A comparative study of different adjuncts to enhance the effects of intrathecal bupivacaine

Background: Spinal anaesthesia is the commonly used technique for lower abdominal surgeries. Adjuvants to bupivacaine have been used to provide good quality of perioperative and postoperative analgesia. The aim of the study was to evaluate the effects of subarachnoid administration of bupivacaine with clonidine, magnesium, dexmedetomidine and saline group.Methods: The prospective, comparative single blind study included 120 patients in American society of anaesthesiologist (ASA) grade I and II, scheduled for lower abdominal surgeries were allocated in four groups. Each group included 15 mg bupivacaine with various adjuvants (30 µg clonidine, 50 mg magnesium sulphate and 3µg dexmedetomidine) were compared with saline group (group S).Results: Time of onset was earlier in groups D and C but delayed in group M. The total power regains (B0) in group D (250.8±18.87), group M (235.23±24.66) and group C (242.70±25.98) were significantly delayed (p<0.05) as compare with group S (180.07±18.53). Demand of analgesia was significantly earlier in group S as compared with groups C, M and D. Similarly, the time of two segment regression was significantly earlier in group S as compared with groups C, M and D (p<0.001). Patients were hemodynamically stable in groups D, C and M as compared to Group S.Conclusions: Dexmedetomidine and clonidine were equally effective and better as compared to magnesium as an adjunct to intrathecal bupivacaine

Effect of epidural volume extension with colloid on dose requirement for intrathecal spinal block: a double blind prospective study

Background: Epidural volume extension (EVE) is a modification of combined- spinal epidural anaesthesia (CSEA) in which fluid is injected in epidural space after the intrathecal block. Fluid in epidural space compress subarachnoid space and causes cephalic spread of intrathecal drug to increase block height. Purpose of study is to determine efficacy of EVE on dose requirement of intrathecal bupivacaine when colloid was used for EVE.Methods: Sixty patients of ASA physical status I or II, scheduled for elective caesarean sections were recruited and randomized into two groups (30 each group). Group 1: CSEA in which spinal block is followed by 10 ml Colloid (HES 6%) in epidural space; Group 2: CSEA but no fluid in epidural space. Onset of sensory block and hemodynamic variables were measured at 5 min. intervals up to 40 minutes then at 10 min. intervals till end of surgery. Ineffective block was top- up by epidural 0.5% bupivacaine in incremental doses.Results: Median effective dose of intrathecal bupivacaine was significantly lower, 4.0 mg (95% CI 4.40-5.60) in group 1 versus 7.0 mg (95% CI 6.93-7.61) in group 2. Only 11 patients required ephedrine in group 1 versus 20 in group 2. Requirement of ephedrine was significantly lower 2.20 (±2.94) mg in group 1 versus 4.0 (±2.88) mg groups 2. Changes in haemodynamic variables from baseline were significantly lower in group 1 than those in group 2.Conclusions: EVE with colloid was effective in lowering dose requirement of spinal bupivacaine while patients hemodynamically were more stable.

An Early Diagnosis of Thalassemia: A Boon to a Healthy Society

The β-thalassemia is a hereditary blood disorders, characterized by reduced or absent synthesis of the hemoglobin beta chain that cause microcytic hypochromic anemia. An early diagnosis, economical test, awareness programs and prenatal screening will be a milestone for the eradication of this genetic disorder and to reduce burden of the health sector of a country subsequently the economics. Initially, the diagnosis of β-thalassemia depends on the hematological tests with red cell indices that disclosed the microcytic hypochromic anemia. Hemoglobin analysis shows the abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A (HbA). In severe anemia, the hemoglobin analysis by HPLC reveals decreased quantities of HbA and increased the level of hemoglobin F (HbF). The decrease level of MCV and MCH are also associated with β-thalassemia. There are various different molecular techniques such as ARMS PCR, allele-specific PCR, Gap PCR, denaturing gradient gel electrophoresis, reverse dot blotting, DGGE, SSCP, HRM, MLPA, sequencing technology and microarray available to identify the globin chain gene mutations. These molecular techniques can be clustered for detection by mutation types and alteration in gene sequences

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N > 3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer

Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals

Non-canonical guanine quadruplex structures are not only predominant but also conserved among bacterial and mammalian promoters. Moreover recent findings directly implicate quadruplex structures in transcription. These argue for an intrinsic role of the structural motif and thereby posit that single nucleotide polymorphisms (SNP) that compromise the quadruplex architecture could influence function. To test this, we analysed SNPs within quadruplex motifs (Quad-SNP) and gene expression in 270 individuals across four populations (HapMap) representing more than 14 500 genotypes. Findings reveal significant association between quadruplex-SNPs and expression of the corresponding gene in individuals (P < 0.0001). Furthermore, analysis of Quad-SNPs obtained from population-scale sequencing of 1000 human genomes showed relative selection bias against alteration of the structural motif. To directly test the quadruplex-SNP-transcription connection, we constructed a reporter system using the RPS3 promoter—remarkable difference in promoter activity in the ‘quadruplex-destabilized’ versus ‘quadruplex-intact’ promoter was noticed. As a further test, we incorporated a quadruplex motif or its disrupted counterpart within a synthetic promoter reporter construct. The quadruplex motif, and not the disrupted-motif, enhanced transcription in human cell lines of different origin. Together, these findings build direct support for quadruplex-mediated transcription and suggest quadruplex-SNPs may play significant role in mechanistically understanding variations in gene expression among individuals

