Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 505 records · Page 28Linked to original sources

PubMed1987

Quinidine attenuates sympathetically induced poststenotic myocardial ischemia.

Beside its antiarrhythmic properties, which in particular are used for the treatment of atrial fibrillation, quinidine is known to have alpha-adrenoceptor blocking properties. On the other hand, atrial fibrillation is reported to cause activation of the sympathetic nervous system which, in turn, reduces coronary blood flow when the coronary reserve is already compromised. Therefore, we tested the effect of quinidine (3 mg/kg i.v.) on the coronary vasculature during electrical stimulation of cardiac sympathetic nerves in the presence and absence of a stenosis on the left circumflex coronary artery. In 7 anesthetized dogs the end-diastolic distal coronary resistance during cardiac sympathetic nerve stimulation in the presence of a severe stenosis on the left circumflex coronary artery increased by 18% before, and decreased by 17% after administration of quinidine. We conclude that quinidine inhibits the vasoconstriction of poststenotic coronary arteries during cardiac sympathetic nerve stimulation and thus might prevent a poststenotic stress-induced myocardial ischemia.

Adrenergic alpha-Antagonists↗

PubMed1987

A 'window of time' during which testosterone determines the opiatergic control of LH release in the adult male rat.

Male rats castrated before puberty (when 26 days of age) showed a progressively decreasing susceptibility to the inhibitory effects of morphine (5 mg/kg) upon LH secretion for up to 28 days after gonadectomy (approximately 100%, 40% and 10% inhibition at 5, 12 and 28 days after castration), but thereafter morphine again caused approximately 50% reduction in serum LH values; the minimum inhibition found at 28 days after castration (age 54 days) occurred at the time at which male rats normally reach puberty. When rats were castrated at 59 days of age, morphine maximally suppressed serum LH concentrations (to less than 70%) 2 and 5 days after castration, but had no effect thereafter. In prepubertal castrates, testosterone replacement between Days 26 and 50 of life resulted in responses to morphine similar to those found in rats castrated after puberty, i.e. serum LH levels were not reduced. Morphine significantly reduced LH levels in prepubertal castrates given testosterone after 60 days of age. Treatment with morphine consistently elevated serum prolactin concentrations (greater than 100%) in castrated rats of all ages, regardless of the time elapsed after gonadectomy. These results indicate a transient fall in the inhibitory opioidergic tone upon LH secretion as the normal age of puberty approaches, that the ability of opiates to alter LH release in adulthood may depend upon testicular steroids secreted during the peripubertal period, and that the LH responses do not reflect general changes in the neuroendocrine response to opiates after castration since the prolactin response to morphine remains intact in rats castrated before and after puberty.

Animals↗

PubMed1987

Pharmacokinetic and pharmacodynamic effects of the novel benzodiazepine antagonist 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one in humans.

2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 8216) is pharmacologically characterized as benzodiazepine antagonist with low inverse agonistic effects. Single oral doses up to 650 mg and subchronic doses up to 100 mg daily for seven days are well tolerated by young healthy volunteers. Plasma concentrations of CGS 8216 are variable, not dose-related and relatively low considering the doses administered. A high plasma concentration ratio of metabolite vs. parent compound (3:1) points to an extensive gastrointestinal first-pass metabolism. CGS 8216 influences the human electroencephalogram similar to anxiolytic and vigilance enhancing drugs in doses which do not change performance of psychometric tests. CGS 8216 antagonizes the diazepam-induced impairment of alertness.

Adult↗

PubMed1987

Rapid change to HMO systems: profile of the Dane County, Wisconsin, experience.

