Exposure assessment to preformed environmental N-nitroso compounds from the point of view of our own studies

The largest human exposure to N-nitrosamines is in the industrial section. Leather tanners are exposed to N-nitrosodimethylamine at levels up to 47 microgram/m3, corresponding to 440 microgram/person/day. Workers in the curing area of tire factories are exposed to N-nitrosomorpholine at levels up to 27 microgram/m3, corresponding to a intake of 250 microgram/person/day. These industrial exposures are considerably greater than exposure via foodstuffs, beer, cosmetics, cutting fluids and herbicides.     

The DNA extruded by rat spleen cells in culture

1. Part of the DNA extruded by cultured rat spleen cells occurs in the form of a low density lipid complex. 2. The present work indicates that this complex is also associated with protein but not with RNA and its elementary properties have been studied. 3. For example, it is destroyed by freezing and thawing or by deoxycholate treatment and small quantities of copper salts added to the medium may either inhibit or stimulate its release depending on the conditions.     

Multiple pathways are involved in the extracellular processing of MHC class I-restricted peptides

T cell stimulation by certain class I-restricted antigenic peptides, such as the HIV 1 gp160-derived peptide, P18, requires peptide processing by angiotensin-1 converting enzyme (ACE) in FCS. We observed that longer versions of P18 and the murine cytomegalovirus pp89-derived core peptide, pMCMV, which could stimulate T cell hybridomas in FCS, were not as sensitive to the ACE inhibitor captopril as P18. Using cell-free soluble murine class I MHC molecules and protease inhibitors, we found that there are pathways of differing efficiency that use enzymes other than ACE for the proteolytic processing of peptides in serum. The kinetics of the generation of T cell stimulatory activity among P18 variant peptides in serum differed with peptide length, and with the nature of amino and COOH-terminal extensions. Such processing occurs in human plasma as well as in FCS. The understanding of this processing, its kinetics, and its inhibitors can lead to better design of peptide-based therapies, including vaccines.     

Provision and quality of dialysis services in Libya

Dialysis is entirely funded by the public health care sector in Libya. Access to treatment is unrestricted for citizens but there is a lack of local information and no renal registry to gather national data. This cross-sectional study aimed to investigate dialysis provision and practice in Libyan dialysis facilities in 2009. A structured interview regarding dialysis capacity, staffing and methods of assessment of dialysis patients, and infection control measures was conducted with the medical directors of all 40 dialysis centers and 28 centers were visited. A total of 2417 adult patients were receiving maintenance dialysis in 40 centers, giving a population prevalence of approximately 624 per million. Most dialysis units were located in the northern part of the country and only 12.5% were free-standing units. Only three centers offered peritoneal dialysis. One hundred ninety-two hemodialysis rooms hosted 713 functioning hemodialysis stations, giving a ratio of one machine to 3.4 patients. Around half of centers operated only two dialysis shifts per day. Nephrologist/internist to patient ratio was 1:40 and nurse to patient ratio was 1:3.7. We found a wide variation in monitoring of dialysis patients, with dialysis adequacy assessed only in a minority. Separate rooms were allocated for chronic viral infection seropositive patients in 92.5% of the units. In general, the provision of dialysis is adequate but several areas for improvement have been identified, including a need for implementation of guidelines, recruitment of more nephrologists, and the development of more cost-effective alternatives such as peritoneal dialysis and transplantation.     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Human and monkey trabecular meshwork accumulate alpha B-crystallin in response to heat shock and oxidative stress

PURPOSE: Oxidative stress and other forms of injury to trabecular meshwork (TM) cells may contribute to changes seen with age and primary open-angle glaucoma. This study was designed to investigate if TM expresses alpha B-crystallin, a small heat-shock protein with chaperone activity, and whether it might be overexpressed under stress conditions. METHODS: The TM from human and monkey eyes, as well as organ and primary cell cultures derived from these eyes, were investigated for alpha B-crystallin by immunohistochemistry, two-dimensional gel electrophoresis, Northern and Western blot analysis. The TM cell cultures were stressed by heat shock (44 degrees C for 15 minutes) or hydrogen peroxide (200 mumol for 1 hour). Semiquantitation of alpha B-crystallin messenger RNA (mRNA) or protein was obtained by densitometry. RESULTS: In both species, alpha B-crystallin could be detected in fresh and cultured TM by two-dimensional gel electrophoresis in conjunction with Western blot analysis. Immunohistochemistry of fresh samples showed that alpha B-crystallin was expressed predominantly in the cribriform area. Protein expression was enhanced in 4- to 7-day organ cultures. Primary cultures from human TM cells expressed two sizes (approximately 0.8 and 1.1 kb) of alpha B-crystallin mRNA in Northern blots. In monkey TM cultures, a 0.8-kb band was observed, which comigrated with lens alpha B-crystallin. In both species, heat shock caused a significant increase in alpha B-crystallin mRNA with a peak after 4 hours. An increase in alpha B-crystallin mRNA also was observed after oxidative stress; however, the onset of mRNA induction was slower. After heat shock, but not after oxidative stress, a transient change in mRNA mobility was observed. Western dot blot analysis showed a 3.4-fold increase in protein 24 hours after heat shock and a 20-fold increase after 48 hours. No constitutive mRNA expression and only a minimal increase 4 hours after heat shock could be observed in simian virus 40 transformed cell lines from human TM. CONCLUSIONS: Overexpression of alpha B-crystallin might be an important mechanism for TM to prevent cellular damage associated with various stress conditions.