Some biochemical changes in the ageing heart of the male garden lizard

The SDH activity of cardiac muscle homogenates reached a peak level in the middle-aged lizards followed by a decline in the old. The inhibition of enzyme activity by oxaloacetate, a competitive inhibitor, declined with advancing age. Both salt and acid solubilities of cardiac muscle collagen declined with advancing age of the lizard. An age-related accumulation of total collagen was evident per organ basis but a reverse trend prevailed on the basis of relative value. Quantitative estimations revealed a loss of DNA in ageing heart; per organ basis the DNA content increased till the lizards were middle-aged showing no further change thereafter. On the other hand the RNA content and the RNA/DNA ratio of cardiac muscle declined between young and middle-aged followed by a rise in the old lizards. The protein content increased with rise in fresh weight of heart during ageing.     

An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.     

Sentinel Lymph Node Localization Using 1 % Isosulfan Blue Dye in Cases of Early Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

To study the use of 1 % isosulfan blue dye in identifying sentinel node, sensitivity and specificity of frozen section and predictive value of sentinel node in predicting other nodal status in the cases of oral cavity and oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion as well as neck dissection as per recommended treatment protocol, were selected from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the induction of general anaesthesia. Neck dissection was performed and first node taking up the blue dye was identified, dissected, removed and was sent for frozen section. In two of the 15 cases a sentinel node was identified (sensitivity of the technique—13 %). Both the sentinel nodes were positive for presence of metastasis on final histopathology (specificity—100 %). However, five cases had nodal metastasis on final histopathological examination of the neck dissection specimen (sensitivity of sentinel lymph node biopsy—40 %). Frozen section examination had a sensitivity and specificity of 100 %. All data was analyzed using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel node is a simple and cheap technique, however, it has low sensitivity as compared to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per op gamma probe localization and using isosulfan dye for sentinel node identification. Sentinel lymph node is representative of nodal status and correlates well with the final histopathological examination of the dissected neck nodes.     

Rosuvastatin 1.2 mg In Situ Gel Combined With 1:1 Mixture of Autologous Platelet‐Rich Fibrin and Porous Hydroxyapatite Bone Graft in Surgical Treatment of Mandibular Class II Furcation Defects: A Randomized Clinical Control Trial

Background: A wide range of regenerative materials have been tried and tested in the treatment of furcation defects. Rosuvastatin (RSV) is a new synthetic, second‐generation, sulfur‐containing, hydrophilic statin with potent anti‐inflammatory and osseodifferentiation mechanisms of action. Platelet‐rich fibrin (PRF) is a platelet concentrate having sustained release of various growth factors with regenerative potential to treat periodontal defects. Porous hydroxyapatite (HA) bone grafting material has a clinically satisfactory response when used to fill periodontal intrabony defects. This double‐masked randomized study is designed to evaluate the potency of a combination of 1.2 mg RSV in situ gel with a 1:1 mixture of autologous PRF and HA bone graft in the surgical treatment of mandibular Class II furcation defects compared with autologous PRF and HA bone graft placed after open‐flap debridement (OFD). Methods: One hundred five mandibular furcation defects were treated with OFD + placebo gel (group 1), PRF + HA with OFD (group 2), or 1.2 mg RSV gel + PRF + HA with OFD (group 3). Clinical and radiologic parameters (i.e., probing depth [PD], relative vertical and relative horizontal clinical attachment level [rvCAL and rhCAL], intrabony defect depth, and percentage of defect fill) were recorded at baseline and 9 months postoperatively. Results: Mean PD reduction was greater in group 2 (3.68 ± 1.07 mm) and group 3 (4.62 ± 1.03 mm) than group 1 (2.11 ± 1.25 mm), and mean rvCAL and rhCAL gain were greater in group 2 (3.31 ± 0.52 and 2.97 ± 0.56 mm, respectively) and group 3 (4.17 ± 0.70 and 4.05 ± 0.76 mm) compared with group 1 (1.82 ± 0.78 and 1.62 ± 0.64 mm). A significantly greater percentage of mean bone fill was found in group 2 (54.69% ± 1.93%) and group 3 (61.94% ± 3.54%) compared with group 1 (10.09% ± 4.28%). Conclusions: Treatment of furcation defects with 1.2 mg RSV in situ gel combined with autologous PRF and porous HA bone graft results in significant improvements of clinical and radiographic parameters compared with OFD alone. These results imply that the combination of RSV, PRF, and HA has synergistic effects, explaining their role as a regenerative material in the treatment of furcation defects.     

