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Biomedical subjects

A Holownia

Publications and source records attributed to A Holownia.

At least 19 recordsLinked to original sources
PubMed2003

Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer.

p53 protein is a critical regulator of the cell cycle and apoptosis and its levels and functions change in response to many stimuli. To assess whether the cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53 protein, we determined poly-ADP-ribose levels, the expression of p53 protein and its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radiotherapy and chemotherapy. All 14 patients included in this study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy decreased G2/M cell numbers but increased S-phase cells by almost 50% compared to ploidy status before therapy, while median p53 expression was doubled (109% increase). p53 phosphorylated on Ser-392 was also increased by approximately 70% in patients treated with radiotherapy and with chemotherapy and correlated with elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53 quantity, posttranslational phosphorylation/dephosphorylation-mediated alterations may play an important role in neoplastic cell proliferation as well as in antiproliferative activity of drugs inducing DNA damage and apoptosis.

Aged↗
PubMed2001

Proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy.

To assess proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy, we performed a flow cytometry analysis (FC) using fresh bronchoscopy specimens from 38 patients with lung cancer. Among 33 males and 5 females, squamous cell carcinoma (NSLC) was recognized in 12 males, 15 males had small cell lung cancer (SCLC) and 6 males had lung cancer with no histological type (LC) defined. Three women had SCLC, 1 had NSCLC and one had LC. Control consisted of 11 COPD patients. The percentage of diploid cells was significantly lower and cells with hypoploid cells were significantly higher in study group before treatment. High percentage of G2M cells characterised NSCLC and LC groups, whether high number of S phase cells characterised NSCLC and SCLC group before treatment. The treatment lowered percentage of G2M cells in NSCLC and CA group, whether diploid, hypoploid and S phase cells did not differ than those from before treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Role of neutrophils in release of some cytokines and their soluble receptors.

Available data suggest that cytokines and soluble cytokine receptors, which are being produced by immunological cells, can modulate the immune response of the host. Although the production of mediators such as TNF-alpha and IL-6 as well as that of their soluble receptors has been extensively studied in tissue cells and mononuclear cells, it has not been fully investigated in neutrophils (PMN). In the present study we examined the ability of PMN to simultaneously release TNF-alpha, IL-6 and their soluble receptors-sTNFRp55, sTNFRp75 and sIL-6R. Concentrations of soluble receptors were compared with expression of membrane-bound TNF and IL-6 receptors. For comparative purposes, similar examinations with autologous peripheral blood mononuclear cells (PBMC) were performed. We found that PMN and PBMC have the same ability to release IL-6 and sTNFRp75. In contrast, there were significant differences in the release of TNF-alpha, sTNFRp55 and sIL-6R between these cells. Reduction in membrane TNF receptor expression, observed in this study, was associated with increase secretion of soluble TNF receptors by PMN and PBMC. The results suggest that PMN can play an essential role in modulating the inflammatory response by affecting the balance between pro-inflammatory mediators, such as TNF-alpha, and anti-inflammatory mediators, such as soluble TNF receptors.

Adult↗
PubMed1999

Acetaldehyde cytotoxicity in cultured rat astrocytes.

The effect of acetaldehyde on astrocytes have been investigated because not only do they play an important role in brain maturation but also recent reports have shown their delayed proliferation following both 'in vivo' and 'in vitro' ethanol exposure. Biochemical parameters related to apoptotic and necrotic processes were examined in primary cultures of rat astrocytes exposed for 4 days to acetaldehyde generated from ethanol by co-cultured alcohol dehydrogenase-transfected Chinese hamster ovary cells. Acetaldehyde levels in the culture media attained concentrations of approximately 450 microM. To study ethanol effects, alcohol oxidation was inhibited by 4-methylpyrazole (an inhibitor of alcohol dehydrogenase). Acetaldehyde but not ethanol increased intracellular calcium levels by 155%. Moreover, significant DNA fragmentation was detected using a random oligonucleotide primed synthesis assay, by flow cytometry and when using agar gel electrophoresis. Transglutaminase activity was elevated in the cells treated with acetaldehyde but when acetaldehyde formation was inhibited by 4-methylpyrazole the enzyme activity was unaffected. Nitrate levels in the culture media were unchanged. Additionally, microscopic examination of cell nuclei revealed chromatin condensation in astrocytes exposed to acetaldehyde. It can be concluded, that in 'in vitro' acetaldehyde exposed rat astrocytes apoptotic pathways are activated.

Acetaldehyde↗
PubMed1998

Paternal alcohol exposure: developmental and behavioral effects on the offspring of rats.

The effect of paternal alcohol exposure on neurochemical and behavioral parameters was investigated using as a model system glial cells derived from newborn rat brain and cultured for 4 weeks. The total brain neurochemical parameters from rats born to mothers sired by an alcohol treated father were also investigated. Enzymatic markers of nerve cell development (enolase isoenzymes and glutamine synthetase) and the defense system (superoxide dismutase) against free radicals formed during alcohol degradation were measured in order to evaluate nerve cell damage. Behavioral locomotor tests (open-field, novelty-seeking, light/dark) were carried out to show long-lasting effects of paternal alcoholization on the offspring. Behavioral and developmental alterations were found until 1 year of age in the offspring and a significant growth retardation was observed in the males. Our results suggest that paternal alcohol exposure produces developmental and behavioral effects in the offspring. The consequence of either alcohol withdrawal during stage one spermatogenesis, or maternal diet supplementation with manganese during pregnancy were investigated. It was observed that some of the effects of paternal alcohol exposure on the offspring may be reversed by these treatments.

