Biochemical and ultrastructural evidences for toxicity of lead through free radicals in rat brain

Studies suggest that some lead-induced toxic effects may occur through free radical production and oxidative stress. This study examined the relationship between brain histopathological alterations and oxidative stress in subchronic lead exposure. Male Albino rats received lead acetate at 0.01%, 0.05% and 0.1% w/v in their drinking water for 30 days. Animals given sodium acetate (0.1% w/v) served as control in the same period. At the end of exposure, blood-lead levels, blood catalase (CAT) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content (in blood and brain) were measured. The brain tissue samples were prepared and analysed by light and scanning electron microscopy. The results show that, the blood-lead levels in treated animals were higher in comparison with control. CAT and SOD activities in animals treated with 0.01% and 0.05% w/v did not increase in comparison with control (P > 0.05) but these values were higher in animals treated with 0.1% w/v lead acetate (P < 0.01). MDA content in blood and brain of animals treated with lead acetate 0.1% w/v, increased significantly (P <0.01), but these values were not significantly increased in other treated animals. No major histopathological alterations were detected in the brains of animals treated with lead acetate at 0.01% and 0.05% w/v. In animals treated with lead acetate 0.1% w/v, demyelinization and collagenous scar formation with neuronal atrophy in hippocampus region was observed. It is concluded that lead acetate induce oxidative stress which has an important role in brain damage in rats.     

Association between measures of morbidity and locomotor disability: diagnosis alone is not enough

This study examines the relationship between different measures of morbidity and locomotor disability in early old age. Data from a community health survey of 858 people aged approximately 58 years living in the West of Scotland were examined for associations between morbidity and locomotor disability. The relationships between presence of chronic conditions, severity and pain from chronic conditions, reported symptoms, self-reported health and locomotor disability were examined using logistic regression. After adjusting for several measures of morbidity, sex and social class, frequency of pain from cardiovascular conditions (OR 5.49, 95%CI 2.64-11.39), frequency of pain from musculo-skeletal conditions (OR 2.79, 95% CI 1.76-4.44) and self-assessed health compared to other people the same age (OR 2.76, 95% CI 1.64-4.65) were the most important predictors of locomotor disability. Inclusion of frequency of pain greatly increased the strength of associations of chronic conditions with locomotor disability. Simple measures of morbidity may mask important associations between particular conditions and locomotor disability. In particular the findings suggest that for surveys of the correlates of locomotor disability, collateral information on the frequency of pain associated with chronic conditions and self-reported health relative to other people of the same age provides additional explanatory power.     

Synthesis of 3'- and 5'-nitrooxy pyrimidine nucleoside nitrate esters: "nitric oxide donor" agents for evaluation as anticancer and antiviral agents

A group of 3'-O-nitro-2'-deoxyuridines, 3'-O-nitro-2'-deoxycytidines, and 5'-O-nitro-2'-deoxyuridines possessing a variety of substituents (H, Me, F, I) at the C-5 position were synthesized for evaluation as anticancer/antiviral agents that have the ability to concomitantly release cytotoxic nitric oxide (*NO). Although these compounds generally released a greater percent of *NO than the reference drug isosorbide dinitrate upon incubation in the presence of l-cysteine, or serum, their cytotoxicity (CC(50) = 10(-3) to 10(-6) M range) was comparable to 5-iodo-2'-deoxyuridine, but weaker than 5-fluoro-2'-deoxyuridine, against a variety of cancer cell lines. No differences in cytotoxicity against nontransfected (KBALB, 143B), and the corresponding transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK(+)) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect. These nitrate esters were inactive antiviral agents except for 5-iodo-3'-O-nitro-2'-deoxyuridine that showed modest activity against HSV-1, HSV-2, and vaccinia virus.     

