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Biomedical subjects

A M Gonzalez

Publications and source records attributed to A M Gonzalez.

89 records · Page 5Linked to original sources
PubMed1986

Effect of aldose reductase inhibitor (sorbinil) on integration of polyol pathway, pentose phosphate pathway, and glycolytic route in diabetic rat lens.

This study examines the effect of an aldose reductase inhibitor (sorbinil) on the flux of specifically labeled glucose through alternative pathways of metabolism in the lens of normal and diabetic rats 1 wk after the induction of diabetes with alloxan. In the diabetic rat lens, there was an apparent increase in the flux of glucose through the pentose phosphate pathway (PPP), as measured by the difference in the yields of 14CO2 from [1-14C]glucose and [6-14C]glucose [C1-C6], this value was 0.087 +/- 0.005 and 0.263 +/- 0.034 mumol X g lens-1 X h (mean + SE of 6 values) for control and diabetic rats, respectively; sorbinil treatment decreased the values to 0.065 +/- 0.008 and 0.171 +/- 0.028, respectively. With glucose tritiated on carbon 2 or 3, it has been shown that the flux of glucose through the polyol route is increased, whereas the flux through the glycolytic pathway is decreased in the diabetic rat lens; both are restored toward normal in the sorbinil-treated diabetic group. These results suggest that the dual effects of diabetes in increasing the lens content of glucose and glucose 6-phosphate and the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens. The inhibition of aldose reductase by sorbinil tends to normalize the redox state of the nicotinamide nucleotides, reimposing the NADPH limitation on the PPP and increasing the availability of NAD+ for the glycolytic route.

Aldehyde Reductase↗
PubMed1985

Preventive treatment of cerebral transient ischemia: comparative randomized trial of pentoxifylline versus conventional antiaggregants.

A comparative study of the prevention of recurrences of cerebral transient ischemic attacks during a 6-month observation period was conducted in 73 patients treated with a combination of acetylsalicylic acid and dipyridamole (ASAD, 1,050 mg + 150 mg/day) and in 65 patients treated with pentoxifylline (PTX 1,200 mg/day, Trental 400 t.d.s.). The patients were randomly assigned to the treatments. Risk factor analysis showed high prevalence of arterial hypertension, hyperlipidemia and smoking in these patients. The two groups were matched in terms of age, sex, blood pressure and site of TIA origin (carotid 63% in the ASAD, 65% in the PTX group). 23 ASAD patients and 9 PTX patients suffered a recurrence. There were 4 nonfatal stroke events with ASAD and 2 with PTX. 80 recurrent TIAs were recorded in 19 ASAD patients compared with 19 such episodes in 9 PTX subjects. The morbidity rates (life table analysis) were significantly lower (p less than 0.05) in the PTX group. The results of the study point to a preventive effect of PTX in terms of the reduction in TIA recurrences.

Aged↗
PubMed1984

Regulation of glucose metabolism in rat adrenal gland in alloxan-diabetes: the possible role of fructose 2,6-bisphosphate.

The level of fructose 2,6-bisphosphate is markedly decreased in the rat V.renal gland in diabetes, falling to 23% of the control value. There is parallel decrease in the flux of 14C-labelled glucose through the glycolytic route and tricarboxylic acid cycle. Only minimal changes in hexokinase (EC 2.7.1.1.), a 22% decrease in Type I hexokinase of the soluble fraction, were observed, highlighting the probable significant involvement of fructose 2,6-bisphosphate in the regulation of glycolysis in the adrenal. In contrast, there was evidence for a marked rise in the flux of glucose through the pentose phosphate pathway, which may be linked to enhanced corticoid synthesis in the diabetic state.

Adrenal Glands↗
PubMed1984

Regulation of alternative pathways of glucose metabolism in rat heart in alloxan diabetes: changes in the pentose phosphate pathway.

The flux of glucose through the pentose phosphate pathway, important in relation to the provision of ribose 5-phosphate for nucleotide and RNA synthesis, was decreased by 70% in the diabetic rat heart in parallel with a similar decreased flux through the glycolytic route. A common factor linking the decreased flux through these alternative routes is the known fall in cardiac hexokinase; in these experiments there is a 50% decrease in Type II hexokinase (EC 2.7.1.1.) in both soluble and particulate fractions. The level of fructose 2,6-bisphosphate, a regulator of phosphofructokinase activity, is decreased by 20% in the alloxan diabetic rat heart, this may be a significant additional factor in the marked decrease in the flux of glucose through the glycolytic route in the myocardium in diabetes.

Animals↗
PubMed1983

The effect of an aldose reductase inhibitor (Sorbinil) on the level of metabolites in lenses of diabetic rats.

This study examined the effect of an aldose reductase inhibitor (Sorbinil, CP 45634, Pfizer, Sandwich, Kent, United Kingdom) on the metabolite profile of the lens during the first week after induction of diabetes with alloxan. The lens content of sorbitol, fructose, glycerol 3-phosphate, and glucose 6-phosphate was, respectively, 0.33 +/- 0.03, 0.55 +/- 0.05, 0.10 +/- 0.01, and 0.074 +/- 0.006 mumol/g (means +/- SEM) in the control group rising to 12.2 +/- 0.52, 3.20 +/- 0.10, 0.76 +/- 0.10, and 0.200 +/- 0.009 in lenses from alloxan-diabetic rats. Sorbinil treatment (40 mg/kg) decreased the lens content of sorbitol to 0.60 +/- 0.06, fructose to 0.85 +/- 0.08, and glycerol 3-phosphate to 0.36 +/- 0.03 mumol/g; glucose 6-phosphate remained unchanged. Significantly, the lens content of glutathione was decreased to 60% of the normal value in the diabetic group, but was sustained at normal levels with Sorbinil treatment. The ATP content of the lens was not altered by diabetes or Sorbinil treatment at this time interval. Sorbinil has no significant effect on the above metabolites in the normal rat lens. The effect of Sorbinil in restoring normal levels of glutathione and glycerol 3-phosphate may be a potentially important facet of the action of this drug. The interlocking of metabolic pathways by the redox state of NAD+/NADH and NADP+/NADPH, their derangement in diabetes, and the wider effects of Sorbinil on the network of reactions in the lens are discussed.

Aldehyde Reductase↗
PubMed1982

Regulation of pathways of glucose metabolism in kidney. Specific linking of pentose phosphate pathway activity with kidney growth in experimental diabetes and unilateral nephrectomy.

The pentose phosphate pathway operates at an elevated level in rat kidney following induction of diabetes and in the compensatory hypertrophy following unilateral nephrectomy in control and alloxan-diabetic rats, as shown by the yields of 14CO2 from [1-14C]glucose, [6-14C]glucose and 3H2O yields from [2-3H]glucose. The elevated flux through the pentose phosphate pathway is correlated with the increased RNA content and weight of the kidney. The direct utilization of NADPH for reductive synthetic reactions and the potential for indirect utilization via the sorbitol route and the linked transhydrogenase reactions of the glucuronate-xylulose pathway, for NADH and ATP generation, are also discussed.

Animals↗
PubMed1982

Anxiety management with schizophrenic outpatients.

Current theoretical speculation and research evidence suggest that elevated anxiety levels and poor anxiety coping skills may be important aspects of the schizophrenic process. Despite the success of various behaviorally oriented stress management techniques with nonpsychotic individuals, research on the effects of these programs as applied to schizophrenics has been scarce. The present study examined the effects of two such techniques, Anxiety Management Training (AMT) and Applied Relaxation Training (R), on schizophrenic outpatients. After 6 weeks of training, both the AMT and R Ss (N = 27) reported significantly lower levels of generalized anxiety on a standard measure, as contrasted to non-treated Wait-List (WL) group Ss (N = 12). In addition, significant positive changes were reported by the Ss' regular outpatient therapists on a number of related, non-targeted behaviors. The results of this study support the idea that short-term anxiety management interventions may be useful in the treatment of schizophrenic patients.

Adaptation, Psychological↗
PubMed1981

Randomised trial of pentoxifylline versus acetylsalicylic acid plus dipyridamole in preventing transient ischaemic attacks.

In a multicentre trial to compare the ability of a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day, group A) to prevent recurrence of transient ischaemic attacks (TIA) with that of pentoxifylline (1200 mg/day, group B), 36 patients received the combination and 30 pentoxifylline. There was no statistically significant difference between the groups as regards age, sex, blood pressure, site of origin of TIA, and incidence of other risk factors. The incidence of recurrent TIAs during 1 year of follow-up was 28% in group A and 10% in group B; this difference was significant (p less than 0.05). The incidence of permanent strokes was similar in the two groups but distinctly lower (4.5%) than that usually reported after untreated TIA.

Aspirin↗
PubMed1977

Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver.

The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions.

Animals↗
PubMedDate not supplied

Carcinosarcoma of the liver: a case report.

Primary hepatic carcinosarcoma is a rare malignant hepatic tumor containing both carcinomatous and sarcomatous elements. A 40-year-old man referred to our liver transplant team because of hepatic cirrhosis was on the waiting list, having undergone all liver tests, ultrasonography, and with normal serum alpha fetoprotein markers every 6 months to search for a tumor. He underwent a liver transplantation without complication. The pathologic findings of the original liver indicated carcinosarcoma. We have reviewed the literature on this subject.

Adult↗
PubMedDate not supplied

Matrix-enabled gene transfer for cutaneous wound repair.

Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet-derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.

Animals↗