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Biomedical subjects

A J Glasky

Publications and source records attributed to A J Glasky.

At least 19 recordsLinked to original sources
PubMed2000

AIT-082, a cognitive enhancer, is transported into brain by a nonsaturable influx mechanism and out of brain by a saturable efflux mechanism.

A fundamental feature of any drug designed to treat a disease of the central nervous system is the ability to cross the blood-brain barrier. Passage across the blood-brain barrier of AIT-082, a cognitive enhancer, was investigated in mice. [(14)C]AIT-082 crossed the blood-brain barrier in young male Swiss-Webster mice with a mean influx constant (K(i)) of 0.6 +/- 0.2 microl g(-1) min(-1). Furthermore, [(14)C]AIT-082 was transported into brain of both young and old male C57BL/6 mice with a K(i) of 0.35 +/- 0.06 and 0.33 +/- 0.02 microl g(-1) min(-1), respectively. There was no significant effect of age or strain on the movement of [(14)C]AIT-082 across the blood-brain barrier in mice. When 110- or 650-fold excess unlabeled AIT-082 was included in the injection solution, the K(i) was not significantly changed in either Swiss-Webster or C57BL/6 mice. This indicated that [(14)C]AIT-082 crossed the blood-brain barrier by a nonsaturable mechanism. The passage of AIT-082 into brain extracellular fluid was confirmed with capillary depletion and microdialysis. The efflux of [(14)C]AIT-082 from brain also was examined. After i.c.v. injection, [(14)C]AIT-082 levels in brain decreased over time with a t(1/2) of 20.0 +/- 1.0 min. Excess unlabeled AIT-082 (600-fold) increased the t(1/2) to 35.5 +/- 3.6 min. Together, these data indicate that AIT-082 moves into brain via a nonsaturable mechanism and is actively transported out of brain.

Age Factors↗
PubMed1997

AIT-082, a novel purine derivative with neuroregenerative properties.

Preclinical and clinical evidence support the effectiveness of neurotrophins in Alzheimer's disease (AD) and neurodegenerative diseases. Delivery of neurotrophins to target sites in the brain remains a major obstacle for their use in humans. Development of orally active agents that mimic the effects of nerve growth factor and other neurotrophins provides a promising alternative therapeutic strategy. AIT-082, a purine analogue, has been shown to reverse age-induced memory deficits in mice and is a growth factor-mimetic agent. It is orally active, rapidly penetrates the blood-brain barrier and induces the production of multiple growth factors at the appropriate target site in the central nervous system (CNS).

Journal Article↗
PubMed1995

AIT-082, a unique purine derivative, enhances nerve growth factor mediated neurite outgrowth from PC12 cells.

AIT-082 is a novel, metabolically stable, derivative of the purine hypoxanthine. Addition of AIT-082 to cultured PC12 cells enhanced significantly nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells. These results suggest a cellular mechanism, the enhancement of NGF-action, that might account for the ability of AIT-082 to restore age-induced working memory deficits in mice.

Aminobenzoates↗
PubMed1994

Effect of AIT-082, a purine analog, on working memory in normal and aged mice.

Because working memory is the primary type of memory which is disrupted by Alzheimer's disease and stroke and during aging, any therapeutic drug for these conditions should improve and/or restore working memory. The win-shift memory paradigm has been shown to be an excellent model of working memory. In the present study, we examined the effects of a novel purine derivative, 4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1- oxopropyl]amino]benzoic acid (AIT-082) and physostigmine (PHY) on working memory. Both AIT-082 and PHY improved memory in young mice and restored memory in mice with mild age-induced memory deficits; however only AID-082 was also effective in subjects with moderate deficits. Neither drug improved memory in mice with severe memory deficits. AIT-082 exhibited effectiveness over a broad dose range (0.5-60 mg/kg), and the effects lasted for seven days after a single high-dose drug administration. AIT-082 was devoid of any effects on performance variables and has not shown any toxic side effects, thus making it an interesting potential treatment for working memory deficits associated with aging, strokes, and Alzheimer's disease.

Aging↗
PubMed1993

Effect of age and strain on working memory in mice as measured by win-shift paradigm.

Working memory is disrupted in Alzheimer's disease and stroke; therefore, any therapeutic drug should restore deficits in working memory. The win-shift foraging paradigm has been demonstrated to be a model of working memory in rats. In the present study, this paradigm was adapted to mice because of the greater ease and economy of testing potential drugs in mice and the wider availability of strains of aged mice with naturally occurring working memory deficits. This study has demonstrated strain differences in the working memory trace and that age induces a deficit that can be detected at 11 months of age in mice. Tacrine and physostigmine enhance the memory trace in normal mice and physostigmine can reverse age-induced working memory deficits in subjects with mild and moderate deficits but not in subjects with severe deficits.

