Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes

Orexins are recently identified neuropeptides that appear to play a role in the regulation of energy homeostasis and arousal. They bind to and activate two closely related G protein-coupled receptors (OXR1 and OXR2), previously described as orphans. In this study we examined involvement of orexins in regulation of insulin secretion from rat pancreatic islets utilizing an in situ perfused pancreas and isolated pancreatic islet models. By means of RT-PCR we found that both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the expression levels of OXR1 were higher than OXR2. In both experimental models applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently stimulated insulin secretion at two different glucose concentrations (6.66 or 26.4 mmol/l), with orexin A being more potent than orexin B. This study demonstrates that orexins A and B modulate insulin secretion in vitro.     

Case report: Role of hepatitis E virus in the etiology of community-acquired non-A,non-B hepatitis in greece

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc.     

Synthesis and structural studies of new copolyimides 2. Influence of pyromellitimide rings on copolymer structure

The reaction of pyromellitic dianhydride (1,2 : 4,5-benzenetetracarboxylic dianhydride) ( 1 ) with L - and D -alanine ( 2 L ) and ( 2 D ) leads to new monomers which were used to synthesize new copolymers. These copolymers were obtained as a product of the condensation of optical isomers of bis[N-(1-chloroformylethyl)]pyromellitimides (CFEP) with poly(ethylene glycol) PEG-2000 ( 5 ). The effect of monomer structure on the structure and thermal properties of the polymers was studied using X-ray diffraction, differential scanning calorimetry and thermogravimetry. The copolymers were compared with similar copolyimides obtained previously from bis(N-chloroformylmethyl)pyromellitimide and poly(ethylene glycol), PEG 2000. The dominating effect of poly(ethylene glycol) comonomer on the crystallinity, structure and thermal stability of these new copolymers is proven.     

Crystalline and disordered state of poly(dihexylsilylene) copolymers

A systematic comparison of random copolymers, derived from poly(dihexylsilylene) (PDHS) by incorporation of monomeric units with shorter unbranched alkyl side chains, has been carried out based on calorimetry, variable temperature UV spectroscopy, and ²⁹Si MAS (magic angle spinning) solid state NMR investigations. Also, hexylmethylsilylene units and branched monomers have been copolymerized. Up to 10% comonomer with shorter linear side chains (i. e., pentyl to propyl) could be incorporated into PDHS without impeding the all-trans order of the crystalline phase. In this case, the UV absorption maximum of the crystalline low-temperature phase was affected only slightly according to the length and fraction of the comonomer side chains. A less ordered crystal structure (λ_max = 345–355 nm) was observed when the content of comonomers with shorter side chains was about 20%. Yet, all these materials form conformationally disordered mesophases. A clear disordering transition and corresponding thermochromism was not observed any more when 50% of propyl side chains were incorporated. The order of the crystalline and the mesophase is also strongly perturbed if only a small fraction (4%) of the side chains are branched at C².     

Immunohistological analysis of the lymphoid infiltrate in cutaneous malignant melanomas

Summary The immunological phenotypes of the lymphoid cells in 39 cutaneous malignant melanomas have been investigated by staining cryostat sections with a panel of 20 monoclonal antibodies against lymphoid cells and their subsets. Staining was performed by the alkaline phosphatase: anti-alkaline phosphatase (APAAP) method in which the substrate label (red) is easily distinguishable from melanin. The lymphoid infiltrates had an essentially identical composition in all cases, consisting of T-lymphocytes associated with both Langerhans cells and HLA-DR-positive tissue macrophages. B-lymphocytes and natural killer cells were either absent or only present in low numbers. The ratio between T8 (suppressor/cytotoxic) and T4 (helper/inducer) lymphocytes varied and showed no correlation with melanoma subtype, level of invasion or magnitude of lymphocytic response. Examination for markers associated with T-cell activation and/or with cell proliferation revealed that all lesions contained HLA-DR-positive T-lymphocytes, whereas expression of the transferrin receptor and the interleukin-2 receptor (Tac-antigen) occurred mainly in melanomas with a significant inflammatory infiltrate. These data support the concept that malignant melanomas are capable of evoking autologous T-cell immune reactions.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

