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31.
Experts agree that overweight and obesity pose a significant public health problem in the United States. Obesity is considered to be a complex, multifactorial disease involving genetics, physiology, psychology, and environment, and is influenced by cultural messages. Comorbidities linked to obesity include coronary heart disease, stroke, hypertension, diabetes mellitus, gout, dyslipidemias, cholecystitis, and gallstones. Pharmacists can help patients with dietary goals by understanding sound principles of weight management. 相似文献
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P Bytzer JM Hansen OB Schaffalitzky de Muckadell 《Canadian Metallurgical Quarterly》1995,157(7):893-897
This study compared two strategies for the management of dyspepsia: therapy based on prompt endoscopy (group 1) vs an empirical treatment strategy with diagnostic endoscopy only in case of therapeutic failure or symptomatic relapse within one year (group 2). Patients without jaundice, bleeding, anaemia, or a previously diagnosed ulcer and with symptoms severe enough to justify empirical H2-blocker therapy were included. Symptoms, drug consumption, and sick-leave days were evaluated through monthly diaries. Patients with non-organic dyspepsia did not receive ulcer drugs. Of 414 patients randomized, 373 completed one year follow-up. In 68 (33%) of the 208 group 1 patients organic disease was found at endoscopy (ulcer in 45 patients). Endoscopy was eventually performed in 136 (66%) of 206 group 2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy since the diagnostic profile was not altered and 40% of the presumed ulcer cases remained undiagnosed. After one year no differences in symptoms or quality of life measures were found. The empirical treatment strategy in dyspepsia was associated with higher costs, mainly due to increases in number of sick-leave days and in ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify H2-blocker treatment. 相似文献
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GM Knudsen S Hasselbalch PB Toft E Christensen OB Paulson H Lou 《Canadian Metallurgical Quarterly》1995,18(6):653-664
Blood-brain barrier permeability to phenylalanine and leucine in four patients with phenylketonuria and in four volunteers was measured five times by the double-indicator method at increasing plasma concentrations of phenylalanine. Based on the permeability-surface area product (PS) from blood to brain (PS1) and on plasma phenylalanine levels, Vmax and the apparent Km for phenylalanine were determined. Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the average Vmax value being 46.7 nmol/g per min and the apparent Km 0.328 mmol/L. Owing to saturation of the carrier, such a relationship could not be established in the patients. In phenylketonuria, PS1 for phenylalanine and leucine decreased significantly by 55% and 46%, respectively. Transport from brain back to blood, PS2, decreased significantly and cerebral large neutral amino acid net uptake was generally decreased in patients with phenylketonuria. In conclusion, the transport of L-phenylalanine across the human blood-brain barrier follows Michaelis-Menten kinetics. In phenylketonuria, brain permeability to large neutral amino acids is reduced by about 50% and net uptake appears decreased. 相似文献
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Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor 总被引:2,自引:0,他引:2
OB Goodman JG Krupnick F Santini VV Gurevich RB Penn AW Gagnon JH Keen JL Benovic 《Canadian Metallurgical Quarterly》1996,383(6599):447-450
The ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the beta2-adrenergic receptor (beta2AR). beta2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin. Ultimately the receptor undergoes internalization, and although the molecular mechanism is unclear, receptor phosphorylation and beta-arrestin binding have been implicated in this processs. Here we report that beta-arrestin and arrestin-3, but not visual arrestin, promote beta2AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits. Moreover, beta-arrestin/arrestin chimaeras that are defective in either beta2AR or clathrin binding show a reduced ability to promote beta2AR endocytosis. Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the beta2AR and beta-arrestin with clathrin. These results show that beta-arrestin functions as an adaptor in the receptor-mediated endocytosis pathway, and suggest a general mechanism for regulating the trafficking of G-protein-coupled receptors. 相似文献
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In patients with insulin-dependent diabetes mellitus while and yellow turpentine baths produced a positive effect on carbohydrate metabolism. White baths were more effective in respect to lipid metabolism, blood viscosity, produced a good effect on plasmic hemocoagulation factors. Both while and yellow turpentine baths were beneficial for capillary blood flow: initially high distal blood flow in patients with prevailing distal polyneuropathy decreased while in patients with macroangiopathy initially subnormal blood flow increased. Both white and yellow turpentine baths promoted better pulse blood filling of the lower limbs and weaker peripheral resistance of large vessels. In patients with non-insulin-dependent diabetes mellitus white and yellow turpentine baths contributed to normalization of carbohydrate metabolism. Yellow baths were more effective in lowering lipids. White baths induced inhibition of platelet aggregation but had no effect on coagulation, yellow baths promoted a reduction of fibrinogen but had no effect on platelet aggregation. Yellow baths produced more pronounced effect than white ones on blood viscosity and microcirculation. Both yellow and white baths stimulated pulse blood filling, corrected peripheral resistance of large and small vessels of the lower limbs. 相似文献
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GC Koo JT Blake A Talento M Nguyen S Lin A Sirotina K Shah K Mulvany D Hora P Cunningham DL Wunderler OB McManus R Slaughter R Bugianesi J Felix M Garcia J Williamson G Kaczorowski NH Sigal MS Springer W Feeney 《Canadian Metallurgical Quarterly》1997,158(11):5120-5128
The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation. 相似文献
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Loss of heterozygosity for 10q23-26 is seen in over 80% of glioblastoma multiforme tumors. We have used a positional cloning strategy to isolate a novel gene, LGI1 (Leucine-rich gene-Glioma Inactivated), which is rearranged as a result of the t(10;19)(q24;q13) balanced translocation in the T98G glioblastoma cell line lacking any normal chromosome 10. Rearrangement of the LGI1 gene was also detected in the A172 glioblastoma cell line and several glioblastoma tumors. These rearrangements lead to a complete absence of LGI1 expression in glioblastoma cells. The LGI1 gene encodes a protein with a calculated molecular mass of 60 kD and contains 3.5 leucine-rich repeats (LRR) with conserved flanking sequences. In the LRR domain, LGI1 has the highest homology with a number of transmembrane and extracellular proteins which function as receptors and adhesion proteins. LGI1 is predominantly expressed in neural tissues, especially in brain; its expression is reduced in low grade brain tumors and it is significantly reduced or absent in malignant gliomas. Its localization to the 10q24 region, and rearrangements or inactivation in malignant brain tumors, suggest that LGI1 is a candidate tumor suppressor gene involved in progression of glial tumors. 相似文献
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The effect of the corticoliberin 2-4 fragment--tripeptide Pro-Pro-Ile (PPI) inducing increase in epileptiform activity of mammal on T. molitor males behaviour has been studied. The "open field" method modified for insects has been used. PPI in doses of 30, 60, 100, 1000 micrograms/kg was injected in hemolymph of the beetles. The horizontal activity (HA), number of turns (TN) and other parameters were registered during 6 min. The tripeptide in dose 30 micrograms/kg was non-effective. PPI in doses 100 and, especially, 1000 micrograms/kg evoked stable decrease in HA that was observed as early as 0.5 h after injection. This effect lasted throughout 4-24 hrs and, apparently, induced by nonspecific action of high doses of the peptide. PPI in dose 60 micrograms/kg produced the significant intensification of stressogenic influence of experimental situation: in 2-4 hrs after injection the level of HA and TN increased. It is suggested that PPI can be regarded as an anxiogenic factor of insects. 相似文献
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