PubMed Health⌕ Search

Biomedical subjects

I Mucsi

Publications and source records attributed to I Mucsi.

At least 19 recordsLinked to original sources
PubMed2005

Serum 25(OH)-vitamin D levels and bone metabolism in patients on maintenance hemodialysis.

AIMS: An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis. METHODS: 69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated. RESULTS: A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = -0.231, p < 0.05), and this association remained significant after controlling for potential covariables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (beta = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure. CONCLUSION: Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.

Absorptiometry, Photon↗
PubMed2001

The use of a second reporter plasmid as an internal standard to normalize luciferase activity in transient transfection experiments may lead to a systematic error.

beta-galactosidase reporter plasmids containing different viral or minimal promoters are commonly used to correct variable transfection efficiencies in transient transfection experiments. The transcriptional activity of these promoters is thought to be stable under most circumstances. To determine if expression of beta-galactosidase from the commonly used beta-galactosidase plasmids remains stable upon stimulation of the cells with agonists we performed transient transfection experiments. CHO cells stably expressing the rat AT(1A) receptor were transfected with RSVbeta- or CMVbeta- or pTKbeta plasmids alone or together with a reporter construct in which luciferase transcription is driven by the c-fos promoter. Luciferase and/or beta-galactosidase activity was measured from the lysate of cells treated with angiotensin II or serum. We found that agonists increased the transcriptional activity of the different beta-galactosidase plasmids. The effect of angiotensin II and serum was different on the different promoters. Finally, cotransfection of other plasmids also modulated beta-galactosidase activity. These agonist induced variations of beta-galactosidase activity may influence the analysis and interpretation of the results in a systematic manner. Consequently we conclude that the use of a second reporter system to control for transfection efficiency in certain types of experiments may lead to a systematic error and is questionable as a general procedure.

Angiotensin II↗
PubMed2001

Combination of benzo[a]phenothiazines with acyclovir against herpes simplex virus.

The combined antiviral effects of some benzo[a]phenothiazines and 9-[2-hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H-benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used to interpret the drug interaction and a synergistic effect was found with a combination of ACV and benzo[a]phenothiazines. The effect of simultaneous application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain during serial passages was also investigated. The combinations of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a low concentration using serial passages of a plaque-purified ACV sensitive HSV-2 strain, reduced the infective virus population. A similar effect was also found on the activity of other benzo[a]phenothiazine derivatives. When the two most effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2 strain during consecutive passages, the infective virus titres were decreased, but their effect was only moderate. These results suggest that a combination of some benzo[a]phenothiazines with ACV might enhance their antiviral activity probably by reduction of the mutagenic rate in the virus populations.

Acyclovir↗
PubMed2001

Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated from Euphorbia species.

The cytotoxicities of nine diterpene polyesters obtained from Euphorbia species were assayed by measuring their effects on the growth of Vero cells. Their antiviral effects on the multiplication of Herpes simplex virus type 2 (HSV-2) were studied by using the virus yield reduction method in cell cultures. With the exception of the strongly cytotoxic 2alpha,5alpha,14beta-triacetoxy-3beta-benzoyloxy-8alpha,15beta-dihydroxy-7beta-isobutanoyloxy-9alpha-nicotinoyloxyjatropha-6(17),11E-diene (CC(50) 3.5 microg/ml), all the tested diterpenes exhibited a pronounced or moderate anti-herpes virus effect (IC(50) values between 2.5 and 8.3 microg/ml). The observed HSV-2 inhibitory activities were not associated with virucidal effects.

Animals↗
PubMed2000

Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension.

