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Biomedical subjects

J Neuman

Publications and source records attributed to J Neuman.

At least 19 recordsLinked to original sources
PubMed1992

Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury.

To test directly whether mitochondrial Mn-superoxide dismutase (Mn-SOD) protects the lung epithelium from oxygen-induced injury, transgenic mice were produced in which the expression of human Mn-SOD mRNA was directly by transcriptional elements from the human pulmonary surfactant protein C gene. Human Mn-SOD mRNA was expressed in a lung-specific manner, and increased Mn-SOD protein was detected within mitochondria of alveolar Type II and nonciliated bronchiolar cells of the distal respiratory epithelium of the transgenic mice. The activity of Mn-SOD, but not catalase, CuZn-SOD, or glutathione peroxidase, was increased in lungs of transgenic mice. Transgenic mice were highly protected from lung injury during exposure to 95% oxygen, surviving significantly longer than nontransgenic littermates. Pulmonary pathology demonstrated decreased hemorrhage, hyaline membrane formation, and alveolar and interstitial edema in transgenic animals. The finding that increased Mn-SOD in distal respiratory epithelial cells confers protection from oxygen injury provides a basis for novel therapies to protect lung from injury during oxygen therapy of acute and chronic lung diseases.

Animals↗
PubMed1991

Significant increase of high-density lipoprotein2-cholesterol under prolonged simvastatin treatment.

In a contribution to a prolonged multicenter study 15 patients with primary hypercholesterolemia were treated with simvastatin, a competitive inhibitor of HMG-CoA reductase. The first part of the study was done in a double-blind fashion comparing the effect of this new drug with that of gemfibrozil during 12 weeks, and after this period on open-label treatment was started with the administration to all the patients of simvastatin in doses ranging from 2.5 to 40 mg q.p.m. Persistent and significant reductions (P less than 0.001) were achieved for total serum cholesterol (TC), LDL-cholesterol (LDL-C), apo B and triglycerides: by 38, 49, 44 and 33%, respectively, after 40 weeks of the open-label extension. From week 12, LDL-C levels were maintained at a cut point less than or equal to 140 mg/dl in every patient throughout the study. At week 40, cholesterol values of HDL subfractions showed a significant increase in HDL2-C (28%, P less than 0.01) and a concomitant reduction in HDL3-C (12%, P less than 0.01) in spite of a nonsignificant elevation of total HDL-C (by 6%). The HDL2-C/HDL3-C ratio rose by 47% (P less than 0.001) and the TC/HDL-C ratio was significantly reduced by 43%: from 6.1 +/- 1.2 to 3.5 +/- 0.7 (mean +/- SD, P less than 0.001). No adverse effects were detected. Our results suggest a conversion of HDL3 into HDL2, which could imply a beneficial effect of simvastatin upon the so-called reverse cholesterol transport, in addition to the striking reduction in atherogenic lipoproteins.

Aged↗
PubMed1990

Evaluation of the high density lipoprotein cholesterol protective effect against atherogenesis in rabbits fed cholesterol supplemented diets.

Plasma high density lipoprotein cholesterol (HDL-C) was evaluated in 15 rabbits fed cholesterol supplemented diets to assess its protective effect on the atherogenic process. From a baseline level of 29 +/- 11 mg/dl (mean +/- SD) the maximum attained for HDL-C was twofold in only three rabbits, whereas total cholesterol (TC) increased 20 fold. Plasma TC/HDL-C ratio rose 80 fold from the baseline (2.4 +/- 0.9) and it was the best parameter that correlated with aortic cholesterol accumulation and pathological scores. Aortic TC content increased 10 fold and free cholesterol/cholesterol esters ratio decreased 20 fold. Pathological studies showed that aortic lesion scores rose from 0 to 4. It can be concluded that the high correlations obtained when TC/HDL-C ratio was plotted against both aortic cholesterol deposition and lesion scores, support the theory of the reverse cholesterol transport and the effectiveness of this index to predict the degree of the atherogenic process. On the other hand, the poor response of HDL-C in this model encourages future research using drugs to increase this parameter in order to normalize TC/HDL-C ratio and avoid lesions.

