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Biomedical subjects

R Reich

Publications and source records attributed to R Reich.

At least 91 records · Page 5Linked to original sources

The involvement of collagenolysis in ovulation in the rat.

Collagenolytic activity in ovarian follicles was previously demonstrated by using synthetic peptides and reconstituted collagen fibers. However, attempts to demonstrate degradation of ovarian collagen and to correlate collagenase activity with ovulation were not successful. By administration of L-(5-3H) proline, we have labeled ovarian and follicular collagen and followed collagenolytic activity by separation of 3H-hydroxyproline (3H-Hyp) from acid hydrolyzates of ovarian tissue by HPLC. The level of ovarian and follicular 3H-Hyp decreased by about 40% on the afternoon of proestrus or after exogenous stimulation of ovulation by human CG (hCG), and this decrease was abolished by blocking the surge of gonadotropins with Nembutal. To verify that the observed reduction in 3H-Hyp was due to the action of a typical collagenase, the collagenous fraction was prepared from ovarian tissue and from preovulatory follicles before and after the ovulatory stimulus. The extracts were treated with trypsin (25 min, 25 C, 0.01 mg/ml) plasmin and p-amino-phenyl-mercuric acetate to fully activate the collagenase extracted along with collagen. Both, enzymatic and chemical activation of collagenase in vitro resulted in degradation of collagen. This degradation could be inhibited by cysteine and EDTA; both are classic inhibitors of mammalian collagenases. The activity of ovarian collagenase increased within 3 h after hCG-stimulation, peaked at 5-fold 6 h after hCG, and declined afterwards. Administration of cysteine (0.001-0.01 mmol) into the bursal cavity of proestrous rats blocked ovulation and breakdown of ovarian collagen in a dose-dependent manner. Cysteine effectively inhibited ovulation even when injected 7 h after the hCG stimulus. Inhibitors of arachidonic acid metabolism prevent ovulation. Indomethacin (inhibitor of cyclooxygenase) and nordihydroguaiaretic acid (inhibitor of lipoxygenase) blocked ovulation and inhibited hCG-induced ovarian collagenolysis. Collectively, these results corroborate the essential role of collagenolysis in follicular rupture in mammals.

Aminocaproic Acid↗

Stimulation of coronary guanylate cyclase by nicorandil (SG-75) as a mechanism of its vasodilating action.

Since there is evidence suggesting that nicorandil (SG-75) relaxes coronary arterial smooth muscle by increasing cGMP levels, the effects of this vasodilator on soluble guanylate cyclase from bovine coronary arteries were studied more closely. It was found that nicorandil stimulated guanylate cyclase dose-dependently (3-30 mM) up to 100-fold the control value. Similar to nitroglycerin but in contrast to sodium nitroprusside, cysteine (0.5-20 mM) was required to obtain this stimulation. All other investigated thiols, except thiosalicylic acid which was partially able to mimic the cysteine effect, were ineffective. As evident from time course studies, nicorandil induced stimulation of guanylate cyclase was characterized by a lag-phase which could be avoided by preincubating the enzyme with nicorandil. The stimulatory effect of nicorandil was diminished in the presence of methylene blue, ferricyanide or hydroquinone. These results give further evidence that a) nicorandil exerts its vasodilating effect via stimulation of guanylate cyclase and b) nitrate esters, such as nitroglycerin or nicorandil, stimulate the enzyme, at least in vitro, only in the presence of cysteine or, to a lesser extent, thiosalicylic acid.

Animals↗

Possible involvement of lipoxygenase products of arachidonic acid pathway in ovulation.

The possible involvement of products of the lipoxygenase pathway of arachidonic acid cascade in ovulation was tested by intrabursal injection of nordihydroguaiaretic acid (NDGA); 5, 8, 11-eicosatriynoic acid (5, 8, 11-ETYA), 3 amino-1-(3 trifluromethyphenyl)-2-pyrazoline hydrochloride (BW755c) and (FPL 55712). All these drugs reduced the number of ova released from the treated ovaries in a dose-dependent manner, without affecting ovulation from contralateral ovaries. NDGA was most potent since it completely blocked ovulation from the treated ovaries in 17/38 rats receiving a dose higher than 0.15 mg/bursa. This effect of NDGA cannot be ascribed to its inhibition of ovarian PGE synthesis. Conversion of labeled arachidonic acid via the lipoxygenase pathway by preovulatory rat follicles was demonstrated by TLC chromatography. Collectively, these results suggest the involvement of products of lipoxygenase pathway of arachidonic acid in ovulation in the rat.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

In vitro effects of cannabinoids on follicular function in the rat.