Dane County (Madison), Wisconsin, has experienced a dramatic transformation of its health services into competing closed-panel health maintenance organizations (HMOs). The change occurred literally overnight after the state, as the dominant employer, implemented price competition. In 1983, 22 percent of the 24,000 state employees in Dane County were enrolled in closed-panel HMOs; in 1984 about 85 percent enrolled in one of seven major competing physician HMO plans. In 1985 state employees basically stayed with the HMO they had chosen in 1984, and the only major shift was continued movement away from the standard fee-for-service plan. The Dane County HMO plans were less costly than fee-for-service plans to the state and to the state employee. Fee-for-service state enrollees self-reported greater use of inpatient hospital services and self-reported poorer health than employees selecting HMOs when controlling for age between the two groups. This article describes these changes, why they occurred, and the initial impact on employees as an example relevant to HMO development that may occur elsewhere.

Adult↗

PubMed1987

Early production of 1,4,5-inositol trisphosphate and 1,3,4,5-inositol tetrakisphosphate by histamine and carbachol in ileal smooth muscle.

We have examined the time course of the formation of inositol mono-, bis-, tris, and tetrakisphosphates (InsP1, InsP2, InsP3, and InsP4, respectively) in slices of the longitudinal muscle of guinea pig small intestine that had been prelabeled with myo-3H-inositol. The agonists employed were histamine and carbachol. InsP3 increases immediately with a time course which is similar to that of the increase in contractile force and remains elevated for the rest of the incubation period. High performance liquid chromatography analysis revealed that InsP3 is composed of two isomers, the 1,4,5- and 1,3,4-isomers. The release of 1,4,5-inositol trisphosphate [Ins(1,4,5)P3] was followed by the rapid accumulation of InsP4 and later on by the formation of 1,3,4-inositol trisphosphate [Ins(1,3,4)P3]. Ins(1,3,4)P3 and InsP4 were identified by co-chromatography with the Ins(1,3,4)P3 and 1,3,4,5-inositol tetrakisphosphate prepared from 3H-Ins(1,4,5)P3 using a kinase from rat brain. The time course of accumulation of these compounds is consistent with a second messenger role of Ins(1,4,5)P3 in initiation of smooth muscle contraction.

Animals↗

PubMed1987

Bubble free cell culture aeration with porous moving membranes.

For the cultivation of mammalian cells a new aeration system was developed. Its construction with hydrophobic porous Accurel hollow fiber membranes and the use in reactors with 1 and 20 l reaction volume will be presented and introduced by means of the cultivation of a genetically manipulated mouse cell line. The mass transfer capacity of this system is demonstrated as a function of gas flow rates through the membrane and of the membrane movement.

Animals↗

PubMed1987

Production of human beta-interferon in mouse L-cells.

Mouse L-cells, producing glycosilated human beta-interferon constitutively, were cultivated on microcarriers in bioreactors, equipped with a bubble-free aeration system up to 22 1 scale. Suitable aeration membrane surfaces and medium exchange rates permitted cultivation up to 8 X 10(6) cells/ml with a specific beta-interferon productivity of 2 X 10(4) U/10(6) cells/day. A correlation was found between the number of cell layers on the microcarriers and the specific human beta-interferon productivity.

Amino Acids↗

PubMed1987

[Anatomically corrected levo-malposition of the great arteries].

The term anatomically corrected malposition of the great arteries describes a very rare form of congenital heart disease. In contrast to corrected transposition of the great arteries (atrioventricular and ventriculo-arterial discordance) there is an atrioventricular and ventriculoarterial concordance. The abnormally located arteries arise above the anatomically correct ventricles, the pulmonary trunk originates above the morphologically right ventricle, the aorta arises above the morphologically left ventricle. The abnormal relation (malposition) between the great arteries results from interposition of bilateral abnormal conal myocardium with absence of aortic valve-mitral valve fibrous continuity. In this case report an anatomically corrected laevomalposition of the great arteries associated with dextrocardia and situs solitus, ventricular septal defect and bilateral abnormal conal myocardium with subpulmonary obstruction in a young infant is presented.

Aorta, Thoracic↗

PubMed1987

[Mucolipidosis type II (I-cell disease) with unusually severe heart involvement].

