A comparison of three different gauge Quincke’s spinal needles in patients undergoing elective surgery under spinal anaesthesia: a prospective randomized study

Background: The present study was conducted to compare three different Quincke’s spinal needles i.e. 23, 25 and 26 gauge in patients undergoing elective surgery under spinal anaesthesia (SA).Methods: The prospective randomized double-blind study was conducted on 150 male patients in the age group of 18-50 yrs., having physical status class I to II, scheduled for elective surgery under SA. Patients were randomly divided into three groups comprising 50 patients each. SA was administered using Quincke’s spinal needles of 23, 25 and 26 gauge in group 1, 2 and 3 respectively. Ease of insertion, number of attempts and time of appearance of CSF and incidence of PDPH was recorded in all the patients.Results: Ease of insertion was graded easy in 98%, 84% and 82% in group 1, 2 and 3 respectively. First attempt success rate was highest in group 1, (98%). Meantime for appearance of CSF beyond hub was maximum in group 3 i.e. 14.60±2.56 sec. Mild PDPH was reported in 6% and 2% patients after 24 hrs in group 1 and group 2 respectively.Conclusions: Finer spinal needle proved to be more dependable in generating less traumatic effect on the dura and preventing PDPH but are technically more difficult thus decreasing first attempt success rate

Microscale Gene Expression Analysis of Tumor-Associated Macrophages

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small number of immune cells. Here, we describe an efficient, sensitive, and cost-effective approach for gene expression analysis of a small number of fluorescence-activated sorted tumor-associated macrophages. Our analyses from the different number of stable, primary, and sorted macrophages suggest 5,000 cells is an optimal number for performing quantitative, real-time PCR analysis of multiple genes. Our studies could detect expression of macrophage-specific genes from cultured primary macrophages, and FACS-sorted macrophages from different biological tissues without introducing biases in comparative gene expression ratios. In conclusion, our kit-based method for quantitative gene expression analysis from a small number of cells found in biological tissues will provide an opportunity to study cell-specific, transcriptional changes

Research and Reviews: Journal of Chemistry Biological Evaluation of Some Amide Group Containing Ligands and Their Complexes with Gd (III) Ions

ABSTRACT The antibacterial activity of some amide group containing ligands and their complexes with Gd(III) ions were tested against two bacterial strains: Escherichia coli, Staphylococcus aureus. All of the complexes possess inhibitory action against the tested strains. The activity of the studies compounds depends on their concentration. The complexes of aminothiazole derivatives were found to have more antibacterial activities than aminopyridines derivatives

Propofol affords no protection against delayed cerebral ischemia in a mouse model of subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is an important contributor to poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. We previously showed that volatile anesthetics such as isoflurane, sevoflurane and desflurane provided robust protection against SAH-induced DCI, but the impact of a more commonly used intravenous anesthetic agent, propofol, is not known. The goal of our current study is to examine the neurovascular protective effects of propofol on SAH-induced DCI. Twelve-week-old male wild-type mice were utilized for the study. Mice underwent endovascular perforation SAH or sham surgery followed one hour later by propofol infusion through the internal jugular vein (2 mg/kg/min continuous intravenous infusion). Large artery vasospasm was assessed three days after SAH. Neurological outcome assessment was performed at baseline and then daily until animal sacrifice. Statistical analysis was performed via one-way ANOVA and two-way repeated measures ANOVA followed by the Newman-Keuls multiple comparison test with significance set a

Structure and Function of Human DnaJ Homologue Subfamily A Member 1 (DNAJA1) and Its Relationship to Pancreatic Cancer

Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been improved over the past 25 years despite an enormous amount of effort. Thus, there is an urgent need to identify truly novel yet druggable protein targets for drug discovery. The human protein DnaJ homologue subfamily A member 1 (DNAJA1) was previously shown to be downregulated 5- fold in pancreatic cancer cells and has been targeted as a biomarker for pancreatic cancer, but little is known about the specific biological function for DNAJA1 or the other members of the DnaJ family encoded in the human genome. Our results suggest the overexpression of DNAJA1 suppresses the stress response capabilities of the oncogenic transcription factor, c-Jun, and results in the diminution of cell survival. DNAJA1 likely activates a DnaK protein by forming a complex that suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear magnetic resonance solution structure of the J-domain of DNAJA1 combined with a bioinformatics analysis and a ligand affinity screen identifies a potential DnaK binding site, which is also predicted to overlap with an inhibitory binding site, suggesting DNAJA1 activity is highly regulated

