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Biomedical subjects

M Molnár

Publications and source records attributed to M Molnár.

At least 19 recordsLinked to original sources

N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents.

OBJECTIVE: With N omega-nitro-L-arginine, a potent inhibitor of nitric oxide synthesis, we tested the hypothesis that nitric oxide plays a functional role in the blunted pressor responsiveness seen during pregnancy. STUDY DESIGN: A group of six pregnant rats were instrumented on the fourteenth day of gestation and studied on days 19 and 20, as well as 7 days post partum. Another group of six virgin rats were similarly prepared and used 5 days after surgery. Blood pressure and heart rate were monitored in conscious freely moving animals before and during the administration of drugs or placebo. Results were analyzed, by one-way repeated-measures analysis of variance, with Dunnett's t test, or by paired t test where applicable. RESULTS: Basal mean arterial pressure and heart rate were 90.8 +/- 3.0 mm Hg and 330 +/- 6 beats/min in pregnant animals and 107.1 +/- 3.2 mm Hg and 315 +/- 7 beats/min in nonpregnant animals. Pressor responses to angiotensin II, vasopressin, and norepinephrine were attenuated in gravid animals. Infusion of N omega-nitro-L-arginine significantly and in a dose-dependent manner increased mean arterial pressure and reduced heart rate. These effects could be completely reversed by L-arginine administration. Changes in mean arterial pressure were higher during pregnancy as compared with postpartum values. N omega-nitro-L-arginine infusion potentiated pressor responses to all three vasopressors, resulting in dose-response curves that were significantly shifted to the left, making them virtually identical in pregnant and postpartum rats. CONCLUSION: Our data support the emerging view that nitric oxide plays a key role in the regulation of blood pressure during pregnancy.

Angiotensin II

Influence of chicken and human lipoproteins on steroidogenesis in granulosa cells of the domestic fowl (Gallus domesticus).

When freshly dispersed granulosa cells from the largest preovulatory follicle were incubated in the presence of very low density (VLDL), low density (LDL), or high density (HDL) lipoproteins isolated from sera of laying hens, production of both basal and LH-stimulated progesterone was significantly increased in a dose-related manner. VLDL, the principal transporter of cholesterol to the ovum, appeared to be the most efficacious. A highly significant potentiation of the steroidogenic action of 8-bromo-cyclic adenosine monophosphate and forskolin was also observed. Human LDL, and especially HDL, caused significant stimulation of progesterone production by these cells. It is suggested that the release of cholesterol from lipoproteins taken up by granulosa cells raises the precursor pool for steroidogenesis. This mechanism is further enhanced by a cyclic AMP-mediated mechanism.

8-Bromo Cyclic Adenosine Monophosphate

Dual action of arachidonic acid on calcium mobilization in avian granulosa cells.

The primary aim of this study was to evaluate the effects of arachidonic acid (AA) on calcium mobilization from intracellular compartments in digitonin-permeabilized granulosa cells isolated from the largest preovulatory follicles of laying hens. At low concentrations (ED50 0.2 microM) AA released 35% 45Ca from the endoplasmic reticulum (ER), whereas at higher concentrations (ED50 16 microM) it stimulated 45Ca efflux from mitochondria. These effects of AA were mimicked at 10-20 times lower concentration by the calcium ionophore A23187. Inositol 1,4,5-trisphosphate (IP3) also stimulated 45Ca efflux from the ER, with a markedly lower potency than AA (ED50 6.2 microM), as well as exhibiting a biphasic response. Heparin abolished the effect of IP3 and luteinizing hormone (LH), but it had no influence on AA-promoted 45Ca efflux. Moreover, the actions of IP3 and AA were additive, indicating that AA and IP3 access different Ca pools in the ER by different mechanisms. Several other unsaturated fatty acids also stimulated 45Ca mobilization from both ER and mitochondria but, with the exception of eicosapentaenoic acid, were significantly less effective than AA. It is concluded that free AA, at submicromolar concentrations that might be viewed as physiological, is a potent calcium mobilizing agent and thus may play an important role in signal transduction in avian granulosa cells, akin to that of IP3. At high (greater than 10 microM) concentrations AA removes Ca2+ from the mitochondria, an action that may be responsible for its reported inhibitory effects on steroidogenesis and other cellular functions.

Analysis of Variance

Biphasic effect of calcium on luteinizing hormone-stimulated cyclic adenosine 3',5'-monophosphate production in granulosa cells of the fowl (Gallus domesticus).

