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Biomedical subjects

D M Berman

Publications and source records attributed to D M Berman.

33 records · Page 2Linked to original sources

On the mechanism of vasodilating action of berberine: possible role of inositol lipid signaling system.

We have studied the effect of the alkaloid berberine on the contraction of guinea pig aortic strips induced by various stimuli. Berberine (25-200 microM) inhibited the response of the strips to norepinephrine and histamine, but did not decrease the high K(+)-elicited contraction. The antagonism of berberine was not competitive because in the presence of the alkaloid, maximum response to agonists could not be obtained. Analysis of the drug's effect on the time course of norepinephrine-induced contraction showed that berberine reduced both the rate and the relative contribution to developed tension of the initial, rapid phase, whereas the slow, later component was less affected. Berberine inhibited the response of aortic strips incubated in 0 mM Ca++ to norepinephrine, but did not reduce caffeine-induced contraction and also inhibited phospholipase C-activated contractile response, which has been ascribed to production of inositol phosphate-3 in smooth muscle cells. In cultured arterial smooth muscle cells (A7r5 line), the alkaloid did not significantly decrease the production of inositol phosphates activated by Arg8-vasopressin. The pattern of berberine action is difficult to reconcile with an involvement of the contractile machinery and suggests that the drug has no effect on the voltage-operated calcium channels. Although an antagonism at the receptors or an increase of cyclic AMP or cyclic GMP cannot be completely excluded, we suggest that at least one component of the berberine inhibitory effect may be due to its action on some step of the chain of events linking receptors to contractile response.

Animals

Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.

The conversion of testosterone into dihydrotestosterone by steroid 5 alpha-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate. Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46X,Y males have male internal urogenital tracts, but female external genitalia. We have described the isolation of a human 5 alpha-reductase complementary DNA from prostate. Subsequent cloning and genetic studies showed that this gene (designated 5 alpha-reductase 1) was normal in patients with 5 alpha-reductase deficiency. We report here the isolation of a second 5 alpha-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5 alpha-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5 alpha-reductase deficiency. These results verify the existence of at least two 5 alpha-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue.

The enzyme steroid 5 alpha-reductase catalyzes the conversion of testosterone into the more powerful androgen, dihydrotestosterone. We previously described the cloning of rat and human cDNAs that encode steroid 5 alpha-reductase and their expression in oocytes and cultured cells. Here, we report the isolation, characterization, and chromosomal mapping of two human steroid 5 alpha-reductase genes. One gene (symbol SRD5A1) is functional, contains five exons separated by four introns, and maps to the distal short arm of chromosome 5. Two informative restriction fragment length polymorphisms are present in exons 1 and 2 of this gene. A second gene (symbol SRD5AP1) has all of the hallmarks of a processed pseudogene and was mapped to the q24-qter region of the X chromosome. In the mouse, a single steroid 5 alpha-reductase gene (Srd5 alpha-1) is linked to Xmv-13 on chromosome 13.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Trypsin affects basal and stimulated osmotic water permeability in isolated toad skin.

1. We investigated the effect of trypsin (Tryp) on basal, stimulated and fluphenazine (FPZ)-inhibited net water flow (Jw) through isolated toad skin (Bufo arenarum). 2. Epidermal Tryp (20 min) promoted an increase in basal Jw which was dose-dependent (maximal with 0.5 mg/ml) and was prevented by a Tryp inhibitor (SBTI). 3. Tryp treatment inhibited the subsequent response to substances known to act before (oxytocin, Oxy) or after cyclic AMP (cAMP) generation (theophylline). 4. Tryp-induced Jw was not additive with the maximal response to Oxy or theophylline and did not modify FPZ's inhibitory effect on stimulated Jw. 5. Dermal Tryp (0.5 mg/ml, 20 min) did not modify basal, but inhibited Oxy and isoproterenol-stimulated Jw, without altering the response to theophylline or db-cAMP. 6. Collectively, our results show a differential action for epidermal and dermal Tryp. Tryp's side-selective action enables its use as a pharmacological tool in the functional dissection of Jw across toad skin.

Animals

Effect of rat cardionatrin I (rat ANF 99-126) on the response of toad skin to angiotensin II.