OBJECTIVE: To determine whether hormone replacement therapy can reverse established renal microvascular damage in type 2 diabetes and hypertension. DESIGN: Prospective, single centre clinical trial. SETTING: Outpatient clinics. PARTICIPANTS: Sixteen diabetic and hypertensive postmenopausal women (age 47-57 years) METHODS: Administration of a cyclic combination of oestradiol and norgestrel orally for 3.5 monthly cycles. RESULTS: Comparing the baseline values, mean (SD) 24-hour urine protein excretion was reduced from 0.452 g (0039) to 0.370 g (0.047) (P < 0.01) and creatinine clearance was increased from 1.68 mL/sec (0.11) to 1.77 mL/sec (0.08) (P < 0.05). Fasting plasma glucose also improved from 6.92 mmol/L (0.47) to 6.51 mmol/L (0.28) (P < 0.05), as did serum total cholesterol from 7.26 mmol/L (0.28) to 6.65 mmol/L (0.14) (P < 0.05). Blood pressure did not change significantly. Univariate linear regression analysis showed no significant correlation between the individual changes in blood pressure, fasting plasma glucose or serum cholesterol and the individual changes in proteinuria or creatinine clearance. CONCLUSIONS: This study shows that hormone replacement therapy may reduce proteinuria, and even improve creatinine clearance, in diabetic and hypertensive postmenopausal women. These effects are additive to nephroprotective therapy, and the mechanisms appear unrelated to conventional risk factors for vascular complications, such as high blood pressure, elevated plasma glucose or serum cholesterol.

Blood Glucose↗
PubMed2000

Apoptosis induction and inhibition of cellular proliferation by angiotensin II: possible implication and perspectives.

The renin-angiotensin system plays a pivotal role in the regulation of fluid, electrolyte metabolism and blood pressure. Molecular cloning and pharmacological studies have defined two major classes of Angiotensin II (Ang II) receptors, designated AT1 and AT2. Recently, it has been well recognized that Ang II, beside its classical physiological actions, is a profibrogenic peptide and displays characteristics of a growth factor. The emerging picture suggests that angiotensin receptor subtypes exert opposing features in many aspects of their biological function, most importantly in cellular growth and proliferation. Accordingly, the proliferative and/or growth-promoting effects of Ang II are thought to be mediated by AT1 receptor, whereas the AT2 receptor subtype may have growth-inhibitory properties. The novel finding that Ang II is able to induce apoptosis by AT2 receptors in diverse cell types is of great scientific interest, as recent studies revealed a role for apoptosis as a deliberate form of cell death in the pathogenesis of various cardiovascular diseases such as heart failure and vascular remodeling. Furthermore apoptotic cell death might occur during the development of progressive glomerulosclerosis. It is tempting to speculate that autocrine-paracrine vasoactive substances such as Ang II might regulate these apoptotic processes during pathogenic conditions.

Angiotensin II↗
PubMed1999

Relative hypoparathyroidism and adynamic bone disease.

Renal bone disease results in significant morbidity in patients with end-stage renal failure. Renal osteodystrophy is a mixture of different conditions with different pathogenetic factors involved. Most recently a new form of renal bone disease, adynamic bone disease, has emerged as the most frequent finding on bone biopsy of patients on dialysis therapy. The etiology of this new entity is not fully understood, but relatively low levels of intact serum parathyroid hormone are frequently associated with this disorder and may play an important role in its pathogenesis.

Bone Diseases, Metabolic↗
PubMed1998

Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.

We compared the efficacy and the long-term effects of nocturnal hemodialysis (NHD) versus conventional hemodialysis (CHD) in controlling serum phosphate levels in patients with end-stage renal disease (ESRD). Patients underwent thrice weekly CHD and were subsequently switched to NHD six nights weekly. In the "acute" study serum and dialysate phosphate were measured during and after dialysis, and the total dialysate was collected to calculate mass solute removal. Although pre-dialysis (1.7 +/- 0.6 vs. 1.5 +/- 0.8 mM) serum phosphate levels were similar in CHD and NHD, respectively, post-dialysis levels were slightly lower with CHD (0.7 +/- 0.2 vs. 0.8 +/- 0.2 mM, P < 0.05). The measured phosphate removed per session of CHD or NHD was comparable, 25.3 +/- 7.5 versus 26.9 +/- 9.8 mumol/session, respectively. On the other hand, the cumulative weekly phosphate removal was significantly higher with NHD as compared to CHD, 75.8 +/- 22.5 versus 161.6 +/- 59.0 mumol/week (P < 0.01). In the "chronic" study serum phosphate levels were measured monthly for five months on CHD and for five months after the patients were switched to NHD. Dietary phosphate intake and the dosage of phosphate binders were tabulated. Serum phosphate levels fell during NHD: 2.1 +/- 0.5 mM at the beginning of the study and 1.3 +/- 0.2 mM five months after being switched to NHD (P < 0.001). At the same time dietary phosphate intake increased by 50%. By the fourth month of NHD therapy none of the patients was taking any phosphate binders. In conclusion, NHD is more effective in controlling serum phosphate levels than CHD, allowing patients to discontinue their phosphate binders completely and to ingest a more liberal diet.

