Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multisystem disease with underlying immune mechanisms. AIMS: To investigate the clinicopathological characteristics of the lesions; immunological alterations in the bronchoalveolar lavage fluid (BALF), peripheral blood, and skin; and correlations between the clinicopathological characteristics and immunological alterations in SSc. MATERIALS/METHODS: Skin biopsies, BALF, and peripheral blood samples were obtained from 19 patients (18 women, one man) with SSc and six age and sex matched healthy controls (HCs). Mononuclear inflammatory cells (MICs), CD4/CD8 cells, tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1-1beta) concentrations were examined in all samples using histological methods, enzyme linked immunosorbent assay, and immunoperoxidase staining. RESULTS: The mean (SD) age of the patients with SSc was 34.8 (2.6) years. Proteinuria, positive rheumatoid factor, and C reactive protein were seen in 15.8%, 26.3%, and 26.3% of patients, respectively. Compared with HCs, there were significantly higher: total MICs (macrophages, lymphocytes), neutrophils, and eosinophils in BALF, blood, and skin (all p<0.05); cytokine concentrations in BALF (TNFalpha, p<0.001; IL-1, p<0.01) and peripheral blood (p<0.01 and p<0.05); and CD8/CD4+ T cells in peripheral blood (p<0.05). Compared with HCs, lesional skin had significantly higher histiocyte cell counts (p<0.05), lower lymphocyte counts (p<0.05), and higher CD4/CD8 ratios (p<0.001). There were significant correlations between cytokine concentrations and CD8+ T cells and forced vital capacity (p<0.001 and p<0.01, respectively). CONCLUSIONS: MICs, CD4/CD8+ cells, and cytokines are altered in SSc. These alterations correlated with the underlying disease process and therefore may have pathogenic, modulatory, and potential prognostic roles in SSc.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Antidiabetic effect of kolaviron,a biflavonoid complex isolated from Garcinia kola seeds,in Wistar rats

Background

Hypoglycaemic effect of kolaviron (KV), (biflavonoid from Garcinia kola) in streptozotocin (STZ)-diabetic rats has been established.

Objectives

To evaluate the possible protective effects of KV on cardiac, renal and hepatic tissues of STZ-diabetic rats.

Methods

This study consists of four groups of 6 rats each. Groups one and two contained non-diabetic and untreated-diabetic rats, respectively. Groups three and four were made up of KV- and glibenclamide (GB) - treated diabetic rats, respectively.

Results

STZ-intoxication caused a significant (p<0.05) increase in the relative weight of liver in diabetic rats. STZ-diabetic rats had significant increase (p<0.05) in the levels of fasting blood glucose (FBG), á-amylase and HbA_1c. A marked and significant (p<0.05) increase in the levels of cardiac, renal and liver marker indices such as serum creatine kinase, lactate dehydrogenase, creatinine, urea and alanine aminotransferase were observed in untreated diabetic rats. Also, untreated diabetic rats had significantly (p<0.05) elevated urinary glucose and protein and, lowered creatinine clearance. In KV- and GB- treated groups, the levels of FBG, á-amylase and HbA_1c were significantly (p<0.05) reduced, while treatment with KV significantly (p<0.05) attenuated the cardiac, renal and liver marker indices.

Conclusion

KV offered significant antidiabetic and tissues protective effects in the rats.     

Characterization of Mycobacterium tuberculosis isolated from cancer patients with suspected tuberculosis infection in Egypt: identification,prevalence, risk factors and resistance pattern

Data are sparse on Mycobacterium tuberculosis infection among patients with cancer in Egypt. We sought to detect the presence of tuberculosis (TB) disease among patients with malignant conditions and suspected TB and to study the main risk factors. Also, we compared different diagnostic procedures and detected the antimicrobial susceptibility of M. tuberculosis isolates against rifampin and isoniazid. One hundred patients were included in this study, all of them had malignant conditions and were suspected by the clinicians of having TB. Identification of M. tuberculosis in different specimens was performed by smear microscopy, followed by Lowenstein–Jensen medium and Mycobacterium growth indicator tube (MGIT) cultures and artus^® real-time PCR. In addition, an indirect MGIT anti-TB susceptibility test was carried out against rifampin and isoniazid. A total of 76% of studied cases were found to be TB positive. The frequencies of TB-positive cases in the bronchogenic, haematological and solid tumour malignancy groups were 21%, 25% and 30%, respectively. Significant differences between pulmonary and extrapulmonary TB in different malignancy groups were recorded. Real-time PCR showed the highest overall diagnostic efficiency. Multidrug-resistance of M. tuberculosis to both rifampin and isoniazid was detected in 28.6% of examined isolates. Infection in cancer patients with TB was significantly more often recorded among elderly patients and those suffering from poverty. Pulmonary TB is more common than extrapulmonary TB in patients with malignancy. Real-time PCR is the most accurate and rapid method for TB diagnosis. MGIT-rifampin resistance may be used as a reliable marker for detection of multidrug-resistant TB. Diagnosis and instituting treatment course for active or latent TB infection are crucial before starting anticancer therapy.     

