Istvan Szakall - Academia.edu (original) (raw)

Papers by Istvan Szakall

Neurochemical Research, 2007

Journal of Neurochemistry, 2003

The mechanisms underlying predisposition to alcohol abuse and alcoholism are poorly understood. I... more The mechanisms underlying predisposition to alcohol abuse and alcoholism are poorly understood. In this study, we evaluated the role of cannabinoid (CB1) receptors in (i) voluntary alcohol consumption, and (ii) acute alcohol‐induced dopamine (DA) release in the nucleus accumbens, using mice that lack the CB1 receptor gene (CB1–/–). CB1–/– mice exhibited dramatically reduced voluntary alcohol consumption, and completely lacked alcohol‐induced DA release in the nucleus accumbens, as compared to wild‐type mice. The gender difference, with female mice consuming significantly more alcohol than wild‐type male mice, was observed in wild‐type mice, whereas this gender difference was nonexistent in CB1 mutant male and female mice. There was also a significant gender difference, with the wild‐type, heterozygous, and mutant females consuming significantly more liquid and food than wild‐type, heterozygous and mutant males. However, the total volume of fluid consumption and food intake did not d...

Magyar Allatorvosok Lapja, 2000

PubMed, 1996

After a critical review of recent research on the whole body chemical composition of laboratory a... more After a critical review of recent research on the whole body chemical composition of laboratory animals, especially that of the mouse, the authors present data on the body composition of a mouse line of different body condition score, varying from normal to double-muscled ("culard", "compact") type. One hundred male and 100 female mice of different compact categories were measured in vivo, using total body electrical conductivity (TOBEC method), then by direct chemical analysis performed on day 77 of life. In male mice, body weight and protein content were found to increase while fat content decreased parallel to the increase in phenotypic condition score. Female mice showed a rather constant fat, protein and ash content in the dry matter of the body. The precision and validity of TOBEC data under 40 grams of body weight proved to be insufficient.

Acta veterinaria Hungarica, 1998

The effect of dietary fat and/or lysine supplementation on the body composition of broiler chicke... more The effect of dietary fat and/or lysine supplementation on the body composition of broiler chickens was studied. Body composition was measured by computed tomography (CT) and direct chemical analysis. Cockerel chicks from a previous experiment (Fekete et al., 1992) were used in this study. Ten chickens from each treatment group were euthanised, deep frozen and subjected to CT. Subsequently the bodies were dissected and ground to obtain homogeneous samples for chemical analysis. Supplementation of the diet with 6 g/kg lysine did not change total body composition but positively influenced the final body weight. In the treatment group receiving 40 g/kg added fat and 3 g/kg feed lysine (F-LYS-I) the higher body weight ran parallel with a higher fat content. The difference between the frozen body weight and final live body weight shows that lysine supplementation increased the water-holding capacity of muscle, which was the best in groups receiving a diet of normal energy content plus hi...

Acta veterinaria Hungarica, 1996

High-yielding dairy cows (n = 34) were divided into high (HD) and low (LD) protein degradability ... more High-yielding dairy cows (n = 34) were divided into high (HD) and low (LD) protein degradability groups after delivery, and used for a feeding trial which lasted up to day 80 +/- 10 of lactation. The cows were regularly weighed, their body condition was scored (BCS), and their reproductive status assessed. Blood samples were taken simultaneously, and ruminal fluid was collected on the last day of the trial. On postpartum day 45 +/- 6 and 11 days thereafter two prostaglandin F2 alpha (PGF2 alpha) injections were administered. The ammonia and urea concentrations of the ruminal fluid were higher in cows of group HD. The C2:C3 ratio was 2.7:1 vs. 2.3:1 in HD and LD cows, respectively. The amino acid and lipid composition of blood reflected the dietary treatments. The BCS and blood urea concentration were slightly higher in HD animals. The average daily milk production of LD cows was 1.5 kg higher than that of HD cows. The pregnancy rates of the two groups at day 200 after calving did no...

Veterinary Record, 1997

Tissue samples from the feet of slaughtered cattle exhibiting different stages of digital dermati... more Tissue samples from the feet of slaughtered cattle exhibiting different stages of digital dermatitis were sectioned and stained with haematoxylin and eosin and silver staining techniques. Three morphological variations of spirochaetes were observed, whereas control samples from feet which were macroscopically negative for digital dermatitis were also negative for spirochaetes. In an immunofluorescence test, [i]Campylobacter faecalis[/i] was found to be abundant on superficial wound smears from the classical ulceration of digital dermatitis.

Journal of Neurochemistry, 2008

A standard way to assess lipid peroxidation (LP)in neurodegenerative diseases is to stimulate LP ... more A standard way to assess lipid peroxidation (LP)in neurodegenerative diseases is to stimulate LP in membrane fragments (MF) from postmortem human brains both normal and diseased. Studies using 0.67 mM iron plus 67 mM hydrogen peroxide showed that stimulated LP is increased in Alzheimer's diseased (AD) brain (Neurosci. Letts: 112, 333-337, 1990). In contrast, 0.1 mM ascorbate-stimulated LP is reduced in AD brain (Mol. Chem. Neuropath. 33, 15-26,1998). We have stimulated LP in MF from human prefrontal cortex with iron, iron plus hydrogen peroxide, hydrogen peroxide and ascorbate. Shown for brevity are two stimulants and the effect of some inhibitors of LP. The ingredients were incubated for 120 min with 0.1 mg protein and buffer. LP was determined spectrophotometrically by the formation of thiobarbituric acid positive reactants. The data shown are the mean ± SEM (N ¼ at least 3). Stimulants were FeCl 2 + H 2 O 2 (both 10 mM) or ascorbate (0.1 mM). Response was measured in nmols MDA/mg protein. Deferoxamine (10 lM), catalase (100 lg/mL) and alpha-tocopherol (Trolox) at 10 lM and are shown as percentage maximal. These findings suggest that all methods of stimulating LP in MFP from human brain are not equivalent. Therefore caution is recommended in the interpretation of differences in LP between presumptive normal and neurodegenerative human brain.

Genomics, 2007

Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development... more Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cisregulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy.

Zeitschrift für Ernährungswissenschaft, 1997

Alcoholism: Clinical & Experimental Research, 2005

Background: Although a large body of evidence suggests a role for the opioid system in alcoholism... more Background: Although a large body of evidence suggests a role for the opioid system in alcoholism, the precise role of-, ␦- ,-, and ORL1-opioid receptors and the physiological significance of their natural genetic variation have not been identified. The method of targeted gene disruption by homologous recombination has been used to knock out (KO) genes coding for opioid receptors, and study their effects on alcohol self-administration. Here we examined the effects of targeted disruption of-opioid receptor (KOR) on oral alcohol self-administration and other behaviors. Methods: Oral alcohol, saccharin and quinine self-administration was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol, or tastant solutions. In preference tests 12% alcohol, 0.033% and 0.066% saccharin, and 0.03mM and 0.1mM quinine solutions were used. Open-field activity was determined in an arena equipped with a computer-controlled activity-detection system. Subjects were tested for three consecutive days. Locomotor activity was assessed on days 1 and 2 (after saline injection, i.p.) and on day 3 (after alcohol injection, i.p.). Alcohol-induced locomotor activity was determined as the difference in activity between day 3 and day 2. Results: Male KOR KO mice in preference tests with 12% alcohol consumed about half as much alcohol as wild-type (WT) or heterozygous (HET) mice, showed lower preference for saccharin (0.033% and 0.066%) and higher preference to quinine (0.1mM) than WT mice. Female KOR KO mice showed similar reduction in alcohol consumption in comparison to WT and HET mice. Partial deletion of KOR in HET mice did not change alcohol consumption in comparison to WT mice. In all genotype-groups females drank significantly more alcohol than males. MANOVA of locomotor activity among KO, WT, and HET mice indicated that strain and sex effects were not significant for alcohol-induced activation (p Ͼ 0.05), while strain x sex interaction effects on alcohol-induced activation could be detected (F 1,55 ϭ 6.07, p Ͻ 0.05). Conclusion: Our results indicating decreased alcohol consumption, lower saccharin preference, and higher quinine preference in KOR KO mice are in line with previous observations of opioid involvement in maintenance of food intake and raise the possibility that the deficient dynorphin/KOR system affects orosensory reward through central mechanisms which reduce alcohol intake and disrupt tastant responses, either as direct effects of absence of-opioid receptors, or as effects of indirect developmental compensatory changes.

Alcohol, 2004

Results of recent studies support the notion that substance self-administration is partially a ge... more Results of recent studies support the notion that substance self-administration is partially a genetically controlled component of addiction tied to habit formation and cellular modification of the striatum. Aiming to define pathways among genomic, neural, and behavioral determinants of addiction, we investigated global striatal gene expression in a paradigm of oral self-administration of alcohol by using genomically very similar alcohol-nonpreferring B6.Cb 5 i 7-α3/Vad (C5A3) and alcohol-preferring B6.Ib 5 i 7-β25A/Vad (I5B25A) quasicongenic mouse strains and their progenitors, C57BL/6By (B6By) and BALB/cJ. Expression of 12,488 genes and expressed sequence tags (ESTs) was studied by using 24 high-density oligonucleotide microarrays. Transcript signal intensity differences were analyzed with z test after iterative median normalization across groups and Hochberg step-down Bonferroni procedure. As expected, striatal transcriptome differences were far more extensive between the independently derived progenitor strains than between the quasi-congenic strains and their background partner, B6By. However, the genes, which were differentially expressed between the quasi-congenic strains and their background partner, were not subsets of the progenitorial differences and were not located on the chromosome segments introgressed into the quasi-congenic strains from the donor BALB/cJ strain that have been so far defined. Although 25 transcripts showed significantly different expression between the progenitor strains, only two transcripts, phosphatidylserine decarboxylase and a hypothetical 21.2-kDa protein, and one transcript, molybdenum co-factor synthesis 2, showed significantly different expression between C5A3 and I5B25A, and between B6By and I5B25A, respectively. The latter three transcripts are not located on previously identified chromosome segments introgressed from the donor BALB/cJ strain, supporting the suggestion of transacting regulatory variations among strains. Exposure to alcohol did not induce statistically significant striatal gene expression changes in any of the mouse strains. In conclusion, the results support the hypothesis that in functional genomic studies the chance of detecting function-relevant genes can be increased by the comparative analysis of quasi-congenic and background strains because the number of functionally irrelevant, differentially expressed genes between genomically similar strains is reduced. Lack of statistically significant alcohol-induced changes in transcript abundance indicated that oral self-administration had subtle effects on striatal gene expression and directed attention to important implications for the experimental design of future microarray gene expression studies on complex behaviors.

Acta Veterinaria Hungarica, 2001

A growth trial was carried out to test the effect of organic, trivalent chromium and L-carnitine ... more A growth trial was carried out to test the effect of organic, trivalent chromium and L-carnitine on the body composition of growing rats. At the same time, an evaluation of different measurement methods (weight of epididymal fat pad, adipocyte morphometry, total body electrical conductivity) was performed. Outbred Wistar rats of 30 days of age were fed diets of different (0, 10 and 20%) protein level. The diets were supplemented with 4 mg/kg Cr as chromium nicotinate, and 100 mg/kg L-carnitine. The experimental feeding lasted 15 days, after a 5-day-long adjustment period. It was found that Cr addition increased feed intake. Both treatments caused changes in body composition, increasing fat and protein deposition. Organic chromium had no effect at either protein level, while Lcarnitine improved the protein retention only at an optimum (20%) protein supply. No statistically significant correlation was found between total body electrical conductivity (TOBEC) and body composition, which could be attributed to the great individual differences. A close correlation was found among total body fat percentage, weight of epididymal fat pad and the adipocyte surface. The data suggest that there is an interaction between dietary protein supply and the effect of repartitioning agents.

Alcohol, 2003

Results of recent studies have indicated an association between voluntary alcohol intake and acti... more Results of recent studies have indicated an association between voluntary alcohol intake and activities of κ-opioid receptor systems in animal models. We assessed the possibility that genetic differences observed in alcohol preference among mouse strains are related to possible polymorphisms of the κ-opioid receptor gene (Oprk1). We compared DNA sequences of the coding region and the promoter/regulatory region of Oprk1