Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation,Stemness, and BrafV600E-Induced Tumorigenesis

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Role of polymer–drug conjugates in organ-specific delivery systems

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer–drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting.     

Evaluation of Genetic Relatedness Among Temperate Pome Fruit Crops of Family Rosaceae Using Arbitrary Oligonucleotide Markers

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - A rationale use of the genetic resources in breeding programs requires an understanding of relationships...     

A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital

Aim:Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs. The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease.Results:Compared to unfractionated heparin group of patients, the average prothrombin time was significantly higher (P < 0.0001) whereas hypokalemia was significantly lower (P < 0.02) in enoxaparin group of patients. Even though recurrence of angina and ADRs such as bleeding, nausea, headache and sudden cough occurred less frequently in the enoxaparin group of patients compared to unfractionated heparin group of patients, the differences were not significant.Conclusions:Antithrombotic therapy with enoxaparin plus aspirin was safer and more effective than unfractionated heparin plus aspirin, in reducing the incidence of ischemic events in patients with unstable angina or myocardial infarction in the early phase.KEY WORDS: Anticoagulant, coronary heart disease, enoxaparin, safety, and efficacy, unfractionated heparin     

Comparative Aesthetic Evaluation of Lip Reconstruction Using Abbe’s Flap in Secondary Cleft Lip Deformities: A Retrospective Study

AimTo objectively evaluate the surgical outcome of deformed cleft lip treated by Abbe’s flap using Digimizer image analysis software.MethodsFifteen Abbe’s flap (AF) reconstruction cases with satisfactory photographic records were acquired in Digimizer image analysis software. Anthropometric landmarks were marked on the lip. Bilateral lip lengths, height and width were measured preoperatively and postoperatively after AF reconstruction for comparison.ResultsIt was observed that by AF reconstruction, we could increase vermillion lip length and Cupid’s bow width, hence providing adequate bulk to the middle of the lip. In addition to it, in some cases we could achieve the acceptable anatomy of the centre of the Cupid’s bow with which it was sometimes disturbed during primary cheiloplasty. Lip length and lip height became proportionately equal bilaterally, leading to adequate lip symmetry in all cases.ConclusionComputer-assisted anthropometric analysis of photographs using Digimizer image analysis software (MedCalc Software, Belgium) demonstrates that AF lip reconstruction technique produces aesthetic lip consistently.     

Effect of exchange blood transfusion on oxygen saturation of neonates with severe neonatal jaundice by pulse oximetry

Objective: To determine if there was any difference in SpO2 readings during exchange blood transfusion (EBT).Methods: A prospective cross-sectional study of neonates with severe neonatal jaundice requiring EBT was conducted. Oxygen saturation was recorded before, immediately and 15 minutes after EBT by using a pulse oximeter. Results: This study included 30 neonates with 20 males and 10 females. The age ranged from 1 to 12 days with a mean of (5.4 ± 2.9) days. Pre-EBT SpO2 ranged from 90％ to 98％ with a mean value of (94.3 ± 2.2)％; SpO2 in the end of EBT ranged from 85％ to 99％ with a mean value of (94.1 ± 3.2)％; SpO2 at 15 minutes after EBT ranged from 77％ to 99％ with a mean value of (94.8 ± 4.1)％. There was no significant difference between SpO2 values at onset of EBT and either immediately or 15 minutes after EBT (P=0.770 and 0.422, respectively). SpO2 showed no significant difference between neonates who were infused with blood of different storage times (<24 h or ≥24 h) at the onset of EBT (P=0.584), immediately (P>0.999) and 15 minutes after EBT (P=0.887). Besides, SpO2 values were compariable in neonates with hematocrit <45％ or ≥45％ at the onset of EBT (P=0.284), immediately (P=0.118) and 15 minutes after EBT (P=0.868). Conclusions: EBT does not affect SpO2 in neonates.     