Prenatal diagnosis of a de novo ring chromosome 11

Ring chromosomes are uncommon findings in prenatal diagnosis. Growth retardation is the most significant manifestation, in particular among patients with rings of larger chromosomes. A 30-year-old gravida 1, para 0 white woman was referred for genetic counseling because of maternal anxiety. Cytogenetic analysis of amniotic fluid cells at 16 weeks gestation revealed an abnormal mosaic female chromosome complement; 46,XX,r(11)(p15q25)[14]/45,XX,-11[7]. The ring 11 showed no detectable loss of chromosomal material at 450 band level. Both parents had a normal karyotype. Fluorescence in situ hybridization demonstrated intact subtelomeric regions in the ring chromosome. A targeted ultrasound evaluation at the time of consultation suggested no significant abnormalities. The parents were counseled and subsequently decided to terminate the pregnancy. The autopsy revealed an immature female fetus with abnormal craniofacial features including brachycephaly, low-set ears and hypertelorism, bicornuate uterus, and calcifications in the renal tubules. The abnormal phenotypes could be a consequence of the ring instability, submicroscopic deletion, and/or alteration of genetic material at the site of fusion.     

Bilateral asynchronous acute epidural hematoma : a case report

Background  

Bilateral extradural hematomas have only rarely been reported in the literature. Even rarer are cases where the hematomas develop sequentially, one after removal of the other. Among 187 cases of operated epidural hematomas during past 4 years in our hospital, we found one case of sequentially developed bilateral epidural hematoma.     

Protective role of vitamin E, 2-deoxy-D-glucose, and taurine on perchloroethylene induced alterations in ATPases

Perchloroethylene (PER) administered by oral gavage for 15 consecutive days, at a dose of 3000 mg/kg body wt. decreased the activities of Na+, K(+)-ATPase and Mg(2+)-ATPase with an increase in the activity of Ca(2+)-ATPase. It also decreased RBC and platelet counts but the WBC count was found to be increased. An investigation of the relative importance of the modulators, vitamin E, 2-deoxy-D-glucose (2DG) and taurine in rendering protection to tissues against PER induced membrane damage was performed. PER administered mice were subjected to vitamin E (400 mg/kg body wt/day), 2DG (500 mg/kg body wt/day by i.p.) and taurine (100 mg/kg body wt/day) administration for 15 days to study their individual effect on ATPase and on certain hematological parameters. Vitamin E, 2DG and taurine treated mice showed a marked reversal of these metabolic changes related to membrane damage caused by PER. These results suggest that PER induced membrane damage may be associated with energy metabolism and hemolysis, which can be effectively prevented by these modulators.     

A combination study design to examine mycophenolate mofetil (MMF) and PTLD in renal transplant patients

Renal transplant recipients who are chronically immunosuppressed by drugs are at a higher risk of developing malignancies. Commonly observed malignancies are several forms of posttransplant lymphoproliferative disorders (PTLD), skin, lip and gynaecological cancers. The risk is associated with many risk factors including the extent of immunosuppression. Mycophenolate mofetil (MMF) is an immunosuppressant, indicated for the prophylaxis of organ rejection in patients receiving allogenic renal and heart transplants. During the European approval of MMF for renal transplantation, the question was raised as to whether the use of MMF was associated with an increased risk of PTLD in comparison with alternate immunosuppressive regimens. In response, F. Hoffman-La Roche Ltd set up a prospective observational cohort study with a companion case-control study. This paper describes the objectives and the methods of these studies along with the rationale of the methodology.     

An Unusually Frequent β-Thalassemia Mutation in an Iranian Province

Iran, a country located on the “thalassemia belt”, is an area with an unusually high prevalence of β-thalassemia (thal). The gene frequency of thalassemia shows great variation within Iran from one area to another. The purpose of this study was to determine the spectrum of β-thal mutations in Sistan-Baluchestan (S-B), a southeastern province of Iran which has a high mutation frequency of about 10%, and to compare this with neighboring provinces and countries. A total of 400 carriers (200 pre-marriage young couples selected at centers conducting prenatal diagnosis programs) with an established diagnosis of β-thal minor, were enrolled into the study. Mutations in the β-globin gene were detected using amplification refractory mutation system (ARMS) and restriction fraction length polymorphism (RFLP). Three hundred and sixty mutant chromosomes (13 different mutations) were detected with the two most common mutations accounting for about 80% of all detected β-thal alleles in this region. The most common mutation by far was IVS-I-5 (G>C) (72.3%), followed by frameshift codons (FSC) 8/9 (+G) (5.8%) and codon 44 (?C) (2.5%). In conclusion, IVS-I-5 and FSC 8/9 (+G) account for about 80% of all mutations in S-B. Sistan-Baluchestan may be regarded as the ‘hot zone’ for the IVS-I-5 mutation.