delta 1-Tetrahydrocannabinol (delta 1-TCH), the major psychoactive constituent of marihuana, was found to suppress the preovulatory surge of gonadotropins and thereby to prevent ovulation in rats, rabbits and rhesus monkeys. These studies suggested that the drug acts primarily on the hypothalamus to suppress luteinizing hormone releasing hormone (LHRH) secretion. The aim of the present study was to examine the direct effect of delta 1-THC, the psychoactive constituent of marihuana and cannabidiol (CBD), one of its nonpsychoactive constituents, on preovulatory rat follicles in vitro. Both cannabinoids inhibited follicular steroidogenesis in a dose-dependent manner. Basal accumulation of progesterone (P), testosterone (T) and estradiol-17 beta (E2) was reduced up to 60% by the highest doses examined (100-200 microM). The luteinizing hormone (LH)-stimulated increase in P and T was inhibited by 75-88% by the highest doses of both cannabinoids (50-200 microM), while E2, accumulation was inhibited by only 40%. It appears that the inhibitory action of cannabinoids is exerted beyond LH binding and activation of adenylate cyclase and prior to pregnenolone formation in the gonadal steroidogenic pathway. In addition to this anti-steroidogenic effect, both cannabinoids induced resumption of meiosis in follicle-enclosed oocytes cultured in hormone-free medium; 200 microM delta 1-THC resulted in 80% maturation and CBD in 75%. It seems that the action of cannabinoids on rat follicles in vitro is unrelated to their psychotropic activity.

Adenylyl Cyclases↗

Effect of clomiphene citrate on preovulatory rat follicles in culture.

The effect of clomiphene citrate was tested on rat preovulatory follicles in culture. Clomiphene inhibited both basal and luteinizing hormone (LH)-stimulated steroid accumulation. The dose-dependent effect of clomiphene was much more pronounced on follicles cultured with LH; while 0.01 mM had no effect, 2 mM clomiphene decreased progesterone accumulation by 97%, estradiol-17 beta by 90% and testosterone by 65% (P less than 0.001). The inhibitory action of the drug was not prevented by addition of 8-Br-cAMP (1 mM) or pregnenolone (1 microgram/ml) to the culture medium. clomiphene (0.01 - 0.5 mM) induced the resumption of meiotic maturation even in LH-free medium in approximately 60% of follicle-enclosed oocytes. At the higher concentrations tested (0.1 - 0.5 mM) degenerative changes were noted in a high proportion of oocytes (30-40%). Follicles incubated for 24 h with clomiphene exhibited dose-dependent atretic-like changes. These effects of clomiphene on preovulatory follicles may account for the discrepancy between ovulation and pregnancy rates observed in women treated with clomiphene.

Animals↗

Norepinephrine in Graafian follicles is depleted by follicle-stimulating hormone.

The purpose of the present study was to measure norepinephrine (NE) in Graafian follicles and correlate changes in its concentration with circulating gonadotropins secreted endogenously or administered exogenously. Graafian follicles were removed from the ovaries of adult cycling rats. The follicles were pooled in groups of 10-13, and NE was determined by high performance liquid chromatography. Follicular NE(picograms per micrograms protein) did not change between 0900 h (3.61 +/- 0.34) and 1300 h (3.12 +/- 0.25) on proestrus, but was reduced significantly to 1.45 +/- 0.16 at 2100 h, which is 4 h after the peak of the gonadotropin surge. There was a further reduction to 0.83 +/- 0.08 in fresh corpora lutea taken on estrus at 0900 h. The decrease in follicular NE was prevented in estrous rats which were either hypophysectomized 24 h previously or treated with sodium pentobarbital at 1330 h on proestrus. To determine which pituitary hormone was responsible for follicular NE depletion, rats were injected at 0900 h on proestrus with LH (5 micrograms), FSH (20 micrograms), LH plus FSH (5 and 20 micrograms, respectively), or PRL (20 micrograms), and follicular NE was determined 4 h later. FSH reduced follicular NE significantly to 1.86 +/- 0.16 compared to both the control (3.12 +/- 0.25) and the PRL-injected group (2.92 +/- 0.32), whereas LH caused a small but nonsignificant decrease (2.49 +/- 0.2). Both LH and FSH doses used resulted in ovulation, as determined by counting tubal ova 12 h after hormonal treatment. We conclude that 1) NE in Graafian follicles is markedly reduced within 4 h after the preovulatory gonadotropin surge in the normal cycling rat; this reduction is prevented when the surge is abolished; 2) the hormone responsible for follicular NE depletion is FSH rather than LH or PRL; and 3) finally, it is suggested that follicular NE may be involved with the formation and/or functioning of the corpus luteum.

Animals↗

The emergence of the Bowery as a psychiatric dumping ground.

