Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.
Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.
Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. 相似文献
The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes. 相似文献
The epidemiology of non-A, non-B hepatitis (NANBH) is still incomplete. To define the prevalence of antibodies against the main causative agent of NANBH, the hepatitis C virus (HCV) and the role of some risk factors, we tested sera from 269 patients on chronic dialysis at the hemodialysis units in our region in central Italy. We utilized the recently developed serological assay. Twenty-nine hemodialysis patients (13.3%) and 3 peritoneal dialysis patients (4.8%) were anti-HCV positive. Of these, 13 (40.6%) had antibodies to hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection. The anti-HCV seropositive patients had been on dialysis longer than the seronegative ones; they had received more transfusions than the others but without a significant difference. The prevalence rate of anti-HCV was statistically significantly higher among hemodialysis patients utilizing the same dialysis equipment for the previous 12 months. 相似文献
Transformation of cloned rat embryo fibroblasts (CREF) with the T24-ras oncogene results in loss of contact inhibition, growth in soft agar and tumor formation in nude mice. Previously we showed that in such cells (CREF T24), the phosphorylation rate of protein synthesis initiation factor 4E (elF-4E) is increased, correlating with an increase in the general rate of protein synthesis. In the present study, we have expressed antisense RNA complementary to elF-4E mRNA in CREF T24 cells using a stably integrated vector. Cells expressing antisense RNA (CREF T24/AS) contained 30-50% of the normal level of elF-4E and exhibited many of the properties of untransformed cells. CREF T24 had a spindle-shaped, refractile appearance, whereas CREF T24/AS grew in ordered, parallel patterns and exhibited contact inhibition similar to untransformed CREF. The rates of growth and protein synthesis in CREF T24/AS were decreased compared to CREF T24 but were not as low as in CREF. The efficiency of growth in soft agar was 11-fold lower for CREF T24/AS compared with CREF T24. The latency period for tumor formation in nude mice was increased from 8 days for CREF T24 to 17-27 days for CREF T24/AS and various clonal lines derived from them. Cell lines established from these CREF T24/AS-derived tumors were shown to have partially regained the elF-4E levels characteristic of CREF T24. These results demonstrate that many of the phenotypic alterations associated with ras-induced malignant transformation can be reversed by a moderate reduction of the translational initiation capacity and therefore may be mediated through a translational mechanism. 相似文献
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism. 相似文献
Several reports show that the prevalence of HBV (hepatitis B virus) carriers in HIV (human immunodeficiency virus) infected populations is significantly higher than in HIV seronegative individuals, independent of the risk group for HIV, that is, homosexuals or drug abusers. In this context, evaluation of the simultaneous presence of HBV and HIV in PBMCs (peripheral blood monuclear cells) is of particular interest for at least 2 reasons: 1) the possible reciprocal influence of the 2 viruses when they infect the same cell; 2) the possibility that HIV-iduced hematological disorders could indirectly influence the settling of HBV in blood cell populations. We report data on the frequency of PCR positivity for HBV DNA in PBMCs from 62 HIV infected patients, rigorously selected by risk group, that is, intravenous use of heroin for at least 3 years and syringe promiscuity. Sixtyseven HIV negative individuals who never used any drug formed the control group. The analysis of the cases positive for HBV DNA in PBMCs showed that 1) the overall prevalence of PCR positivity found in HIV infected patients was significantly lower than that registered in the control group; 2) PCR positivity among the subjects who were HBsAg negative and anti-HBV positive was extremely low in the HIV infected patients (3.7%) but quite frequent in the HIV negative subjects (37.0%). The results support the hypothesis that, unlike the HIV negative individuals, our HIV infected patients exhibited HBV DNA in PBMCS almost exclusively when they presented with active HBV replication. 相似文献