Biomedical subjects

J Molnár

Publications and source records attributed to J Molnár.

At least 19 recordsLinked to original sources

PubMed1992

Mechanism of chlorpromazine binding by gram-positive and gram-negative bacteria.

Chlorpromazine forms charge-transfer complexes with xanthene dyes in bacteria. These complexes permit the differentiation of Gram-positive and Gram-negative bacteria in both light and polarization microscopy. The birefringence induced by the charge-transfer complex might explain the molecular basis of bacterial staining. The charge-transfer complexes formed between chlorpromazine and xanthene dyes accumulate in the bacterial cell, mainly inside the bacterial cell wall. The complexes give the cells a color, which depends on the chemical composition of the staining structure, and in particular the polysaccharides of the cell wall in bacteria. Metachromatic granules were seen inside Gram-positive bacteria after chlorpromazine and rose bengal staining. Although the nature of these granules remains unclear, this type of binding may have a role in the inhibition of biochemical processes in the bacterial cells.

Binding Sites↗

PubMed1992

Overexpression and purification of enzymatically active recombinant integrase protein of Rous sarcoma virus.

The carboxy-terminal domain of polymerase gene of Rous sarcoma virus was cloned into an expression vector under the control of lac regulatory elements, resulting in the plasmid pMF1413. Upon isopropyl-beta-D-thiogalactopyranoside induction, viral integration (IN) protein was expressed in large quantity in Escherichia coli. The expressed recombinant protein was prepurified by successive washing of the bacterial pellet with 0.1 M NaCl and detergents. Further purification was performed in high yield by standard chromatography methods. The purified enzyme revealed selective DNA cleaving activity on supercoiled plasmid with the LTR-LTR junction fragment. The reaction was metal ion dependent, with a preference for Mn2+ over Mg2+, and showed substrate specificity at 1 mM MnCl2.

Avian Sarcoma Viruses↗

PubMed1992

Central effects of tricyclic compounds on the endocrine system--an in vitro study.

The present study involves the effects on corticotropin (ACTH) release of neuro- and thymoleptic tricyclic antidepressant compounds (TrcACs: chlorpromazine, promethazine, haloperidol, imipramine, amitriptyline) and their interactions with lysine-8-vasopressin (LVP) and corticosterone (B). As an in vitro model, 14-day monolayer pituitary cell cultures of Wistar rats were employed. The ACTH concentrations of the supernatant media were measured by radioimmunoassay. TrcACs augmented ACTH release; their combination with LVP, however, did not result in further stimulation; moreover, when combined with TrcACs + LVP, B did not inhibit, but rather paradoxically increased their ACTH-releasing action. As none of these phenomena were followed by relevant changes in intracellular cyclic adenosine monophosphate content, the mechanism of action may be proposed to involve a protein kinase C route.

Adrenocorticotropic Hormone↗

PubMed1992

Effects of some tricyclic psychopharmacons and structurally related compounds on motility of Proteus vulgaris.

A simple test for the evaluation of drugs interfering with bacterial motility was established with Proteus vulgaris. With this model, promethazine, 7-hydroxy-chlorpromazine, imipramine, 7,8-dioxochlorpromazine and acridine orange were shown to exert significant motility and swarming inhibitory action on Proteus vulgaris strains at subinhibitory concentrations. Quinidine enhanced the antimotility effect of promethazine. The antimotility effect of promethazine was synergized by proton pump inhibitors omeprazole and abscissic acid, but antagonized by extracellular potassium and sodium ions.

Abscisic Acid↗

PubMed1992

Antiplasmid activity: loss of bacterial resistance to antibiotics.

The antiplasmid activity of tricyclic compounds, e.g. phenothiazines, dibenzoazepines, dibenzocykloheptene derivatives and some stereoisomers, was shown on E. coli in vitro. Some ring-substituted phenothiazine and cannabis derivatives had only an antibacterial effect. Promethazine, a selected phenothiazine, cured antibiotic resistance and lactose fermentation of E.coli, tumour inducing ability of Agrobacterium tumefaciens and nodule formation of Rhizobium meliloti. Plasmids of different E.coli strains were eliminated with varying frequency. The antiplasmid activity of the compounds can be due to the increased membrane permeability. Inhibition of DNA gyrase and complex formation with the supercoiled form of plasmid DNA can lead to the cessation of plasmid replication in the bacterial cells. In addition, in vivo plasmid curing was demonstrated at a low frequency.

Antidepressive Agents, Tricyclic↗

PubMed1992

[Formulation and in vitro investigation of antibacterial vaginal suppositories. Part 2. In vitro membrane diffusion and microbiologic studies].

After the physical parameters had been determined, the in vitro drug liberation from vaginal suppositories containing 100 mg of antibacterial agent (sulphadimine, chloramphenicol, gentamicin-sulphate) was studied by membrane diffusion and microbiological methods. Among the vehicles available in Hungary the hydrophylic Massa macrogoli was found to be the best for this purpose. Among the lipophilic bases the in vitro drug liberation of the French Suppocire NA product was significantly better (p < 0.05) compared to the other lipophilic bases. This vehicle is recommended by the authors for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well. In the first part of the publication the formulation and some important physical parameters of lipophilic and hydrophilic antibacterial suppositories for vaginal use were described. In the present paper the drug liberation ability of the compositions with proper physical parameters was studied. The published results were obtained from measurements performed 1 week after formulation.

Anti-Infective Agents, Local↗

PubMed1991

Mesencephalic sites of action of an enkephalin analogue (D-Met2, Pro5)-enkephalinamide and naloxone on the anterior pituitary of male rats.

(D-Met2, Pro5)-Enkephalinamide and naloxone injected into the dorsal raphe nucleus affected luteinizing hormone (LH) and prolactin (PRL) release. Drugs given into the reticular tegmental nucleus and dorsal part of the periaqueductal gray matter induced a PRL response and their administration into the central superior midbrain raphe nucleus caused changes in growth hormone (GH) secretion. The inferior colliculus and the lateral part of the periaqueductal gray matter were ineffective sites.

Animals↗

PubMed1991

[Elevated pentachlorphenol in urine following Fungifen therapy].

Urinary pentachlorophenol (PCP) was monitored in male volunteers exposed to Fungifen solution which is a readily accessible pharmaceutical product containing 1% of PCP as active ingredient, and is recommended for the local treatment of interdigital mycoses. PCP absorbed readily through the skin and its elimination was slow. After the topical application of Fungifen maximum levels of urine-PCP ranged from 109 to 1290 micrograms/liter. In a single case a peak value of 3200 micrograms/liter was measured. At the same time, PCP could be detected in the saliva too. Urinary preexposure levels (ranged around 10 micrograms/liter) were reached within 75 and 90 days, respectively. Maximum urinary levels represent exposures corresponding to occupational ones, known from other studies. The toxicity of PCP as well as the health risk of the Fungifen use to the great masses of the people (including pregnant women and children) are discussed.

Adult↗

PubMed1991

The influence of charge transfer complex formation on the antibacterial activity of some tricyclic drugs.

1. Phenothiazines and structurally related drugs are effective in eliminating bacterial plasmids. 2. Charge transfer complex formation between chlorpromazine and xanthine dyes with different electron acceptor activities (e.g. fluorescein, eosin, erythrosin and rose bengal) was detected by differential spectrophotometry. Charge transfer complexes were formed between the strong electron acceptor rose bengal and various tricyclic drugs. 3. On the basis of the wavelength shift, the binding energies of drugs and dyes were estimated. 4. The temperatures dependence of the reaction indicates charge transfer complex formation rather than a chemical reaction between drugs and dyes. 5. The anti-plasmid action of the phenothiazines was decreased in the presence of xanthine dyes. As a consequence of competitive inhibition between bacterial binding sites and xanthine dyes, the binding energy of drugs in the plasmid replication system could be determined in the presence of dyes. 6. Drugs with binding energies in the range of 0.23-2.31 kcal/mol can inactivate the plasmid replication system.

Bacteria↗

PubMed1991

99-m technetium (Dupont Cardiolite) investigations in postinfarction patients with Holter-checked silent ischaemia.

Sixteen middle-aged, normotensive, slightly overweight male patients with previous myocardial infarction were studied during Holter-checked silent myocardial ischaemia. As reference, stress and late 201-T1 scintigraphy served for comparison with Cardiolite-MIBI silent ischaemic perfusion scan, both carried out in planar mode. The circumferential profiles differed in 9 cases, on region of interest basis the segment number difference was 10, but the late distribution segment number was near to both ischaemic numbers. The quantitative scores were distinctive (ratio 133-128/103) indicating the silent ischaemia appeared in the peri-infarct area. The silent ischaemic MIBI and stress 201-T1 ischaemic score difference was reduced by means of repeated SPECT investigation. With gated radionuclide ventriculography there was -4.3% difference between the left ventricular ejection fractions, measured with first pass MIBI technique during silent ischaemia and afterwards in basal state. The impairment of the left ventricular function was reflected on the stroke pattern of our Holter-based radiocyclogram, as well. Taking the 43.7-48.0 = -4.3% "ischaemic shift" into consideration it was a close correlation (r = 0.90) between the two kinds of ejection fraction determination. The major rhythm failures (occurring during the 24 h Holter monitoring) decreased to a higher degree the left ventricular ejection fraction than silent ischaemia or silent ischaemia and minor rhythm failure together (38-42-50%).

Coronary Disease↗

PubMed1990

[Myasthenia gravis: results of thymectomy in 550 patients].

Report is giving on 550 myasthenic patients who underwent thymectomy during the last 18 years. Results of thymectomy are analysed in separate groups and according to different aspects, including thymic tumours (13.63%), operations in childhood (9.64%), and combined cases (11.1%). The results are evaluated according to Disability Status Scale based on a point-system. Successive improvement was observed in the three series concerning the results of operation. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined group, in long-lasting myasthenia and in tumourous cases, too. There are quite a few factors influencing the results, such as the interval between the disease onset and thymectomy, the patients' age, thymoma, crisis-danger and the activity of the thymus gland reflecting in the number of the germinative centres. The more active the thymus, the better the results.

Humans↗

PubMed1990

[Adenocarcinoma (Klatskin tumor) of the hepatic duct simulating viral hepatitis].

The authors review the experiences obtained during investigation of a patient with Klatskin tumor and whose clinical syndromes were developing as of virus hepatitis. In the first two weeks of the illness the clinical symptoms, the chemical laboratory findings and among the virus investigations the positive (experimental) Non-A Non-B hepatitis virus antigen suggested the existence of virus hepatitis. Later the laboratory investigations and the symptoms showed on obstructive icterus. The subsequent performed investigations as ultrasonography and PTC--showed the Klatskin tumor, which was proven by the operation performed and histology. The patient is free from the complaints more than 1 year after the operation, moreover recidivation or metastasis was not indicated by the investigations performed in the latest time.

Adenocarcinoma↗

PubMed1990

Synergistic effect of promethazine with gentamycin in frequently recurring pyelonephritis.

The effects of promethazine were studied in children with frequently recurring pyelonephritis which was not associated with urological abnormalities. The results of three methods of treatment were compared: 10 children were given a combination of gentamycin and promethazine for 7 days (Group 1), 11 received gentamycin treatment alone for 10 days (Group 2), and 19 (Group 3) were on long-term oral antibiotic prophylaxis (5.6 +/- 2.1 years) with episodes of intensive treatment of recurrences. In a 3-year follow-up period, the number of pyelonephritis recurrences was significantly lower in Group 1 than in Groups 2 and 3. Six out of 19 children in Group 3 had renal scarring. The authors suggest a synergistic effect between gentamycin and promethazine therapy. Promethazine increases antibiotic sensitivity, which could contribute to the elimination of recurring urinary tract infections.

Adolescent↗

PubMed1990

Myasthenia gravis: effect of thymectomy in 425 patients. A 15-year experience.

We report 425 myasthenic patients who underwent thymectomy during the last 15 years. The authors analyse the results of thymectomy in separate groups, including thymomas (12.7%), childhood myasthenia (9.4%) and combined cases (12.4%). They evaluate the results according to the Disability Status Scale based on a points system. Three series were evaluated: patients operated upon between 1972-1977, 1977-1982 and 1982-1987. Although the results in all three series were good, there has been steady improvement over the years. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined (immunological) group, in long-lasting myasthenia and in thymomas. Factors influencing the results of thymectomy were patients' age, time interval between onset of disease and thymectomy, resistence to therapy and thymic tumour. Thymic activity as reflected in germinal centres can also influence the results: the more active the thymus, the better the results.

