Dose-related effects of Ampligen (poly(I).poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis

The antifibrotic effect of the mismatched double-stranded RNA, Ampligen (poly(I).poly(C12U)), was evaluated in a bleomycin-mouse model of pulmonary fibrosis. Mice received a single intratracheal dose of bleomycin (0.125 U/mouse) or saline (50 microL) at the beginning of the experiment, followed by 5 or 6 intraperitoneal injections of Ampligen (1.0, 5.0, 10.0, 15.0, or 25.0 mg/kg) or saline at regular intervals for 2 weeks. Ampligen did not produce increased mortality or weight loss by itself. However, it produced varying degrees of mortality in combination with bleomycin. Five injections of 10 mg/kg Ampligen or three injections of 25 mg/kg Ampligen plus three injections of 10 mg/kg Ampligen in combination with bleomycin .produced significant reductions in lung collagen accumulation as indicated by lung hydroxyproline content compared to the bleomycin control group. Animals receiving bleomycin plus Ampligen at all dosages had significantly reduced prolyl hydroxylase activity compared to the bleomycin control group. Lipid peroxidation and bronchoalveolar lavage fluid (BALF)-supernatant protein content for the groups receiving bleomycin plus Ampligen were not reduced compared to the bleomycin control group. In the BALF-supernatant, the activity of acid phosphatase, a lysosomal enzyme produced by neutrophils, monocytes, and macrophages, was significantly decreased in the group receiving bleomycin plus 10 mg/kg Ampligen. Also, selected BALF differential immune cell counts were reduced in some of the groups receiving bleomycin plus Ampligen, but not in a consistent or dose-dependent manner. The results of this study indicate that Ampligen can significantly reduce the bleomycin-induced increased collagen accumulation and may be therapeutically useful in the management of lung fibrosis in humans.     

Predictors of GBV-C infection among patients referred for renal transplantation

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.     

Isolation of acidophilic methane-oxidizing bacteria from northern peat wetlands

Acidic northern wetlands are an important source of methane, one of the gases that contributes to global warming. Methane oxidation in the surface of these acidic wetlands can reduce the methane flux to the atmosphere up to 90 percent. Here the isolation of three methanotrophic microorganisms from three boreal forest sites is reported. They are moderately acidophilic organisms and have a soluble methane monooxygenase. In contrast to the known groups of methanotrophs, 16S ribosomal DNA sequence analysis shows that they are affiliated with the acidophilic heterotrophic bacterium Beijerinckia indica subsp. indica.     

p values, hypothesis tests, and likelihood: implications for epidemiology of a neglected historical debate

It is not generally appreciated that the p value, as conceived by R. A. Fisher, is not compatible with the Neyman-Pearson hypothesis test in which it has become embedded. The p value was meant to be a flexible inferential measure, whereas the hypothesis test was a rule for behavior, not inference. The combination of the two methods has led to a reinterpretation of the p value simultaneously as an "observed error rate" and as a measure of evidence. Both of these interpretations are problematic, and their combination has obscured the important differences between Neyman and Fisher on the nature of the scientific method and inhibited our understanding of the philosophic implications of the basic methods in use today. An analysis using another method promoted by Fisher, mathematical likelihood, shows that the p value substantially overstates the evidence against the null hypothesis. Likelihood makes clearer the distinction between error rates and inferential evidence and is a quantitative tool for expressing evidential strength that is more appropriate for the purposes of epidemiology than the p value.     

Determination of fibrin and fibrinogen split products by their anticoagulant activity

A new diagnostic method to determine fibrinogen and fibrin splitting products is based on the fact that high-molecular fragments acting as specific inhibitors of fibrin self-assembly compose these products. Fibrinogen and fibrin splitting products are detected and determined quantitatively by prolongation of coagulation time in the test with the standard monomeric fibrin. The number of units of anticoagulating activity in the studied urine are the results of the determinations. Sensitivity of the method if necessary may be increased by adding of a certain amount of the fibrinogen and fibrin splitting products to the test that makes a favourable background for the action of the products. The method is rather sensitive, reliable and simple. It may be used in ordinary clinical laboratories. The method proved to be quite satisfactory when testing renal diseases at the clinic. It is of great significance for early detection of the transplanted kidney rejection. The new method is compared with the known immunological method which consist in determination of the inhibitory effect of the fibrinogen and fibrin splitting products on agglutination of erythrocytes of specific antibodies; the erythrocytes being subjected to "tanning" and "loading" with fibrinogen. A satisfactory correlation is found between the results of two methods.     