The atrial natriuretic peptide cardionatrin I (cardionatrin I is ANF 99-126) was used in studies directed to assess its effects on osmotic water permeability (Posm) and short-circuit current (SCC) in isolated toad skin. Results showed that ANF 99-126 (10(-7) M) added to the dermal side of the skin had no effect on basal Posm or SCC. However, ANF 99-126 (3.3 x 10(-8) M) was able to produce a 50% reversible inhibition of the maximal Posm response to angiotensin II (AII) (3.2 x 10(-8) M). These effects were seen when the skins were preincubated with ANF 99-126 for 10 min or less before the addition of AII. Longer preincubation appeared to inactivate ANF 99-126 through proteolysis. ANF 99-126(10(-7) M) failed to inhibit the SCC response to AII (10(-5) M) in toad skin. These results are compatible with a modulatory function for ANF on several systems including those involved in the regulation of extracellular fluid volume.

Angiotensin II

Basal and amiloride-induced short-circuit current across isolated toad skin (Bufo arenarum).

We have previously demonstrated that amiloride (amil) addition to the isolated ventral pelvic (VPel) skin of Bufo arenarum toad induces negative short-circuit current values, which are equivalent to the isotopically measured net chloride transport. In the present work, we found that exposure of various regions of toad skin to amil yielded different values of short-circuit current (aSCC): negative aSCC was found in the VPel and ventral pectoral skin, while those of the dorsal one were not different from zero. The distinct values of aSCC found show a regional difference in the active chloride absorption, probably related to postural adaptations. A possible role of this adaptation would be related to chloride participation in the saline balance of the animals, or the maintenance of epithelial integrity.

Amiloride

Reversed short-circuit current across isolated skin of the toad Bufo arenarum.

Short-circuit current (SCC) across isolated pelvic skin of the toad Bufo arenarum has been shown to be reflected by the algebraic sum of net sodium and chloride transport. After the animals had been maintained in tap water, amiloride--an apical sodium channel blocker--led to a reversal of potential difference (rPD) across this preparation, to which corresponded a reversed short-circuit current (rSCC). Both rSCC and rPD were abolished by dermal treatment of skins with the metabolic inhibitor dinitrophenol, or by omission of chloride ion from the Ringer solution bathing both sides of the skin. There was a significant positive correlation between rSCC and isotopically determined net chloride transport after amiloride. An inhibitory action of amiloride on unidirectional chloride fluxes was detected, but only early after drug addition. rSCC was absent in skins of toads exposed to 110 mmol/l NaCl in tap water during 10 days. Together, our results suggest that amiloride addition--by inhibiting active sodium movement--can in certain conditions reveal the existence of an inward active chloride transport.

Amiloride

Comparative effects of angiotensin II on osmotic water permeability in the toad (Bufo arenarum).

The possible relationship between the renin-angiotensin system and water balance in the toad Bufo arenarum has been indirectly explored. A positive correlation was found between the hydrosmotic response of ventral pelvic toad skin to angiotensin II (A II) and some age indicators (body weight, snout-urostyle length or head width). A different hydrosmotic response for oxytocin and isoproterenol (but not for A II) was found between four cutaneous regions of toad body. We conclude that A II may not be directly involved in the regulation of water balance mediated by water absorption across the skin of Bufo arenarum toads.

Angiotensin II

Phenothiazines increase active sodium transport across the isolated toad skin.

Fluphenazine (FPZ) and trifluoperazine (TFP) are phenothiazine derivatives commonly used as antipsychotic tranquilizers. Their mechanism of action is incompletely understood. Epidermal addition of each drug promoted biphasic short-circuit current (SCC) changes across isolated pelvic skin of Bufo arenarum toads. By means of radiotracers fluxes, SCC was found to be given by the algebraic sum of net sodium and chloride transport. A readily stimulant effect was detected a low concentrations (from 1 X 10(-6) mol/l up to 1 X 10(-4) mol/l for FPZ, from 1 X 10(-5) mol/l up to 3.2 X 10(-4) mol/l for TFP) above which inhibition prevailed. Dermal FPZ also stimulated SCC. A higher concentration and time threshold were required. Epidermal 1 X 10(-5) mol/l FPZ stimulation was partially reversible, with a diminished membrane resistance and enhancement of sodium influx, without alteration of sodium efflux or net chloride transport. It could be prevented by amiloride pretreatment, or diminished by dermal sodium removal. Variation of epidermal bulk pH from 5.8 to 8.7 demonstrated that ionized and nonionized molecules contribute to FPZ's effect. Our results suggest that SCC stimulation elicited by FPZ and TFP may be a consequence of direct or indirect modifications on apical sodium conductance.

