Circulating immune complexes augment severity of antibody-mediated myasthenia gravis in hypogammaglobulinemic RIIIS/J mice

Experimental autoimmune myasthenia gravis (EAMG) is severe in RIIIS/J mice, despite a significant B cell immunodeficiency and a massive TCR V beta gene deletion. Severity of EAMG in RIIIS/J mice is greater than MHC-identical (H-2(r)) B10.RIII mice, suggesting the influence of non-MHC genes as an EAMG-potentiating factor in this strain. To delineate the role of deleted TCR V beta genes in RIIIS/J mice, we obtained (RIIIS/J x B10.RIII)F(1) (V beta(b/c)) x RIIIS/J (V beta(c)) backcross mice using Mendelian genetic methods and immunized them with acetylcholine receptor. EAMG susceptibility was not elevated in mice with V beta(c) genotype having 70% V beta gene deletion. Next, we performed microarray analysis on 12,488 spleen cDNAs obtained from spleens of naive RIIIS/J and B10.RIII mice. In RIIIS/J mice, 263 cDNAs were overexpressed and 303 cDNAs were underexpressed greater than 2-fold, compared with B10.RIII mice. TCR gene expression was augmented, whereas NK receptor, C1q, and C3 gene expressions were diminished in RIIIS/J mice. RIIIS/J mice also had increased lymph node T cell counts, elevated serum anti-AChR Ab levels, and serum C3 and C1q-conjugated circulating immune complex levels. A direct correlation between increased serum C1q-conjugated circulating immune complex levels and disease severity was observed in RIIIS/J mice.     

Pulmonary protective effects of hyberbaric oxygen and N-acetylcysteine treatment in necrotizing pancreatitis

The purpose of this study is to analyze the protective effect of combining N-acetylcysteine (NAC) and hyberbaric oxygen (HBO) treatment in the lung tissue during acute pancreatitis. Sixty Sprague-Dawley male rats were randomly divided into five groups; Group I; Control group (n=12), Group II; pancreatitis group (n=12), Group III; pancreatitis + NAC treatment group (n=12), Group IV; pancreatitis + HBO treatment group (n=12), Group V; pancreatitis + HBO + NAC treatment group (n=12). HBO was applied postoperatively for 5 days, twice a day at 2.5 fold absolute atmospheric pressure for 90 min. Lung tissue was obtained for measuring malondialdehyde (MDA), superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) levels along with histopathological tissue examinations. This study showed that all three treated groups (HBO alone, NAC alone and combined HBO+NAC treatment) had pulmonary protective effects during acute necrotizing pancreatitis.     

THE INFLUENCE OF DIETARY α‐SOLANINE ON THE WAXMOTH Galleria mellonella L

Plant allelochemicals are nonnutritional chemicals that interfere with the biology of herbivores. We posed the hypothesis that ingestion of a glycoalkaloid allelochemical, α‐solanine, impairs biological parameters of greater wax moths Galleria mellonella. To test this idea, we reared wax moths on artificial diets with 0.015, 0.15, or 1.5 mg/100 g diet of α‐solanine. Addition of α‐solanine to the diet affected survival of seventh‐instar larvae, pupae, and adults; and female fecundity and fertility. The diet containing the highest α‐solanine concentration led to decreased survivorship, fecundity, and fertility. The diets supplemented with α‐solanine led to increased malondialdehyde and protein carbonyl contents in midgut and fat body and the effect was dose‐dependent. Dietary α‐solanine led to increased midgut glutathione S‐transferase activity and to decreased fat body glutathione S‐transferase activitiy. We infer from these findings that α‐solanine influences life history parameters and antioxidative enzyme activities in the midgut and fat body of G. mellonella.     

The relationship between serum prolactin levels and disease activity in patients with Behcet's disease

The aim of this study was to determine the serum levels of prolactin in patients with Behcet's disease and to evaluate its correlation with disease activity. Serum prolactin levels were measured by a chemiluminescence method in 32 patients with Behcet's disease and compared with 20 age-and sex-matched healthy controls. The patients with Behcet's disease were subdivided into two groups according to disease activity: active (18 patients; 13 men and five women, average age 34.0 +/- 6.5 (28-48) years), and inactive (14 patients; 10 men and four women, average age 32.7 +/- 3.1 (22-49 years). Patients with active Behcet's disease had higher serum prolactin levels than the inactive and control groups. Prolactin levels in patients with active Behcet's disease differed significantly from the healthy control subjects (p < 0.05) only, but not the inactive group. Four patients out of 32 (12.5%) Behcet's disease patients showed mild hyperprolactinemia. All four of these cases were from the active Behcet's disease group. Prolactin levels were correlated with ESR (p < 0.05) and CRP (p < 0.05) levels in the active BD group, but not in the inactive BD and control groups. Our results suggest a possible role for this immunoregulatory hormone in the disease expression and pathogenesis of Behcet's disease.     

