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Biomedical subjects

A Glover

Publications and source records attributed to A Glover.

At least 19 recordsLinked to original sources
PubMed1991

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates.

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

Acetylcarnitine↗
PubMed1990

Attenuation of the early anterior negativity of median nerve somatosensory evoked potential in the MPTP-treated monkey.

Median nerve somatosensory evoked potentials (SEP) were recorded in 7 Cynomolgus monkeys, before and after the administration of N-Methyl 1,4 Phenyl 1,2,3,6 tetrahydropiridine (MPTP), a neurotoxin which induces a parkinsonian syndrome in primates. Following MPTP administration, the amplitude of the negative component recorded at 15 ms over the frontal derivations (N15) decreased by 70% or more. This amplitude reduction was not modified by administration of dopamine precursors. These findings shed light on recent findings in human parkinsonian patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Systemic 1-methyl,4-phenyl,1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates.

Following MPTP administration, 4 Cynomolgus monkeys developed a parkinsonian syndrome, accompanied by specific changes of both pattern visual evoked potential and electroretinogram. Retinal dopamine and dihydroxyphenylacetic acid contents were measured in the 4 MPTP-treated monkeys and in 3 normal monkeys. Dopamine and dihydroxyphenylacetic acid levels were significantly lower in the retinas of the MPTP-treated animals (p less than 0.001), suggesting that dopamine has a specific function in the visual system of primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Merbarone: an antitumor agent entering clinical trials.

Merbarone was developed to clinical trial stage on the basis of its 'curative' activity against P388 and L1210 leukemias and moderate activity against B16 melanoma and M5076 sarcoma. Its activity appears to be schedule-dependent favoring a longer duration of administration. The mechanism of action of merbarone is not yet established but it does induce single strand breaks in DNA apparently without binding to DNA. The pharmacokinetic data in the dog indicate that clearance mechanisms may be saturable. Merbarone is hydroxylated at the 4' position in the rat, mouse and dog, and glucuronidated in the dog. Parent drug and the hydroxy metabolite are excreted in the urine. If saturable clearance mechanisms also pertain to man, this will mean that infusion rate (and therefore steady state concentrations reached) may be a significant factor in determining acute toxicity. Preclinical toxicology studies revealed that major target tissues are in the lymphoid organs, bone marrow, gastrointestinal tract and kidney. Some behavioral signs of reversible central nervous system toxicity were observed. Phase I trials have commenced using only a 5-day continuous intravenous infusion schedule based on the preclinical data. The pharmacokinetic information from these trials will be crucial for further clinical development of the compound, including selection of the optimal schedule(s) for phase II/III evaluation.

Animals↗
PubMed1985

Nocturnal penile tumescent evaluation of erectile function in insulin-dependent diabetic men.

This study compared nocturnal penile erections in four age-matched groups of young subjects: diabetic patients with and without erectile problems, psychogenically impotent men and healthy control subjects. All men were assessed under similar conditions during three nights, each for a total of 156 study nights. Diabetic impotent men exhibited a significantly decreased number of erectile episodes (p less than 0.05) and episodes of maximum tumescence per night (p less than 0.01). They also spent significantly less time in tumescence (p less than 0.005) and in simultaneous rapid eye movement sleep and tumescence (p less than 0.005). Diabetic men without sexual problems, psychogenically impotent men, and normal control subjects did not differ. Diabetic men in both groups spent less sleep time in rapid eye movement sleep and had longer latencies to onset of rapid eye movement. The decreased time in erection noted in impotent diabetic patients was no longer significant when adjusted for differences in duration of rapid eye movement sleep. In comparison to healthy control subjects and psychogenically impotent men, non-impotent diabetic men did show significantly diminished circumferential increases during erections, similar in degree to impotent diabetic patients (p less than 0.05).

Adult↗
PubMed1978

Polymorphonuclear cell function in the various polar types of leprosy and erythema nodosum leprosum.