Influence of mutation of the HFE gene on the progression of chronic viral hepatitis B and C in Moroccan patients

The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. The aim of the present study was to measure the frequencies of the common HFE gene mutations in Moroccan subjects with chronic viral hepatitis B and C and to assess their influence on the progression of liver disease. H63D and C282Y mutations were screened by the polymerase chain reaction followed by restriction fragment length polymorphism analysis in 170 chronic hepatitis B patients, 168 chronic hepatitis C patients, and 200 healthy controls. A very small proportion of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV; 1.8% and none, respectively) were heterozygous for the C282Y mutation, that is, rates not statistically different from those observed in healthy control (2%, P > 0.05). Similarly, the frequency of the H63D allele was not significantly different between HBV (13.8%) or HCV (14.3%) patients and controls (13.5%, P > 0.05). Multivariate analysis showed that carriers of the H63D mutation infected with HBV are at higher risk to progress towards an advanced liver disease when compared with patients infected with HBV with wild‐type (OR = 2.45, 95% CI = 1.07–5.58). In contrast, no association between HFE mutated HCV‐infected patients and an increased risk of disease progression was found (OR = 1.24, 95% CI = 0.61–2.50, P = 0.547). In conclusion, in Morocco the frequency of the HFE C282Y allele is very low and H63D mutation carriage occurs in almost 14% of the patients, a rate similar in chronic hepatitis patients and healthy controls. In the case of chronic hepatitis B, the carriage of the H63D variant represents a risk factor of evolution towards a more active disease. J. Med. Virol. 83:2096–2102, 2011. © 2011 Wiley Periodicals, Inc.     

Influence of dipyridamole and its combination with NO donor or NO synthase inhibitor on adjuvant arthritis

The anti-arthritic and anti-inflammatory effects of dipyridamole and the possible involvement of NO in the dipyridamole action are not yet clear. The aim of this study was to evaluate the effects of dipyridamole alone and in combination with either the nitric oxide donor, sodium nitroprusside (SNP) or the non-selective nitric oxide synthase inhibitor, L-NG- monomethyl arginine (L-NMMA), on pathogenesis of adjuvant-induced arthritis model in rats. The results of the present work showed that prophylactic administration of dipyridamole alone and dipyridamole administration in combination with either low dose of SNP or L-NMMA significantly ameliorated pathogenesis of adjuvant arthritis in rats as evidenced by significant decrease in arthritis index, hind paws volume, loss of body weight, hyperalgesia compared with control vehicle (1% DMSO) treated adjuvant arthritic rats. Inflammatory cellular infiltrate in synovium of ankle joint and pannus formation were also markedly inhibited. Interleukin-10(IL-10) levels were significantly increased in these groups of animals. In contrast, a high dose of SNP counteracted the anti-inflammatory and anti-arthritic effects of dipyridamole. The inhibitory effect of therapeutic administration of dipyridamole alone on adjuvant arthritis syndrome was not significantly different from that of vehicle administration. In conclusion, dipyridamole has prophylactic but not therapeutic anti-arthritic and anti-inflammatory effects that appear to be dependent on inhibition of NO synthase. A synergistic combination between dipyridamole and NO synthase inhibitor or low dose of NO donor may have prophylactic and therapeutic values in autoimmune diseases like RA.     

Respiratory impairment in coke oven workers: relationship to work exposure and bronchial inflammation detected by sputum cytology

Coke oven workers are at excess risk of developing lung cancer and may be at risk for chronic obstructive lung disease (COLD). We have studied 3799 male workers to assess the relationship between the two diseases. Repeated lung function and sputum cytology tests were obtained over a 3-year period. Sputum samples were assessed using standardized methods; in addition to metaplastic and neoplastic changes, we reproducibly assessed the presence and extent of acute and chronic inflammatory changes. Spirometric flow rates (FEV1) were significantly reduced in workers most exposed to coke oven emissions, particularly in those with excessive inflammatory cells and regular metaplasia in sputum. The presence of reactive bronchial epithelial cells and metaplasia were potent predictors of an abnormal FEV1/FVC. Studies like these may offer a means to investigate the relationship between COLD and lung cancer. Such changes in sputum may identify individuals at risk of developing both diseases.     

The ethics of psychopharmacological research in legal minors

Research in psychopharmacology for children and adolescents is fraught with ethical problems and tensions. This has practical consequences as it leads to a paucity of the research that is essential to support the treatment of this vulnerable group. In this article, we will discuss some of the ethical issues which are relevant to such research, and explore their implications for both research and standard care. We suggest that finding a way forward requires a willingness to acknowledge and discuss the inherent conflicts between the ethical principles involved. Furthermore, in order to facilitate more, ethically sound psychopharmacology research in children and adolescents, we suggest more ethical analysis, empirical ethics research and ethics input built into psychopharmacological research design.