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.     

Acculturation and psychosocial stress show differential relationships to insulin resistance (HOMA) and body fat distribution in two groups of blacks living in the US Virgin Islands

The objective of this study was to determine whether acculturation and psychosocial stress exert differential effects on body fat distribution and insulin resistance among native-born African Americans and African-Caribbean immigrants living in the US Virgin Islands (USVI). Data collected from a non-diabetic sample of 183 USVI-born African Americans and 296 African-Caribbean immigrants age > 20 on the island of St. Croix, USVI were studied. Information on demographic characteristics, acculturation and psychosocial stress was collected by questionnaire. Anthropometric measurements were taken, and serum glucose and insulin were measured from fasting blood samples. Insulin resistance was estimated by the homeostasis model assessment (HOMA) method. The results showed that in multivariate regression analyses, controlling for age, education, gender, BMI, waist circumference, family history of diabetes, smoking and alcohol consumption, acculturation was independently related to logarithm of HOMA (InHOMA) scores among USVI-born African Americans, but not among African-Caribbean immigrants. In contrast, among USVI-born African Americans psychosocial stress was not significantly related to InHOMA, while among African-Caribbean immigrants psychosocial stress was independently related to InHOMA in models that included BMI, but not in those which included waist circumference. This study suggests that acculturation and psychosocial stress may have a differential effect on body fat distribution and insulin resistance among native-born and immigrant blacks living in the US Virgin Islands.     

Competitive inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM

Competitive-inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM are described. These assays can be readily performed with commercial antisera and a recently developed method for purifying human IgA and IgM with high yield. The assays described are specific, with undetectable (<0.5%) cross-reactivity between the immunoglobulin classes in all systems, except with purified IgM, which cross-reacted to 1.9% with the IgG enzyme immunoassay.Minimal detectable concentrations of 2.5±0.8 ng/ml for IgG 4.2±0.9 ng/ml for IgA and 7.2±1.4 ng/ml for IgM were recorded, indicating that these assays are particularly sensitive. There is little within-assay variation (mean coefficient of variation = 3.9%), although the between-assay variation was substantially greater (mean coefficient of variation = 23.5%). These assay systems appear to be particularly suited to the measurement of immunoglobulin production by lymphocytes in culture. In such studies the assay must be specific, sensitive and be capable of discriminating between levels of immunoglobulin produced in response to various experimental treatments.     

Signalling during hypoxia in human T lymphocytes – critical role of the src protein tyrosine kinase p56Lck in the O2 sensitivity of Kv1.3 channels

T lymphocytes encounter hypoxia when they migrate to pathological sites such as tumours and wounds. The inability of T cells to provide an efficient defence at these sites can in part be explained by the hypoxic environment. Kv1.3 channels, important components of the T cell activation process are inhibited by hypoxia and their inhibition accounts for a hypoxia-induced decrease in T cell proliferation. Although Kv1.3 channels play a key role in T cell O₂ sensing, the signalling mechanisms mediating their response to hypoxia are still not understood. In this study, we show that the src-protein tyrosine kinase p56Lck (Lck) is required for Kv1.3 channel response to hypoxia. Pre-exposure to the src inhibitor PP2 abolished the hypoxia-induced inhibition of Kv1.3 channels in primary human T lymphocytes. Moreover, Kv1.3 channel sensitivity to hypoxia was lost in Lck-deficient Jurkat T cells. Further studies with recombinant Kv1.3 channels showed that Kv1.3 channels lack intrinsic O₂ sensitivity, but delivery of Lck into the cells and transfection of a constitutively active Lck (Y505FLck) restored their sensitivity to hypoxia. Although Lck is necessary for the Kv1.3 channel response to hypoxia, it does not directly inhibit Kv1.3 channels. Indeed, under normal oxygen tension, delivery of active Lck into L929 cells and overexpression of Y505FLck did not decrease recombinant Kv1.3 currents. On the contrary, activation of endogenous src kinases increased wild-type Kv1.3 currents in T lymphocytes. Our findings indicate that Lck is required for the acute response to hypoxia of human T lymphocytes as it is necessary to confer O₂ sensitivity on Kv1.3 channels.     

Physician assistant education in the United States.

As physician assistant (PA) programs developed in the 1960s, curriculum models emerged around the central themes of physician-dependent practice and competency-based education. By 2007, there were 136 accredited programs in the United States, with 108 (79%) offering a master-degree curriculum. PA program preclinical and clinical curricula are typically evenly divided in length, and the typical U.S. PA program has a full-time attendance curriculum of 26.5 continuous months. In academic year 2005-2006, the typical PA student was a 27-year-old white woman with a 3.4 overall grade point average and 29 months of prior health care experience who matriculated with a baccalaureate degree into a master-degree PA program. In the 2005 application cycle, the number of applicants per available seat was 2.25 for both allopathic medical schools and PA programs. The transition to a predominately master-degree curriculum resulted in new challenges for PA faculty development, and the number of PA educators with terminal academic degrees continues to lag behind the educational needs of training programs. The topic of PA specialty training and recognition remains controversial. Although the PA profession has prospered since inception, concerns exist regarding workforce issues such as the appropriate balance of autonomy and supervision, role delineation, and the continuing trend toward specialization. The omission or inaccurate classification of PAs within U.S. health care access and workforce literature projects an incomplete picture, and it is important to consider the contributions PAs have made and will continue to make in addressing the nation's health care needs.     

Effects of different speeds of induction with sevoflurane on the EEG in Man

The effects of two kinds of induction speed of sevoflurane anesthesia on the EEG pattern were compared in the same individual using medical student volunteers: a first exposure of 4% was given, followed after full recovery, by incremental doses of 1, 2 and 4% successively, each being administered for 10min. The arterial blood level of the anesthetic was measured using gaschromatograph. The changes of EEG pattern during fast induction with 4% were not represented by the abbreviation of those observed during the slow induction with the incremental doses. The administration of 4% induced a sudden appearance of high voltage, rhythmic slow waves of 2–3Hz at 1–3min when the arterial blood anesthetic level increased maximally, which was then followed by a pattern of faster activities of 10–14Hz mixed with 5–8Hz slow waves. In contrast, the administration of incremental doses induced an increase in frequency and amplitude of EEG activities in the light plane, followed by their decreases in deeper planes. The final EEG patterns were identical for both these methods of induction. These findings confirmed our previous hypothesis that not only the arterial blood level of anesthetics but the rate of its increase are important factors determining the EEG pattern of anesthesia.(Avramov MN et al.: Effects of different speeds of induction with sevoflurane on the EEG in man. J Anesth 1: 1–7, 1987)