Mucolipidosis II (I-cell disease), an autosomal recessive inborn error of mucolipid metabolism with defective transport of lysosomal enzymes is described in a young infant. Besides the typical findings as a result of the "lysosomopathy", this case presented an unusual and distinct cardiac involvement: a cardiomyopathy with dilatation of the left ventricle and signs of an endocardfibroelastosis.

Cardiomyopathy, Dilated↗

PubMed1986

Release of leukotrienes into the perfusate of calcium-ionophore stimulated rabbit lungs. Influence of 5-lipoxygenase inhibitors.

UNLABELLED: Arachidonic acid and the calcium ionophore A23187 are known to provoke a pulmonary artery pressor response, edema formation and release of thromboxane B2 (TxB2) and 6-keto prostaglandin-F1 alpha (6-keto PGFl alpha) into the recirculating perfusion fluid of isolated blood-free perfused rabbit lungs. Here we investigated the release of leukotrienes (LTs) by repetitive 0.1 microM A23187 challenge in the presence or absence of cyclooxygenase and 5-lipoxygenase inhibitors. RP-HPLC analysis of perfusion fluid extracts persistently showed peaks with retention times of authentic LTC4, -D4, -E4 and -B4. Fractionated RP-HPLC eluate subjected to radioimmunoassay (RIA) with LTC4 and LTB4 antibodies showed two major peaks of immunoreactivity corresponding to those compounds and minor immunoreactivity with LTD4 and LTE4 in accordance with the stated cross-reactivities of the LTC4 antibody. Good correlation for both LTB4 and LTC4 levels measured by RP-HPLC versus RIA of collected HPLC peaks was found. Five to ten min after A23187 challenge, LTC4, -D4 and -B4 levels ranged from 800 to 1600 pg/ml perfusate. LTC4 reached a maximum level at 20 min whereas LTB4 slightly increased over a 35 min period. Upon repeated A23187 challenge, interrupted by rinsing phases with fresh perfusion fluid, the LT release was reproducible several times with increasing reaction strength. This performed in presence of increasing concentration of the 5-lipoxygenase inhibitors AA-861 or U-60,257 caused a dose-dependent inhibition of the release of all LTs with an IC50 of approximately 10(-8) to 10(-7) M and 10(-6) M, respectively. Cyclooxygenase inhibition with acetylsalicylic acid at doses completely suppressing the A23187 induced pressor response did not inhibit the peptidoleukotriene release and only slightly depressed LTB4 release. CONCLUSION: using a rapid and sensitive extraction and RP-HPLC method isolated lungs are found to release nanomolar amounts of LTs into the perfusate upon repetitive A23187 challenge, suppressed by 5-lipoxygenase inhibition.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Immunohistological localization of 17 beta-estradiol and testosterone in the ovary of the rainbow trout (Salmo gairdneri Richardson) during the preovulatory period.

Antisera (AS) raised in rabbits against 17 beta-estradiol (E) and testosterone (T) were tested for their suitability to localize E and T on deparaffinized, rehydrated sections of preovulatory trout ovaries, using the unlabeled antibody technique. Conventional control experiments demonstrated the specificity of the staining reactions. Furthermore, no staining was observed after the removal of T-specific antibodies by affinity chromatography, or following gonadectomy when non-gonadal tissue sections of male trout were incubated with T-AS. Antiserum, raised against 11-oxotestosterone and devoid of antibodies cross-reacting with T, did not stain ovarian sections. The loci at which E and T are detected in the somatic compartment are consistent with the two-cell concept of estrogen synthesis, where aromatizable androgens are produced in the thecal/interstitial layer and serve as substrates for estrogen synthesis in granulosa cells. Both steroids were detected in yolk vesicles from the stage of endogenous vitellogenesis. T-AS showed affinity for nuclei of vitellogenic oocytes. Nucleoli were not stained.

Animals↗

PubMed1986

Opiates induce long-term increases in prodynorphin-derived peptide levels in the guinea-pig myenteric plexus.

