Effects of a K+ATP channel opener, lemakalim, on systemic, coronary and regional vascular dynamics in conscious dogs: comparison with nifedipine, adenosine, nitroglycerin and acetylcholine

The systemic, coronary and regional vascular responses to the K+ATP channel opener lemakalim were compared to other potent vasodilators (i.e., nifedipine, adenosine, nitroglycerin and acetylcholine). Experiments were performed in 12 conscious dogs 2 to 4 weeks after implantation of aortic catheters and flow probes on the ascending aorta, left circumflex coronary, celiac, mesenteric, renal and iliac arteries, and solid-state miniature pressure gauges in the left ventricular cavity. Dose-response curves induced by bolus injection (i.v.) were examined. For doses that reduced total peripheral resistance by 22%, lemakalim reduced celiac (-28 +/- 2%), mesenteric (-24 +/- 3%), renal (-17 +/- 3%) and iliac (-18 +/- 3%) vascular resistances (i.e., by amounts similar to those observed with the other vasodilators, except for adenosine, which increased renal resistance). At these doses, lemakalim induced a greater decrease (-52 +/- 3%) (P < .05) in coronary resistance, as compared with nifedipine (-35 +/- 3%), adenosine (-38 +/- 3%), nitroglycerin (-25 +/- 2%) and acetylcholine (-32 +/- 3%). However, when near maximal vasodilation was elicited, adenosine elicited the greatest (P < .05) decrease in coronary resistance (-81 +/- 1%), as compared with lemakalim (-74 +/- 2%), nifedipine (-67 +/- 2%), nitroglycerin (-63 +/- 2%) and acetylcholine (-72 +/- 1%). Both the time to maximal increases in regional blood flow and the time for recovery in all vascular beds were significantly prolonged for lemakalim compared with the other vasodilators. Thus, the K+ATP channel opener lemakalim dilates the coronary bed out of proportion to other vascular beds, is relatively more potent at lower doses than other vasodilators and exhibits a delayed and more prolonged action in all regional vascular beds.     

Copy number differences in the 195 bp repeated satellite DNA from Trypanosoma cruzi and Trypanosoma rangeli: potential use for epidemiologic surveys

Detection of a nondistended pyriform sinus on cross-sectional imaging studies represents a diagnostic dilemma. The finding may be an inconstant physiologic phenomenon without clinical significance, or it may be due to tissue thickening and lack of pliability related to neoplasia or inflammation. Rescanning during respiratory maneuvers may clarify the anatomy, but full patient cooperation is needed. We demonstrate a method (turning the patient's head away from the side of the nondistended sinus) that induces distention of the pyriform sinus but does not require active patient participation.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection

Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle.     

Managing medical emergencies

A simple dental procedure can quickly escalate into a medical emergency. Management of six common emergencies is described.     

Antiserum against Escherichia coli J5 contains antibodies reactive with outer membrane proteins of heterologous gram-negative bacteria

The binding of IgG in antiserum to Escherichia coli J5 to the surface of Enterobacteriaceae and to cell wall fragments released from serum-exposed bacteria was studied in a search for potentially protective epitopes other than lipopolysaccharide (LPS). IgG titers to multiple heterologous gram-negative smooth bacteria increased following incubation of the bacteria in serum and decreased following absorption with serum-exposed heterologous bacteria. IgG eluted from absorbing bacteria bound to at least three conserved bacterial outer membrane proteins (OMPs), but not LPS, as assessed by immunoblotting. The same OMPs were present in LPS-containing macromolecular cell wall fragments released by incubation of heterologous gram-negative bacteria in human serum. Part of the protection offered by J5 antiserum could be from binding of IgG to conserved OMPs at the bacterial surface or to OMPs in cell-wall fragments released from dying bacteria.     

Recovery of SDS-protein and DNA using commercial automated gel electrophoresis apparatus

Forty-seven children afflicted with acute leukemia were studied at the Tata Memorial Hospital Bombay to record the occurrence of oral manifestations prior to and during chemotherapy. Lymphadenopathy was the most frequent single finding suggestive of leukemia during head and neck examination. Gingival abnormalities, bleeding gums and oral mucosal pallor were the other findings on initial oral examination. Due to immunosuppression caused by the chemotherapy drugs oral mucosal ulcerations, uncontrolled herpes, candidiasis and pseudomoniasis were observed.     

Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells

Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-alpha, IFN-beta, IFN-gamma, IL-2 or tumor necrosis factor (TNF)-alpha and, unlike the induction of IFN-gamma production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.