Impact of cycling temperatures on Fusarium verticillioides and Fusarium graminearum growth and mycotoxins production in soybean

BACKGROUND: Fusarium graminearum and F. verticillioides are two very important mycotoxigenic species as they cause diverse diseases in crops. The effects of constant and cycling temperatures on growth and mycotoxin production of these species were studied on soybean based medium and on irradiated soya beans. RESULTS: F. graminearum grew better when was incubated at 15, 20 and 15–20 °C (isothermal or cycling temperature) during 21 days of incubation. Maximum levels of zearalenone and deoxynivalenol (39.25 and 1040.4 µg g^?1, respectively) were detected on soya beans after 15 days of incubation and the optimal temperature for mycotoxin production was 15 °C for zearalenone and 20 °C for deoxynivalenol. F. verticillioides grew better at 25 °C in culture medium and at 15/20 °C and 15/25 °C on soybean seeds. Fumonisin B₁ was produced only in culture medium, and the maximum level (7.38 µg g^?1) was found at 15 °C after 7 days of incubation. CONCLUSION: When growth and mycotoxin production under cycling temperatures were predicted from the results under constant conditions, observed values were different from calculated for both species and substrate medium. Therefore, care should be taken if data at constant temperature conditions are to be extrapolated to real field conditions. Copyright © 2012 Society of Chemical Industry     

CuBr2‐induced charge screening on photoactive nanocolloidal polypyrrole:poly(styrene sulfonate) composite multilayer thin‐film counter electrodes for high‐efficiency dye‐sensitized solar cells

Nanocolloidal polypyrrole (PPy):poly(styrene sulfonate) (PSS) particles were synthesized by chemical oxidative polymerization using 15 wt% of PSS. The highly processable polymer composite (PPy:PSS) was spin‐coated at 4000 rpm on fluorine‐doped tin oxide glass and subsequently employed as a counter electrode (CE) for dye‐sensitized solar cells (DSCs). PPy:PSS multilayer (one, three, five) CEs were treated with CuBr₂ salt, which enhances the efficiency of the DSCs. Optical studies reveal that a bulkier counterion hinders interchain interactions of PPy which on salt treatment shows a moderate redshift in absorption maxima. Salt‐treated PPy:PSS films exhibit lower charge transfer resistance, higher surface roughness and better catalytic performance for the reduction of I₃^?, when compared with untreated films. The improved catalytic performance of salt‐treated PPy:PSS multilayer films is attributed to charge screening and conformational change of PPy, along with the removal of excess PSS. Under standard AM 1.5 sunlight illumination, salt treatment is shown to boost the efficiency of multilayer PPy:PSS composite film‐based DSCs, leading to enhanced power conversion efficiency of 6.18, 6.33 and 6.37% for one, three and five layers, respectively. These values are significantly higher (ca 50%) than those for corresponding devices without CuBr₂ salt treatment (3.48, 2.90 and 2.01%, respectively). © 2016 Society of Chemical Industry     

Effect of Pasteurization and Retort Processing on Spectral Characteristics,Morphological, Thermal,Physico‐Mechanical,Barrier and Optical Properties of Nylon‐Based Food Packaging Materials

The effect of pasteurization and retort processing on spectral, morphological, thermal, physico‐mechanical, barrier and optical properties of three different packaging materials viz., PP/N6/PP, PET/N6/cPP and SiO_x‐PET/N6/cPP were studied. These packaging materials were packed with distilled water, which acted as a food simulant. Subsequently, these pouches were subjected to different thermal processing conditions such as pasteurization and retort processing. Both the processing techniques found to have retained the mechanical properties of all packaging materials. Water vapour transmission rate (WVTR) and oxygen transmission rate (OTR) of nylon‐based combinations were increased after processing. Gloss found to decrease invariably irrespective of the material and increases with the severity of the treatment. XRD diffractogram shows changes in crystal structure as a result of thermal processing, and SEM analysis shows the crystal fragmentation. Absorption of water by the amide group of nylon 6 was observed, which could be a reason for the increase in OTR and WVTR. Copyright © 2014 John Wiley & Sons, Ltd.     

The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin

Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma.