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Biomedical subjects

M Khatami

Publications and source records attributed to M Khatami.

At least 37 records · Page 2Linked to original sources

Ascorbate regeneration in bovine ocular tissues by NADH-dependent semidehydroascorbate reductase.

Despite its fast autoxidation in vitro, ascorbate remains in its reduced form in vivo, indicating a special mechanism may be involved in its regeneration. The presence of an NADH-dependent reductase system, semidehydroascorbate reductase (SDR), for regeneration of ascorbate from its partially oxidized form, semidehydroascorbate (SDA), was demonstrated in bovine ocular tissues after extraction in Triton X-100. Highest SDR activity was detected in retinal extracts in the order of retina greater than pigment epithelium-choroid = ciliary body greater than iris. Minimal or no activity was observed in lens extracts or in aqueous fluid. Freezing and thawing, or boiling, destroyed the NADH-dependent SDR activity. NADH oxidation was significantly reduced (22% of total activity) when assays with retinal extracts were performed at 5 degrees C. Treatment with 4 mM, N-ethylmaleimide reduced the rate of NADH oxidation to 73 or 42% compared with control values with retinal or ciliary body extracts, respectively.

Animals↗

Kinetics of ascorbate transport by cultured retinal capillary pericytes. Inhibition by glucose.

Accumulation of radioactive L-[carboxyl-14C]-ascorbic acid by cultured bovine retinal capillary pericytes was studied. Kinetic analysis of the transport showed a time-dependent, saturable system with an apparent Km of 76.0 microM and a Vmax of 42 pmole/micrograms DNA/min. A facilitated carrier diffusion process was established on the basis that the system was not sensitive to 2,4-dinitrophenol, ouabain, or reduced sodium concentration in the incubation media, and that the carrier system demonstrated stereospecificity for an ascorbate analogue, dehydroascorbate, and for sugar analogues such as alpha-D-glucose and 3-0-methyl-D-glucose (3-0-MG), but not for beta-D-fructose or L-glucose. Transport of ascorbate by cultured pericytes was insulin-insensitive. 3-0-Methyl-D-glucose inhibited ascorbate transport into pericytes in a non-competitive manner with a Ki of 22 mM. These results indicate that, in cultured retinal capillary pericytes, a common facilitated carrier diffusion system is involved in the transport of ascorbate and sugar analogues such as alpha-D-glucose or 3-0-MG.

Animals↗

Experimental ocular onchocerciasis in cynomolgus monkeys.

Infection of cynomolgus monkeys with microfilariae (Mf) of Onchocerca lienalis was studied as a model for human ocular onchocerciasis. Normal monkeys and immunized monkeys were given intracorneal/subconjunctival, intracameral, or intravitreal injections of Mf or bovine serum albumin (control). Selected animals were given diethylcarbamazine citrate (DEC) orally (15 mg/kg) daily after the ocular infection. Following intravitreal challenge, living Mf and fibrinous exudates were visible by slit-lamp in both the anterior chamber and vitreous. Eosinophils and macrophages surrounded the Mf in the vitreous, with degranulated eosinophils adherent to the Mf. Eosinophils infiltrated the uvea and surrounded the retinal vessels. After intracorneal injection of Mf, living Mf were visible by slit-lamp biomicroscopy in the cornea for 3 days, with minimal inflammation of the corneas occurring over the 7 days after injection. Intracamerally injected Mf induced anterior uveitis. The extent of the inflammatory reactions was not substantially altered by DEC treatment following intraocular injection of Mf. In vitro proliferative responses of peripheral blood leukocytes to a crude Mf antigen were not observed in infected monkeys and proliferative responses to mitogen declined in these animals. Responses to mitogen were inhibited by addition of Mf antigen in vitro in normal monkeys. Circulating IgG antibodies were present in the sensitized, intracorneally, and intravitreally challenged animals. No obvious correlations were present between IgG antibody level and ocular inflammation.

Animals↗

Alprazolam vs amitriptyline in depressions with reduced REM latencies.

This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.

Adolescent↗

Characterization of glucose transport by bovine retinal capillary pericytes in culture.

The transport of D-glucose and its non-metabolizable analog, 3-o-methyl-D-glucose (3-o-MG), by cultured bovine retinal capillary pericytes was characterized. A preference for D-glucose over L-glucose uptake by pericytes indicated a stereospecific process. The 3-o-MG transport appeared to follow complex kinetics. At low substrate concentrations, 3-o-MG transport had an apparent Km of 1.53 mM and a Vmax of 0.50 nmol (microgram DNA)-1 min-1 at 37 degrees C. A reduced extracellular sodium concentration, energy poisons, and exogenous insulin did not significantly influence 3-o-MG uptake. Inhibition of the uptake or efflux of 3-o-MG by cytochalasin B or phloretin, respectively, and the demonstration of a 'counter transport' phenomenon showed that 3-o-MG transport by retinal capillary pericytes in culture was a carrier-mediated process.