The subcutaneous administration of a single dose of an opiate agonist (levorphanol) or antagonist (naloxone) to guinea pigs results in an at least 3-fold elevation of dynorphin and alpha-neoendorphin-immunoreactivity in the longitudinal muscle myenteric plexus preparation. The effects are time- and dose-dependent, significant elevations first being observed 6 h after treatment and lasting for up to 24 h. Pretreatment levels of opioid peptides were observed after 8 days. Combined injection of the narcotic agonist and antagonist, at sufficiently high doses, resulted in an additive effect of the individual drugs. The respective stereoisomers dextrorphan and (+)-naloxone did not affect prodynorphin-derived peptide concentrations. An increase of endogenous opioids was also observed after administration of the nonopiate clonidine, a compound which, like opiates, alters the activity of the myenteric plexus. It is suggested that feedback mechanisms in the myenteric plexus are responsible for the elevation of endogenous opioid peptides following exposure to exogenous opiates. Using a monoclonal antibody (3-E7), which recognizes virtually all endogenous opioid peptides, it was found that levels of higher molecular material were also increased upon opiate challenge. This suggests that a single dose of an exogenous opiate results in an increase in peptide synthesis.

Animals↗

PubMed1986

In vitro metabolism of steroid hormones in the liver and in blood cells of male rainbow trout (Salmo gairdneri Richardson).

Male rainbow trout show high plasma androgen levels beginning with the period of full spermatogenesis until the end of spermiation. The difficulties in explaining the steroid levels in regard to the concomitant changes of the plasma GTH concentrations prompted investigations into whether the steroid demand may be met in part by extragonadal steroid metabolism. The results of in vitro experiments with liver tissue fit into the concept of an interrenal-liver-gonad axis of androgen production, since increased amounts of C-19 steroids were detected in the media after incubation of hepatic tissue with cortisol. 17 beta-Hydroxysteroid dehydrogenase and hydroxysteroid glucuronyltransferase activities were shown to be associated with blood cells of mature males. The fact that unidentified products from incubations with 17 beta-estradiol, testosterone, and 17 alpha-hydroxyprogesterone were also found suggests that other steroid metabolizing enzymes are also associated with blood cells. The possibility is discussed that, assuming the blood cell activities are relevant in vivo, a production of potent androgens or the formation of water soluble steroid derivatives could proceed in the blood (e.g., 11-ketoandrostenedione----11-ketotestosterone; testosterone----testosterone glucuronide), possibly affecting the organism's steroid balance.

17-alpha-Hydroxyprogesterone↗

PubMed1986

Paradoxical LH and prolactin responses to naloxone after chronic treatment with morphine.

A series of experiments was conducted in adult male rats to study the development of tolerance to and dependence on morphine in the neural processes controlling LH and prolactin secretion. The central mechanisms controlling both these hormones became tolerant following chronic application of the opiate agonist; this was seen in the form of diminished responsiveness to the agonist with time. There was an apparently greater degree of tolerance in the mechanisms regulating LH secretion than in those regulating prolactin secretion. In parallel experiments, the opiate antagonist naloxone was used to test for the development of dependence in rats chronically treated with morphine. While behavioural signs of physical dependence (withdrawal) were evident, the LH and prolactin responses proved to be the same as those observed in response to acute administration of opiate agonists (i.e. naloxone respectively decreased and increased serum LH and prolactin concentrations in animals chronically treated with morphine). This paper may represent the first report of such paradoxical responses to naloxone. It also demonstrates that opioid tolerance and dependence may exist as two separate phenomena in vivo.

Animals↗

PubMed1986

Effect of cholera toxin and pertussis toxin on opioid tolerance and dependence in the guinea-pig myenteric plexus.

