Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract

Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered

Automatic Segmentation of Colon in 3D CT Images and Removal of Opacified Fluid Using Cascade Feed Forward Neural Network

Purpose. Colon segmentation is an essential step in the development of computer-aided diagnosis systems based on computed tomography (CT) images. The requirement for the detection of the polyps which lie on the walls of the colon is much needed in the field of medical imaging for diagnosis of colorectal cancer. Methods. The proposed work is focused on designing an efficient automatic colon segmentation algorithm from abdominal slices consisting of colons, partial volume effect, bowels, and lungs. The challenge lies in determining the exact colon enhanced with partial volume effect of the slice. In this work, adaptive thresholding technique is proposed for the segmentation of air packets, machine learning based cascade feed forward neural network enhanced with boundary detection algorithms are used which differentiate the segments of the lung and the fluids which are sediment at the side wall of colon and by rejecting bowels based on the slice difference removal method. The proposed neural network method is trained with Bayesian regulation algorithm to determine the partial volume effect. Results. Experiment was conducted on CT database images which results in 98% accuracy and minimal error rate. Conclusions. The main contribution of this work is the exploitation of neural network algorithm for removal of opacified fluid to attain desired colon segmentation result

Vibrational Spectra & Intramolecular Force Constants of S-Methyl-N,N-dimethyldithiocarbamate : Study of Characteristic Tertiary Thioamide Bands

1082-108

Charge Transfer & Metal Complexes of Dithiocarbamate Esters

980-98

Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates caspase-independent cancer cell death

Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an aggressive and distinct subtype of breast cancer, was recently attributed to increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and decreased accumulation of reactive species. In this study, we demonstrate the unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD mimics (MnTE-2-PyP5+ and MnTnBuOE-2-PyP5+) to catalyze oxidation of ascorbate, leading to the production of excessive levels of peroxide, and in turn cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate treatment, was fully reversed by the administration of exogenous catalase, showing that hydrogen peroxide is essential for cell death. Cell death as a consequence of the action of MnP+ascorbate corresponded to decreases in GSH levels, prosurvival signaling (p-NF-κB, p-ERK1/2), and in expression of X-linked inhibitor of apoptosis protein, the most potent caspase inhibitor. Although markers of classical apoptosis were observed, including PARP cleavage and annexin V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did not reverse the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear translocation of apoptosis-inducing factor, suggesting the possibility of a mechanism of caspase-independent cell death. Pharmacological ascorbate has already shown promise in recently completed phase I clinical trials, in which its oxidation and subsequent peroxide formation was catalyzed by endogenous metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based catalyst (such as MnP) carries a large therapeutic potential as an anticancer agent by itself or in combination with other modalities such as radio- and chemotherapy. © 2013 Elsevier Inc

Effect of alliums on total lipid in plasma and tissues of Japanese quails (<i>Coturnix coturnix japonica</i>)<i> </i>with respect to age and sex

187-191Dietary onion and garlic caused an increase in the level of liver and plasma total lipids in Coturnix oturnix japonica. This increase could be due to the effect of an increased feed intake, bile production, digestion and absorption that in turn caused an increased utilisation of dietary fat, increased transfer of dietary lipids to the liver and/or due to increased lipogenesis as such. However, there was no increase in the muscle lipid content. This effect in the muscle could be due to inhibitory effect of onion or garlic on lipoprotein lipase activity. Further, the changes in the tissue total lipid level in the control group due to change in age and sex were also observed

<span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">Effect of onion (<i>Allium cepa</i> Linn.) and garlic (<i>Allium sativum</i> Linn.) on plasma triglyceride content in Japanese quail (<i>Coturnix coturnix japonicum</i>)</span>

88-90<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">Dietary onion and garlic caused an increase in the level of plasma triglyceride which could be due to insulin like activity of dietary alliums and other factors that promote lipogenesisi in growing stages. Changes in the plasma triglyceride level in the control group due to change in age and sex were also noted. The triglyceride level was more in female birds when compared to males of similar age group. The plasma trigelyecride level increased with age in both sex except for the level being similar in the 6 and 9-week old females and 3 and 6-week old male birds. The results suggest that the effects of alliums in growing and adult stages may be different which needs further study.</span