Changes of excitatory and inhibitory neurotransmitters in the colon of rats underwent to the wrap partial restraint stress.

BACKGROUND: Animal models proposed to reproduce some of the human irritable bowel syndrome (IBS) symptoms are based on the hypothesis that psychosocial stressors play a pivotal role in the IBS etio-pathology. We investigated the wrap restraint stress (WRS) model with the aim to analyze the morphological changes of the entire colonic wall of these animals that showed some of the human IBS symptoms such as visceral hypersensitivity. METHODS: Male Wistar rats were used and WRS was maintained for 2 h. Abdominal contractions (AC) were recorded in the colon-rectum by balloon distension. Fecal pellets were quantitated. Colonic specimens were examined by routine histology, immunohistochemistry and western blot. KEY RESULTS: WRS animals were characterized by: (i) increase in AC number and fecal pellets mean weight; (ii) clusters of mononucleated cells, increase in eosinophilic granulocytes and mast cells in the mucosa; (iii) increase in CGRP-immunoreactive (IR) nerve fibers in the lamina propria; (iv) decrease in myenteric NK1r-IR and nNOS-IR neurons and in submucous nNOS-IR neurons; (v) decrease in SP-IR nerve fibers in the muscle wall; (vi) reduction in S100ß-IR glia in the entire colonic wall; (vii) increase in CRF1r-IR myenteric neurons; (viii) no change in ChAT-IR neurons, smooth muscle cells and interstitial cells of Cajal. CONCLUSIONS AND INFERENCES: The present results support the consistency of the WRS as a potential model where part of the human IBS signs and symptoms are reproduced. The changes in glial cells and in excitatory and inhibitory neurotransmitters might represent the substrate for the dysmotility and hypersensitivity.

Influence of tachykinin NK2 receptors on intestinal sensitivity and motility in newborn rats.

The effect of tachykinin neurokinin NK(2) receptors activation on intestinal propulsion and colorectal sensitivity was studied in 7-15 days old newborn rats. In a first set of experiments investigating the intestinal transit, the selective NK(2) receptor agonist, [betaAla(8)]NKA-(4-10) was used. It produced an increase of the small intestinal transit measured by charcoal test of 54%, that was inhibited in a dose-dependent manner by nepadutant ([N(4)-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-L-asparaginyl-L-aspartyl-L-tryptophyl-L-phenylalanyl-L-2,3-diaminopropionyl-L-leucyl]-C-4.2-N-3.5-lactam-C-1.6-N-2.1-lactam), a known selective NK(2) receptor antagonist, orally administered 2-48 h before the challenge with the NK(2) receptor agonist. Nepadutant did not affect the basal intestinal propulsion and showed a good oral bioavailability and long duration of action. In another set of experiments investigating visceral sensitivity, a fixed distension volume of a balloon inserted intrarectally in 14-15 days old newborns rats produced abdominal contractions (AC) that were increased after colonic application of acetic acid (50 microl, 0.5%). In this latter condition nepadutant, at 0.5 and 2.5 mg/kg p.o., significantly reduced the resulting AC. In control rats, untreated with acetic acid, nepadutant did not affect AC evoked by colorectal distension. These findings show for the first time two models to assess intestinal motility and visceral sensitivity in newborn rats and indicate nepadutant as a valuable tool to assess the role of NK(2) receptors in the intestinal propulsive and nociceptive activity in infants.

Duration and spread of an entomopathogenic fungus, Beauveria bassiana (Deuteromycota: Hyphomycetes), used to treat varroa mites (Acari: Varroidae) in honey bee (Hymenoptera: Apidae) hives.

A strain of the fungus Beauveria bassiana (Balsamo) Vuillemin (Deuteromycota: Hyphomycetes) isolated from varroa mites, Varroa destructor Anderson & Trueman (Acari: Varroidae), was used to treat honey bees, Apis mellifera L. (Hymenoptera: Apidae), against varroa mites in southern France. Fungal treatment caused a significant increase in the percentage of infected varroa mites compared with control treatments in two field experiments. In the first experiment, hives were treated with a formulation containing 0.37 g of B. bassiana conidia per hive and in the second experiment with a dose of 1.0 g of conidia per hive. The percentage of infected varroa mites also increased in the nontreated (control) hives, suggesting a movement of conidia, probably via bee drift, among the hives. Mite fall was significantly higher among treated hives compared with control hives on the sixth and eighth days after treatment in the first experiment. These days correspond to previously published data on the median survivorship of mites exposed to that fungal solate. The interaction of treatment and date was significant in the second experiment with respect to mite fall. Increases in colony-forming unit (cfu) density per bee were observed in all treatments but were significantly higher among bees from treated hives than control hives for at least a week after treatment. The relationship between cfu density per bee and proportion infected was modeled using a sigmoid curve. High levels of infection (>80%) were observed for cfu density per bee as low as 5 x 102 per bee, but the cfu density in hives treated with 0.37 g generally dropped below this level less than a week after treatment.

The COX inhibitors indomethacin and meloxicam exhibit anti-emetic activity against cisplatin-induced emesis in piglets.