Both cAMP and Ca2+ play important roles in the steroidogenic action of LH in hen granulosa cells. However, the interaction of these intracellular messengers is not fully understood. In the present study we used two calcium ionophores (ionomycin and A23187), as well as trifluoperazine (TFP), an inhibitor of calmodulin, to investigate LH- and forskolin-induced cAMP production in granulosa cells isolated from the largest (F1) preovulatory follicle of White Leghorn laying hens. Between 0.1 and 1.0 microM, both ionophores significantly potentiated cAMP responses to LH in the presence of 0.1 mM extracellular Ca2+. When calcium was omitted from the medium, ionophores had no effect. When either calcium was raised above 1 mM, or the concentration of ionophores was increased above 1 microM, LH-induced cAMP production was drastically inhibited. In the presence of 0.5-2.0 mM calcium, A23187 inhibited forskolin-promoted cAMP synthesis. TFP, while having no effect on basal cAMP, suppressed LH-induced responses and the potentiating effect of ionomycin. It is concluded that for full activation of the adenylate cyclase/cAMP system by LH, Ca-calmodulin is required at a site upstream from the catalytic component of the enzyme. However, high intracellular Ca2+ and/or other effects of ionophores (such as uncoupling of oxidative phosphorylation) inhibit LH-induced cAMP production.

Adenylyl Cyclases

Low-dimensional chaos in event-related brain potentials.

The quantification of a chaotic system, such as the nervous system, can be made by calculating the correlation dimension (D2) from a sample of the data it generates. The encephalogram was recorded from the vertex during an auditory "odd-ball" paradigm and was signal-averaged to reveal the event-related potentials (ERPs). A new method for continuously estimating D2, the "Point-D2" (PD2), was determined from the same data, and it also was signal-averaged. The PD2 method was found to be more accurate than others currently used for investigating finite data; it also was found to track nonstationarities that arise within the data. A significant (p < .001) PD2-decrease accompanied the ERPs evoked by target stimuli; the PD2 onset-latency and peak did not correlate with any ERPs. The very short latency suggests that the PD2-decrease may be associated with "selective stimulus set," an interpretation that has been related to early cortical ERP components.

Acoustic Stimulation

Inflammatory changes in facioscapulohumeral muscular dystrophy.

Fifteen patients (10 familial and 5 sporadic cases) with facioscapulohumeral dystrophy were studied with regard to the presence of inflammatory changes. Mononuclear infiltrations were not characteristic of any stage of the disease, but they may be present in differing degrees during the whole course of the process. However, their lack or presence was uniform in the affected families, suggesting that the appearance of infiltrations may be genetically determined. Parallel with the presence of cell infiltrations, the serum creatine kinase (CK) activity was moderately increased and the progress of the disease was slightly accelerated. The relation of these phenomena to polymyositis and the diagnostic difficulties are discussed.

Adolescent

[General experiences in dental screening of adolescents].

The dental and mouth hygiene of youth of 14 to 19 years of age have been separately analyzed from the results of the general dental screen test performed between 1985 and 89 by the Clinic of Prosthetic Dentistry of Budapest. The global DMF-T index of the first national sites was 8.99 and the OHI-S index was 1.37.

Adolescent

[General aspects of planning fixed dentures on implants].

Designing of fixed replacements also containing the implant abutment is determined by that none of the implant kinds can be regarded as first rate abutment tooth in view of loadability. In the course of designing bridges the prosthetic principles regarding the weaker or damaged periodontic teeth are followed. Burning sensation is a common complaint in the patients suffering from a contact allergic reaction of the oral cavity. Several studies are available in the literature for testing the allergenicity of dental materials. Standard test series were designed to detect allergens present in plastics and metals used in prosthetic dentistry. The epicutaneous patch-test was carried out with Finn Chamber. The test material was placed into the chamber, which was applied on the back of the patients for 24 or 48 hours, and was read after removal at fixed intervals. The authors stress the desirability of the allergic prescreening in dentistry.

Dental Implantation, Endosseous

Pressor responsiveness to endothelin is not attenuated in gravid rats.