Cross-Over Studies↗
PubMed1997

Dominant-negative SMAD-3 interferes with transcriptional activation by multiple agonists.

Smad proteins have recently been identified as mediators of transcriptional activation by members of the transforming growth factor-beta superfamily. To determine if Smads might also be involved in inducing gene transcription in response to other agonists, expression vectors for dominant-negative Smad proteins were constructed. These plasmids were transiently cotransfected with luciferase reporter genes and the effects of various agonists on reporter gene activity evaluated in NIH 3T3 cells. Dominant-negative Smad3, but not other dominant-negative Smads, reduced stimulation of the plasminogen activator inhibitor-1 (PAI-1) and other gene promoters by phorbol ester, cAMP, and platelet-derived growth factor. Activation of the PAI-1 promoter by TGF-beta or prostaglandin F2 alpha, and transactivation by c-Jun or JunB were not inhibited by dominant-negative Smad3, supporting the specificity of this mutant. These results suggest that Smad3, like CREB-binding protein (CBP), may participate in transcriptional activation by multiple agonists.

3T3 Cells↗
PubMed1997

Adynamic bone disease: pathogenesis, diagnosis and clinical relevance.

In the past several years significant attention has been directed to the study of adynamic bone disease in uremic patients. Several reports have provided additional information about the prevalence of adynamic bone disease in different countries. It has now become clear that the pathogenesis of adynamic bone disease cannot be ascribed to one single aetiological factor, but rather to a host of complex factors. From recently published papers we have learned about the mechanism of downregulation of the parathyroid hormone/parathyroid hormone-related peptide receptor on osteoblast-like cells, which may be a very important step in the pathogenesis of adynamic bone disease. A provocative hypothesis attempts to link the widespread use of erythropoietin to the emergence of adynamic bone disease-lacking excessive aluminium accumulation. It appears from some studies that bone-specific alkaline phosphatase might become a valuable tool in differentiating high turnover from low/normal turnover bone disease; however, further studies are needed to establish the role of this marker in the diagnosis of adynamic bone disease. Several papers discussed the pros and cons of lowering the calcium concentration of the dialysate in order to prevent adynamic bone disease. The results of these studies help us to understand the pathogenesis and the clinical relevance of this lesion in attempts to provide better care for our patients.

Alkaline Phosphatase↗
PubMed1996

Extracellular signal-regulated kinase and the small GTP-binding protein, Rac, contribute to the effects of transforming growth factor-beta1 on gene expression.

The kinases and regulatory proteins that convey signals initiated by transforming growth factor-beta (TGF-beta) to the nucleus are poorly characterized. To study the role of the extracellular signal-regulated kinase (ERK) pathway in this process, we transiently transfected NIH 3T3 fibroblasts with TGF-beta-responsive luciferase reporter genes and expression vectors designed to interrupt this kinase cascade. Mitogen-activated protein (MAP) kinase phosphatase-1 and a dominant negative MAP/ERK kinase 1 mutant reduced stimulation of plasminogen activator inhibitor-1 (PAI-1) promoter activity by TGF-beta1 from 11.5- to 4-fold and 4.9-fold, respectively. Similar results were observed with the type I collagen promoters. TGF-beta1 increased ERK1 activity 4.5-fold at 5 min and 3. 1-fold at 3 h, while Jun kinase and p38 activity were not affected. Cotransfection of a dominant negative mutant of the small G protein, Rac, but not dominant negative Ras, Cdc42, or Rho mutants, reduced the effects of TGF-beta1 on the PAI-1 promoter by approximately half. In support of a role for Rac in signaling by TGF-beta, GTP binding to Rac was increased 3.7-fold following exposure of NIH 3T3 cells to TGF-beta1 for 3 min. These findings indicate that TGF-beta1 modulates gene expression partly through ERK and Rac in NIH 3T3 cells.

3T3 Cells↗
PubMed1994

The influence of branched polypeptide carriers on the immunogenicity of predicted epitopes of HSV-1 glycoprotein D.