Animals↗
PubMed1987

Treatment of acute myocardial infarction with subcutaneous heparin at low doses.

Heparin has been used intensively in the treatment of acute myocardial infarction and preinfarction angina (PA) at full doses as a single drug by us. However, heparin may be used at smaller doses for similar purposes. These doses are not exactly anticoagulant, even though they reduce blood hypercoagulability, and act mainly in an antithrombotic capacity. We studied 529 patients with acute myocardial infarction, of whom 262 were treated with subcutaneous heparin at low doses (5000 IU every 12 h) and 267 received conventional therapy without antithrombotic drugs. Heparin used was Heparina (Abbott) and Liquemine (Roche), in vials with the equivalence 1 cm3 = 50 mg = 5000 IU. Blood rheologic factors (thromboelastography, platelet adhesiveness, total blood viscosity, and number of platelets) were determined in all patients, those treated with heparin at low doses and also the control group, before and after the 30-day treatment period. Diagnosis was based on clinical symptoms, laboratory studies, and electrocardiogram examination. In both the 262 patients treated with heparin at low doses and in the control group of 267 patients, baseline values of rheological factors were high. After 30 days (i.e., after study completion) these high values which are statistically significant compared with normal values, with p less than 0.0001 for both groups, remained constant in the control group who did not receive heparin. On the contrary, in the group treated with heparin at low doses, all these factors changed. Heparin provides protection against thrombosis by increasing the negative charge of the vessel wall and by other reactions at the endothelial surface. Heparin requires a plasmatic component called antithrombine III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Pilot study of the effect of raubasine on platelet biological activity.

A pilot study was carried out to determine the action of raubasine (ajmalicine) an alkaloid derived from Rauwolfia serpentina, on platelet biological function in 14 patients selected because they were at risk due to complications of atherosclerosis. The determinations of platelet aggregation were done ex vivo and the following substances were used as inducing agents: adenosine diphosphate (2.5 and 5.0 X 10(-6) mol/l), collagen (0.05 mg/ml), and epinephrine (adrenaline) (1.68 X 10(-4) mol/l). 12 out of the 14 patients treated showed a reduction in platelet aggregation in at least 2 of the 3 test curves. This reduction was statistically significant for collagen (p less than 0.02) and epinephrine (p less than 0.01). A statistically significant (p less than 0.05) prolongation of the latency period of aggregation produced by collagen was found in 12 out of 14 patients and a prolongation of recalcification time produced by the reduction in platelet factor 3 was found in 9 out of 14 patients. In addition to the fact that the effect of a reduction in platelet aggregation was more evident in the second wave, these results suggest that raubasine has an inhibitory action on the release reaction of the platelets. The results obtained merit further study to confirm this property of the drug.

Adult↗
PubMed1986

Effect of bezafibrate on low levels of high density lipoprotein cholesterol in normolipidemia. Study in coronary patients and their first degree relatives.

A pharmacological study was carried out in a group of 20 subjects composed of 13 coronary patients and 7 normal close relatives (first degree) who were considered at a high risk for coronary heart disease (CHD) because of their low levels of high density lipoprotein cholesterol (HDLch) (mean +/- SD: 34.1 +/- 5.2 mg/dl) and their high total cholesterol/HDLch (Tch/HDLch) ratio (mean +/- SD:6.7 +/- 1.1), despite their normal serum lipid values. With the purpose of normalizing these parameters they were submitted to a 4-month treatment with bezafibrate, a hypolipidemic agent which has a known effect in increasing HDLch and in decreasing the Tch/HDLch ratio. At the end of the study total serum cholesterol and triglycerides decreased significantly by 10 and 30%, respectively (p less than 0.01). HDL increased in its cholesterol content by 33% reaching a value of 45.4 +/- 9.8 mg/dl (mean +/- SD, p less than 0.01) as well as in its apolipoprotein A1 (Apo A1) content (13%, p less than 0.02). HDL2 subfraction also rose in cholesterol and in Apo A1: by 90 and 38%, respectively (p less than 0.01). HDL3 subfraction rised only its cholesterol content by 24% (p less than 0.01). Tch/HDLch ratio was significantly reduced (p less than 0.01) to a value of 4.6 +/- 0.9 (mean +/- SD). Total serum Apo B diminished by 14% (p less than 0.01). No adverse effects were observed during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Elevation of high density lipoprotein cholesterol (cHDL) and reduction of the total cholesterol/cHDL index in the treatment of hyperlipoproteinaemias IIb and IV with bezafibrate.

