ABSTRACT
Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion.
Subject(s)
Brain Ischemia/drug therapy , Cerebrovascular Circulation/drug effects , Oxygen Consumption/drug effects , Reperfusion , Sirolimus/pharmacology , Sirolimus/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Antipyrine/analogs & derivatives , Antipyrine/pharmacokinetics , Blood Gas Analysis , Blood Pressure/drug effects , Carbon Isotopes/pharmacokinetics , Disease Models, Animal , Hemodynamics/drug effects , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Male , Oncogene Protein v-akt/metabolism , Rats , Rats, Inbred F344 , Signal Transduction/drug effects , Time FactorsABSTRACT
AIM: It is well known that vitamin D plays an important role in maintaining bone homeostasis and in regulating calcium absorption. The active form of vitamin D interacts with its receptor the VDR that is expressed in multiple tissues and it is involved in platelets (PLTs) function. In the present study we evaluate PLTs' VDR expression in osteoporotic as opposed to healthy subjects. METHODS: We enrolled in the study 77 women with postmenopausal osteoporosis, 33 healthy women of childbearing age, 49 healthy men, and 11 healthy women matched with patients for age and postmenopausal period. Thirty-nine patients had had one femoral fracture occurred after the age of fifty and attributable to primary osteoporosis. Bone mineral density, markers of bone metabolism and VDR levels were measured in all the subjects. RESULTS: Our data show that VDR level is lower in patients as respect to controls and is positively correlated with bone density, but not with markers of bone metabolism. We also found a decrease in the phosphorus levels in patients without differences in vitamin D levels and in the dietary calcium intake. CONCLUSION: The lower VDR expression in osteoporotic could indicate a lower ability to respond to vitamin D, and could be the explanation of the increase in the PTH and decrease in the phosphorus levels in patients with respect to controls.
Subject(s)
Blood Platelets/cytology , Osteoporosis/metabolism , Receptors, Calcitriol/metabolism , Vitamin D/metabolism , Adult , Aged , Blood Platelets/metabolism , Bone Density , Bone and Bones/metabolism , Dose-Response Relationship, Drug , Female , Femoral Fractures/metabolism , Humans , Male , Middle Aged , Phosphorus/metabolismABSTRACT
BACKGROUND: Hepatitis C virus is the most important aetiologic agent for non A-non B hepatitis. The study of the prevalence of hepatitis C in health care workers is of primary interest because of the possible chronic evolution and the risk of cirrhosis and liver cancer. OBJECTIVES: The purpose of this study was to determine the prevalence of HCV among health care workers in 5 main hospitals and local health units in Turin and analyze the influence of occupational and non occupational risk factors. METHODS: Health care personnel were administered anonymous questionnaires and testing for anti-HCV antibody was performed. RESULTS: Prevalence rates in 4517 health care workers was 1.97%; the prevalence was higher in elderly workers (> 45 years) than in younger ones. The risk analysis did not reveal any significant correlation between HCV seroconversion and accidental blood exposure. However, a significant correlation was found with non-occupational risk factors. Unapparent infection was an unimportant risk factor for seroconversion. CONCLUSIONS: Hepatitis C prevalence in the population under study was comparable to that found in the general population. These results point to the need to reconsider the assumption that there is an increase of risk of seroconversion for health-care workers, in the absence of any occupational accidental exposure to hepatitis C virus.