Effect of age on lipid peroxidation in a short-lived species of reptile, Calotes versicolor

The lipid peroxidation potential, measured as a thiobarbituric acid-reactive substance (TBA-RS) increased with advancing age in liver, brain and kidney of a short-lived species of reptile, Calotes versicolor. The same parameter did not show a significant change in an ageing heart. The pattern of age changes in lipid peroxidation potential in this species shows similarity with the findings in a majority of mammalian species. While suggesting a commonality in a basic mechanism of ageing between reptiles and mammals, the results also partially support the free radical theory of ageing.     

High beta integrin expression is differentially associated with worsened pancreatic ductal adenocarcinoma outcomes

Outcomes in pancreatic ductal adenocarcinoma (PDAC) are known to be worse in tumors with high integrin β1 expression, but targeted monotherapy against this integrin has not been effective. Seven other beta integrins are expressed in mammalian biology and they are known to have overlapping and compensatory signaling in biological systems. However, their roles in PDAC are poorly understood and have not been systematically compared to integrin β1 biology. In this study, we analyzed the clinical outcomes against beta integrin 1-8 (ITGB1-8) expression in PDAC samples from two large independent cohorts, The Cancer Genome Atlas (TCGA) and {"type":"entrez-geo","attrs":{"text":"GSE21501","term_id":"21501"}}GSE21501. Biological function and tumor microenvironment composition were studied using Gene Set Enrichment Analysis and xCell. Expression of all eight beta integrins is significantly increased in PDACs relative to normal pancreatic tissues (all P<0.001). ITGB1, 2, 5, and 6 have similarly enriched gene patterns related to transforming growth factor (TGF)-β, epithelial mesenchymal transition, inflammation, stemness, and angiogenesis pathways. Homologous recombination defects and neoantigens are increased in high-ITGB4, 5, and 6 tumors, with decreased overall survival in high-ITGB1, 5, and 6 tumors compared to low expression tumors (hazard ratios 1.5-2.0). High-ITGB1, 2, and 5 tumors have increased fibroblast infiltration (all P<0.01) while endothelial cells are increased in high-ITGB2 and 3 tumors (all P<0.05). Overall, beta integrin expression does not correlate to immune cell populations in PDACs. Therefore, while all beta integrins are overexpressed in PDACs, they exert differential effects on PDAC biology. ITGB2, 5, and 6 have a similar profile to ITGB1, suggesting that future research in PDAC integrin therapy needs to consider the complementary signaling profiles mediated by these integrins.     

Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis

OBJECTIVE: The aim of this study was to examine whether intravenous immunoglobulin (IVIg) preparations contain anti-oxLDL and anti-anti-oxLDL antibodies. BACKGROUND: Oxidized low-density lipoprotein (oxLDL) is one of the major players in atherogenesis. IVIg can reduce atherosclerosis in experimental animal models. METHODS: Six commercial IVIg preparations were tested for the presence of anti-oxLDL antibodies by EIA. Inhibition studies were performed with the different IVIg preparations and IgGs purified from a pool of sera from patients with high anti-oxLDL antibody levels. Absorption assays were carried out to evaluate the presence of anti-idiotypes against anti-oxLDL antibodies in IVIg preparations. RESULTS: IVIg preparations tested had various degrees of reactivity towards oxLDL. Absorption experiments suggested that the reactivity was specific because it could be effectively absorbed by oxLDL and not by an irrelevant antigen PPD. The reactivity was smaller than that observed with the IgG from the pool with high anti-oxLDL antibody levels. Inhibition studies with IVIg demonstrated 20-45% inhibition of anti-oxLDL binding to oxLDL, compared to 76% inhibition by the pool with high anti-oxLDL levels. To investigate the presence of anti-idiotypes against anti-oxLDL antibodies within IVIg, F(ab')2 fragments of IVIg IgG were used to absorb IgG F(ab')2 fragments from the pool of sera with high anti-oxLDL levels. The decreased binding to oxLDL of the absorbed supernatants shows that IgG F(ab')2 fragments of the IVIg preparations had high inhibitory capacities ranging from 65 to 90%. CONCLUSIONS: IVIg preparations contain both anti-oxLDL and anti-anti-oxLDL activity. This finding may explain the immunomodulating effect of IVIg in atherosclerosis.