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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 19 recordsLinked to original sources
PubMed2004

Alcohol, wine and mental health: focus on dementia and stroke.

The relative risks of coronary heart disease (CHD) and overall mortality are reduced by moderate consumption of alcoholic beverages, particularly wine, which has major implications for public health. It appears likely that this beneficial effect of alcohol will soon be extended to some mental disorders. Although data on psychosis and mood and anxiety disorders are currently lacking, it appears that the relative risks of developing ischaemic stroke and Alzheimer's or vascular dementia are also lowered by moderate alcohol consumption. Such findings are still tentative because of the inherent methodological problems involved in population-based epidemiological studies, and it is unclear whether the benefit can be ascribed to alcohol itself or to other constituents specific to wine such as polyphenols. Plausible biological mechanisms have been advanced for the protective effect of alcohol and wine against CHD, many of which will also play roles in their protective actions against cerebrovascular disease and dementia. The specific antioxidant properties of wine polyphenols may be particularly important in preventing Alzheimer's disease. Because of the substantially unpredictable risk of progression to problem drinking and alcohol abuse, the most sensible advice to the general public is that heavy drinkers should drink less or not at all, that abstainers should not be indiscriminately encouraged to begin drinking for health reasons, and that light to moderate drinkers need not change their drinking habits for health reasons, except in exceptional circumstances.

Alcohol Drinking↗
PubMed2001

Effects of isatin on atrial natriuretic peptide-mediated accumulation of cGMP and guanylyl cyclase activity of PC12 cells.

We have previously demonstrated that isatin (indole-2,3 dione), an endogenous compound widely distributed in mammalian tissues and body fluids, effectively inhibits atrial natriuretic peptide (ANP) receptor binding and ANP-stimulated guanylyl cyclase activity of rat membrane preparations. In the present study the effects of isatin on ANP-mediated accumulation of cGMP and guanylyl cyclase (GC) activity of PC12 cells were studied. Isatin (0.1 mM) effectively inhibited ANP-stimulated GC-activity of broken cells but was nearly inactive in attenuating ANP-dependent accumulation of cGMP in intact PC12 cells. The ATP-analogue adenylylimidodiphosphate (AMP-PNP) slightly potentiated the ANP effect on GC activity in broken cell preparations and significantly reduced GC sensitivity to isatin. Isatin caused a more pronounced reduction of ANP-dependent cGMP accumulation in cells grown in the presence of 10% embryonal calf serum (ECS) than in 0.5% ECS. The data obtained suggest that, in intact cells, the manifestation of the isatin effect on ANP-mediated signal transduction may depend on intracellular factor(s), possibly interacting at the kinase domain.

Adenylyl Imidodiphosphate↗
PubMed2001

Neurotrophins: possible role in affective disorders.

Various monoamine hypotheses of affective disorders have been unable to provide a complete explanation for the observed clinical findings. Recently Duman et al. (1997) have produced a molecular and cellular theory of depression which seems to be a worthy successor to these hypotheses. Whereas the earlier theories were unable to explain the time lag between antidepressant drug administration and lightening of affect, Duman's group pinpoints intracellular mechanisms, in the right time frame, which decrease or increase the generation of neurotrophic factors necessary for the survival of certain neurons, particularly in the hippocampus. This new concept may lead to novel therapeutic approaches. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

The influence of isatin on guanylyl cyclase of rat heart membranes.

The influence of indole-2,3 dione (isatin) on particulate guanylyl cyclase (GC) from rat heart membranes was investigated in the presence of adenylylimidodiphosphate (AMP-PNP). The latter activated GC in a concentration-dependent manner and 100 microM isatin abolished this effect. The IC(50) value, 2 microM, for the inhibition of stimulation of GC induced by 50 microM AMP-PNP, was close to the upper physiological level of isatin. These results indicate that isatin may interact with GC independently of its regulation by natriuretic peptides.

Adenylyl Imidodiphosphate↗
PubMed1999

Efficacy of isatin analogues as antagonists of rat brain and heart atrial natriuretic peptide receptors coupled to particulate guanylyl cyclase.

