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Biomedical subjects

A Maran

Publications and source records attributed to A Maran.

49 records · Page 3Linked to original sources

Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment.

We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients (plasma glucose less than 10 mM). We studied 10 nonobese NIDDM patients in a crossover, randomized, double-blind, placebo-controlled fashion. Each patient was studied 4 times: after a run-in period with placebo, after 3 mo of placebo treatment, after 3 mo of glibenclamide treatments, respectively, and after 3 mo of sulfonylurea treatment during an acute exogenous Intralipid infusion. Ten normal, nondiabetic subjects served as the control group. Glibenclamide treatment decreased plasma FFAs. When these substrates were exogenously increased, plasma FFAs were comparable with placebo and baseline concentrations. In NIDDM patients, baseline and placebo blood total KB concentration was significantly higher than in control subjects (216 +/- 22 and 244 +/- 25, respectively vs. 127 +/- 18 microM; P less than 0.01). Glibenclamide treatment significantly decreased total KBs to 177 +/- 19 microM (P less than 0.05). When FFAs were exogenously increased, total KBs were similar to the placebo and baseline period. In the baseline study, the AcAc/3-BOH ratio was 0.72 +/- 0.06 in control subjects, whereas in NIDDM patients, the ratio was 1.61 +/- 0.13 at baseline (P less than 0.001 vs. control subjects), 1.66 +/- 0.15 during placebo, 1.57 +/- 0.09 during glibenclamide (NS vs. baseline), and 1.51 +/- 0.23 during glibenclamide plus placebo FFAs. Both the AcAc interconversion rate to 3-BOH and the 3-BOH interconversion rate to AcAc were significantly lower in NIDDM patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of chronic alcohol intake on carbohydrate and lipid metabolism in subjects with type II (non-insulin-dependent) diabetes.

PURPOSE: To study the effects of chronic alcohol intake on carbohydrate and lipid metabolism in subjects with non-insulin-dependent (type II) diabetes (NIDDM). To also evaluate the effect of alcohol withdrawal on metabolic control. PATIENTS AND METHODS: The study group consisted of 46 alcohol-consuming patients with NIDDM (NIDDM-B group), 35 non-alcohol-consuming patients with NIDDM (NIDDM group), and 40 normal control subjects. All patients were admitted to the hospital. Carbohydrate and lipid metabolism was assessed in these individuals immediately on admission to the hospital and during the following days. RESULTS: In the NIDDM-B group, blood alcohol (ethyl alcohol) concentration was very low. However, chronic alcohol intake was associated with higher fasting and postprandial glucose concentrations and higher hemoglobin A1c. No significant differences were found in C-peptide levels. Moreover, higher concentrations of 3-hydroxybutyrate and free fatty acids were observed in the NIDDM-B group than in the NIDDM group. No differences were found in triglyceride concentrations, acid-base patterns, or electrolyte levels. The metabolic effects of alcohol completely waned after 3 days of complete withdrawal. CONCLUSION: Chronic alcohol intake causes deterioration in metabolic control of persons with NIDDM. The effects induced by alcohol are completely reversed after a few days of withdrawal. Strict metabolic assessment is necessary when alcohol is an important constituent of the diet.

3-Hydroxybutyric Acid↗

Induction of c-Ha-ras gene expression by double-stranded RNA and interferon requirement.

The addition of double-stranded RNA (dsRNA) to NIH 3T3 cells led to an increase in the RNA levels of c-Ha-ras. The double-stranded configuration was required for the increase in c-Ha-ras mRNA levels, as heat-denatured dsRNA and single-stranded RNA did not have any effect. Nuclear run-on transcription experiments indicated that the increase in c-Ha-ras mRNA levels stimulated by dsRNA was due to transcriptional activation of the gene. The induction of c-Ha-ras gene expression by dsRNA was inhibited by anti-beta interferon antibodies, suggesting that interferon might mediate the induction.

Animals↗

Endocrinologic and metabolic manifestations of the acquired immunodeficiency syndrome.

