COMPARATIVE CLINICAL STUDY OF THE HAEMORRHOIDECTOMY AND KSHARASUTRA TRANSFIXATION WITH TWO INCISIONS IN THE MANAGEMENT OF PROLAPSED HAEMORRHOIDS

Kshara-sutra transfixation (KST) is one of the most efficacies and worldwide accepted treatments of hemorrhoids because of its effectiveness and less complication rate. Hemorrhoidectomy (HMD) is the procedure of choice for treatment of grade three and four hemorrhoids, which is a painful method for a relatively benign disease. There are a few studies available analyzing the effectiveness of Ksharasutra transfixation as an initial treatment for grade three and four symptomatic internal hemorrhoids. Arsha (hemorrhoids) is engorgement of the hemorrhoidal venous plexus, characterized by bleeding per rectum, constipation, pain, prolapse and discharge. It is manifested due to improper diet, prolonged standing and faulty habits of defecation causing derangement of Tridosha. The Kshara sutra Transfixation method in Arshas was studied in comparison with hemorrhoidectomy. Kshara sutra trans-fixation with two incision on the bulged mass in Arshas was employed in 15 patients, and 17 patients were dealt with hemorrhoidectomy. The study revealed a better result of the Kshara sutra Transfixation with two incision on the bulged mass group in comparison with hemorrhoidectomy. The observations revealed that maximum advantages like minimum hospital stay, no bleeding during or after operation, no post-operative anal stenosis, a low cost-effective and more acceptable to different categories of people, etc. were recorded in the Kshara sutra-treated group. Statistically, Kshara-sutra Transfixation for Arshas was found to be highly significant (There are significant difference among the PODS with reference to the mean grades. The corresponding F-value is given by 7.486535 which is highly significant at 1% level) and effective management. No adverse effects were noted during the follow-up period

In vitro characterization and in vivo assessment of equine tendon-derived progenitor cells

Tendinitis is a common cause of breakdown injury in equine athletes and accounts for 30% to 50% of all racing injuries. The last decade has seen significant development in mesenchymal stem cell (MSC)-based therapies in tendon repair. The focus on tendon-derived progenitor cells (TDPCs) for tendon healing is based on the rationale that stem cells obtained from tendons are more phenotypically-committed or ‘primed’ for tenogenesis than cells from other tissues. The overall objective of this body of research is to characterize and evaluate equine tendon-derived progenitor cells for tendon healing in horses. TDPCs were isolated via a differential adhesion preplating screen that has been successfully used to isolate skeletal muscle-derived stem cells. Cell suspensions obtained via collagenase digestion of equine lateral digital extensor tendon (n=4) were serially transferred into adherent plates every 12 hrs for 4 days. TDPCs obtained from the initial, third and seventh preplates were used for subsequent analyses. Growth/proliferation and basal tenogenic gene expression of the three TDPC fractions were largely similar. Preplating and subsequent monolayer expansion did not alter the immunophenotype (CD29+, CD44+, CD90+, and CD45−) and trilineage differentiation capacity of TDPC fractions. Overall, TDPCs were robustly osteogenic but exhibited comparatively weak adipogenic and chondrogenic capacities. These outcomes indicate that preplating does not enrich for tendon-derived progenitors during in vitro culture, and ‘whole tendon digest’-derived cells are as appropriate for cell-based therapies. In vitro growth characteristics of matched equine TDPCs and bone marrow MSCs (BM-MSCs) during monolayer expansion were assessed (n=6). Subsequently, third passage TDPCs and BM-MSCs were cultured on acellular tendon matrices for 7 days with or without insulin-like growth factor supplementation. Matrix production and matrix gene expression were analyzed at the end of in vitro culture. During monolayer expansion, at each passage, the yield of TDPCs was 3-fold higher than the matched BM-MSCs. The viability of TDPCs on acellular tendon matrices was 1.6-2.8 fold higher than BM-MSCs. New collagen and glycosaminoglycan syntheses were significantly greater in TDPC groups and in IGF-I–supplemented groups. The mRNA concentrations of collagen type I and III, and cartilage oligomeric matrix protein (COMP) were not significantly different between TDPC and BM-MSC groups. These in vitro results demonstrated that TDPCs may offer a useful resource for cell-based therapies for tendon healing. Lastly, the efficacy of TDPCs in an in-vivo equine flexor tendinitis model was evaluated. Collagenase-induced tendinitis was created in both front superficial digital flexor (SDF) tendons (n=8). Four weeks later, the forelimb tendon lesions were treated with 1 x 107 autogenous TDPCs or saline. Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical and histological characteristics. Collagen I and III, COMP and tenomodulin mRNA levels were similar in both TDPC and saline groups and higher than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater than the saline group’s and similar to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different. Histological assessment of the repair tissues with Fourier transform-Second Harmonic generation imaging demonstrated that collagen alignment was significantly better in TDPC group than in the saline controls. In summary, TDPC administration improved the histological and biomechanical properties of collagenase-induced tendinitis lesions