Animals↗
PubMed1997

Acetaminophen metabolism and cytotoxicity in PC12 cells transfected with cytochrome P4502E1.

Although a number of studies confirm the important role of metabolites in the cytotoxicity of acetaminophen, its precise mechanisms remain unknown. Acetaminophen is metabolized by microsomal enzymes. Cytochrome P4502E1 (CYP2E1) mediated N-hydroxylation results in the formation of N-acetyl-benzo-quinoneimine, a highly reactive intermediate. We examined biochemical parameters related to necrotic and apoptotic processes in acetaminophen-exposed PC12 cells is and in a PC12 cell line genetically engineered to express human CYP2E1. Both the [3H]thymidine incorporation test and the protein assay uniformly showed dose- and time-related significant growth retardation in both cell lines exposed to the drug. This was more evident in CYP2E1-transfected cells. Moreover, the cytotoxic effect of acetaminophen was increased as evidenced by lactate dehydrogenase activity in the culture medium. Both random oligonucleotide primed synthesis assay and enzyme-linked immunosorbent assay revealed significant DNA fragmentation in both cell lines, which was greater in transfected cells, reaching about 11% of total cellular DNA. These results were confirmed by flow cytometry and microscopic examination of cell nuclei. Intracellular calcium levels were increased only in transfected cells, approximately threefold when 5 mM acetaminophen was administered for 48 h. These results indicate the cytotoxic effects of acetaminophen via apoptosis, necrosis, and growth retardation. While the precise mechanism remains obscure, it seems that DNA fragmentation and apoptotic cascade represent a preliminary biochemical event in acute cell death, and that acetaminophen bio-transformation by CYP2E1 stimulates this pathway.

Acetaminophen↗
PubMed1996

Development of glial cells cultured from prenatally alcohol treated rat brain: effect of supplementation of the maternal alcohol diet with a grape extract.

The aim of this work was to investigate the effect of supplementation of a maternal alcohol diet with a grape extract on glial cell development. Glial cells were cultured during 4 weeks from cortical brain cells of the new born offspring in DMEM medium supplemented with fetal calf serum. Enzymatic markers of nerve cell development were measured (enolase isoenzymes and glutamine synthetase). Since alcohol consumption produces free radicals the antioxidant system superoxide dismutase was also investigated. Compared to the decrease found in only alcohol treated animals, all parameters except neuron-specific enolase were antagonized and even stimulated after grape extract supplementation. The effect was more important after only 1 month than 3 months of treatment. Also in the total brain an alcohol antagonizing effect and a glutamine synthetase activation were found. Our data demonstrate that addition of a grape extract to the maternal alcohol diet may partially or completely overcome the alcohol induced retardation of glial cell development.

Animals↗
PubMed1995

The effect of ethanol on HSP70 in cultured rat glial cells and in brain areas of rat pups exposed to ethanol in utero.

Prenatal exposure to alcohol is associated with a cluster of symptoms called Fetal Alcohol Syndrome with a characteristic pattern of neuroanatomy and biochemical changes. In recent years it has been shown, that stress exposed cells rapidly increase transcription and translation of heat shock protein genes resulting in an increased appearance of these proteins. It has also been found that heat shock proteins, especially the HSP70 family play a role as molecular chaperons maintaining the native conformation of proteins and participating in protein transport in particular cellular compartments. The aim of this study was to determine the effect of chronic maternal alcohol consumption on HSP70 content in the different regions of the brain of the newborn rats as well as to examine in vitro the effect of ethanol on HSP70 content in cultured glial cells. Chronic maternal ethanol consumption resulted in increased HSP70 in the following regions of developing brain: hippocampus, cerebellum, olfactory bulbs, frontal cortex and septum. Moreover, ethanol applied in vitro, increased HSP70 content in primary astroglial cultures and astrocytes but not in oligodendrocyte cultures. The above described changes may be important in brain maturation and may play a role in Fetal Alcohol Syndrome.

Alcoholism↗
PubMed1993

Inhibition of non-enzymatic lipid peroxidation by 'Essentiale' a drug enriched in phosphatidylcholine in ethanol-induced liver injury.

The effect of 'Essentiale'--a drug, now clinically listed in European countries in the treatment of liver diseases was examined in ethanol-induced liver injury in rats (free access to a 20% ethanol solution for 3 months). The antioxidant enzymes, SOD (superoxide dismutase), CAT (catalase), GSH-R (glutathione reductase), non-protein and total SH groups as well as TBA-rs contents were investigated. Following treatment, we found beneficial effects in SOD and CAT activities. The above enzyme activities were restored after a 3-month drug administration. Furthermore, 'Essentiale' treatment normalized TBA-rs levels in the liver. These effects have been briefly discussed.

