Percutaneous vertebroplasty for acute vertebral body fracture and deformity in multiple myeloma: a short report

We describe seven patients with multiple myeloma who were treated for acute vertebral body fractures with percutaneous vertebroplasty to a total of 14 vertebrae. Six of the seven patients had at least a 50% decrease in their pain scores at 24 h following vertebroplasty. There were no procedure-related complications. These encouraging results prompt us to suggest further large-scale evaluation of this procedure in myeloma patients.     

Holter monitoring in patients with mitral stenosis and sinus rhythm

To determine the type and frequency of supraventricular arrhythmias in patients with mitral stenosis and sinus rhythm we studied 63 such patients, mean (sd) age 48.8 (8.2) years, by 24 hour ambulatory ECG monitoring. Thirty-five patients (55.6%) had supraventricular tachyarrhythmias. Twenty-five (39.7%) had paroxysmal atrial tachycardia, 14 (22.2%) atrial fibrillation, 8 (12.7%) multifocal atrial tachycardia and 5 atrial flutter. Ninety-five per cent (101) of episodes were asymptomatic and 96% non-sustained. Supraventricular premature beats occurred in 59 patients with couplets and triplets in 40 (63.5%) and 28 (44.4%), respectively. Frequent supraventricular premature beats, couplets, triplets and episodes of paroxysmal arrhythmias were commoner in patients greater than 50 years. Ectopic atrial rhythms with varying P wave morphology occurred in 12 patients (19%). Nine patients (14.3%) had suffered systemic embolic episodes. We conclude that supraventricular ectopic and tachyarrhythmias occur frequently in patients with mitral stenosis and sinus rhythm and that most paroxysms are non-sustained and asymptomatic.     

Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E2 in radiation damage

Damage to intestinal epithelium limits the use of ionizing radiation (IR) in cancer therapy. Prostaglandins (PGs), generated through the action of cyclooxygenase-1 (COX-1) and COX-2 protect the intestinal stem cells from IR. In previous studies, we demonstrated that the RNA-binding protein CUGBP2 regulates the stability and translation of COX-2 mRNA by interacting with AU-rich sequences in 3' UTR. Here, we demonstrate a dynamic antagonistic relationship between CUGBP2 and COX-2. Both CUGBP2 and COX-2 are rapidly induced after IR in intestinal crypt epithelial cells in mice, but CUGBP2 protein expression is observed immediately and COX-2 protein expression is delayed. In contrast, administration of bacterial lipopolysaccharide induced COX-2 expression and PGE(2), resulting in the inhibition of CUGBP2 expression and radioprotection of the intestine. These effects were reversed by NS398, a COX-2-specific inhibitor, suggesting that lipopolysaccharide-mediated inhibition of CUGBP2 is a PG-dependent mechanism. Furthermore, CUGBP2 expression is higher in COX-1(-/-) and COX-2(-/-) mice than wild-type controls at basal conditions, which is further increased after IR.     

Right ventricular failure: a comorbidity or a clinical emergency?

Heart Failure Reviews - There has been ample data providing a convincing perception about the underlying mechanism pertaining to left ventricle (LV) hypertrophy progressing towards LV failure. In...     

Epigallocatechin gallate attenuates fibroblast proliferation and excessive collagen production by effectively intervening TGF‐β1 signalling

Pulmonary fibrosis (PF) poses a huge burden to the patients and society due to lack of an effective treatment drug. Activation of fibrocyte, fibroblast and myofibroblasts are important steps in the development of PF. Targeting this common pathway with natural chemicals may lead to the development of new drug regimens for PF treatment. In this study, PF was induced in male Wistar rats by intratracheal administration of Bleomycin (BLM). Epigallocatechin gallate (EGCG) was administered to one of the groups of rats to test its efficacy against the development of PF. Bleomycin‐induction resulted in significant elevation of matrix metalloproteinase (MMP)‐2 and ‐9 expression, increased RNA and protein expression of transforming growth factor (TGF)‐β1, Smads and alpha‐smooth muscle actin (α‐SMA). EGCG treatment normalized the BLM induced aberrations in these rats. The protective role of EGCG was also validated in vitro using the WI‐38 fibroblast cell line. TGF‐β1 incubated cells exhibited increased fibroblast proliferation and hydroxyproline levels with a concomitant decrease in the expression of MMPs 2 and 9. An increase in protein expression levels of p‐Smad, α‐SMA and type I collagen (COL1A) was also exhibited by fibroblasts upon TGF‐β1 incubation. Simultaneous treatment of EGCG to WI‐38 cells significantly decreased these protein expressions alongside normalizing the MMPs expression. The study revealed that EGCG inhibited fibroblast activation and collagen accumulation by inhibiting TGF‐β1 signalling and thus can be considered as an effective drug against PF.     

A novel apoptosis-inducing metabolite isolated from marine sponge symbiont Monascus sp. NMK7 attenuates cell proliferation,migration and ROS stress-mediated apoptosis in breast cancer cells

The marine environment has a remarkable source of natural products mainly from marine fungi, which have been a central source of novel pharmacologically bioactive secondary metabolites. In this study, the search for a new potential apoptosis-inducing metabolite is focused on marine sponge-associated symbionts. A total of sixteen different sponges were obtained from the Gulf of Mannar region, India, and twenty-three different marine fungal strains were isolated and tested for antiproliferative activity by the MTT assay. Out of these, Monascus sp. NMK7 associated with the marine sponge Clathria frondifera was found to have a promising antiproliferative property. Furthermore, to isolate the pure active metabolite, the crude material was subjected to column chromatography and HPLC. Structural characterization was conducted by a variety of spectroscopic techniques including UV, IR, MS and NMR. The obtained results from the MS and NMR spectroscopy determined 418.5 Da to be the molecular weight and C₂₄H₃₄O₆ to be the molecular formula of the metabolite, indicating the presence of monacolin X (NMKD7). NMKD7 was found to induce dose-dependent cytotoxicity in different human breast cancer cell lines MCF-7, T47D, MDA-MB-231, MDA-MB-468 and MCF-10A normal breast cell after 24 h of exposure. For elucidating the possible mode of cell death, T47D and MDA-MB-468 cells were treated with NMKD7 for 24 h to examine the morphological change of the chromatin (PI & AO/EB). Therefore, it has been suggested as the possible mechanism of apoptosis, and apart from this, it has also exhibited antibacterial and anti-migratory properties as well as induced the ROS stress (DCFH-DA), which causes the mitochondrial membrane potential difference (Rhodamine-123), the loss of cell membrane integrity and eventually cell death. Thus, the present study features a novel promising apoptosis-inducing metabolite (NMKD7) with minimal toxicity, suggesting its potential for biotechnological applications, and substantiates that it should be further considered for the elucidation of molecular targets and signal transduction pathways.

The marine environment has a remarkable source of natural products mainly from marine fungi, which have been a central source of novel pharmacologically bioactive secondary metabolites.     

Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF). Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.