Optimisation of age at first calving in Karan Fries cattle

The study was conducted on the performance records of age at first calving (AFC) spread over a period of 15 years on Karan Fries crossbred cattle maintained at Livestock Research Centre. Data of 676 cows were collected and analysed by Least Squares Technique to examine the effect of non-genetic factors on age at first calving. Period of birth was classified into 5 periods (I-V) and season of calving into 4 seasons (winter, summer, rainy and autumn) to see the effect of non-genetic factors on age at first calving. Effect of period of birth was significant on age at first calving while season of calving showed non-significant effect on age at first calving. The overall least squares mean of age at first calving was 1043.40±6.64 days. For the optimisation of age at first calving with regard to milk productivity, analysis was carried out by class interval method. Age at first calving was classified into 7 classes and its average means of milk yield were obtained by using Least Squares Technique where optimum level of age at first calving was obtained at 885–1100 days based on higher milk yield and numbers of animal observed in different classes. From the study, it was concluded that optimum age at first calving could be achieved through proper nutrition and management practices. However, to determine the optimum level of age at first calving, much emphasis should be given to maximum profit rather than maximizing milk production

Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models

MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer

Aberrant glucose metabolism is one of the hallmarks of cancer that facilitates cancer cell survival and proliferation. Here, we demonstrate that MUC1, a large, type I transmembrane protein that is overexpressed in several carcinomas including pancreatic adenocarcinoma, modulates cancer cell metabolism to facilitate growth properties of cancer cells. MUC1 occupies the promoter elements of multiple genes directly involved in glucose metabolism and regulates their expression. Furthermore, MUC1 expression enhances glycolytic activity in pancreatic cancer cells. We also demonstrate that MUC1 expression enhances in vivo glucose uptake and expression of genes involved in glucose uptake and metabolism in orthotopic implantation models of pancreatic cancer. The MUC1 cytoplasmic tail is known to activate multiple signaling pathways through its interactions with several transcription factors/coregulators at the promoter elements of various genes. Our results indicate that MUC1 acts as a modulator of the hypoxic response in pancreatic cancer cells by regulating the expression/stability and activity of hypoxia-inducible factor-1α (HIF-1α). MUC1 physically interacts with HIF-1α and p300 and stabilizes the former at the protein level. By using a ChIP assay, we demonstrate that MUC1 facilitates recruitment of HIF-1α and p300 on glycolytic gene promoters in a hypoxia-dependent manner. Also, by metabolomic studies, we demonstrate that MUC1 regulates multiple metabolite intermediates in the glucose and amino acid metabolic pathways. Thus, our studies indicate that MUC1 acts as a master regulator of the metabolic program and facilitates metabolic alterations in the hypoxic environments that help tumor cells survive and proliferate under such conditions

Structure and Function of Human DnaJ Homologue Subfamily A Member 1 (DNAJA1) and Its Relationship to Pancreatic Cancer

Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been improved over the past 25 years despite an enormous amount of effort. Thus, there is an urgent need to identify truly novel yet druggable protein targets for drug discovery. The human protein DnaJ homologue subfamily A member 1 (DNAJA1) was previously shown to be downregulated 5- fold in pancreatic cancer cells and has been targeted as a biomarker for pancreatic cancer, but little is known about the specific biological function for DNAJA1 or the other members of the DnaJ family encoded in the human genome. Our results suggest the overexpression of DNAJA1 suppresses the stress response capabilities of the oncogenic transcription factor, c-Jun, and results in the diminution of cell survival. DNAJA1 likely activates a DnaK protein by forming a complex that suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear magnetic resonance solution structure of the J-domain of DNAJA1 combined with a bioinformatics analysis and a ligand affinity screen identifies a potential DnaK binding site, which is also predicted to overlap with an inhibitory binding site, suggesting DNAJA1 activity is highly regulated