Aging↗
PubMed1987

Imunovir in the treatment of immunodepression of diverse etiology.

Immunodepression associated with a variety of situations such as cancer or any of its major modalities of treatment (surgery, irradiation, or chemotherapy) has been effectively alleviated with Imunovir (inosine pranobex-BAN), and this has been associated with demonstrable clinical benefit to these patients. One hundred and six immunodepressed patients with solid tumors undergoing radiotherapy were treated with either Imunovir or placebo; 64% of Imunovir-treated patients were immunorestored after 3 months compared to 23% in the placebo group. Imunovir was also effectively used in 75 patients with malignant hematological disorders both as an immunorestorative agent given prophylactically to prevent infection and as a therapeutic agent to treat infections in these immunodepressed patients. In different studies involving surgical patients treated with either Imunovir or placebo, 70-81% of hypoergic or anergic patients in the Imunovir group became normoergic by day 14 of treatment compared to 5-17% of the placebo group, and this enhanced immunorestoration was associated with lower incidence of local sepsis (P less than 0.05), systemic sepsis (P less than 0.025), and postoperative mortality (P less than 0.05).

Female↗
PubMed1987

Isoprinosine (inosine pranobex BAN, INPX) in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.

The immunopharmacologic effects of Isoprinosine (INPX) have been associated with clinical benefit to the patient in a number of conditions characterized by immunodeficiency of diverse etiology. Immunodepressed homosexuals at risk of developing acquired immunodeficiency syndrome (AIDS) treated with placebo or INPX experienced an increase in the function and number of immunocompetent cells associated with clinical improvement. A multicenter trial designed to confirm these results has demonstrated that INPX produced an increase in natural killer (NK)-cell activity, total T cells, and T-helper cells, with certain effects persisting for months after completion of the 28-day treatment period. INPX-treated patients also experienced clinical improvement and decreased incidence of progression to AIDS. The administration of INPX for longer periods to patients with frank AIDS under a compassionate-use protocol has also proved useful. Clinical benefit associated with INPX treatment has been demonstrated in other patients with a depressed immune response, such as aged patients, cancer patients, severely burned patients, ill patients, and surgery patients. This program of clinical trials supports the therapeutic use of INPX in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.

AIDS-Related Complex↗
PubMed1986

Inosiplex treatment of acquired immunodeficiencies: a clinical model for effective immunomodulation.

Patients with various conditions associated with immunologic deficiency (cancer, radiotherapy, surgery, burns, aging, prodromal Acquired Immunodeficiency Syndrome, were treated with inosiplex (INPX) at a dose of 3-4 g/day for periods of time ranging from 1 week to several months. Patients were evaluated clinically, and immunologically with the following assays; natural killer (NK) cytotoxicity, T-lymphocyte count, mitogen-induced proliferation, E rosettes, and skin test reactivity. The data resulting from this large and varied population were quite consistent and reproducible, and indicated that INPX treatment was effective in simultaneously reducing the incidence of complications, infections and mortality while enhancing the immune status of the patient. It has therefore been concluded that an immunopharmacologically active agent such as INPX can elicit important clinical benefits in patients with disorders of diverse etiology, perhaps through modulation of an immunologic defect that is common to a variety of seemingly unrelated conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1978

Isoprinosine: an overview.

Isoprinosine appears to have a relatively low degree of both acute and chronic toxicity in both rodent and nonrodent species. Preclinical studies have demonstrated that isoprinosine can inhibit the growth of both DNA and RNA viruses as well as potentiate cell-mediated immune response both in vitro and in vivo. Clinical studies with rhinovirus, herpesvirus, and influenza virus infections in man demonstrated that isoprinosine treatment reduced clinical symptoms and enhanced certain cell-mediated immune responses compared to placebo-treated controls.

Animals↗
PubMed1966

Magnesium pemoline: enhancement of brain RNA polymerases.

The stimulation by magnesium pemoline of systems that synthesize brain nucleic acid was studied in vivo and in vitro. There are differential effects between true RNA polymerase and pseudo-RNA polymerase. The selective stimulation of true RNA polymerase by magnesium pemoline was not observed with stimulants of the central nervous system and psychotropic agents.

Animals↗