L-thyroxine increases susceptibility of adult rats to low K+-induced ventricular fibrillation, and sinus rhythm restoration in old rats

Hypokalaemia increases the risk for life-threatening arrhythmias; however, data about interaction with thyroid status are lacking. The aim of this study was to investigate vulnerability of l-thyroxine (T(4))-treated adult and old rats to low K(+)-induced ventricular fibrillation (VF) as well as the ability of the heart to recover sinus rhythm. The experiments were performed on isolated heart preparations using the heart of 4- and 20-month-old female Wistar rats without and with feeding with T(4) 50 microg (100 g day)(-1) over a period of 2 weeks. Perfusion of the isolated heart with oxygenated Krebs-Henseleit solution at constant pressure was followed by perfusion with K(+)-deficient solution until occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused with normal solution for 10 min, during which sinus rhythm was restored. ECG, left ventricular pressure (LVP) and coronary flow were continuously monitored. The results showed that compared with untreated rats, the onset of low K(+)-induced ventricular premature beats was delayed and their number was significantly decreased in both T(4)-treated groups. Nevertheless, VF occurred earlier in T(4)-treated than in non-treated adult rats (6.78 +/- 0.28 vs. 9.59 +/- 0.55 min, P < 0.05), whereas the difference was not significant in aged animals. Furthermore, sinus rhythm appeared earlier in old T(4)-treated rats compared with non-treated rats (7.18 +/- 0.57 vs. 8.94 +/- 0.64 min, P < 0.05), whereas in adult hearts it set in at practically the same time regardless of treatment. In conclusion, our results indicate that administration of a pharmacological dose of T(4) can increase the risk of low K(+)-induced VF in adult but not in old animals; in the latter it even facilitated restoration of sinus rhythm. Moreover, enhanced mechanical function was observed in both adult and old T(4)-treated hearts.     

Prevention of postoperative peritoneal adhesions: effects of lysozyme, polylysine and polyglutamate versus hyaluronic acid

OBJECTIVE: Intraperitoneal adhesions are an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. In the present study we hypothesized that a combination of polypeptides with different surface properties, resulting in fine disperse low-soluble complexes, could be of benefit in the prevention of abdominal adhesions. MATERIAL AND METHODS: Various polypeptides including lysozyme, polyglutamate, polylysine and combinations of all three were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The extent of peritoneal adhesions to the injured area was measured and expressed as a percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and the Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function caused by the chemicals. RESULTS: Significant differences were seen among the treatment groups (p<0.001). Both polyglutamate and lysozyme, and polyglutamate together with polylysine significantly decreased adhesion formation as compared to hyaluronic acid. The polylysine-polyglutamate combination was still visible macroscopically on the peritoneal surface after 1 week, though not after 1 month. The polyglutamate-lysozyme mixture was less effective than these individual components alone. The chemicals did not show any toxic effects or altered function in macrophage cell culture. CONCLUSIONS: Lysozyme, polyglutamate and, most effectively, a polyglutamate-polylysine combination significantly decreased experimental abdominal adhesion formation. A strong mechanical connection to the wound and prolonged attendance in the surface were noted. Peritoneal phagocyte function did not seem to be influenced by the chemicals.     

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM:To study the inflammatory bowel disease-5 locus（IBD5）and interleukin-23 receptor（IL23R）gene variants in UC patients and test for gene-gene interaction.METHODS:The study population（n=625）was comprised of 320 unrelated ulcerative colitis（UC）patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus（IGR2198a₁ rs11739135,IGR2096a₁ rs12521868,IGR2230a₁ rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367）and two of the IL23R gene（rs1004819,rs2201841）were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency（P=0.032）in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers（P=0.004,OR=1.606;95%CI:1.160-2.223）and the SNP rs2201841 for homozygotes（P=0.030,OR=1.983;95%CI:1.069-3.678）.Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a₁ C or IGR2096a₁ T allele,the highest OR was calculated in the presence of SLC22A4T allele（P=0.005,OR=2.015;95%CI:1.230-3.300）.There was no association with UC for any combinations of rs1004819 and IGR2230a₁.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.     

The prevalence and distribution of human papillomavirus genotypes in oral epithelial hyperplasia: proposal of a concept

Background:  Evidence is accumulating for the aetiological role of human papillomavirus (HPV) in the pathogenesis of potentially malignant oral mucosal lesions and squamous cell carcinomas.
Methods:  Paraffin tissue sections from 49 patients with 'white patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH).
Results:  Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ≥ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed.
Conclusions:  The high prevalence of HPV infection in hyperplastic 'white patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions – flat, exophytic, wart-like or papillary proliferations – could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis.     

Elevated plasma nociceptin level in patients with Wilson disease

Plasma level of nociceptin, the endogenous agonist of orphanin FQ/ORL1 receptor was found to be significantly elevated in Wilson disease patients (13.98+/-2.44pg/ml, p<0.001, n=20) compared to age-matched healthy controls (9.18+/-1.63pg/ml, n=25). Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutation of the gene ATP7B leading to toxic copper accumulation in the liver and other organs such as brain, kidney and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found. It is suggested that elevated plasma nociceptin level found in Wilson disease patients is due to inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N (APN) and endopeptidase 24.15) by the toxic copper deposits in liver and/or brain.     

The first genetically supported case of chronic benign pemphigus (Hailey-Hailey disease in Hungary

Hailey-Hailey disease, or chronic benign pemphigus (MIM# 169600), is a genodermatosis arising in adult age with recurrent vesicles and erosions primarily in the flexural areas. It is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion in the suprabasal layers of the epidermis. ATP2C1, encoding the human secretory pathway Ca(2+)-ATPase (hSPCA1), was recently identified as the defective gene in Hailey-Hailey disease. More than 82 different ATP2C1 mutations have been described up to date. In this study, a case of Hailey-Hailey disease is presented where a nucleotide change (1402C > T) in the decoding region of ATP2C1 resulted in a premature stop mutation (R468X). This defect has been reported earlier in a patient of European descent. A brief molecular genetic review of the disorder is also given.     

Plasma HIV-1 load and disease progression in HIV-Infected patients in Hungary

Nucleic Acid Sequence Based Amplification (NASBA) is a suitable method for the quantification of HIV-1 RNA in plasma and serum samples. Since determination of the viral load appears to be a valuable marker for the prediction of disease progression and for monitoring the efficiency of antiretroviral therapy, the National AIDS Committee initiated the introduction of NASBA in Hungary at the end of 1996. We obtained plasma samples from patients with ARC and AIDS of the Szt. László Hospital, Budapest. We found an increased viral burden in untreated AIDS (CDC group C) patients compared to untreated ARC (CDC group B) patients. In plasma samples of clinically stable ARC and AIDS patients treated with antiretroviral drugs we detected relatively low HIV-1 RNA copy levels while similarly treated ARC and AIDS patients with progressive disease had high HIV-1 RNA copy numbers. The CD4⁺ T-cell count was lower in AIDS patients compared to ARC patients, as expected. In general, there was an inverse correlation (r = -0.487, P < 0.0001) between CD4⁺ T-cell counts and HIV-1 RNA levels. We concluded that measurement of HIV-1 RNA plasma level has an important role in assessing prognosis and effects of antiretroviral therapy in HIV-infected patients.     

Hypoxia alters gene expression in the gonads of zebrafish (Danio rerio)

The objectives of this study were to characterize gene expression responses to hypoxia in gonads of mature zebrafish (Danio rerio), and to start characterizing modes of action by which hypoxia could potentially alter reproduction. Adult male and female zebrafish were maintained under normoxia (7mgO(2)/L), moderate hypoxia (3mgO(2)/L), and severe hypoxia (1mgO(2)/L) for 4 and 14 days and changes in gene expression in gonadal tissues (n=5 per sex per treatment) were evaluated using a commercial 21,000 gene zebrafish oligonucleotide microarray. Differentially expressed genes were determined using ANOVA (p<0.05), and enriched gene ontology (GO) categories (p<0.01) identified using GeneSpring GX software. Short-term (4d) exposure to hypoxia affected expression of genes associated with the initial adaptive responses such as: metabolism of carbohydrates and proteins, nucleotide metabolism, haemoglobin synthesis, reactive oxygen species metabolism, and locomotion. Prolonged (14d) hypoxia affected a suite of genes belonging to different GO categories: lipid metabolism, reproduction (e.g., steroid hormone synthesis), and immune responses. Results of the present study demonstrate that reproduction likely would be affected by hypoxia via multiple modes of action. These include previously hypothesized mechanisms such as modulation of expression of steroidogenic genes, and downregulation of serotonergic pathway. In addition, we propose that there are multiple other points of disruption of reproductive system function linked, for example, to reorganization of lipid transport and other mechanisms involved in responding to hypoxia (e.g., hydroxysteroid dehydrogenase alterations, downregulation of contractile elements, etc.).     

Bone disorders in experimentally induced liver disease in growing rats

AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats. METHODS: Fischer-344 rats (n=55) were used. Carbon tetrachloride (CCl4), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (Fmax) of the femora were determined. The results in animals treated with DEN+PB+CCl4(DPC, n = 21) were compared to those in untreated animals (UNT, n = 14) and in control group treated only with DEN+PB (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.     

Prevention of postoperative peritoneal adhesions: Effects of lysozyme,polylysine and polyglutamate versus hyaluronic acid

Objective. Intraperitoneal adhesions are an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. In the present study we hypothesized that a combination of polypeptides with different surface properties, resulting in fine disperse low-soluble complexes, could be of benefit in the prevention of abdominal adhesions.Material and methods. Various polypeptides including lysozyme, polyglutamate, polylysine and combinations of all three were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The extent of peritoneal adhesions to the injured area was measured and expressed as a percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and the Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function caused by the chemicals.Results. Significant differences were seen among the treatment groups (p<0.001). Both polyglutamate and lysozyme, and polyglutamate together with polylysine significantly decreased adhesion formation as compared to hyaluronic acid. The polylysine–polyglutamate combination was still visible macroscopically on the peritoneal surface after 1 week, though not after 1 month. The polyglutamate–lysozyme mixture was less effective than these individual components alone. The chemicals did not show any toxic effects or altered function in macrophage cell culture.Conclusions. Lysozyme, polyglutamate and, most effectively, a polyglutamate–polylysine combination significantly decreased experimental abdominal adhesion formation. A strong mechanical connection to the wound and prolonged attendance in the surface were noted. Peritoneal phagocyte function did not seem to be influenced by the chemicals.