To investigate the role of synthetic polypeptide carriers in inducing an epitope-specific immune response relevant for vaccine design, peptides comprising two distinct regions of herpes simplex virus type I glycoprotein D (1-23 and 273-284) have been conjugated to the branched polypeptides with polylysine backbone, poly[L-Lys-(DL-Alam)] (AK), or poly[L-Lys-(Leui-DL-Alam)] (LAK) and to keyhole limpet haemocyanin (KLH). The magnitude, fine specificity and isotype distribution of the conjugate-, peptide-and carrier-specific antibody responses were characterized in immunized BALB/c and CBA mice. Conjugates containing the polypeptide carrier AK were the most effective in inducing HSV gD-peptide-specific antibody responses while KLH peptide conjugates resulted in conjugate-specific antibody responses without measurable peptide specificity. The efficacy of AK-peptide conjugates was verified by the dominant appearance of peptide-specific antibodies belonging to functionally efficient IgG isotopes, accompanied by low levels of carrier specific antibody responses. Preimmunization of BALB/or CBA mice with AK conjugates comprising the 1-23 or 276-284 HSV peptides resulted in prolonged survival of animals infected with a lethal dose of infectious HSV-1. The potency of these conjugates in eliciting a protective immune response shows a close correlation with the relative levels of conjugate-induced virus-specific antibodies and the neutralizing activity of sera as measured in preimmunized survivors.

Amino Acid Sequence↗
PubMed1992

Combined effects of flavonoids and acyclovir against herpesviruses in cell cultures.

The combined antiviral effects of some flavonoid compounds and acycloguanosine (acyclovir, Zovirax) were studied on the multiplication of herpes simplex virus types 1 and 2 in HEp-2 cells and on pseudorabies (Aujeszky) virus in chick embryo fibroblast cells by the yield reduction method. The flavonoids quercetin, quercitrin (quercetin-3-L-rhamnoside) and apigenin exhibit antiviral activity against these herpesviruses, and acyclovir is currently one of the most effective antiherpetic agents. In these studies, the simultaneous application of flavonoids with acyclovir resulted in an enhanced antiviral activity. A mathematical formula was used to interpret the drug interaction, resulting in FIC (fractional inhibitory concentration) indices. Meaning a synergic interaction, all combinations exhibited synergy, FIC values of 0.6-0.8 being commonly observed.

Acyclovir↗
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↗
PubMed1986

The role of guanyl nucleotide binding proteins in the formation of inositol phosphates in adrenal glomerulosa cells.

A non-hydrolysable GTP analogue enhanced the formation of [3H]inositol polyphosphates in permeabilized adrenal glomerulosa cells. Pertussis toxin, which ADP-ribosylated Ni, failed to influence angiotensin-induced formation of 3H-labelled inositol phosphates and the incorporation of [32F]phosphate into phosphatidylinositol and phosphatidic acid. These results show that Ni is present and a G-protein activates phospholipase C also in glomerulosa cells, however, it is not Ni which couples angiotensin receptors to the enzyme.

Adenosine Diphosphate Ribose↗
PubMed1985

Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids.

The inhibitory effect of four flavonoid compounds on virus multiplication and their influence on the intracellular cyclic AMP (cAMP) level were studied in cell cultures. Quercetin and quercitrin reduced the yields of Human (alpha) herpesvirus 1 (HSV-1) and Suid (alpha) herpesvirus 1 (pseudorabies virus), but hesperidin and rutin had no effect. Further, quercetin and quercitrin elevated the intracellular level of cAMP, whereas hesperidin and rutin did not alter the cAMP level. Both antiviral activity and cAMP-enhancing effect were dependent on the concentrations of the flavonoids, and these effects turned out to be parallel. This study suggests that a relation exists between the antiviral effect and the cAMP-enhancing activity of flavonoids.

Animals↗
PubMed1984

Combined antiviral effects of flavonoids and 5-ethyl-2'-deoxyuridine on the multiplication of herpesviruses.

The combined antiviral effects of quercetin, quercitrin and 5-ethyl-2'-deoxyuridine on the multiplication of herpes simplex virus type 1 (HSV-1) and pseudorabies virus were studied in vitro by the yield reduction test. Quercetin in combination with 5-ethyl-2'-deoxyuridine had an additive antiviral effect on either herpes-virus. The combined application of quercitrin and 5-ethyl-2'-deoxyuridine showed a synergic effect on pseudorabies virus.

Antiviral Agents↗