DOC2 isoforms play dual roles in insulin secretion and insulin-stimulated glucose uptake

Aims/hypothesis

Glucose-stimulated insulin secretion (GSIS) and insulin-stimulated glucose uptake are processes that rely on regulated intracellular vesicle transport and vesicle fusion with the plasma membrane. DOC2A and DOC2B are calcium-sensitive proteins that were identified as key components of vesicle exocytosis in neurons. Our aim was to investigate the role of DOC2 isoforms in glucose homeostasis, insulin secretion and insulin action.

Methods

DOC2 expression was measured by RT-PCR and western blotting. Body weight, glucose tolerance, insulin action and GSIS were assessed in wild-type (WT), Doc2a ^?/? (Doc2aKO), Doc2b ^?/? (Doc2bKO) and Doc2a ^?/?/Doc2b ^?/? (Doc2a/Doc2bKO) mice in vivo. In vitro GSIS and glucose uptake were assessed in isolated tissues, and exocytotic proteins measured by western blotting. GLUT4 translocation was assessed by epifluorescence microscopy.

Results

Doc2b mRNA was detected in all tissues tested, whereas Doc2a was only detected in islets and the brain. Doc2aKO and Doc2bKO mice had minor glucose intolerance, while Doc2a/Doc2bKO mice showed pronounced glucose intolerance. GSIS was markedly impaired in Doc2a/Doc2bKO mice in vivo, and in isolated Doc2a/Doc2bKO islets in vitro. In contrast, Doc2bKO mice had only subtle defects in insulin secretion in vivo. Insulin action was impaired to a similar degree in both Doc2bKO and Doc2a/Doc2bKO mice. In vitro insulin-stimulated glucose transport and GLUT4 vesicle fusion were defective in adipocytes derived from Doc2bKO mice. Surprisingly, insulin action was not altered in muscle isolated from DOC2-null mice.

Conclusions/interpretation

Our study identifies a critical role for DOC2B in insulin-stimulated glucose uptake in adipocytes, and for the synergistic regulation of GSIS by DOC2A and DOC2B in beta cells.     

Kinetics and intracellular location of intramolecular disulfide bond formation mediated by the cytoplasmic redox system encoded by vaccinia virus

Poxviruses encode a redox system for intramolecular disulfide bond formation in cytoplasmic domains of viral proteins. Our objectives were to determine the kinetics and intracellular location of disulfide bond formation. The vaccinia virus L1 myristoylated membrane protein, used as an example, has three intramolecular disulfide bonds. Reduced and disulfide-bonded forms of L1 were distinguished by electrophoretic mobility and reactivity with monoclonal and polyclonal antibodies. Because disulfide bonds formed during 5 min pulse labeling with radioactive amino acids, a protocol was devised in which dithiothreitol was present at this step. Disulfide bond formation was detected by 2 min after removal of reducing agent and was nearly complete in 10 min. When the penultimate glycine residue was mutated to prevent myristoylation, L1 was mistargeted to the endoplasmic reticulum and disulfide bond formation failed to occur. These data suggested that viral membrane association was required for oxidation of L1, providing specificity for the process.     

The ICH guidance in practice: stress degradation studies on indinavir sulphate and development of a validated specific stability-indicating HPTLC assay method

A sensitive, selective, precise and stability-indicating high-performance thin layer chromatography (HPTLC) method for analysis of indinavir sulphate both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride/chloroform/methanol/10% v/v ammonia (4:4.5:1.5:0.05, v/v/v/v). Densitometric analysis of indinavir sulphate was carried out in the absorbance mode at 260 nm. This system was found to give compact spots for indinavir sulphate (Rf value of 0.43 +/- 0.02, for six replicates). Indinavir sulphate was subjected to acid and alkali hydrolysis, oxidation, dry and wet heat treatment, and photo degradation. The drug undergoes degradation under acidic and basic conditions, oxidation, dry and wet heat treatment, and photo degradation. Also the degraded products were well resolved from the pure drug with significantly different Rf values. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the range of 100-6000 ng/spot with significantly high value of correlation coefficient r2 = 0.997 +/- 0.64. The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.999 +/- 0.002 in the working concentration range of 1000-6000 ng/spot. The LOD and LOQ were 40 and 120 ng/spot, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of acid degradation process. Arrhenius plot was constructed and activation energy was calculated.