Polymorphonuclear leukocyte motility, both in vivo and in vitro, and reduction of Nitro Blue Tetrazolium was studied in tuberculoid and lepromatous leprosy patients and a group of lepromatous patients with erythema nodosum leprosum (ENL). A profound defect in random migration, chemotaxis, and chemokinesis was found in lepromatous patients with and without complicating ENL, and marked depletion of skin window migration confirmed these in vitro findings. Tuberculoid patients exhibited a mild defect in polymorphonuclear leukocyte motility. Serum inhibitors of normal polymorphonuclear leukocyte chemotaxis were found in all types of leprosy, but sera from lepromatous and ENL patients were most inhibitory. Resting levels of Nitro Blue Tetrazolium reduction were normal in all three groups. Reconstitution of polymorphonuclear leukocyte cells from normal and ENL patients with ENL serum, however, showed increased Nitro Blue Tetrazolium reduction well above the normal range, whereas reconstitution with normal, lepromatous, and tuberculoid sera failed to increase Nitro Blue Tetrazolium reduction above the normal values.

Chemotaxis, Leukocyte↗
PubMed1978

Inhibitory effect of prostaglandin A1 on neutrophil motility.

Using Boyden chambers, Prostaglandin A1 (PGA1) was shown to inhibit directed movement of polymorphonuclear (PMN) leucocytes to the chemoattractants endotoxin-activated serum and casein, and in random migration systems. Depressed chemotaxis could not be entirely attributed to defective random migration, as the drug was shown to inhibit both chemokinesis (stimulated random migration) and "true chemotaxis". In addition, PGA1 inhibited the movement of neutrophils out of capillary tubes and substantially reduced hexose monophosphate shunt (HMPS) activity. Mice injected with PGA1 demonstrated significantly less PMN movement into trypticase-soy-broth-induced peritoneal exudates, and it is postulated that during inflammatory processes release of PGA1 increases cell accumulation at the site, thereby amplifying the inflammatory response.

Chemotaxis, Leukocyte↗
PubMed1978

The effect of chemotactic factors and agents which influence neutrophil movement on anaerobic glycolysis and hexose monophosphate shunt activity.

The effects of two chemotactic factors, endotoxin activated serm (EAS) and casein and a number of drugs known to affect intracellular cyclic nucleotide levels and various froms of neutrophil movement, on neutrophil anaerobic glycolysis and hexose monophosphate shunt (HMPS) activity were assessed. EAS caused stimulation of glycolysis. HMPS activity and NBT reduction, but casein was without effect on glycolysis and NBT reduction and inhibited HMPS activity. Drug known to increase intracellular cAMP levels caused a depression of HMPS activity whereas those reported to elevate cGMP had a variety of effects. Glycolysis was not affected by any of these agents. These results indicate a lack of relationship between cyclic nucleotide effect on cell motility and neutrophil glycolysis and HMPS activity.

Caseins↗
PubMed1978

Defective neutrophil motility and recurrent infection. In vitro and in vivo effects of levamisole.

Eighteen patients with primary abnormalities of neutrophil chemotaxis are described. The most common clinical presentation was one of recurrent upper respiratory tract infection (nine patients) or recurrent pyoderma (seven patients), and two children had a history of oropharyngeal candidiasis and recurrent skin sepsis. Of these eighteen patients, sixteen had intrinsic polymorphonuclear leucocyte (PMN) defects as shown by diminished random migration and movement towards endotoxin-activated serum. PMN chemotaxis towards casein was, however, normal. In nine out of the latter patients, there was an associated inability of the serum to generate chemotactic factors. PMN from two adult patients, both suffering from recurrent boils, moved normally both in random and directed systems, but sera from these patients contained heat-stable inhibitors of neutrophil chemotaxis. In vitro levamisole treatment (10(-3) M) markedly improved the PMN function. When patients were treated with levamisole, however, no clinical response was noted, although PMN movement improved in a number of cases.

Adolescent↗
PubMed1977

Depressed neutrophil motility in patients with recurrent herpes simplex virus infections: in vitro restoration with levamisole.

