moreover, our results suggest that ginger reduces the incidence of postoperative nausea and vomiting, as well antiemetic drug demand; however, these effects are not statistically significant compared to placebo, which may be explained by underdosing. CONCLUSIONS: According to our thorough meta-analysis ginger is safe and well tolerated, and decreases the severity of PONV, and may lower the incidence of postoperative nausea and vomiting, which in turn may reduce antiemetic drug demand, suggesting that ginger may be a useful alternative to antiemetic medications to alleviate PONV.

Capsaicin and capsiate could be appropriate agents for treatment of obesity: A meta-analysis of human studies.

Consumption of capsaicin or its nonpungent analogues, capsinoids has been reported to affect energy expenditure and fat oxidation, although available data are still controversial. The aim of the present study was to conduct a meta-analysis regarding the effects of these substances on energy expenditure and respiratory quotient, with special emphasis on the role of body mass index (BMI) of the participants. Medical databases were systematically searched for papers. Of the 627 trials identified, 9 provided results suitable to be included in analysis. Data analysis showed that after ingestion of capsaicin or capsinoids the energy expenditure increased (245 kJ/day, 58.56 kcal/day, p = 0.030) and the respiratory quotient decreased (by 0.216; p = 0.031) indicating a rise in fat oxidation. Studies with mean BMI of the participants below 25 kg/m2 failed to report any effect of capsaicin or capsinoids on the energy expenditure (p = 0.718) or on the respiratory quotient (p = 0.444), but studies with mean BMI exceeding 25 kg/m2 demonstrated an increase in energy expenditure (292 kJ/day, 69.79 kcal/day, p = 0.023) and a marked decrease in respiratory quotient (-0.257, p = 0.036). Our data clearly suggest that capsaicin or capsiate could be a new therapeutic approach in obesity promoting a negative energy balance and increased fat oxidation.

Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).

Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR.