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Biomedical subjects

G Balogh

Publications and source records attributed to G Balogh.

At least 37 records · Page 2Linked to original sources

Estimation of impurity profiles of drugs and related materials: part 19: theme with variations. Identification of impurities in 3-oxosteroids.

Due to the varied reactions leading to the 3-oxo group in steroids and the reactivity of its environment, a large number of impurities related to this group are formed during the reaction steps and the degradation studies. In this paper the experiences from the authors laboratory with the 3-oxo-related impurities in 19-nor-4-ene-3-oxosteroids (norgestrel, norethisterone, nandrolone, its esters and Nestorone) as well as corticosteroids (prednisolone, mazipredone, etc) are presented. The impurities include saturated 3-ones, 1-ene-3-ones, 5(10)-ene-3-ones, 3-deoxo and 3-ethinyl-3,5-diene derivatives, 6-ene, 8(14)-ene, 6,8(14)-diene, 6-hydroxy (alpha and beta), 10beta-hydroxy and 6-one derivatives in 4-ene-3-oxosteroids and 8(9)-ene, 9(11)-ene, 11alpha-hydroxy, 11-oxo and 4-ene-3-one derivatives in 11beta-hydroxy-1,4-diene-3-oxosteroids. The chromatographic, spectroscopic and hyphenated techniques used in this study include TLC, GC, HPLC with diode array UV detector, GC-MS, LC-MS and NMR methods.

Chromatography, High Pressure Liquid↗

[Mycoplasma pneumoniae epidemic as zoonosis].

At a secondary school in Budapest, in the first class, 30 students became sick with fever and upper respiratory catarrhal symptoms between September 19 and October 31, 1995. Two children were hospitalized with a diagnosis of pneumonia, in case of the two children treated at the Szent László Hospital, suspect of Mycoplasma infection raised which was also confirmed by cold agglutination test. During the epizootiological examination on the spot they found a terrarium in the classroom where the students raised a Syrian gold hamster family. Mycoplasmas were isolated from the lung samples of the hamsters during the pathological examination which proved to be Mycoplasma pneumoniae. Owing to the close etiologic relationships between epidemiological anamnesis, characteristics of the epidemic, as well as findings of patients and pathological or histological findings in the hamsters together with the results of bacteriological examinations, the epidemic should be considered as a zoonosis.

Animals↗

Modulation of lipid unsaturation and membrane fluid state in mammalian cells by stable transformation with the delta9-desaturase gene of Saccharomyces cerevisiae.

The composition and physical state of membrane lipids determine the dynamic nature of membranes, which in turn, could directly be linked to the activity of various membrane-associated cellular functions. To better understand the molecular basis of different membrane-related phenomena we established a novel strategy to alter unsaturation of mammalian cell membranes with an identical genetic background. We transfected L929 mouse fibroblastoid cells with DNA constructs containing the Delta9-fatty acid desaturase gene (Ole1) of S. cerevisiae under the control of desaturase promoters derived either from wild type or mutant strains of the dimorphic fungus H. capsulatum.

Animals↗

Influence of age on 1,25(OH)2-vitamin D3 activation of protein kinase C in rat duodenum.

We have studied age-related changes in the non-genomic regulation of protein kinase C (PKC) by 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] and their role in 1,25(OH)2D3-dependent calcium uptake in the rat duodenum. Treatment of duodenal mucosae from 3 month-old (young) rats with hormone physiological concentrations (0.1 nM) induced an acute and transient stimulation of total tissue PKC activity which was maximal at 1 min (+80%). The responses were evidenced up to 10 nM 1,25(OH)2D3. The duodenum from 22 to 24 month old (aged) rats exhibited higher basal PKC activity which was not significantly modified after addition of the hormone. In the young duodenum PKC activation by 1,25(OH)2D3 was dependent on extracellular Ca2+ influx as it could be abolished to a great extent by EGTA and the Ca2+ channel blocker verapamil. In addition, the Ca2+ ionophore A23187 elicited a marked stimulation of duodenal mucosae PKC in young rats but was without effects in aged animals. 1,25(OH)2D3 increased the influx of 45Ca2+ in duodenal mucosae of young rats in a dose-(0.1-1 nM) and time-(1-10 min) dependent fashion. This response to the hormone was impaired in aged animals. Similarly as 1,25(OH)2D3, the PKC activator dioctanoylglycerol (DOG) rapidly (1-5 min) increased [45Ca2+] influx in duodena from young rats whereas the response to DOG was blunted in senescent animals. Furthermore, PKC inhibitors (bisindolylmaleimide, staurosporine and compound H7) abolished 1,25(OH)2D3 stimulation of Ca2+ uptake in the young duodenum. These results suggest that 1,25(OH)2D3 regulates PKC activity in the mammalian duodenum by a non-genomic mechanism which involves the rapid influx of extracellular Ca2+, and that activation of PKC, in turn, mediates hormone stimulation of intestinal Ca2+ uptake. The data also indicates that 1,25(OH)2D3 regulation of Ca2+ transport through the PKC messenger system is impaired with aging.

Age Factors↗

Evidence for a lipochaperonin: association of active protein-folding GroESL oligomers with lipids can stabilize membranes under heat shock conditions.

During heat shock, structural changes in proteins and membranes may lead to cell death. While GroE and other chaperone proteins are involved in the prevention of stress-induced protein aggregation and in the recovery of protein structures, a mechanism for short-term membrane stabilization during stress remains to be established. We found that GroEL chaperonin can associate with model lipid membranes. Binding was apparently governed by the composition and the physical state of the host bilayer. Limited proteolysis of GroEL oligomers by proteinase K, which removes selectively the conserved glycine- and methionine-rich C terminus, leaving the chaperonin oligomer intact, prevented chaperonin association with lipid membranes. GroEL increased the lipid order in the liquid crystalline state, yet remained functional as a protein-folding chaperonin. This suggests that, during stress, chaperonins can assume the functions of assisting the folding of both soluble and membrane-associated proteins while concomitantly stabilizing lipid membranes.

Adenosine Triphosphatases↗

Estimation of impurity profiles of drugs and related materials. Part 16: Identification of the side-products of the ethinylation step in the synthesis of contraceptive gestogens.

A new apolar impurity (3,17 alpha-diethinyl-13-ethyl-3,5-gonadiene-17-ol, IIb) was detected and identified in norgestrel with the aid of thin-layer and high-performance chromatography and spectroscopic techniques. IIb is the product of the acid-catalysed dehydration of an overethinylated side product (Ib) of the ethinylation step in the synthesis of norgestrel. IIb can be determined by thin-layer densitometry and high-performance liquid chromatography. Another impurity (17 alpha-ethinyl-13-ethyl-4-gonene-17-ol, IV), originating from a side product of the Birch reduction step in the synthesis of norgestrel was also detected and identified. The spot of IV overlaps with that of IIb in the TLC system of USP XXIII but can be separated and quantification by more selective TLC systems and by gas chromatography.

Chromatography, High Pressure Liquid↗

Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known mechanisms protecting cells from various stresses is the heat-shock response which results in the induction of the synthesis of heat-shock proteins (HSPs or stress proteins). A large body of information supports that stress proteins--many of them molecular chaperones--are crucial for the maintenance of cell integrity during normal growth as well as during pathophysiological conditions, and thus can be considered "homeostatic proteins." Recently emphasis is being placed on the potential use of these proteins in preventing and/or treating diseases. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce the accumulation of HSPs in patients with chronic disorders such as diabetes mellitus, heart disease or kidney failure. Here we show that a novel cytoprotective hydroxylamine derivative, [2-hydroxy-3-(1-piperidinyl) propoxy]-3-pyridinecarboximidoil-chloride maleate, Bimoclomol, facilitates the formation of chaperone molecules in eukaryotic cells by inducing or amplifying expression of heat-shock genes. The cytoprotective effects observed under several experimental conditions, including a murine model of ischemia and wound healing in the diabetic rat, are likely mediated by the coordinate expression of all major HSPs. This nontoxic drug, which is under Phase II clinical trials, has enormous potential therapeutic applications.

Animals↗

[The frequency of left atrial spontaneous echo contrast and its clinical significance in mitral valve insufficiency].

The authors investigated the frequency of left atrial spontaneous echo contrast in mitral valve disease. They also tested whether there was any correlation between the presence of left atrial spontaneous echo contrast and the severity of the mitral valve disease. Echocardiographic investigations were performed using both transthoracal and transesophageal echocardiographic methods employing monoplane transducer. The authors carried out 273 transesophageal investigations over a period of 2 years and found left atrial spontaneous echo contrast in 85 patients, who had mitral valve disease. Of this, in 18 cases thrombi were also detected in the left atrium and/or auricula. The diagnoses of mitral stenosis were made in 24 patients, of whom in 12 cases the stenosis were found to be severe, whilst in 12 cases to be moderate. Furthermore insufficiency of the mitral valve was detected in 35 cases. 20 patients had artificial mitral valve implanted, they received long term anticoagulant treatment. 59 patients had no spontaneous echo contrast. 14 patients had previous embolic events of which 9 were cerebral and in other cases arteries of the kidney, eye and extremities were affected. 71 patients had no history of embolism. The authors concluded that mitral valve disease, particularly mitral stenosis is frequently associated with left atrial spontaneous echo contrast. It has been also observed, that the more severe the mitral valve disease, the greater the probability of left atrial spontaneous echo contrast. In all cases where thrombi were found, left atrial echo contrast were demonstrated and the risk of embolism is high. In these cases anticoagulant therapy is suggested.