Adolescent↗

PubMed1990

Hypophysial trophic hormone response to adrenalectomy and ether stress in rats bearing anterior pituitary tissue in third ventricle of the brain.

Inhibitory effect of anterior pituitary tissue implanted into the brain on trophic hormone secretion was studied under resting conditions and after adrenalectomy or ether stress. The weight of pituitary gland in rats bearing anterior pituitary graft in the third ventricle was decreased and the body weight gain was retarded. The levels of ACTH, PRL and GH, but not those of FSH and LH in plasma were significantly lower as compared with all control groups. There was a pituitary ACTH, PRL and GH response to adrenalectomy and ether stress in these rats. Besides supporting literary data on the inhibitory effect of additional pituitary grafts on the adenohypophysis, these findings indicate that pituitary implants did not cause any appreciable alteration of pituitary responsiveness, at least to adrenalectomy or ether stress.

Adrenal Glands↗

PubMed1989

Regulation of the gonadotropin-releasing hormone (GnRH) neuronal system: morphological aspects.

This paper gives a brief survey of the structural organization of the GnRH neuronal system and of the chemically identified axons impinging directly on GnRH neurons. There are great species differences in the localization of the GnRH nerve cells. In the human and monkey brain, they are concentrated in the medial basal hypothalamus. GnRH neurons project not only to the median eminence, but terminate also on other nerve cells including GnRH elements. Under physiological circumstances the GnRH neurons are influenced by nervous structures in- and outside the medial basal hypothalamus and by ovarian and other hormones. Recent, primarily immunocytochemical studies indicate that catecholaminergic, serotoninergic, GABA-ergic, opioid peptidergic, immunoreactive substance-P and corticotropin releasing factor-immunoreactive axons synapse on GnRH neurons. These findings provide morphological basis for the view that neurons operating with these compounds can act directly on GnRH release. Direct connections of the GnRH neurons demonstrated so far does not exclude the possibility that these neurotransmitters or neuromodulators influence GnRH release also at other levels of the CNS.

Animals↗

PubMed1989

Transitory increase in plasma FSH and LH levels induces early vaginal opening and corpus luteum formation in ovarian transplants of rats ovariectomized at 20 days of age.

The effect of a transitory increase in plasma FSH and LH levels on puberty has been investigated. Hormonal changes were induced by bilateral ovariectomy (OVX) at 20 days of age followed by implantation of two ovaries (donor animals 20-day-old) beneath the kidney capsule 1, 2 or 3 days later. In an other group of animals the two interventions were made in reversed order. Rats in which OVX was made first showed early vaginal opening. If ovarian implantation preceded OVX, these two interventions did not affect the time of vaginal opening. More than 1/3 of the ovarian implanted animals exhibiting early opening of the vagina contained corpora lutea three days after vaginal opening. FSH and LH levels of OVX + ovary implanted rats were from the third day on following implantations markedly different from the OVX controls and were in the range of intact or sham-operated rats. The present findings indicate that a transitory increase in plasma gonadotropin levels around twenty days of age may lead to precocious puberty.

Age Factors↗

PubMed1989

Antimicrobial and immunomodulating effects of some phenolic glycosides.

Several phenolic glycosides, i.e. acteoside, desrhamnosyl acteoside, and purpureaside A, B and C, exerted weak antibacterial effects on Escherichia coli. Acteoside had antiplasmid effects, including F'lac plasmid elimination, and inhibited kanamycin resistance transfer in E. coli. Acteoside, desrhamnosyl acteoside and purpureaside A displayed antiviral effect on Aujeszky virus. All of the phenolic glycosides decreased some human leucocyte functions, including rosette formation, mitogen-induced blast transformation and phagocytic activity in vitro. The purpureaside C had significant proinflammatory action, however, other phenolic glycosides showed neither proinflammatory nor antiinflammatory effect on carrageenin-induced inflammation in vivo.

Animals↗