Amiloride

Angiotensin converting enzyme in the toad Bufo arenarum.

Angiotensin converting enzyme activity (ACEA) was determined in serum, kidney, whole skin and isolated epithelia homogenates of the South American toad Bufo arenarum. ACEA was present in the tissues and serum of the toad. The activity was higher in the kidney, as compared to that of the whole skin or isolated epithelium. Captopril, teprotide and EDTA, caused a significant decrease in the ACEA. Possible physiological roles for the presence of ACEA in the toad are discussed.

Animals

Asbestos and health in the Third World: the case of Brazil.

Almost all of the asbestos used in Brazil is mined by an enterprise wholly owned by two European multinational companies, which also produce and market over two-thirds (by weight of asbestos) of the products made from asbestos. About 80 percent of the asbestos used in Brazil is finally consumed in the form of asbestos cement: for roof tiles and roofing panels, wall-board, and domestic and industrial water tanks. A survey of consumer literature and advertising printed by Eternit, S.A., and Brasilit, S.A., disclosed no mention of a potential danger from exposure to asbestos dust, and no recommendations for cutting down exposure to that dust. The situation at smaller, Brazilian-owned firms is reputed to be disastrous from the standpoint of workers' exposure to asbestos dust at the point of production. At a large asbestos-cement manufacturing plant owned by Eternit, however, exposure to asbestos dust (according to company records) seemed to be kept under 2.0 fibers per cc., the present standard for the United States.

Air Pollutants, Occupational

Inhibition of stimulated osmotic water flow by fluphenazine, a calmodulin inhibitor, in the isolated toad skin.

The effects of fluphenazine, a phenothiazine calmodulin inhibitor, on the osmotic water flow (Posm) across isolated skins of Bufo arenarum toads were tested. Fluphenazine inhibited the increase in Posm induced by agents known to act through the cyclic AMP system (oxytocin, db-cAMP, theophylline, KCl and isoproterenol). The inhibitory effect was faster and more intense when the drug was present in the epidermal bath, and persisted after rinsing the preparation for 100 min. Our results indicate that phenothiazine's action may be primarily exerted at a site distal to cyclic AMP generation.

Animals

How cheap is a life?

The oweners of capital in the United States have successfully transferred most of the costs of industrial casualties onto the working class and the public at large. This has been accomplished by the creation of the privately owened workers' compensation insurance system and the corporate-dominated safety establishment. This "compensation-safety establishment" has been able to take over most of the federal apparatus created by the Occupational Safety and Health Act of 1970. Nevertheless, workers and unions and their allies have begun to challenge the establishment's hegemony over job health and safety policy for the first time in seventy years.

Accident Prevention

Why work kills. A brief history of occupational safety and health in the United States.

In the early 20th century, U.S. monopoly corporations responded to the movement against work accidents by setting up a business-controlled "compensation-safety establishment," which kept down compensation costs but did little to improve working conditions. The "establishment" was able to keep the issue of occupational safety and health out of public debate until the late 1960's through its control of research, education, compensation, and government appointments in the area, and by creating the public impression that the problems of occupational disease were almost nonexistent. Despite the occurrence of sporadic rank-and-file uprisings, unions have been seriously involved in health and safety only since the late 1960's, when they mobilized in an effort to pass the Occupational Safety and Health Act of 1970. The passage of the OSHA law was made possible by the help of progressive professionals, worker dissatisfaction, the new environmental consciousness, and a general climate of social unrest. Although the corporate elite, through the "compensation-safety establishment," has been able to dominate the operation of the federal institutions created by the new law, the question of occupational health and safety is now on the permanent agenda of workers, unions, and the public.

Accidents, Occupational