Isatin is an endogenous indole and an inhibitor of atrial natriuretic peptide (ANP) receptors coupled with particulate guanylyl cyclase (GC). In this study, several isatin analogues were tested as inhibitors of ANP-stimulated GC in rat brain and heart membranes. None of these analogues affected activity in the absence of ANP, or stimulated ANP-induced activity. In both tissues, some 5-substituted isatins (5-hydroxyisatin, 5-methylisatin, and 5-aminoisatin) exhibited more effective inhibitory activity than isatin itself, with IC50 values in the range 1.3-20 microM. The efficacy of other analogues varied and was not consistent between the two tissues, raising the possibility of receptor heterogeneity and relative selectivity of inhibition. Some substituted isatins may have a role as pharmacological tools for investigating the physiological roles of natriuretic peptides and their receptors.

Animals↗
PubMed1998

Interaction of isatin with type-A natriuretic peptide receptor: possible mechanism.

The effect of isatin on rat brain particulate guanylate cyclase (GC) was investigated. The enzyme was stimulated by atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and urodilatin, but not by C-type natriuretic peptide (CNP). Their effects were not additive, pointing to action via the GC-A receptor. Isatin, in dose-dependent manner, abolished this stimulation. The non-hydrolysable ATP analogue, adenylylimidodiphosphate, potentiated the effects of submaximal doses of ANP, BNP and urodilatin on this particulate GC-A, and attenuated or abolished sensitivity to isatin. These results suggest that isatin antagonises the generation of second messenger by GC-A; this sensitivity might be regulated at an ATP binding site, possibly a protein kinase-like domain.

Adenosine Triphosphate↗
PubMed1998

Effect of extract of Rhazya stricta, a traditional medicinal plant, on rat brain tribulin.

Rhazya stricta leaves, which have both antidepressant and sedative properties in animal models, are widely used in folk medicine in the Arabian peninsula. In this study, the effects of oral administration of leaf extracts on rat brain tribulin levels [endogenous monoamine oxidase (MAO) A and B inhibitory activity], were determined. In an acute study, low doses brought about an increase in MAO A inhibitory activity, while intermediate doses caused a significant reduction. The highest doses had no significant effects on activity. There were no significant effects on MAO B inhibitory activity at any dose. Subchronic administration (21 days) caused a significant decrease in MAO A inhibitory activity, most prominent at low dosage, and an increase in MAO B inhibitory activity. Acute intramuscular administration also resulted in a similar pattern. Such paradoxical effects were at least partially explained when different extracts of the leaves were used; a weakly basic chloroform fraction caused an increase in MAO A inhibitory activity, whereas butanol extracts brought about a decrease. These fractions had no significant effects on MAO B inhibitory activity. The findings show that Rhazya stricta leaves contain at least two different components that affect MAO inhibitory activity in opposite directions. It may be that the antidepressant and sedative actions of the plant are explicable in terms of these different components.

Animals↗
PubMed1998

Resistance of aryl-substituted phenylalanines to decarboxylation in the rat.

1. The in vivo decarboxylation of analogues of DL-phenylalanine with methoxy, ethoxy or methylenedioxy substituents on the aromatic nucleus was assessed in the rat by measuring urinary excretion of the corresponding phenylacetic acids and beta-phenylethylamines. Only trace amounts of these amines and acids were excreted. 2. o-Tyrosine was readily decarboxylated, a property that may be attributed to the position and nature of the substituent on the aromatic nucleus. 3. Some phenylpyruvic acids derived from these amino acids exhibited a certain degree of decarboxylation to phenylacetic acids or reduction to phenyllactic acids in the rat.

Animals↗
PubMed1998

The provision of enabling services to higher-risk pregnant women and children in Medicaid managed care.

As managed care organizations become the major payer model for the higher-need, higher-risk population of Aid to Families with Dependent Children women and children, they would benefit from looking at lessons learned during the past decade as policy makers and providers struggled to identify less costly, but effective strategies to reduce morbidity and mortality associated with poor birth outcomes. This article discusses the experience of one community in providing enabling services, the opportunity for new partnerships, measuring the outcomes, and the financing of enabling services in a managed care model.