Effect of tocilizumab on ischemia-reperfusion-induced oxido-inflammatory renal damage and dysfunction in rats

Ischemia-reperfusion-induced (I/R) renal damage is a pathogenic process that starts with ischemia, then progresses through oxidative stress and inflammation. Tocilizumab (TCZ), a recombinant human monoclonal antibody produced against the IL-6 receptor, will be tested against renal I/R injury. TCZ is known to lower the levels of proinflammatory cytokines and oxidant mediators while raising the amounts of antioxidant molecules. Our purpose is to evaluate the biochemical and histological effects of TCZ against I/R-induced oxido-inflammatory kidney damage and dysfunction in rats. Animals were divided into 3 groups as renal I/R (RIR), I/R+ TCZ (IRT), and healthy group (HG). TCZ was administered at a dose of 8 mg/kg to the IRT group (n=6) of the animals, and distilled water as a solvent was administered intraperitoneally (ip) to the RIR (n=6) and HG (n=6) groups. Then, two hours of ischemia and six hours of reperfusion were applied to the left kidneys of IRT and RIR animals. TCZ significantly inhibited the increase in the levels of malondialdehyde (MDA), nuclear kappa B (NF-κB), tumour necrosis factor alpha (TNF-α), interleukin 1-β (IL-1β), IL-6, creatinine (Cr) and blood urea nitrogen (BUN) and decrease in total glutathione (tGSH) with I/R in renal tissue. TCZ also attenuated severe histopathological damage due to I/R in renal tissue. TCZ protected renal tissue from I/R-induced oxidative and inflammatory damage. These results indicate that TCZ may be useful in the treatment of renal I/R injury.     

Caspase signalling in the absence of apoptosis drives Jnk‐dependent invasion

Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloprotinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade.     

Moxifloxacin-tetracycline-lansoprazole triple therapy for first-line treatment of Helicobacter pylori infection: a prospective study

Aim: To document the efficacy and tolerability of 14‐day moxifloxacine–tetracycline–lansoprazole (MTL) regimens for Helicobacter pylori (Hp) eradication as a first‐line therapy. Method: Fifty‐six Hp‐positive patients were enrolled. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and Hp infection was diagnosed through histologic examination of antral and body bioptic samples. Primary end point of this study was to evaluate the eradication rate of 14‐day MTL regimen therapies. Hp eradication was assessed using the 13C urea breath test performed. All patients were asked to fill in a validated questionnaire to report therapy‐related side effects. Each symptom was graded from absent or present. Results: Fifty‐six patients (29 men and 27 women) were enrolled. The studied therapeutic regimens were completed by 96.4% patients. Two dropouts occurred in the MTL group because of side effects. The eradication rate in MTL regimens was 55.4%. The overall prevalence of side effects was high in the MTL group. Conclusion: The MTL regimen failed to achieve the recommended eradication rates and had higher adverse effect rate. Hence, MTL regimen does not seem to be a suitable choice as a first‐line Hp eradication therapy.     

THE EFFECTS OF XANTHOTOXIN ON THE BIOLOGY AND BIOCHEMISTRY OF Galleria mellonella L. (LEPIDOPTERA: PYRALIDAE)

The effects of a dietary plant allelochemical, xanthotoxin (XA), on survivorship, development, male and female adult longevity, fecundity, and hatchability of the greater wax moth Galleria mellonella L. were investigated. Oxidative stress indicators, the lipid peroxidation product, malondialdehyde (MDA), and protein oxidation products, protein carbonyl (PCO) contents, and activities of a detoxification enzyme glutathione S‐transferase (GST) activity were determined in wax moth adults. The insect was reared from first‐instar larvae on an artificial diets containing XA at 0.001, 0.005, or 0.1% to adult stage in laboratory conditions. Relative to the controls, the diets containing XA concentrations led to decreased survivorship in seventh instar, pupal, and adult stages. Compared to control diet (77.7%), the highest dietary XA concentration decreased survivorship to adulthood to 11.0%. The highest XA concentration (0.1%) reduced female longevity from 10.4 to 5.7 days and decreased egg numbers from 95.0 to 33.5 and hatchability from 82.7 to 35.6%. The lowest XA concentration (0.001%) led to about a sixfold increase in MDA content. XA at high concentrations (0.005 and 0.1%) increased MDA (by threefold) and protein carbonyl (by twofold) contents decreased GST activity. The highest dietary XA concentration decreased GST activity from 0.28 ± 0.025 to 0.16 ± 0.005 μmol/mg protein/min. We infer from these findings that XA‐induced oxidative stress led to decreased biological fitness.