Animals↗
PubMed1991

The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury.

There appears to be increasing evidence that ethanol toxicity may be associated with an increased production of reactive oxygen intermediates. In rats we studied the effect of 4 weeks of ethanol ingestion on the liver cytosolic defense system against active oxygen species. Compared with the control rats, the ethanol-fed animals had a significantly higher liver malondialdehyde content and significantly lower reduced glutathione level. Moreover, ethanol feeding resulted in a decrease of superoxide dismutase and catalase activities while glutathione peroxidase activity was only slightly diminished. Thus, prolonged ethanol administration profoundly modified the hepatic status of the enzymatic defense system leading to lipid peroxidation that may disrupt vital functions of liver cells.

Animals↗
PubMed1991

The effect of Heparegen and D-penicillamine on the activity of some ammonia metabolizing enzymes in liver and brain of rats intoxicated with ethanol.

This paper reports data on the effect of two drugs: Heparegen (thiazalidine-4-carboxylic acid) and D-penicillamine on the blood ammonia concentration and on some ammonia metabolizing enzymes in liver and brain of rats intoxicated with ethanol. It seems, that both drugs decrease ammonia concentration and simultaneously elevate liver and brain glutamine synthetase activity. The effect of D-penicillamine on the nitrogen metabolism in the damaged liver appears to be more favorable than that of Heparegen.

Alcoholic Intoxication↗
PubMed1990

Ethanol decreases the level of sulfhydryl compounds in red blood cells and changes their hematological pattern in rats.

The level of sulfhydryl compounds in red blood cells (RBCs) and plasma and some haematological parameters were investigated in rats treated with ethanol for 4 weeks (daily dose of 6g/kg, 30% w/v, p.o.). After ethanol ingestion, the significant decrease of non-protein - SH groups were observed in RBCs and plasma. In treated rats, the mean corpuscular haemoglobin concentration (MCHC) was decreased and the mean corpuscular volume (MCV) was increased. There is a positive correlation between these two parameters and decreased content of sulfohydryl groups in RBCs.

Animals↗
PubMed1987

The changes in sulfhydryl compounds in plasma, liver and brain after acute and chronic ethanol administration in rats.

The content of sulfhydryl compounds in proteins and non-proteins of plasma, liver and brain after acute and chronic ethanol administration was investigated in rats. After ethanol ingestion for 4 weeks (6 g/kg, day 30% w/v) significant changes were observed in plasma proteins and in liver proteins and non-proteins. In brain proteins and non-proteins we did not find any changes in sulfhydryl compounds content after acute and chronic ethanol administration.

Alanine Transaminase↗
PubMed1986

Plasma and liver amino acids in rats after administration of ethanol or acetaldehyde.

The changes in the level and pattern of free amino acids in plasma and liver after ethanol or acetaldehyde intoxication has been investigated in rats. After administration of 30% (w/v) ethanol, 6 g kg-1, or 1.5% (w/v) acetaldehyde, 0.3 ml kg-1, for 4 weeks we found a decrease in plasma and liver branched-chain amino acids and an increase in plasma aromatic amino acids and methionine. The results are analogous to those found in studies of damaged liver.

Acetaldehyde↗
PubMed1976

The effect of conditioned stimuli signalling food upon the autochthonous instrumental responses in dogs.

Food CSs, presented (i) concomitantly with SD controlling bar pressing for food, or (ii) on the background of non-discriminated bar pressing (FR 1/15), suppress instrumental performance but elicit undiminished conditioned salivation. This result supports Soltysik-Konorski's model of CNS mechanism controlling food-oriented behavior which postulates drive inhibition by taste-consummatory neurons.

Animals↗
PubMedDate not supplied

The effect of immunostimulatory drugs on sulfhydryl compounds in plasma, liver and brain after ethanol-induced liver injury in rats.

Sulfhydryl compounds in plasma, liver and brain of rats treated with two immunostimulant drugs, isoprinosine and levamisole, after alcoholic liver injury have been investigated. After use of both drugs for 6 days we found partially beneficial effect on the SH-groups in plasma and liver. No changes in nonprotein SH compounds were observed in rat brain after treatment with isoprinosine, levamisole or ethanol. Furthermore, levamisole shortens the time necessary for the return of AlAT activity to normal value.

Animals↗
PubMedDate not supplied

The effect of heparegen on antioxidant enzyme activities in ethanol-induced liver injury in rats.

SOD, CAT, GSH-Px, and sulfhydryl compounds MDA contents in liver of rats treated with heparegen for 7, 14, and 21 days after alcoholic liver injury have been investigated. After use of this drug, we found beneficial effects on GSH-Px activity, sulfhydryl compounds (total and nonprotein), and MDA content and a partially beneficial effect on SOD and CAT activities. These enzyme activities after 21 days of drug administration were restored. Furthermore, heparegen shortens the time necessary for the return of AIAT and GGTP to normal value. This enzymatic data are supported by histological studies in light microscopy.

Animals↗