The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism

Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk

The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat polymorphism at intron 4 of the Cyp19 gene revealed the presence of six common and two rare alleles. Contingency table analysis revealed a significant difference in allelic distribution between cases and controls (χ2 5df = 13.52, P = 0.019). The allele measuring 171 bp was over-represented in cases; of 14 individuals homozygous for this allele, 13 were cases. These individuals had a higher incidence of cancer in family members and an earlier age at diagnosis than other cases. In sequencing Cyp19's coding exons and regulatory regions, we discovered a perfect association between a silent polymorphism (G→A at Val80) and the high-risk genotype. Our conclusion is that constitutional genetic variation at the Cyp19 locus is associated with the risk of developing breast cancer, with the 171-bp allele serving as the high-risk allele. © 1999 Cancer Research Campaig

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

The catabolism of ATP and other nucleotides participates partly in the important function of nucleotide salvage by activated cells and also in removal or de novo generation of compounds including ATP, ADP, and adenosine that stimulate purinergic signaling. Seven nucleotide pyrophosphatase/phosphodiesterase NPP family members have been identified to date. These isoenzymes, related by up conservation of catalytic domains and certain other modular domains, exert generally non-redundant functions via distinctions in substrates and/or cellular localization. But they share the capacity to hydrolyze phosphodiester or pyrophosphate bonds, though generally acting on distinct substrates that include nucleoside triphosphates, lysophospholipids and choline phosphate esters. PPi generation from nucleoside triphosphates, catalyzed by NPP1 in tissues including cartilage, bone, and artery media smooth muscle cells, supports normal tissue extracellular PPi levels. Balance in PPi generation relative to PPi degradation by pyrophosphatases holds extracellular PPi levels in check. Moreover, physiologic levels of extracellular PPi suppress hydroxyapatite crystal growth, but concurrently providing a reservoir for generation of pro-mineralizing Pi. Extracellular PPi levels must be supported by cells in mineralization-competent tissues to prevent pathologic calcification. This support mechanism becomes dysregulated in aging cartilage, where extracellular PPi excess, mediated in part by upregulated NPP1 expression stimulates calcification. PPi generated by NPP1modulates not only hydroxyapatite crystal growth but also chondrogenesis and expression of the mineralization regulator osteopontin. This review pays particular attention to the role of NPP1-catalyzed PPi generation in the pathogenesis of certain disorders associated with pathologic calcification

ICAR: endoscopic skull‐base surgery

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In vitro comparison of equine tendon- and bone marrow-derived cells expanded with FGF-2 prior to culturing with tendon matrix and IGF-I

This study was performed to determine the effects of fibroblast growth factor-2 (FGF-2) on monolayer expansion of equine tendon- and bone marrow-derived cells prior to culture with autogenous acellular tendon matrix and insulin-like growth factor-I (IGF-I). Progenitor cells were isolated from six young adult horses, expanded in monolayers with FGF-2, and cultured with autogenous acellular pulverized tendon and IGF-I for seven days. Initial cell isolation and subsequent monolayer proliferation were assessed. In the cell: pulverized tendon cultures, cell viability, expression of collagen types I and II, and cartilage oligomeric matrix protein (COMP) mRNAs, collagen and glycosaminoglycans (GAG) syntheses were assessed. Tendon-derived cells proliferated significantly more rapidly in the initial monolayer expansion cultures in comparison to bone marrow-derived cells. Further, monolayer expansion with FGF-2 significantly increased the cell numbers of tendon-derived cells. Expression of collagen type I, collagen type III and COMP mRNAs was higher in tendon-derived cell groups than bone marrow-derived cell groups. However, IGF-I supplementation significantly increased collagen type I and type III mRNA expression in only the bone marrow-derived cell groups. IGF-I supplementation significantly increased collagen synthesis of bone marrow-derived cells. Monolayer expansion with FGF-2 followed by IGF-I supplementation significantly increased proteoglycan synthesis in tendon-derived cells. In summary, tendon-derived cell cultures generated more cells and showed increased matrix synthesis following monolayer expansion with FGF-2 when compared to bone marrow-derived cells. In vivo experiments using FGF-2 expanded tendon-derived cells are warranted to evaluate the effects on tendon healing