We analysed the effects of four cyclooxygenases (COX) inhibitors on cisplatin-induced emesis in piglets. Ninety-five animals receiving cisplatin (5.5 mg kg(-1), i.v.) were observed for 60 h. One hour prior to cisplatin, controls (n=29) were dosed with a saline solution while experimental animals received an i.v. or i.p. injection of one of the COX inhibitors. Additional injections of COX inhibitor were given at 15 and 39 h after cisplatin administration (or every 6h in one group receiving diclofenac). The latencies to the first emetic episode (EE) compared to controls (2.1+/-0.4 h) increased in groups receiving naproxen (4.66+/-0.94 h, n=9, 30 mg kg(-1)) and indomethacin (6.19+/-1.13 h, n=7, 10 mg kg(-1)) i.v. Indomethacin significantly decreased the incidence of both the acute (by 40%) and delayed (by 66%) phases of emesis. The total number of EE during the 60 h compared to controls (28.3+/-1.9 EE) was significantly reduced in piglets receiving indomethacin (14.9+/-3.2 EE, n=7) and meloxicam (17.6+/-3.6 EE, n=11, 0.3 mg kg(-1)). Four piglets receiving meloxicam (0.3 mg kg(-1), i.v.) did not vomit during the delayed phase. The anti-emetic activity of two COX inhibitors suggests that prostaglandins contribute to the activation of the emetic reflex in response to cisplatin.

A nonpeptide vasopressin V(1a) receptor antagonist, SR 49059, does not prevent cisplatin-induced emesis in piglets.

We determined the pharmacological and the antiemetic properties of SR 49059, a selective nonpeptide V(1a) receptor antagonist, on cisplatin-induced emesis in the piglet. Firstly, we clearly demonstrate that SR 49059 is a potent V(1a) receptor antagonist in vitro and in vivo in the piglet. In binding studies, [3H]-SR 49059 exhibited high affinity for V(1a) receptors in piglet liver membranes (K(d) of 0.76 +/- 0.12 nM and B(max) of 138 +/- 22 fmol/mg prot.). In vivo, in decerebrate piglets, SR 49059 (1 mg/kg iv) antagonized AVP (500 ng/kg iv)-induced hypertension for at least 150 min and also blocked, for at least 270 min at 3 mg/kg iv, the pressor responses to exogenous LVP. After single and repeated iv or icv administration, we studied the antiemetic properties of SR 49059 on cisplatin-induced emesis in piglets. Animals receiving an emetic dose of cisplatin (5.5 mg/kg, iv) were observed continuously for 60 h. Piglets acting as controls were iv administered with vehicle 15 min prior to cisplatin infusion (T0(-15min)), while experimental animals received a single iv administration of SR 49059 at the dose of 1 or 3 mg/kg. In additional piglets, we administered SR 49059 (3 mg/kg) every 12 h from T0(-15min) to T48(-15min) (cumulative dose, 15 mg/kg). Another set of animals - observed only during the acute phase - was administered with SR 49059 (10 mg/kg) every 3 h from T0(-15min) to T15(-15min) (cumulative dose, 60 mg/kg). Lastly, 10 piglets were given a bilateral icv injection of SR 49059 (500 microg and 1500 microg/side) 1 h prior to cisplatin infusion. In all groups treated with SR 49059, the latency of the first emetic episode and the incidence of vomiting during the acute, the delayed and the cumulative phases remained statistically similar to that observed in controls, suggesting that V(1a) receptors are not involved in the onset and completion of nausea and vomiting.

Characterization of lipopolysaccharide-induced emesis in conscious piglets: effects of cervical vagotomy, cyclooxygenase inhibitors and a 5-HT(3) receptor antagonist.

The emetic response to intraperitoneal (i.p., 0.5, 2, 8 mg kg(-1)) and intravenous (i.v., 200 microg kg(-1)) administration of bacterial lipopolysaccharides (LPS) was characterized in conscious piglets observed for 4 h. The latencies and the incidence of the emetic response to LPS (i.p.) decreased and increased, respectively, in a dose-dependent manner. In 14 additional piglets, a bilateral vagotomy performed 4 h prior to LPS administration abolished the vomiting induced by i.p. LPS (2 mg kg(-1)), and decreased its incidence by 77% in the i.v. injected animals. Sham-operated animals (n=6) exhibited a similar emetic pattern to the controls injected intraperitoneally with LPS (2 mg kg(-1)). In 7 piglets, the administration of granisetron, a 5-HT(3) receptor antagonist (i.v., 2 mg kg(-1)), 30 min prior to the i.p. LPS injection (2 mg kg(-1)) failed to reduce significantly the emetic activity; whereas, in 6 animals, a combination of meloxicam (0.3 mg kg(-1)) and indomethacin (5 mg kg(-1)), two cyclooxygenase (COX) inhibitors, administered per os 1.5 h prior to the i.p. LPS (2 mg kg(-1)) abolished the emetic response to endotoxins. The present results show that the activation of the medullary "vomiting centre" in response to i.p. administration of LPS is mediated via vagal afferents and is likely to involve prostaglandins.

Refrigerator content and hospital admission in old people.

We assessed whether the refrigerator contents of elderly people could be related to subsequent admission to hospital. 132 patients aged over 65 years had a thorough assessment of their refrigerator contents and the numbers and dates of admission were recorded. Elderly people with empty refrigerators were more frequently admitted (p=0.032) in the month after assessment and three times sooner than those who did not have empty refrigerators (34 vs 100 days, p=0.002).