3-O-Methylglucose↗

The effects of glucose and an aldose reductase inhibitor on the sorbitol content and collagen synthesis of bovine retinal capillary pericytes in culture.

The absolute rate of collagen synthesis by cultured bovine retinal capillary pericytes, determined using the specific radioactivity of proline in the cellular amino acid pool, was compared in media containing different concentrations of glucose (5, 10 or 40 mM) and Sorbinil (0.0 or 0.1 mM), an inhibitor of aldose reductase. The absolute rate of collagen synthesis, in proline molar terms, by pericytes in medium with 5 mM glucose was 3.3 +/- 1.9 (S.D.) pmol 10(-7) cells 24 hr-1, and increased significantly to 8.8 +/- 3.7 pmol 10(-7) cells 24 hr-1 when the glucose concentration was increased to 40 mM. Sorbinil (0.1 mM) reduced the elevated sorbitol contents of pericytes induced by high concentrations of glucose, but did not significantly change the absolute rate of collagen synthesis per cell.

Aldehyde Reductase↗

Induction and down-regulation of conjunctival type-I hypersensitivity reactions in guinea pigs sensitized topically with fluoresceinyl ovalbumin.

Type-I hypersensitivity reactions were induced in guinea pigs by repeated topical/conjunctival application of fluoresceinyl ovalbumin (FL-OA). The ocular reactivity in early responding animals was maximal between 16 and 25 days and decreased exponentially thereafter. Desensitized eyes responded minimally to compound 48/80 but maximally to histamine. Unilateral sensitization and challenge with FL-OA produced desensitization of the immunized eye, but the reactivity of the contralateral eye persisted. A significant reduction in conjunctival stained mast cells was found in repeatedly challenged eyes. The desensitization therefore was due to a loss of reactive mast cells. Systemic infection with Ascaris suum, after repeated topical challenge with FL-OA had led to desensitization, produced a reappearance of type-I hypersensitivity reactions toward both FL-OA and ascarid antigens.

Administration, Topical↗

Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin.

Repeated topical applications of fluoresceinyl ovalbumin (FL-OA) to the conjunctival sac of guinea pigs sensitized them for conjunctival type 1 hypersensitivity reactions and mast cell degranulation. Guinea pigs infected with Ascaris suum, with high titers of circulating anti-A suum IgE and IgG1 antibody, also produced conjunctival type 1 reactions on topical challenge with A suum antigen. These reactions were no more intense than those of animals topically sensitized and challenged with FL-OA, which in some instances had no detectable serum homocytotropic antibody. Persistently reactive animals that had undergone repeated type 1 conjunctival reactions had histological findings (eg, papillary changes with extensive epithelial eosinophil infiltrates, epithelial thickening or thinning, numerous goblet cells, subepithelial lymphoid cell infiltrates, and new vessel formation) resembling those of human atopic vernal conjunctivitis.

Animals↗

Increased solubility of newly synthesized collagen in retinal capillary pericyte cultures by nonenzymatic glycosylation.

The effect of increasing glucose concentration on the solubility of newly synthesized collagen was studied in bovine retinal capillary pericyte (BRCP) cultures. Synchronized pericytes were labeled with [3H]-proline in media containing either 5, 10, 20 or 40 mM glucose, or 5 mM glucose and 100 micrograms/ml beta-aminopropionitrile fumarate (BAPN). The relative rate of collagen synthesis in the medium (soluble collagen) was significantly increased, and the rate in the cell layer (insoluble collagen) was decreased, by an elevated glucose concentration. The increase in collagen solubility with 20 and 40 mM glucose (over normal, 5 mM glucose) was 14 and 42%, respectively, of that obtained with BAPN. BAPN and 4-deoxypyridoxine inhibited BRCP lysyl oxidase activity, but elevated glucose concentrations did not. Increased nonenzymatic glycosylation of newly synthesized collagen was demonstrated in BRCP cultures co-labeled with L-[14C]-glucose and L-[3H]-proline. The increase in collagen solubility with elevated glucose concentrations therefore appears to be the result of the inhibition of lysyl-derived cross-link formation because of an increased nonenzymatic glycosylation of the epsilon-amino groups of lysyl residues of newly synthesized collagen in culture.