The endocrine abnormalities associated with acquired immunodeficiency syndrome (AIDS) are reviewed. These include adrenal insufficiency, hyporeninemic hypoaldosteronism, panhypopituitarism, hypogonadism, and alterations in thyroid function tests. AIDS-related infections or neoplasms may lead to hypercalcemia, whereas malabsorption may cause hypocalcemia. The possibility that AIDS-associated cachexia and hypertriglyceridemia may be caused by cachectin (tumor necrosis factor) is discussed, along with possible therapy for cachexia with megestrol acetate. Ketoconazole, sulfonamides, and pentamidine have specific, potentially deleterious metabolic effects when used in AIDS patients. Because treatment of endocrinological abnormalities of AIDS is often effective, improved diagnosis and appropriate therapy of these abnormalities will result in improved quality of life and, possibly, longer survival of patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Characterization of the double-stranded RNA implicated in the inhibition of protein synthesis in cells infected with a mutant adenovirus defective for VA RNA.

In the absence of VA RNAI, protein synthesis in adenovirus-infected HeLa cells fails at late times of infection because of defective initiation. The defect is due to the activation of a protein kinase that phosphorylates the alpha-subunit of initiation factor eIF-2. The kinase responsible for the translational defect is DAI, the double-stranded RNA (dsRNA)-activated inhibitor of protein synthesis, which is present in uninfected HeLa cells at a basal level and in a largely inactive, latent state. In vitro it can be activated by incubation with ATP and low concentration of dsRNA. Previous studies suggested that RNA generated during the course of infection can activate DAI. We show here that the activator RNA has the properties of dsRNA: it chromatographs with dsRNA, can be denatured and reannealed, and is destroyed by a dsRNA-specific nuclease. At least some of the dsRNA is viral. It hybridizes to DNA sequences in the center of the viral genome, principally between map units 47 and 51 and 73 and 76, consistent with an origin in the symmetrical transcription of both viral DNA strands.

Adenosine Triphosphate↗

Pleuroperitoneal shunting for recalcitrant pleural effusions.

From March 1, 1984, to Nov. 1, 1985, six patients underwent pleuroperitoneal shunting for either malignant (n = 5) or benign (n = 1) effusions intractable to the usual therapy. A modified double-valve Denver peritoneovenous shunt was inserted under local anesthesia in each case, and fluid from the right or left pleural space was shunted to the subhepatic space or pelvic area. No early complication was recognized in the perioperative period. Each shunt is working in the patients who are alive, and both functioned up to the time of death in the two who have died. Intraoperative pressures simultaneously recorded from both the chest and abdomen indicated that spontaneous flow would not occur without active pumping. All pleural effusions, including the solitary bilateral one, were alleviated by pumping the shunt 20 times four times a day. Two of the patients with cancer died after 1 and 2 months of unrelated events, with their symptomatic pleural effusions relieved. Two are alive at 20 and 10 months, respectively. The long-term follow-up revealed no erosions, shunt failures, infections, or symptomatic pleural effusions.

Follow-Up Studies↗

Action of Pennisetum typhoides double-stranded ribonuclease on viral ds RNAs.

A ribonuclease that preferentially cleaves natural and synthetic double-stranded (ds) RNAs has been partially purified from Pennisetum typhoides. The enzyme degrades [3H]poly(rA) X poly(rU) to acid-soluble products. The ds RNase does not degrade RNA:DNA hybrid but appears to have about 18% activity against single-stranded (ss) RNAs under the assay conditions used for the cleavage of ds RNAs. The RNase has a molecular weight of 35,000 daltons as determined from gel filtration using Sephadex G-200. The ds RNase shows an absolute requirement for divalent cations Mg++ or Mn++ and monovalent cations K+ or Na+. The specificity of the enzyme towards ds RNA template is supported by the inhibition of cleavage of ds RNAs by ethidium bromide and Penicillium chrysogenum viral ds RNA. The enzyme preparation acts on ds RNAs isolated from Saccharomyces cerevisiae and P. chrysogenum virus. The purified ds RNase also cleaves the in vitro transcriptional products of adenovirus DNA and this activity is inhibited by 5 mM ethidium bromide suggesting that ds regions of adenovirus RNA are involved in the cleavage process.

Adenoviridae↗

Double-stranded RNA specific nuclease from germinating embryos of Pennisetum typhoides.