Comparative study of intrathecal hyperbaric versus isobaric ropivacaine: A randomized control trial

Background: Hyperbaric ropivacaine produce more reliable sensory and motor block, with faster onset, better quality of muscles relaxation than isobaric ropivacaine. So, this study was designed to compare the efficacy of hyperbaric ropivacaine with isobaric ropivacaine in patients undergoing lower abdominal surgery. Methods: A randomized controlled double blind study in two groups of patients. group A (n=35) received 3 ml of isobaric ropivacaine 6 mg/ml (18 mg). Group B (n=35) received 3 ml of hyperbaric ropivacaine 6 mg/ml (18 mg). The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block, intensity, and duration of motor block were recorded. Statistical Analysis: Block characteristics were compared using the two-tailed Mann - Whitney U-test. The proportion of side effects was compared using the Chi-square test. Results: The median time of onset of sensory block at the T10 dermatome was 4.4±1.3 min in group B and 6.0±1.03 min in group A. The median time to maximum block height was 16.7±3.7 min in group A and 12.03±1.96 min in group B. The median duration of complete motor recovery (B0) was significantly shorter in the heavy ropivacaine group (166.5±11.7 min) compared with the isobaric ropivacaine group (192.9±9.6 min). Conclusions: Intrathecal hyperbaric ropivacaine provides more rapid, adequate, and good quality of sensory and motor block with rapid post-operative recovery as compare to isobaric ropivacaine

Effect of epidural volume extension with colloid on dose requirement for intrathecal spinal block: a double blind prospective study

Background: Epidural volume extension (EVE) is a modification of combined- spinal epidural anaesthesia (CSEA) in which fluid is injected in epidural space after the intrathecal block. Fluid in epidural space compress subarachnoid space and causes cephalic spread of intrathecal drug to increase block height. Purpose of study is to determine efficacy of EVE on dose requirement of intrathecal bupivacaine when colloid was used for EVE.Methods: Sixty patients of ASA physical status I or II, scheduled for elective caesarean sections were recruited and randomized into two groups (30 each group). Group 1: CSEA in which spinal block is followed by 10 ml Colloid (HES 6%) in epidural space; Group 2: CSEA but no fluid in epidural space. Onset of sensory block and hemodynamic variables were measured at 5 min. intervals up to 40 minutes then at 10 min. intervals till end of surgery. Ineffective block was top- up by epidural 0.5% bupivacaine in incremental doses.Results: Median effective dose of intrathecal bupivacaine was significantly lower, 4.0 mg (95% CI 4.40-5.60) in group 1 versus 7.0 mg (95% CI 6.93-7.61) in group 2. Only 11 patients required ephedrine in group 1 versus 20 in group 2. Requirement of ephedrine was significantly lower 2.20 (±2.94) mg in group 1 versus 4.0 (±2.88) mg groups 2. Changes in haemodynamic variables from baseline were significantly lower in group 1 than those in group 2.Conclusions: EVE with colloid was effective in lowering dose requirement of spinal bupivacaine while patients hemodynamically were more stable.

Association of −330 interleukin-2 gene polymorphism with oral cancer

Background & objectives: Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (− 330A>C) gene polymorphisms with the susceptibility to oral cancer. Methods: The SNP in IL-2 (−330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. >Results: IL-2 (−330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; PC) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. >Interpretation & conclusions: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (−330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population

Integrated transcriptomic and regulatory network analyses uncovers the role of let-7b-5p, SPIB, and HLA-DPB1 in sepsis

Abstract Sepsis has affected millions of populations of all age groups, locations, and sexes worldwide. Immune systems, either innate or adaptive are dysregulated due to the infection. Various biomarkers are present to date, still sepsis is a primary cause of mortality. Globally, post-operative body infections can cause sepsis and septic shock in ICU. Abnormal antigen presentation to T-cells leads to a dysregulated immune system. miRNAs are sparkly evolved as biomarkers due to their high sensitivity and efficiency. In this work, we analyzed high-throughput mRNA data collected from Gene Expression Omnibus (GEO) and linked it to significant miRNAs and TFs using a network-based approach. Protein–protein interaction (PPI) network was constructed using sepsis-specific differentially expressed genes (DEGs) followed by enrichment analyses and hub module detection. Sepsis-linked decrease transcription of the classical HLA gene such as HLA-DPB1 and its interplay with miR-let-7b-5p and transcription factor SPIB was observed. This study helped to provide innovative targets for sepsis