High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16GIy and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects. 相似文献
The midportion of the anterior cruciate ligament (ACL) of rabbits was partially transected, and the effect of hyaluronan (HA) on its healing was determined. A 1% solution of HA (HA group) or physiological phosphate-buffered saline (control group) was administered intraarticularly, at 0.1 ml/kg body weight, once a week from 1 week after the operation. Two, 4, and 6 weeks after the initiation of HA administration, the ACLs were examined grossly, histologically and immunohistochemically. At 2 weeks, the lacerated portions were completely covered with scar-like tissue in both groups. These tissue areas were smaller in the HA group than in the control group. Histologically in the HA group, the regularity of collagen fibers (indicating the maturity of regenerated collagen fibers) had increased compared to findings in the control group, and the number of fibroblastic cells decreased gradually at a significantly faster rate. The number of inflammatory cells and blood vessels decreased gradually in both groups, with these values being lower in the HA group at each time point but not significantly so. Immunohistochemical examination of the repaired tissue revealed strong staining with anti-chondroitin sulfate proteoglycan antibody in the HA group 2 weeks after the first HA administration. The staining gradually became reduced, with the rate of reduction being faster in the HA group than in the control group. The stimulation of chondroitin sulfate proteoglycan production and the faster reduction of it in the HA group suggests that HA facilitated tissue repair and inhibited the formation of scar tissue. 相似文献
The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca2+-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity. 相似文献
A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid. 相似文献
A number of 2-substituted 4,5-diphenylthiazoles were synthesized by the nucleophilic substitution of 2-methylsulfonyl-4,5-diphenylthiazole with various sodium alkoxides, amines, and carbanions of active methylene compounds. 2-Methylsulfonyl-4,5-diphenylthiazole was obtained by the potassium permanganate oxidation of 2-methylthio-4,5-diphenylthiazole in the presence of a phase-transfer catalyst. 2-Ethoxy-4,5-bis(4-methoxyphenyl) thiazole was prepared in a similar manner. 2-Ethynyl-4,5-diphenylthiazoles were synthesized by the palladium catalyst cross-coupling reaction of 2-iodo-4,5-diphenylthiazole with monosubstituted acetylenes. These compounds were tested for inhibitory activity against blood platelet aggregation in vitro. Among them, 2-alkoxy-, and 2-(4-methylpiperazin-1-yl)-4,5-diphenylthiazole were found to have potent inhibitory activity. 相似文献
Upon autopsy of mice injected with the crown-of-thorns starfish (Acanthaster planci) lethal factor, a change in color of the liver, swelling of the gall bladder and jaundice were observed. After administration of the lethal factor into mice, activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), acid phosphatase (ACP) and alkaline phosphatase (ALP) were significantly elevated in serum. Hepatic ALP also increased markedly but hepatic GOT, GPT and ACP showed a tendency to decrease. Activity of hepatic LDH first decreased and then returned to control level. Histopathological studies showed that severe degenerative changes such as enlargement and necrosis of hepatocytes were caused in the mouse liver by the lethal factor. These results strongly suggested that the A. planci lethal factor is a potent hepatotoxin. 相似文献
Background: Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.
Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.
Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity. 相似文献
We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload. 相似文献