The activity of erythrocyte enzymes in rats subjected to running exercises

Summary The studies were carried out on male Wistar rats subjected to running within an electric rotating drum. The animals were divided into four experimental groups, differing one from another as to the duration of training. Each training session lasted 30 days. In the first group the daily run lasted 3 min, in the second group 5 min; in the third group, a 1 min run on the first day, and one min longer on each successive day; in the fourth group a 2 min run on the first day and for two min longer on each successive day.The determinations made prior to and after training included the peripheral blood erythrocyte (Er) and reticulocyte (Ret.) count, the hemoglobin concentration (Hb) and packed cell volume (PCV) and, determined by spectrophotometric methods, the activity of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR). Training induced an improvement of all enzymatic activities. The heavier the physical exertion, the more intensive was the enzymatic activity of red blood cells, due to the intensification of bone marrow erythropoetic activity under physical exertion and the appearance of young red cells in peripheral blood. All the experimental groups revealed a drop in erythrocyte count (Er), hemoglobin concentration (Hb), and hematocrit values (PCV), as well as an increase in the reticulocytes count (Ret) and in the activity of all the enzymes investigated. In the fourth group anemia was detected: prolonged endurance training decreased the RBC by 24.2%, Hb by 31.1%, PCV by 26.2% and increased the reticulocyte count by 881.6%. Pronounced loading with physical effort leads to shifts in the glucose utilization ratio along particular erythrocyte metabolic pathways. This change in enzymatic activities may prove to be one of the causes of faster elimination of old RBCs.     

Nutritional Support in Head and Neck Radiotherapy Patients Considering HPV Status

Malnutrition is a common problem in patients with head and neck cancer (HNC), including oropharyngeal cancer (OPC). It is caused by insufficient food intake due to dysphagia, odynophagia, and a lack of appetite caused by the tumor. It is also secondary to the oncological treatment of the basic disease, such as radiotherapy (RT) and chemoradiotherapy (CRT), as a consequence of mucositis with the dry mouth, loss of taste, and dysphagia. The severe dysphagia leads to a definitive total impossibility of eating through the mouth in 20–30% of patients. These patients usually require enteral nutritional support. Feeding tubes are a commonly used nutritional intervention during radiotherapy, most frequently percutaneous gastrostomy tube. Recently, a novel HPV-related type of OPC has been described. Patients with HPV-associated OPC are different from the HPV− ones. Typical HPV− OPC is associated with smoking and alcohol abuse. Patients with HPV+ OPC are younger and healthy (without comorbidities) at diagnosis compared to HPV− ones. Patients with OPC are at high nutritional risk, and therefore, they require nutritional support in order to improve the treatment results and quality of life. Some authors noted the high incidence of critical weight loss (CWL) in patients with HPV-related OPC. Other authors have observed the increased acute toxicities during oncological treatment in HPV+ OPC patients compared to HPV− ones. The aim of this paper is to review and discuss the indications for nutritional support and the kinds of nutrition, including immunonutrition (IN), in HNC, particularly OPC patients, undergoing RT/CRT, considering HPV status.     

Analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds

BackgroundThe aim of this study was to assess the analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds.Patients and methodsTwenty adult patients, who underwent surgical treatment of third–degree burn wounds under general anesthesia, were included. Two of the patients underwent surgery twice. During surgery, patients received 50–100 μg fentanyl every 20–30 min and, after surgery, patients received 100 mg ketoprofen twice daily. Additionally, ten patients (group 1) received 50 μg sufentanil added to the burn wound dressings soaked in octenidine and phenoxyethanol while 10 patients (group 2) received 25 μg sufentanil added to the same dressings. The rescue analgesic, which was administered when pain intensified, was 5 mg subcutaneous morphine. Plasma sufentanil concentrations were assayed at 1, 2, 3, and 6 h after surgery completion and when pain was reported, along with pain intensity evaluation.ResultsSufentanil was not detected in the serum of any patients. Rescue morphine was given during the postoperative period (24 h) in one patient in group 1 (who underwent surgery twice) and three patients in group 2. The mean sufentanil concentration in dressings was higher in group 1 (0.13 ± 0.03) than group 2 (0.06 ± 0.03 μg/mL; p < 0.001). The group 1 patient who received rescue morphine had a sufentanil concentration of 0.10 μg/mL, which was the lowest concentration in group 1. Group 2 patients who received rescue morphine had sufentanil concentrations of at least two–fold lower (0.03–0.05 μg/mL). No adverse effects were observed.ConclusionsSufentanil in dressings after burn wound surgery provides effective and safe analgesia and the sufentanil concentration in dressings should be ≥0.10 μg/mL in a solution of octenidine and phenoxyethanol.