Child Health Services↗
PubMed1997

Brain-derived neurotrophic factor in human platelets.

A sensitive, capture enzyme-linked immunosorbent assay (CELISA) has been applied to the accurate and reproducible measurement of brain-derived neurotrophic factor (BDNF) protein in normal human blood platelets, a mean concentration of 1.03 +/- 0.04 ng (SEM)/mg of platelet protein being observed. The method, which requires only 10 ml blood, is now suitable for the investigation of a variety of clinical disorders.

Blood Platelets↗
PubMed1997

Metabolism of phenylethanolamines and 2-oxo-2-phenylethylamines in the rat.

1. The metabolism of a series of phenylethanolamines and 2-oxo-2-phenylethylamines was examined in vivo in the rat. 2. The urinary excretion of the corresponding mandelic acids was, in general, considerably greater for 2-oxo-2-phenylethylamines than for the corresponding phenylethanolamines. Of the putative metabolites of the former class of compounds only phenylglyoxals yielded mandelic acids.

Animals↗
PubMed1997

HIV and the dental profession.

In order to assess the response of dentists to the increasing incidence of HIV, a study was conducted to explore their attitudes, knowledge and the additional costs involved in treating HIV positive patients. The response of dentists to the increasing incidence of HIV positive patients is influenced by their fears and concerns about HIV, their knowledge about the disease, and their attitudes towards providing care for HIV patients. The results of this research suggest that the negative response to HIV patients from dentists can be attributed to several factors. Dentists are afraid of contracting the virus, they do not trust the honesty of HIV patients, and they believe there are additional costs involved in treating these patients. In order to provide quality dental treatment for HIV patients, dentists must overcome their misperceptions and feelings of anxiety and fear about HIV. Education is a major weapon in the fight against HIV. Dentists agree there is a need for continuing education despite the fact that their overall knowledge about HIV is good.

Adult↗
PubMed1996

Isatin: a link between natriuretic peptides and monoamines?

Isatin is an endogenous indole with a distinctive distribution in brain and tissues. In the brain, the highest levels have been found in the hippocampus (0.1 microgram/g), and an immunocytochemical stain has shown specific localization within particular cells. In vitro, its most potent known actions are as an inhibitor of monoamine oxidase B (IC50 approximately 3 microM), and of atrial natriuretic peptide (ANP) receptor binding and ANP-induced guanylate cyclase (both with an IC50 approximately 0.4 microM). In vivo, isatin administration (10-200 mg/kg) causes an increase of monoamine neurotransmitter levels in the brain. Isatin is anxiogenic in animal models at doses of 10-20 mg/kg and sedative at higher doses. Its anxiogenic effects are unlikely to be due to inhibition of monoamine oxidase, but may possibly stem from interaction with the ANP system. Isatin may mediate a link between monoamines and the natriuretic peptide system, and its analogues may provide new pharmacological tools.

Animals↗
PubMed1996

Anxiolytic activity of intraventricularly administered atrial natriuretic peptide in the rat.

Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.

Animals↗
PubMed1996

Somatostatin receptor imaging: predictive and prognostic considerations.

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.

Carcinoid Tumor↗
PubMed1996

Paracetamol (acetominophen) sulphoconjugation in man: no correlation with tyramine sulphoconjugation.

There is considerable evidence that subjects vulnerable to endogenous depression excrete less tyramine sulphate after an oral dose of free tyramine than controls (the tyramine test). In this study, 26 psychiatric inpatients, exhibiting a wide range of responses to the test, and 10 normal controls were challenged with oral doses of paracetamol and tyramine on two separate occasions. Urinary output of paracetamol sulphate and paracetamol glucuronide in all subjects was monitored but there were no significant correlations with tyramine sulphate output. Thus, the output of these metabolites appears to be under complex control, and paracetamol cannot be substituted for tyramine in the "tyramine test". The basic deficit responsible for low values in the tyramine test is unlikely to stem from sulphate depletion or a generalised disturbance of the sulphation system, and remains obscure.

Acetaminophen↗