A double-stranded RNA specific nuclease (ds RNase) has been purified from the pearl millet Pennisetum typhoides. The purification involved S-30 preparation from the germinating embryos, DEAE-cellulose and DNA-cellulose chromatography. The partially pure enzyme preferentially solubilized the synthetic double-stranded polynucleotide [3H]poly(rA) . poly(rU); the degradation of [3H]poly(rC) was fourteen fold lower under the same assay conditions. Furthermore, the ds RNase activity was inhibited to an extent of 58% by ethidium bromide, which is known to intercalate with double-stranded RNAs. Active sulfhydryl groups were found to be necessary for the ds RNase activity since the enzyme action was inhibited by N-ethylmaleimide. Ethidium bromide and N-ethyl-maleimide did not significantly inhibit the ss RNase activity. In contrast, diethyl pyrocarbonate inhibited ss RNase activity completely and ds RNase by 58%. Heating the enzyme for 20 min at 50 degrees C resulted in drastic loss of both enzyme activities. The ds RNase showed maximum activity in the pH range of 6.5 to 7.5. The enzyme acts in vitro on E. coli 30S precursor ribosomal RNA and the cleavage products migrated in the region of mature 23S and 16S rRNAs.

Endoribonucleases↗

Partial purification and characterization of a double-stranded RNA-specific nuclease from human placenta.

A double-stranded RNA-specific nuclease (ds RNase) has been isolated and partially purified from human placenta by DEAE-cellulose and DNA-cellulose column chromatography. Denatured DNA-cellulose retained most of the single-stranded RNA-specific nuclease (ss RNase) activity, whereas the ds RNase came out in the void volume. N-ethylmaleimide at a concentration of 5 mM, selectively inhibited ds RNase activity by 60% under the conditions in which the ss RNase activity was inhibited to an extent of 7%. The ds RNase was specifically inhibited by Penicillium chrysogenum viral ds RNA and by ethidium bromide. The partially purified ds RNase showed requirements for Mg+ whereas Mn2+ and NH4+ ions were inhibitory. The DEAE-enzyme cleaved 32P-labelled 45S ribosomal precursor RNAs from Yoshida ascites sarcoma cells into species that had similar electrophoretic mobilities as the mature rRNAs.

Ammonia↗

Nasal histamine and heparin in chronic rhinitis.

Histamine and heparin, both free and cellular, were assayed in the nasal mucosa of 11 atopic and 15 nonatopic patients undergoing turbinectomy for chronic rhinitis. There was no significant difference between the free and cellular histamine levels of the atopic and nonatopic patients. There was also no significant difference between the free heparin levels of atopic and nonatopic patients. Mean cellular heparin was, however, significantly greater in the nonatopic group. This finding, together with the results of mast cell counting, suggests either that in atopic patients heparin stores are already depleted prior to turbinectomy, or that in nonatopic individuals nasal mast cells contain an excess of heparin in nonreleasable stores.

Adult↗

[Frequent occurrence of diabetes mellitus after corticosteroid treatment in mixed cryoglobulinemia. An HCV-related complication?].

The hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations in many individuals. Among these, diabetes mellitus (DM) can be included, as such a metabolic disorder has been demonstrated to be more frequent in chronic hepatitis C than in liver disease due to other causes. Recently, we have observed that most patients affected with HCV-associated mixed cryoglobulinemia (13 out of 15, 86.7%), that were at baseline normoglycemic, developed DM following corticosteroid treatment (prednisone > 25 mg/daily) for at least three months. Conversely, when we consider a control group including 36 HCV negative patients affected with various immunomediated disorders, i.e., systemic lupus erythematosus, myasthenia gravis, poly/dermatomyositis and chronic inflammatory demyelinating polyneuropathy, that were initially normoglycemic, corticosteroid induced DM (prednisone > 25 mg/daily for at least three months) occurred only in 16.7% of subjects. Moreover, in other two HCV positive patients suffering from myasthenia gravis, prolonged corticosteroid treatment was complicated by DM. These data, that are still unclear from a pathophysiologic viewpoint, seem to indicate corticosteroid induced DM as a further, unusual extra-hepatic manifestation of the HCV infection.

Adult↗