The aim of this study was to evaluate the effect of synthetic human/porcine endothelin (ET-1) on mean arterial blood pressure (MAP) in pregnant and non-pregnant rats and to compare this to the effects of two well characterized agonists, angiotensin II (AII), and vasopressin (VP). On day 14 of gestation (parturition day 22) polyethylene catheters were chronically implanted in the abdominal aorta for monitoring of MAP and in the vena cava for administration of drugs. Pressor responsiveness was measured in conscious freely moving animals on day 20 and again on the 7th day post-partum. All three agonists increased MAP in a dose related manner. However, whereas the sensitivity of pregnant rats (P) to AII and VP was significantly blunted compared to postpartal (PP) measurements, the MAP responses to ET-1 were the same in both groups. Moreover, the combined administration of ET-1 at a subpressor dose (0.05 pmol/100 g bw) and AII or VP at effective doses significantly potentiated (particularly in P) the pressor effects of AII and VP. These results demonstrate that ET-1 and possibly other vasoactive substances of endothelial origin, override the compensatory mechanism of normal pregnancy with respect to the blunted responsiveness to AII and VP. Such a mechanism may be of particular relevance in the evolution of pregnancy-induced hypertension.

Angiotensin II

Steady-state responses from the cat auditory cortex.

Responses to 350 ms trains of clicks with 10-100 Hz repetition rate were recorded from the auditory cortices of six cats. Click trains of 30-50 and 90-100 Hz elicited a clear steady-state response (SSR) in awake state. SSRs were small or absent below 30 Hz and in 60-70 Hz stimulus range. In slow wave sleep the optimal rate to elicit SSR shifted towards lower frequencies. 90 Hz SSR was largest in paradoxical sleep. SSRs were strongly suppressed by barbiturate anesthesia. The amplitude of the SSR from the medial geniculate body (MGB) in two cats gradually decreased from 20 to 100 Hz and was more resilient to barbiturate anesthesia than the cortical SSRs. Only low amplitude or no SSRs could be recorded from vertex, visual and association cortices and from the hippocampus in control recordings. The results suggest different generation mechanisms for SSRs recorded from cat auditory cortex and MGB. Human auditory SSRs resemble cat auditory cortical SSRs more than those recorded from cat MGB. The results imply that auditory SSRs in humans are generated in the cortex.

Acoustic Stimulation

Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.

Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.

Adult

PGF2 alpha and PGE2 binding to rat myometrium during gestation, parturition, and postpartum.

The specific binding of prostaglandins (PG) F2 alpha and E2 was studied in a rat myometrial membrane-enriched fraction during the latter part of gestation and parturition, as well as in the postpartal period. Tritiated PGE2 and PGF2 alpha binding was specific, saturable, time dependent, and directly proportional to the amount of membrane protein. Scatchard analysis indicated the presence of high-affinity (Kd2) and low-affinity (Kd2) binding sites for both PGs. The affinity of both binding sites for PGF2 alpha and the apparent Kd2 for PGE2 remained essentially the same throughout gestation and post-partially and were similar to nonpregnant rats. The apparent Kd1 of PGE2, however, increased by 10-fold from day 21 of gestation to 1 day postpartum. Although the maximal binding capacity of the high-affinity (Bmax1) and low-affinity (Bmax2) binding sites of PGF2 alpha showed a nonsignificant increase compared with prepartum values, reaching maximal values 12-24 h postpartum, those of PGE2 showed a significant increase on the third day after delivery. The concentration of prostanoids in uterine venous plasma and amniotic fluid increased significantly with approaching parturition, whereas plasma progesterone decreased, raising the estradiol-progesterone ratio 25-fold. After unilateral fetectomy, the binding sites for PGF2 alpha and PGE2 increased significantly compared with the contralateral pregnant horns. Administration of the PG synthetase inhibitor, indomethacin, also increased two- to threefold both PGF2 alpha and PGE2 binding compared with the placebo group, whereas intrauterine administration of PGF2 alpha and PGE2 significantly reduced it.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous

Ca2+ release and InsP3 production in avian uterine cells: effects of PGF2 alpha and AVT.