Adolescent↗

[Central bronchoplastic procedures in Hungary and their outcome (198-1993)].

Bronchoplastic procedures involving the main carina are declared as central bronchoplasties. A nation-wide collection of these interventions performed between 1980 and 1993 is analysed. The study is on a total of 154 operations, that were 16 bifurcation resections and 14 stem bronchus resections without parenchyma sacrifice, 61 sleeve or wedge pneumonectomies and 63 tracheal sleeve or wedge right upper lobectomies or carina-plasties. Surgery alone-without multimodality therapy-was the choice of treatment almost exclusively. About 90% of these interventions were performed for highly malignant, histologically peripheral-type, but centrally located bronchial cancers. The hospital mortality and morbidity were found up to 30% (an average of appr. 17%), depending on surgical subsets. Cause of death were surgical at 11% (leakage, anastomotic dehiscence and bleeding) and non surgical at 5.8% respectively. Complications at another 9% were related to surgery. Data of survival suggest, that nodal state is the strongest predictor, but the unfavourable N2 group comprises longer survivors as well. Certain part of this kind of interventions is to be chosen without alternatives (isolated tracheobronchial resections without parenchyma-resection, extended pneumonectomies) while extended lobectomies are alternatives of the extended pneumonectomies in strict conditions. A central bronchoplastic procedure is justified only with hope of complete resection for its high complication rate.

Anastomosis, Surgical↗

Age-associated decrease in inositol 1,4,5-trisphosphate and diacylglycerol generation by 1,25(OH)2-vitamin D3 in rat intestine.

The hormonal form of vitamin D3, 1,25(OH)2-vitamin D3(1,25[OH]2D3), stimulates the breakdown of membrane phosphoinositides, generating inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) in a variety of cell systems. Several studies suggest that alterations in the receptor-mediated phosphoinositide cascade are involved in the pathophysiology of aging. Therefore, the formation of IP3 and DAG were determined under basal conditions and after stimulation with physiological concentrations of 1,25(OH)2D3 in duodenum from young (3-mo-old) and aged (24-mo-old) rats. The hormone induced a transient and biphasic formation of IP3 and DAG. Values obtained in young rats peaking at 15 s (51% and 42% above basal levels for IP3 and DAG, respectively) and at 3 min (90% and 74% above basal levels for IP3 and DAG, respectively) were significantly decreased in duodenum from senescent animals (IP3: +20% and DAG: +18% above basal level at 15 s; and IP3: +18% and DAG: +29% above basal level at 3 min). The 1,25(OH)2D3-induced generation of DAG in both young and aged duodenum was effectively inhibited in the presence of neomycin, a phospholipase C (PLC) inhibitor, and was dependent on extracellular Ca2+. After the biphasic response, the levels of DAG generated by the hormone (10 min stimulation) remained elevated; the elevation occurred in the absence of IP3 production; and the elevated levels were not abolished by neomycin, implying that phospholipids other than phosphoinositides are the source of DAG. This 1,25(OH)2D3-dependent late phase of DAG generation was also diminished in aged animals. The precise molecular basis and the physiological significance of decreased liberation of IP3 and DAG by 1,25(OH)2D3 in the aged rat duodenum remains to be determined.

Aging↗

Estimation of impurity profiles of drugs and related materials. 12. Isolation and identification of an isomeric impurity in danazol.

We report on a new isomeric impurity of danazol. This impurity designated as isodanazol was detected by reversed-phase high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Its structure was determined after separation by preparative HPLC. Mass spectrometry revealed the isomeric nature of the impurity while the UV spectrum indicated profound difference in the isoxazole moieties. The structure of the isomeric isoxazole ring in isodanazol was determined by NMR spectroscopy using COSY, HETCOR and NOE measurements. The difference between the UV spectra of danazol and isodanazol is explained on the basis of the difference between the aromaticities of their isoxazole rings supported by quantum chemical calculations. The quantitative determination of the impurity down to the 0.05% level can be performed by HPLC, gas chromatography and TLC densitometry.

Chromatography, Gas↗

["Loop"-drainage in the management of recurrent extra-sphincteric perianal fistulae].

This work covers the loop seton drainage tube treatment of multiply recurring high-spreading extrasphincteric perianal fistulas in 14 patients. The drainage loop setons make possible the rinsing of the wound after fistulectomy and bi-directional drainage of the wound discharge. Strangulation of the wound, and hence the development of recurrence, is prevented by means of controlled formation of scar tissue. The sphincteral musculature of the anus is protected from damage. 25 fistulas which recurred in the 14 patients were treated successfully by this method. None of the patients developed incontinence. 1 fistula recurred. With regard to the pull-out method, in the case of high-spreading multiply recurring extrasphincteric or suprasphincteric perianal fistulas.

Adult↗

[Preventive measures for early and late locomotor complications from thoracoplasty and myoplasty].

Two basic methods of prevention of early- and late-occurring complications after thoracoplastic and myoplastic surgery are defined by the authors: I. The function protective surgical method and technique: by the retention of rib 1, the extramuscular periosteal thoracoplastic surgery, resection of as few ribs as possible, total performance of thoracoplastic and myoplastic surgery, epidural assuaging of pain. II. Perioperative physiotherapy and correct rehabilitative treatment, where gymnastics plays the most important role, and also combined application of the different special methods of physiotherapy, can also contribute to favourable results. 17 patients data have been processed and set out in the report. They show the efficiency of the applied methods. Planned and purposeful co-operation between the surgeon and the physiotherapist is needed in the medical treatment of patients.

Adult↗

[Excerpts from the investigations of pipecuronium bromide with NMR spectroscopy].

The synthesis of Pipecuronium bromide together with the investigation of its impurity profile required the solution of a number of analytical and structural problems. NMR spectroscopical methods received a major role in the structure elucidation of the synthesized compounds. The quantitative assessment of contaminations was also realized by 1H NMR spectroscopy. Out of the large amount of undertaken investigations, here we provide the structural characterization of the contaminating regiosimers of an important intermediate (5 alpha-androst-2-en-17-on) formed in the course of the synthesis, together with the NMR signal assignments of the end-product (Pipecuronium bromide) as measured in D2O and a mixture of CDCl3/DMSO-d6. The structure of a minor contamination of the end-product is also given.

Androstane-3,17-diol↗

[Current treatment of thoracic empyema in adults].

Experiences obtained with 400 cases of thoracal empyema are described. The fact that the rate of lethality was 18.7% until present points out to the severity of the disease. The semi-conservative therapeutical methods used by the author (drainage, drainage and pleura lavage, pleura lavage and thoracoscopy, balance drainage) are presented. With their sensibly more frequent use the rate of operation could be reduced by 8% (from 36.5% to 28.5%) and the lethality rate by 7.6% (from 18.7% to 11.1). Further improvement of the results may be expected of the increased number of early detection (basic care), concentration of empyemic patients in special institutes (departments, wards) and due to it of a more efficient special treatment of uniform contemplation.

Drainage↗

Estimation of impurity profiles of drugs and related materials. Part VIII: Combined application of high-performance liquid chromatography and NMR spectroscopy in the impurity profiling of drugs.

The usefulness of the joint application of HPLC and NMR spectroscopy in drug impurity profiling is demonstrated by the following examples: (1) identification of Z and E isomers of 17 alpha-ethynyl-4-oestrene-3 beta, 17-diol-3-acetate-17-(3'-acetoxy-2'-butenoate) in ethynodiol diacetate; (2) identification of the p-tolyl analogue as the impurity of enalapril maleate; (3) identification and quantification of 2'-dehydro-pipecuronium bromide in pipecuronium bromide. The possibilities of utilizing NMR spectroscopy for the identification and quantification of the impurities with and without their isolation are discussed.

Androstane-3,17-diol↗

[Prevention and treatment of thoracic empyema resulting from traumatic hemothorax].

Authors report on their experiences with the treatment of thoracic empyema developing from the suppuration of haematoma following thoracic injury. In 30 of 82 patients suppuration of the thoracic cavity has developed. 6 of the 30 patients with empyema were treated first in our Department all 6 healed on drainage whereas in 24 patients, admitted from other departments, the following measures were necessary: 2 pleura lavages under the control of thoracoscope, 3 early decortications, 14 decortications, 5 lung resections and decortications with a decrease of the respiratory surface. Attention is called to the necessity of early and adequate treatment which is a prevention of complication (suppuration). Light is given to the factors which most frequently promote suppuration of the thoracic cavity, developing from traumatic haemothorax. Attention is called to secure the necessary personal and material conditions to the preventive treatment.

Adult↗

Use of Nizoral cream in dermatomycoses.

Nizoral cream containing ketoconazole was studied in 56 patients suffering from different dermatomycoses. In cases of uncertain clinical symptoms microscopic examination and cultivation were also performed to establish a diagnosis. According to the author's observations, in the treatment of mycotic skin diseases Nizoral cream proved to be generally as effective as the other currently used antimycotics.

Administration, Cutaneous↗