The random migration and chemotaxis of neutrophils from 10 patients with recurrent infections with herpes simplex virus were assessed. Chemotaxis to endotoxin-activated serum was markedly diminished in this group, but random migration was only mildly reduced, and chemotaxis to hydrolyzed casein was normal. The effects of the immunostimulant drug levamisole on the chemotaxis of neutrophils were assessed both in vitro and in patients after 150 mg of the drug was taken daily for three days. The defective chemotactic response could be corrected in vitro by treatment of the neutrophils with 10(-3) M levamisole. Of 10 patients treated with levamisole, five showed improved chemotaxis after three days, but no improvement in neutrophil function was observed in the other patients.

Cell Movement↗
PubMed1977

The in vitro effects of histamine and metiamide on neutrophil motility and their relationship to intracellular cyclic nucleotide levels.

Histamine at concentrations of 1 x 10(-5) M to 5 x 10(-5) M consistently increased neutrophil movement as measured in Boyden chambers. This effect was entirely caused by stimulation of chemokinesis (stimulated random migration) and true chemotaxis was inhibited by these concentrations. This inhibition of chemotaxis could be abolished by pretreatment with metiamide, an H-2 receptor antagonist, and levamisole, but not by diphenylhydramine, an H-1 receptor antagonist. Metiamide at similar concentrations produced a mild stimulation of chemokinesis but has no effect on true chemotaxis. The histamine effects on neutrophil motility were associated with increased levels of intracellular cAMP wehreas cAMP levels were unaffected. Agents known to elevate intracellular cAMP levels produced effects on neutrophil motility similar to those of histamine. It is suggested that histamine exerts a 2-fold effect on neutrophil motility mediated via an H-2 receptor site and associated with elevated levels of cAMP.

Cell Movement↗
PubMed1977

The effect of PHA-activated MN-cell supernatants on polymorphonuclear leucocyte function.

The effect of PHA-activated mononuclear-cell (MN) supernatants on various polymorphonuclear-leucocyte (PMN) functions were assessed. Treatment of PMN with PHA-activated MN-cell supernatants resulted in greater electrophoretic mobility, indicating an increase in the negative surface charge. PMN directional motility was inhibited in the presence of active supernatants but was not affected by a pulse exposure of the PMN to these supernatants. Neither control nor active supernatants were chemotactic for PMN, but treatment of these cells with active supernatants produced an increase in their phagocytic activity, their ability to reduce NBT and in their glucose oxidation through the hexosemonophosphate shunt. Bactericidal capacity of these PMN was unaltered. Specific loss of leucocyte inhibitory factor (LIF) activity from supernatants of PHA-activated MN cells followed their absorption with PMN cells but not with human MN cells or guinea-pig peritoneal exudate cells. Furthermore, acquired inhibition of migration of the absorbing PMN was observed.

Blood Bactericidal Activity↗
PubMed1976

T and CR+ lymphocyte profile in leprosy and the effect of treatment.

Thymus-derived lymphocytes (T lymphocytes) and complement receptor-bearing lymphocytes (CR+ lymphocytes) were estimated by using erythrocyte rosettes and erythrocyte-antibody-complement rosettes as markers in untreated lepromatous and untreated tuberculoid patients and in healthy controls. Treated lepromatous cases were also investigated. Ten cases of untreated lepromatous patients were reassessed 6 months or more after therapy commenced. A significant decrease in both percentages and absolute numbers of CR+ cells in the untreated lepromatous leprosy subjects was observed. This decrease showed a return to normal levels after treatment. The percentage of T cells in the untreated lepromatous cases was normal; however, the absolute numbers of T cells and the total lymphocyte count showed a significant decrease. After therapy, the T cell population was unchanged but the total number of lymphocytes increased significantly with treatment. The absolute number of T and CR+ cells was significantly less in the untreated than in the treated lepromatous patients.

Blood Cell Count↗
PubMed1976

In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils.

Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced.

Caseins↗
PubMed1976

Isolation of human eosinophils and their lymphocyte-like rosetting properties.

A method for the isolation of large numbers of almost pure human eosinophils from peripheral blood using hypague-ficoll density gradients, gelatin sedimentation and carbonyl iron is described. Eosinophils were obtained from patients with parasitic infections, allergic reactions, undiagnosed eosinophilias and normal volunteers. Erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosettes were formed by a number of eosinophils.

Cell Separation↗