Leishmanial lipid suppresses tumor necrosis factor alpha, interleukin-1beta, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial-mediated pathway

OBJECTIVE: Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis-inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA. METHODS: Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme-linked immunosorbent assays for cytokines, NF-kappaB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and cytochrome c in the cell lysate and of NF-kappaB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence-activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid-induced apoptotic pathway in SFMCs. RESULTS: Leishmanial lipid inhibited the release of tumor necrosis factor alpha, interleukin-1beta, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-kappaB p65 levels in SFMCs, in a dose-dependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down-regulation of Bcl-2. CONCLUSION: These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis-inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.     

Gastric adenocarcinoma in a patient re-infected with <Emphasis Type="Italic">H. pylori</Emphasis> after regression of MALT lymphoma with successful anti-<Emphasis Type="Italic">H. pylori</Emphasis>therapy and gastric resection: a case report

Background

Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection.

Case presentation

We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence.

Conclusions

Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high.

     

Assessing the Impact of a Pertussis Active Surveillance Program on Provider Testing Behavior,Minnesota 2005–2009

Objectives. The Minnesota Department of Health, in collaboration with the Centers for Disease Control and Prevention, implemented the Pertussis Active Surveillance Project to better understand pertussis epidemiology. We evaluated the program’s impact.Methods. Clinics in 2 counties were offered free diagnostic testing and an educational presentation covering pertussis epidemiology. Clinics were identified as either active or intermittent, with active clinics testing 33% or more of the total number of months enrolled. We used generalized estimating equations to assess changes in provider testing behavior over the project period.Results. Ninety-seven clinics enrolled, with 38% classified as active. Active clinics were more likely to use the state lab for diagnostic testing and had a larger staff. During the project period, a decline in days coughing at the time of visit occurred in both jurisdictions.Conclusions. Providing clinics with free diagnostic testing influenced their participation levels. Among active clinics, results suggest changes in provider testing behavior over the course of the project. However, given the lack of robust participation, this resource-intensive strategy may not be a cost-effective approach to evaluating trends in pertussis epidemiology.Pertussis, or whooping cough, is a communicable respiratory disease caused by the Gram-negative coccobacillus Bordetella pertussis. Although the disease is vaccine preventable, it remains endemic in the United States, with cyclical peaks occurring every 3 to 5 years.1 Since the 1980s, incidence rates of pertussis have been rising in all age groups,1–5 with adults and adolescents experiencing significant increases.6 Paralleling national trends in pertussis activity, Minnesota reported a peak period in 2004 that continued into 2005 with an average yearly rate of 29.2 per 100 000 cases. A subsequent peak period started in 2008 that continued into 2010 with an average annual rate of 20.9 per 100 000 cases.7 Minnesota experienced a shift in the median age between these 2 peak periods, from 13 to 11 years.Although reportable in all states, pertussis frequently goes unrecognized.4,8–10 Provider knowledge regarding pertussis epidemiology and clinical practice is inconsistent, limiting the reliability of passive surveillance systems to accurately capture disease incidence.11 The natural progression of the disease, beginning with nonspecific upper respiratory system symptoms and ending with a persistent paroxysmal cough, creates an ambiguous clinical picture for the purpose of diagnosis.5,12 This is especially true for adults and adolescents, in whom disease presentation may be mild, atypical, or difficult to differentiate from other upper respiratory tract infections.4,8,11–13 Studies have indicated that 12% to 32% of adults and adolescents with a cough of unknown etiology lasting 1 to 2 weeks are seropositive for pertussis.14 For these reasons, national and statewide estimates of pertussis incidence may be greatly underestimated.6,11,15,16In an effort to address the issues around provider awareness and underreporting of pertussis, the Minnesota Department of Health (MDH) collaborated with the Centers for Disease Control and Prevention and 2 local public health agencies on an initiative to increase recognition and testing of suspect pertussis cases through education and free pertussis testing incentives. This initiative, the Pertussis Active Surveillance Project (PASP), ran from 2005 to 2009 (51 months total). We report here the results of a program evaluation of PASP, focusing on the factors associated with clinic participation and changes in provider testing behavior over time.     

Phenotypic and Genotypic Characterization of Canadian Clinical Isolates of Vibrio parahaemolyticus Collected from 2000 to 2009

Vibrio parahaemolyticus is the leading bacterial cause of food-borne illness due to the consumption of contaminated seafood. The aim of the present study was to determine the population of its subtypes and establish a better understanding of the various types of V. parahaemolyticus strains that are causing human illness in Canada. The subtypes for 100 human clinical isolates of V. parahaemolyticus collected between 2000 and 2009 were determined by performing serotyping, ribotyping, pulsed-field gel electrophoresis, and multilocus sequence typing. Within this panel of strains, there was a high level of diversity (between 22 and 53 subtypes per method), but the presence of predominant clones with congruent subtypes between the various methods was also observed. For example, all 32 isolates belonging to sequence type 36 (ST36) were from serogroup O4, while 31 of them were ribotype EcoVib235-287, and 24 of the 32 were SfiI pulsed-field gel electrophoresis (PFGE) pattern VPSF1.0001. With regard to the presence of known virulence genes, 74 of the 100 isolates were PCR positive for the presence of the thermostable direct hemolysin (tdh); and 59 of these 74 strains also contained the second virulence marker, the tdh-related hemolysin (trh). The detection of trh was more predominant (81%) among the clinical isolates, and only four (4%) of the clinical isolates tested negative for the presence of both tdh and trh. This database, comprising 100 clinical isolates of V. parahaemolyticus strains from Canada, forms a baseline understanding of subtype diversity for future source attribution and other epidemiologic studies.     

A Review on Basic Biology of Bacterial Biofilm Infections and Their Treatments by Nanotechnology-Based Approaches

Biofilms are responsible for causing 80% of human infections including chronic infections like-cystic fibrosis, endocarditis and osteomyelitis. The growing ability of the biofilm to resist most of the available antibiotics has caused a serious threat to different life forms. Plenty of research work has already been reported, and some are ongoing to combat this serious health issue worldwide. Recent developments in nanotechnology have given a great boost in dealing biofilm infections. The unique size-dependent properties for antibacterial and antibiofilm activities provide the nanoparticles better options to eradicate biofilms. Here, the authors have discussed the basic biology of bacterial biofilm and their impact on human health. In addition, different nanotechnology-based strategies to overcome serious health issues caused by biofilm infections have been highlighted.

     

Pharmacological Studies on the Effect of the Treatment of Swiss A Mice with Diospyrin,a Tumour-inhibitory Plant Product,and its Synthetic Derivatives

Diospyrin, a bisnaphthoquinonoid plant product and its derivatives have shown significant inhibitory activities against murine tumours in vivo . Studies on the haematological status, serum protein and creatinine levels, activities of several serum glycolytic enzymes, and histopathology of the mice inoculated with Ehrlich ascites carcinoma were carried out after treatment with diospyrin and four synthetic derivatives. The prognostic significance of the pharmacological parameters acting as markers of the diseased state was evident from these findings. Normal mice were also studied before and after treatment with these compounds which did not cause noticeable adverse effects on the vital parameters, thereby indicating the possibility of the utilization of diospyrin and derivatives as appropriate therapeutic agents.