Primary cultures of smooth muscle cells isolated from the shell gland ("uterus") of the domestic hen were permeabilized with digitonin and loaded with 45Ca2+ in the presence of ATP. When these cells were stimulated with prostaglandin F2 alpha (PGF2 alpha), arginine vasotocin (AVT), or D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], there was a rapid, biphasic, and dose-related release of 45Ca2+ from nonmitochondrial pools. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate, an inhibitor of phospholipase C, had no effect on PGF2 alpha - and Ins(1,4,5)P3-promoted 45Ca2+ efflux, whereas it significantly inhibited AVT-stimulated and a stable analogue of GTP-stimulated 45Ca2+ release. In fura-2-loaded intact cells, both PGF2 alpha and AVT increased intracellular Ca2+ levels [( Ca2+]i) in a dose-related manner in the presence of extracellular Ca2+. However, omission of extracellular Ca2+ prevented a PGF2 alpha, but not AVT-induced, rise in [Ca2+]i In D-myo-[3H]inositol-labeled cells, 10 nM AVT caused a rapid, two- to threefold increase in [3H]-Insp3, whereas PGF2 alpha up to 1 microM was infective. Raising PGF2 alpha to 10 microM increased total inositol phosphates by 22% over controls (P less than 0.05). These results point to marked differences in the mechanisms by which AVT and PGF2 alpha regulate [Ca2+]i in uterine smooth muscle cells. It is suggested that the two agonists act in concert to initiate oviposition.

Animals

Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2 alpha: comparison with oxytocin.

The effects of prostaglandin F2 alpha (PGF2 alpha) on intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP) generation in human myometrial cells were evaluated and compared to the effects of oxytocin. Basal [Ca2+]i levels were 146 and 153 nM in the absence and presence of 1 mM extracellular Ca, respectively. In Ca-containing medium, both PGF2 alpha and oxytocin significantly (P less than 0.01) increased [Ca2+]i over control values, eliciting half-maximal stimulation (ED50) at 4 and 1 nM, respectively. In Ca-free medium the potency of PGF2 alpha to raise [Ca2+]i was drastically reduced (ED50, 2 microM), whereas that of oxytocin remained the same, although maximal responses were markedly decreased. PGF2 alpha had no effect on total IP production in the concentration range that significantly raised [Ca2+]i. However, at a 100 times higher concentration (10 microM), PGF2 alpha produced a maximum 48% increase in total IP, with a rapid (15-30 s) rise in IP3 and IP2, followed by IP1. A similar increase in IP production was obtained when [Ca2+]i levels were raised by A23187 to the same level as that obtained with 10-50 microM PGF2 alpha. The effect of PGF2 alpha was dependent on extracellular Ca and could be suppressed by verapamil, but not by pertussis toxin, or phorbol ester. In contrast, the potencies of oxytocin to raise IP and [Ca2+]i were similar and independent of extracellular Ca2+, and could be suppressed by pertussis toxin and phorbol ester, but not by verapamil. These data provide evidence that in isolated human myometrial cells, PGF2 alpha and oxytocin trigger an increase in [Ca2+]i by different mechanisms. The action of PGF2 alpha depends on extracellular Ca2+, whereas oxytocin activates the G-protein-dependent phospholipase-C-IP3-Ca2+ signal-transducing pathway, complemented by the influx of extracellular Ca2+.

Calcium

Intracellular free calcium concentration in lymphocytes of patients with muscular dystrophies.

Intracellular free calcium concentration [( Ca2+]i) of human peripheral blood lymphocytes was determined by fluorescence spectroscopic measurements with quin2 in patients with different types of muscular dystrophy and in controls. The [Ca2+]i level in lymphocytes showed a significant increase in adult type (facioscapulohumeral and limb-girdle) muscular dystrophies, while it showed a decrease in Duchenne dystrophy as compared to the values of age- and sex-matched controls. The data obtained suggest an alteration in the effectiveness of the calcium pump in lymphocytes and may represent a sign of generalized membrane damage in these hereditary muscle diseases.

Adult

[Chronic Guillain-Barré syndrome (diagnostic and therapeutic possibilities)].

The authors survey the clinical features and therapeutic results of their patients with chronic inflammatory polyneuropathy. There was an antecedent virus infection in the case history of 5 out of 7 patients. In one patient the chronic polyneuritis developed in association with previously verified SLE, in an other one the autopsy has proved giant lymphadenopathy. The symptoms and signs have evolved slowly in 6 patients, one patient relapsed in 4 months after the first acute attack. The initial and main symptom was the hypotonic muscle weakness of lower extremities. All of the patients mentioned paresthesias and on the lower extremities of 4 patients even hypesthesias of distal type might be revealed. The tendon reflexes were always very slow or absent. In the CSF the classical changes, excess of protein content with normal cell count were found. The electroneurography has shown increased distal latencies and reduced motor and sensory nerve conduction velocities. The steroid treatment and in 2 patients the plasmapheresis were successful, however the recovery was always incomplete and residual disabilities persisted. The electrophysiological and CSF findings did not change parallel with the relief of clinical symptoms and signs.

Adult