Aminopropionitrile↗

Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high-glucose concentration.

The influence of glucose concentration on cell multiplication and protein synthesis was studied in synchronized, long-term cultures of bovine retinal microvessel pericytes. The cell multiplication rate and the mitotic rate were reduced in media containing 20 mM glucose to 57% and 54%, respectively, of that obtained in media containing 5 mM glucose. Elevated glucose, however, did not change the DNA content of individual cells. Protein and collagen synthesis were measured by the incorporation of radioactive proline and lysine, or the posttranslational production of hydroxyproline and hydroxylysine, respectively. High glucose stimulated protein and collagen synthesis per cell 2.2 +/- 0.10 (SD) and 2.1 +/- 0.06 times, respectively. Aspirin (0.5 mM), an inhibitor of nonenzymatic glycosylation, did not alter the effect of elevated glucose concentration on protein and collagen synthesis.

Animals↗

Nonenzymatic glycosylation of bovine retinal microvessel basement membranes in vitro. Kinetic analysis and inhibition by aspirin.

Incubation of intact bovine retinal microvessels or isolated retinal microvessel basement membranes (RVBM) with radioactive D-glucose or L-glucose, followed by basement membrane collagenous protein purification, resulted in the isolation of nonenzymatically glycosylated RVBM collagens. Type IV collagen was identified in the RVBM by selective salt fractionation, SDS-polyacrylamide gel electrophoresis, amino acid analysis, and immunoprecipitation with specific antibody. Kinetic analysis of the condensation of glucose with RVBM was carried out by labeling retinal microvessel basement membranes with D-[2-3 H]-glucose and D-[6-14 C]-glucose. The rate constant for aldimine product formation, k1, was 1.95 +/- 0.24 (SD) X 10(-4) mM-1 h-1, and the rate constant for the reversed reaction, k-1, was 5.9 +/- 1.0 X 10(-2) h-1. Based on a rate constant for the Amadori rearrangement, k2, of 8.8 +/- 1.0 X 10(-3) h-1, which was the rate-determining step, the half life of this reaction was 80 +/- 9 h. These data may be useful in estimating the glycosylation of retinal microvessel basement membranes in vivo. The nonenzymatic glycosylation of retinal microvessel basement membrane proteins was progressively inhibited by increasing concentrations (0.1 to 2.0 mM) of aspirin.

Animals↗

A one year follow-up of the multimodal treatment for chronic pain.

Twenty-three outpatients with chronic pain began a 3-part treatment package designed to provide symptom control, stimulus control and social system modification. Fourteen patients completed the full course of therapy. The remaining 9 patients were designated as partial completers. A mean of 22.9 weekly hour long therapy sessions resulted in statistically significant decreases in pain, depression, anxiety and medication intake. These improvements were maintained at 1 year follow-up. This study is consistent with the notion that chronic pain is maintained by a combination of inter- and intrapersonal factors. A controlled comparison of this treatment program with other treatments for chronic pain is indicated.

Adult↗

Amino acid sequence adjacent to a sulfhydryl group exposed on illumination of bovine rhodopsin.

Two sulfhydryl groups of bovine rhodopsin, available for chemical modification only after bleaching, were specifically labeled with radioactive iodoacetamide. The labeled protein was extensively reduced and alkylated and digested with pronase, and peptides were purified by gel filtration chromatography, anion and cation exchange chromatography, and high pressure liquid chromatography. Purified peptides were detected by their radioactivity, UV spectral properties, and by their fluorescence after reaction with fluorescamine. Sequence analysis of a highly purified peptide established the sequence S-carboxamido[14C]methyl cysteinyl-prolyl-glycine as the site of one of the light-exposed sulfhydryl groups of bovine rhodopsin.

Amino Acid Sequence↗

Psychotropic agents in opiate addiction: a brief review.

Psychotropic agents are frequently utilized in the detoxification and maintenance of opiate addicts as well as in the treatment of their underlying psychopathology. Review of reports of studies conducted to data indicates that schizophrenia, depression, and anxiety in opiate addicts appear to respond to appropriate treatment with psychotropic drugs. Although nonaddictive psychoactive compounds cannnot be completely substituted for methadone in detoxification, their effects on the rate of methadone withdrawal warrant further study. To evaluate the results of treatment of addicts with psychoactive compounds, parameters that should be studied include the effects of these compounds on illicit drug use, methadone requirements, relapse and dropout rates, and social behavior.

Anti-Anxiety Agents↗