Recombinant CD4-Pseudomonas exotoxin hybrid protein displays HIV-specific cytotoxicity without affecting MHC class II-dependent functions

The present study describes several in vitro activities of CD4(178)-PE40, a recombinant protein containing a portion of human CD4 linked to active regions of Pseudomonas aeruginosa exotoxin A. Using assays for cell viability, we demonstrate that the hybrid toxin displays highly selective cytotoxicity for HIV-infected T lymphocytes. In a latently infected human T-cell line which is inducible for HIV expression, toxin sensitivity is observed only upon virus induction. At concentrations which readily kill HIV-infected T cells, CD4(178)-PE40 has no observable cytotoxic effects on uninfected human cell lines expressing surface major histocompatibility complex (MHC) Class II molecules, and does not interfere with cellular responses known to be dependent on functional association between CD4 and MHC Class II molecules.     

Retained surgical sponge after laparotomy

Erosion of a retained surgical sponge into the intestine is an unusual occurrence and may make its appearance months or years later. The demonstration of a distended bowel by the barium-impregnated mass with multiple polypoidal filling defects in a patient who has undergone previous laparotomy should lead the physician to suspect a retained surgical sponge. Surgical intervention is rewarding.     

Thyroid tuberculosis

Thyroid tuberculosis is a rare disease. Its incidence is low even in countries where prevalence of pulmonary tuberculosis is high (0.1–0.4%). In literature, there are only a few cases which were diagnosed as thyroid tuberculosis. It can be explained by a high resistance of the thyroid gland to infectious processes. However, the prevalence of tuberculosis has increased worldwide and thyroid involvement can be a primary manifestation of the disease. The incidence of extrapulmonary tuberculosis has been showing a progressive increase in the recent years(Barnes and Weatherstone, 1979). The most frequent clinical presentation is a solitary thyroid nodule that may present as a cystic nodule. It may also present as thyroid abscess with pain, fever and other non-specific signs and symptoms. ATT results in complete cure therefore it is important to differentiate it from other form of thyroiditis. Patients are usually euthyroid, but cases of hypothyroidism and hyperthyroidism are described. For accurate diagnosis of thyroid tuberculosis, clinical and radiological features are nonspecific and histological examination is required for confirmation of diagnosis. PCR may help in diagnosis. The authors encounter 3 cases of thyroid tuberculosis in last 5 year which are described in this article. The aim of this study is to review all the cases published in literature to describe clinical presentation, appropriate diagnostic method and possible treatment options of the disease.     

Differential effects of route of T‐2 toxin exposure on hepatic oxidative damage in mice

T‐2 toxin is the most toxic among mycotoxins and poses a potential health hazard for both humans and animals. At high doses, T‐2 toxin can cause shock‐like syndrome that can result in death. We evaluated the effect of time course and route of exposure on hepatic oxidative damage in mice and it is only such study so far to compare the effects of dermal and subcutaneous exposure of T‐2 toxin. Mice were exposed to 1 LD50 of T‐2 toxin either by percutaneous (5.94 mg/kg body weight) or subcutaneous (1.54 mg/kg body weight) route and sacrificed at 0, 1, 3, and 7 days postexposure. Analysis of a number of serum biochemical variables, antioxidant enzymes activity, gene and protein expression by immunoblot assay showed time and route dependent effects of T‐2 induced hepatic oxidative damage. Time dependent increase in protein carbonyl content and protein oxidation was seen in serum and liver. Results of our study may provide possible mechanism for developing medical countermeasures against T‐2 toxin. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 64–73, 2015.     

Efficacy and safety of pegylated-interferon α-2a in hemodialysis patients with chronic hepatitis C

AIM： To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS： Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk （group A）. The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group （group B）. At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response （SVR） was assessed. Side effects were monitored.
RESULTS： Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients （82.4%） in group A and in one patient （7.1%） in group B （P = 0.001）. Sustained virological response was observed in 11 patients （64.7%） in group A and in one patient in group B （7.1%）. Biochemical response parameters normalized in 10/14 patients （71.4%） at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them （25%） at the end of the 48 wk. In five patients （22.7%） therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding.
CONCLUSION： SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.     

Use of pleural fluid C-reactive protein in diagnosis of pleural effusions

The aims of the study were to assess whether C-reactive protein (CRP) is a sensitive marker for discriminating between transudative and exudative and pleural effusions to evaluate whether it can be used to distinguish inflammatory pleural effusions from other types of effusion. Pleural fluid and serum CRP levels were obtained in 97 patients with pleural effusion, using an immunoturbidimetric method (Olympus AU-600 autoanalyser). We compared CRP levels between transudates and exudates, inflammatory effusions and other types of effusion. According to the criteria used, 16 patients were included in the transudate group and 81 patients in the exudate group. Pleural fluid CRP levels were significantly lower in the transudate group (P<0.04; 14.9 +/- 4.9 mg l(-1) and 35.5 +/- 4.9 mg l(-1) respectively). Also, the ratio of pleural fluid to serum was significantly lower in the transudate group (P<0.009; 0.8 +/- 0.5 mg l(-1) and 2.8 +/- 0.7 mg l(-1), respectively). In the exudate group, 35 patients had neoplastic effusions, 10 chronic non-specific pleurisy, 19 tuberculous pleurisy, 16 parapneumonic effusion and one Dressler Syndrome. When these sub-groups were compared, the parapneumonic effusion subgroup CRP levels (mean 89 +/- 16.3 mg l(-1)) were significantly higher than those in the other subgroups, other exudate of neoplastic effusion, tuberculous pleurisy and chronic non-specific effusion and the transudate group (P<0.0001; P<0.0001; P<0.0004 and P<0.0001, respectively). The ratio between pleural fluid and serum CRP was significantly higher in the parapneumonic effusion subgroup than in the neoplastic subgroup (P<0.0002; 6.6 +/- 2.7 mg l(-1) and 1 +/- 0.2 mg l(-1), respectively). Pleural fluid CRP levels > 30 mg l(-1) had a high sensitivity (93.7%) and specificity (76.5%) and a positive predictive value of 98.4%. In the differential diagnosis of pleural effusions, higher CRP levels may prove to be a rapid, practical and accurate method of differentiating parapneumonic effusions from other exudate types. Although the high level of CRP obtained in the exudate group may be due to the number of patients with parapneumonic effusion who were included, the pleural CRP level may also be helpful in discriminating between exudative and transudative pleural effusions.     

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia‐induced vascular leakage and oedema in rat brain

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia‐induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF‐A site were identified and validated with a Ramachandran plot. The active site residues of VEGF‐A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF‐A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O₂). Additionally, the best candidate molecule's efficacy was assessed in male Sprague‐Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor‐A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor‐A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib‐treated rats. Vascular endothelial growth factor‐A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia‐induced vasogenic oedema by regulating VEGF levels.