The drastic reduction of State Hospital population in New York over the past decade has led to a demographic relocation of the mentally ill, rather than any real decline in the rate or severity of mental disorders. Unable to function on their own in society and without adequate supportive facilities available, many discharged patients live in the streets and eventually end up on the Bowery, where they are cared for at The Men's Shelter. Studies have shown that over 50% of the current Bowery population has a history of mental illness and that alcoholism is often a secondary, rather than primary diagnosis. The most frequently encountered diagnostic syndromes are mentioned and commented upon. Possible alternative treatment interventions are suggested.

Age Factors↗

Indication of the metarhodopsin I-II transition by absorption-changes of Eriochromblack T.

The dye eriochromblack T (erio T), added to an aqueous suspension of bovine retinal outer segments solubilized by digitonin, shows a light-induced absorption-increase at lambda = 645 nm. Erio T is shown to directly interact with miscellar metarhodopsin I and metarhodopsin II. The absorption-changes of erio T can be regarded as an indication of the transition from the metarhodopsin I conformation (with associated Ca2+) to the metarhodopsin II conformation (with associated H+).

Animals↗

Effect of electric fields on the absorption spectrum of dye molecules in lipid layers. V. Refined analysis of the field-indicating absorption changes in photosynthetic membranes by comparison with electrochromic measurements in vitro.

The comparison of light-induced absorption changes in photosynthesis with electrochromic spectra of the isolated pigments in vitro is renewed more thoroughly and described in detail, involving new measurements of the linear electrochromism of oriented chlorophyll beta [6]. 1. The coincidence of the maxima and minima in the in vivo spectrum with those in the in vitro superposition is better than in previous studies [4]. 2. The molar ratio of the pigments now used for the superposition of the in vitro spectra is the same as that in vivo. 3. From this and from surface-pressure/area diagrams of the chlorophylls on a water surface, conclusions are drawn concerning the preferential orientations of the dipole moment differences of the red and blue absorption bands of the bulk chlorophylls in the membrane. 4. From the comparison of the electrochromism of the carotenoids with the absorption change at 520 nm in vivo, it is concluded that the bulk of the carotenoids are oriented at a rather flat angle in the membrane (approximately 16 degrees).

Carotenoids↗

The effect of Ca2+ on the metarhodopsin I-II transition. I. Experiments.

The effect of Ca2+ on kinetics and equilibrium of the Meta I-II transition was studied in rhodopsin-digitonin-solutions using flash-photometry. With increasing Ca2+-concentrations the Meta I-II-equilibrium is shifted to Meta I. The pH-dependence of the Meta I-II equilibrium is suppressed by Ca2+. To obtain the same effect as with bivalent cations about the 10-fold concentration of univalent ions is required. Ca2+-ions have also an effect on the rate of equilibrating Meta I-II: with increasing Ca2+-concentration the rate-constants of the rapid and slow component decrease and become equal to the value at pH8. This observation can be described as an inhibition of the catalytic effect of protons by Ca2+. Similar results are obtained with Mg2+, whereas K+ and Na+ are practically ineffective. In the presence of the Ca2+-blocking agents verapamil (Isoptin) and D-600 the rate of equilibrating Meta I-II is reduced. These and several former observations can be explained by a model in which the Meta I-II transition is coupled with the separation of negative fixed charges, which can be clamped by Ca2+.

Animals↗

The effect of Ca2+ on the metarhodopsin I-II transition. II. Model calculations and hypothesis on a molecular mechanism of visual excitation.

The model for the effect of Ca2+ on the Meta I-II transition (cf. Part I) is formulated quantitatively and in detail. The clamping forces of Ca2+, which shift the equilibrium to the closed MI-conformation, are taken into account in the law of mass action by a higher value for the association constant of Ca2+ with MI than with MII. Thus the main features of the experimental curves of delta MII-absorption-change as a function of Ca2+- and H+-concentration can be reproduced by a few simple association equilibria. The agreement can be improved by calculating with a conformative coupling between two rhodopsin molecules. In a further modification of the model also the observed increase of delta MII in the alkaline beyond pH 9 is reproduced. Finally, the models lead to an opening and closing mechanism for a Ca2+-permeable pore across the disc membrane, thus contributing to a hypothesis of visual excitation.

Calcium↗

The murdered child and his killers.

The authors studied 112 cases of child homicide in New York City in 1968-1969 to identify contributing social and psychiatric factors and to determine the fate of the surviving siblings and the degree of involvement of the city's social agencies with the families. There was a pattern of long-term familial child maltreatment extending to the siblings and continuing after the murders. The victims were usually illegitimate preschoolers; the assailants, usually the mothers or their paramours, had backgrounds of assaultiveness and social deviance and killed in impulsive rage. Reports of sexual abuse of victims or of suicide or psychosis among assailants were rare. The authors present case illustrations and offer guidelines for improved prevention by psychiatrists and social workers.

Child Abuse↗