A study was carried out in 21 patients with Type IIb or Type IV hyperlipoproteinaemia to evaluate the effect of treatment with 600 mg bezafibrate per day over a period of 3 months. The results of the lipid parameters studied showed that there were significant reductions after 1 and 3-months' treatment, respectively, of 19% and 16% total cholesterol, 55% and 57% triglycerides, 19% and 15% calculated cLDL, and 55% and 58% calculated cVLDL. Over the same times, there was a significant increase in cHDL of 35% and 41%, respectively. The cT/cHDL index decreased significantly from a mean basal value of 7.81 +/- 1.44 to 4.76 +/- 0.96 after 1 month and to 4.75 +/- 0.90 after 3 months, corresponding to a 39% reduction in both instances. This index was reduced to 5.0 or less in 76% of the patients. At the end of the trial there was normalization of hyperlipoproteinaemia in 17 (81%) of the 21 patients. Tolerance of bezafibrate was satisfactory. Only 2 patients suffered mild abdominal pain, which disappeared within a few days. One patient presented slight, transitory neutropenia at the end of the 3 months of treatment.

Adult↗
PubMed1978

Oropharyngeal excretion of Epstein-Barr virus by patients with lymphoproliferative disorders and by recipients of renal homografts.

In an attempt to associate oropharyngeal excretion of Epstein-Barr (EB) virus with lymphoproliferative disorders other than infectious mononucleosis, we tested throat gargles collected from adult subjects for the EB virus. Nine (16%) of 55 healthy persons were positive. High EB virus-excretion rates were found among patients with active acute lymphocytic leukemia (6/6, 100%), among renal homograft recipients during the third to 12th month after transplantation (26/30, 87%), and among critically ill patients with leukemia-lymphoma (14/19, 74%). Moderately high excretion rates were found among patients with myeloma (7/16, 44%), patients with poorly differentiated lymphocytic lymphoma (5/11, 44%), critically ill patients with solid cancers (15/37, 41%), and patients with chronic myelogenous leukemia (8/21, 38%). Our data suggested that the higher than normal excretion rate is realted to the basic disease process and to the general health status but not to the duration of cancer chemotherapy.

Antineoplastic Agents↗
PubMedDate not supplied

The response of contractile and non-contractile vacuoles of Paramecium calkinsi to widely varying salinities.

Paramecium calkinsi from tidal marshes survive a wide salinity range. Fluid output of contractile vacuoles of these cells decreased as salinity of the medium to which they were acclimated increased, and both pulse rate and vacuole volume were used to regulate output. When cells were first exposed to more dilute medium, contractile vacuoles greatly increased volume so that fluid output increased even though pulse rate decreased. In cells shifted to a more concentrated medium, contractile vacuole output decreased by decreasing pulse rate. The contractile vacuole is surrounded by a set of collecting structures which change form as the salinity changes. Distensible ampullae are found in media of low salinity and collecting canals are found in media of high salinity. When cells are shifted from high salinity to low, the number of ampullae increases and the number of canals decreases. When cells are shifted from low salinity to high, the number of ampullae decreases and the number of canals decreases. Other non-contracting vacuoles also appear in response to a hypoosmotic shock. These include vacuoles within the cell as well as "blisters" on the surface. The number and frequency of blisters increases with the size of the hypoosmotic shock. They detach from cells without resulting in any visible loss of cytoplasm. Non-contractile vacuoles may play a role in sequestering and removing excess water that the contractile vacuoles cannot handle.

Adaptation, Physiological↗