Opioid tolerance and dependence are characterized in terms of inhibitory and excitatory neuronal mechanisms. Bacterial toxins were used to investigate these phenomena in the isolated guinea-pig ileum (GPI) and mouse vas deferens (MVD). Cholera toxin (CT) and pertussis toxin (islet activating protein; IAP) have been demonstrated to selectively impair the function of either the stimulatory or inhibitory nucleotide regulatory protein, mediating the signal transmission to the adenylate cyclase. It has been found that CT failed to affect electrically evoked twitch tension in naive and tolerant GPI and MVD. Twitch tension evoked by excitatory drugs, e.g. neurotensin, was attenuated in the GPI, but not in the MVD. CT did not interfere with the actions of opioids or nonopioids in either the GPI or the MVD. Similarly, IAP failed to affect electrically evoked twitch tension. It virtually lacked an effect on the inhibitory action of opioids and nonopioids on electrically stimulated naive and tolerant GPI and MVD. On the other hand, both CT and IAP dose-dependently attenuated the naloxone precipitated withdrawal contracture in the GPI rendered opioid-dependent. These findings may suggest that opioid receptors at nerve terminals of the GPI and the MVD are not linked to adenylate cyclase, and those receptors relate to the state of tolerance. In contrast, opioid receptors located at nerve somata may be linked to adenylate cyclase. Those receptors may be associated with the development of dependence. The experiments with CT suggest a synaptic excitatory input of neighboring nerve elements necessary for the generation of a withdrawal contracture.

Adenylate Cyclase Toxin↗

PubMed1985

Polyclonal anti-idiotypic opioid receptor antibodies generated by the monoclonal beta-endorphin antibody 3-E7.

Anti-idiotypic antibodies were raised in rabbits against the monoclonal beta-endorphin antibody 3-E7. These antibodies inhibit beta-endorphin binding to the 3-E7 antibody, binding of 3H-diprenorphine to solubilized opioid receptors and the binding of 125I-beta-endorphin to rat brain membranes. Exposure of NG-108CC15 hybrid cells to anti-idiotypic antibodies produces an opioid-like inhibition of PGE1-stimulated cAMP accumulation. These data suggest that the antibodies raised by the anti-idiotypic route both bind to and activate opioid receptors.

Animals↗

PubMed1985

Opioid dependence in the guinea-pig myenteric plexus is controlled by non-tolerant and tolerant opioid receptors.

The experiments concerned the association of opioid dependence with specific opioid receptors. Previous investigations have demonstrated that tolerance may be confined to only one type of opioid receptor. These findings could suggest that dependence develops invariably only with receptors which have been rendered tolerant. We report here that in the guinea-pig isolated ileum, which has been made selectively tolerant to a mu-receptor agonist, naloxone may precipitate a sign of dependence at mu-receptors chronically activated and at naive kappa-receptors. Furthermore, suppression of the withdrawal contracture in preparations rendered dependent on a mu-receptor agonist can be achieved by very low concentrations of a kappa-agonist, e.g. dynorphin A. These findings challenge the current concept that confines drug dependence only to that opioid receptor type which has been activated chronically.

Animals↗

PubMed1985

Generalization tests with intraventricularly applied pro-enkephalin B-derived peptides in rats trained to discriminate the opioid kappa receptor agonist ethylketocyclazocine.

Rats were trained in a two-lever food-reinforced procedure to discriminate between the effects of saline and the opioid kappa receptor agonist ethylketocyclazocine. After acquisition of this discrimination, generalization tests with opioid peptides such as beta-endorphin, alpha-neoendorphin, dynorphin A and some dynorphin-derived peptides were conducted. The rats dose-dependently generalized the effects of intracerebroventricularly injected ethylketocyclazocine but not beta-endorphin, alpha-neoendorphin, dynorphin A1-8, dynorphin A1-13, D-Cys2-L-Cys5-dynorphin A1-13 or dynorphin A. D-Cys2-L-Cys5-dynorphin A1-13, in contrast to dynorphin A itself, dose-dependently caused analgesia and catatonia that was reversible with naloxone. Studies into the receptor preference of this derivative, using the technique of "selective tolerance", revealed that this dynorphin derivative is almost devoid of kappa-receptor activity.

Animals↗