Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Characteristics of the ventilatory status of the lungs in workers in the electronics industry

To establish the effects of occupational respiratory noxae on the state of the bronchopulmonary system a study of the working environment and examinations of workers from the electronics industry whose workplaces were near tin baths and in conductor soldering shops were carried out. The following chemical noxae were found to be present in the working environment: lead, tin, calophonium and ethyl alcohol, all in permitted concentrations. Comparison of the state of lung ventilation in workers from the electronics industry (n = 120) and control workers (n = 129) pointed to a major increase in total air flow resistance during calm breathing in the exposed workers. The obstructive changes were mainly localized in the small airways.     

The effect of occupational noxae in the tobacco industry on pulmonary function in exposed workers]

A study was carried out to determine respiratory hazards to workers in tobacco manufacture. The investigations at the workplace included analysis of the work technology and measurements of chemical pollutants and dust concentrations in the work rooms. Ventilatory lung function tests were performed in 95 workers exposed to tobacco dust and in 129 control workers. Results of workplace analysis showed the presence of tobacco dust levels exceeding the maximum permissible concentrations. The values of some lung function tests for exposed workers non-smokers were significantly lower than for control workers non-smokers. They could be attributed to the effect of occupational noxae on the respiratory system.     

How to confirm occupational asthma

A methodological overview is provided on the important question of how to confirm occupational asthma in routine work. Recent knowledge gained in immunology and occupational allergy has been utilized, supplemented by an overview of recent publications on the diagnosis and pathophysiology of occupational asthma. The aim of the paper is to facilitate decision making for an investigator dealing with individual cases of occupational asthma. Moreover, by presenting stepping-stones in the diagnostic cascade, the author hopes to encourage the less experienced to conduct a comprehensive and cause-oriented diagnostic procedure. Methods which are being worked on at present (standardization) are discussed in more detail. Finally, the research goals in the understanding, confirmation, and prevention of occupational asthma are listed.     

Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. I: conceptual and numerical issues.

A cubic spline function for describing the verapamil concentration profile, resulting from the verapamil absorption input to be evaluated, has been used. With this method, the knots are taken to be the data points, which has the advantage of being computationally less complex. Because of its inherently low algorhythmic errors, the spline method is less distorted and more suitable for further data analysis than others. The method has been evaluated using simulated verapamil delayed release tablet concentration data containing various degrees of random noise. The accuracy of the method was determined by how well the estimates of input rate and extent represented the true values. It was found that the accuracy of the method was of the same order of magnitude as the noise level of the data. Spline functions in convolutional modeling of verapamil formulation bioavailability and bioequivalence, as shown in the numerical simulation investigation, are very powerful additional tools for assessing the quality of new verapamil formulations in order to ensure that they are of the same quality as already registered formulations of the drug. The development of such models provides the possibility to avoid additional or larger bioequivalence and/or clinical trials and to thus help shorten the investigation time and registration period.     

Effect of imaging time on the values of the sacroiliac index

Quantitative scintigraphy of the sacroiliac joints was performed in a group of normal subjects and a group of subjects with unilateral and bilateral sacroiliitis. The aim of the study was to determine whether the time intervals of imaging had any effect on the values of the sacroiliac index. Imaging was performed every 30 min up to 300 min and the indices were calculated at the time intervals mentioned. We found that the values of the sacroiliac index increased in the group of normal subjects until 150 min after the application of the radiopharmaceutical, and that in the group of subjects who had sacroiliitis they increased until 210 min. The results show that the time interval optimal to quantitative sacroiliac joint imaging is at least 3 1/2 h after administration of the radiopharmaceutical.     

Primary vesicoureteric reflux--our 20 years' experience.

AIM: The aim of this study is to compare the Lich-Gregoir procedure and antireflux ureterocystoneostomy at the vertex of the bladder (AUVB) based on 20 years' clinical experience. METHODS: Over a period of 20 years (1978 - 1998) 1280 children were operated on, 368 bilaterally, which resulted in 1648 antireflux ureterocystoneostomies being performed. Of the total of 1648 antireflux ureterocystoneostomies, AUVB was performed in 1032 ureteric units and the Lich-Gregoir procedure in 616 ureteric units. Between 1978 and 1992 we performed only AUVB, and from 1992, both AUVB and the Lich-Gregoir procedure. RESULTS: The final result was evaluated 2 years after the operation. Satisfactory results were achieved in 93.5 % with AUVB and in 96 % with the Lich-Gregoir procedure. The postoperative failure rate was 6.5 % for the AUVB and 4 % for the Lich-Gregoir operations. The recurrence rate was higher with AUVB (5 %) than with the Lich-Gregoir procedure (1.5 %), but postoperative stenosis was more frequent with the Lich-Gregoir procedure (2.5 %). CONCLUSIVE: Today, as the first operative method we prefer to employ the Lich-Gregoir procedure. If the result of the Lich-Gregoir procedure is unsatisfactory, we recommend the AUVB for the first and second recurrence operation. Finally, in cases of repeated VUR recurrence of postoperative stenosis, as the last operation we perform antireflux ureteroileocystoplasty with an intussuscepted segment of the ileum.     

Interferon Gamma Alters the Phenotype of Rat Thymic Epithelial Cells in Culture and Increases Interleukin-6 Production

Rat thymic epithelial cells (TEC) in long-term culture were characterized by anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic analysis performed by a large panel of mAbs showed that the highest percentage of these cells was of the subcapsular/medullary type. Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC expression by TEC in culture as confirmed by immunohistochemistry and flow cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma- treated cultures showed higher interleukin-6 (IL-6) activity, compared to the control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6 activity was probably not a consequence of increased TEC number in IFN-gammatreated cultures because IFN did not significantly stimulate TEC proliferation in vitro. In contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is not only a regulatory molecule for T-cell proliferation, but could also be an autocrine growth factor for thymic epithelium.