Clinical challenges with excipients in insulin formulations and role of concentrated insulin

Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins

The psbO gene for 33-kDa precursor polypeptide of the oxygen-evolving complex in Arabidopsis thaliana - nucleotide sequence and control of its expression

The 33-kDa polypeptide of the oxygen-evolving complex of photosystem II is nuclear-encoded. The single psbO gene of Arabidopsis thaliana, as suggested by Southern hybridization, has been isolated from the genomic library and sequenced. The sequence analysis has revealed that the psbO gene harbors two introns and encodes a precursor polypeptide of 332 amino acid residues; the first 85 amino acid residues represent the transit peptide and the following 247 amino acids constitute the mature polypeptide. The hydrophilic nature of the 33-kDa protein is confirmed by the presence of 27% charged residues. Northern analysis of the total RNA from Arabidopsis indicates that a 1.2-kb transcript represents the psbO gene. It is expressed in a tissue-specific manner - the steady-state transcript levels being highest in the leaves and virtually undetectable in the roots. Also, expression of the psbO gene is development-dependent and regulated by light in young Arabidopsis seedlings. In a constitutively photomorphogenic mutant of Arabidopsis, pho2 (plumular hook open 2), the psbO gene is de-repressed in young, dark-grown seedlings, resulting in increased transcript abundance compared to the wild-type. These studies, thus, define the influence of at least one regulatory component for psbO expression

DABCO promoted one-pot synthesis of dihydropyrano(c)chromene and pyrano[2,3-d]pyrimidine derivatives and their biological activities

AbstractA simple and efficient one-pot synthesis of heteroaryl substititued dihydropyrano(c)chromenes and pyrano[2,3-d]pyrimidines has been developed via initial Knoevenagel, subsequent Micheal and final heterocyclization reactions of heteroaryl aldehyde, malononitrile and barbituric acid/ dimedone. 1,4-Diazabicyclo [2.2.2] octane (DABCO) has been used as a catalyst. Short reaction time, environment friendly procedure and excellent yields are the main advantages of this procedure. All synthesized compounds have shown good antimicrobial activity against different microbial stains

Rapid Solvent-free Synthesis of Aromatic Hydrazidesunder Microwave Irradiation

A variety of aromatic hydrazides has been synthesised by solvent-free hydrazinolysis ofcorresponding esters with hydrazine hydrate under microwave irradiation

The Impedance and Firing-Angle Model Based Control of TCSC using N-R and AD Techniques

Volume 2 Issue 6 (June 2014

Endoscopic Ultrasound-Guided Random Omental Fine Needle Aspiration: A Novel Technique for the Diagnosis of Peritoneal Carcinomatosis

Background/Aims Diagnostic abdominal paracentesis has been described in literature to have variable sensitivity of 50%–75% for the detection of peritoneal carcinomatosis (PC). We believe that random needle aspirates from the omentum, even in the absence of obvious deposits by endoscopic ultrasound (EUS), could prove malignancy in patients with PC. Methods Consecutive patients who underwent EUS for diagnosis and staging of cancer and found to have ascites were included after obtaining informed consent. EUS-guided fine needle aspiration (EUS-FNA) from random sites in the omentum was performed through the transgastric route using a linear echoendoscope. Results Fifty-four patients underwent EUS during October 2015 to April 2017 for detection, staging, or FNA of a suspected malignant lesion. Ascites was seen in 17 patients and 15 patients who fulfilled the criteria were included. The procedure was successful in all patients. Cytology was suggestive of malignancy in 12 (80%) but not suggestive of malignancy in 3 (20%) patients. Three patients who tested negative had hyperbilirubinemia with biliary obstruction. Their ascitic fluid analysis result was also negative. Conclusions Random FNA of the omentum in patients with malignancy-related ascites is highly effective in the diagnosis of PC and could be employed during EUS evaluation of malignancies

FAST DISSOLVING ORAL FILMS: A TABULAR UPDATE

Fast-dissolving oral films have emerged as alternative dosage forms for the patients who experience difficulties in swallowing traditional oral solid dosage forms such as tablets, capsules, and syrups etc.   These dosage forms disintegrate or dissolve very quickly within seconds when placed in the mouth cavity without need of water or chewing. Due to fast dissolution it provide faster onset of action, bypassing the first pass metabolism, reducing gastric degradation and metabolism of drugs and thus enhance their oral bioavailability. These properties of oral films with patient convenience and compliance made popular and accepted dosage form for pediatric and geriatric as well as adult population. These formulations are suitable for cough, cold, sore throat, allergenic conditions, nausea, pain, hypertension and CNS disorders, epilepsy and many more diseases. The present review provides up to date review in fast dissolving oral films in tabular form so researches can easily track various technologies/research in design and development of oral fast dissolving film. Keywords: Mouth dissolving films, Oral dispersible film, Oral dissolving film, Oral disintegrating film

Anterior communicating artery aneurysm clipping versus coiling: A comparative study of 50 cases

Introduction: Aneurysmal Subarachnoid Hemorrhage (aSAH) remains a devastating and often fatal form of stroke. The aneurysm is targeted for obliteration to prevent re-bleeding and to manage the possible complications from the event. Endovascular coiling has emerged as a less invasive alternative to conventional surgical clipping to treat aneurysms.Patients and methods: This study was done in 50 cases of anterior communicating (Acommm) aneurysm presented in the department of neurosurgery, SMS medical college, Jaipur from November 2015 to August 2016 to evaluate the outcome of both modalities used in the treatment of ruptured Acommm aneurysm. 50 patients with Hunt and Hess (H&H) grade I, II or III were classified into two groups of microsurgical clipping and endovascular coiling.Results: Mortality rate was comparable in both groups that were 21. 21% in the clipping group and 23. 52% in the coiling group. Good Glasgow outcome score (GOS) were found in 60. 60% of clipping and 58. 58% of coiling group. All the complications found to be more in clipping group but that were not statistically significant except for hyponatremia which was significantly higher in clipping group(P=0. 007).Conclusion: There was no statistically significant difference in GOS at 6 month of follow up between the two groups. We recommend further interventional studies with larger sample sizes and longer follow up for better evaluation of the modalities

Comparative analysis of expressed sequence tags (ESTs) between drought-tolerant and -susceptible genotypes of chickpea under terminal drought stress

<p>Abstract</p> <p>Background</p> <p>Chickpea (<it>Cicer arietinum </it>L.) is an important grain-legume crop that is mainly grown in rainfed areas, where terminal drought is a major constraint to its productivity. We generated expressed sequence tags (ESTs) by suppression subtraction hybridization (SSH) to identify differentially expressed genes in drought-tolerant and -susceptible genotypes in chickpea.</p> <p>Results</p> <p>EST libraries were generated by SSH from root and shoot tissues of IC4958 (drought tolerant) and ICC 1882 (drought resistant) exposed to terminal drought conditions by the dry down method. SSH libraries were also constructed by using 2 sets of bulks prepared from the RNA of root tissues from selected recombinant inbred lines (RILs) (10 each) for the extreme high and low root biomass phenotype. A total of 3062 unigenes (638 contigs and 2424 singletons), 51.4% of which were novel in chickpea, were derived by cluster assembly and sequence alignment of 5949 ESTs. Only 2185 (71%) unigenes showed significant BLASTX similarity (<1E-06) in the NCBI non-redundant (nr) database. Gene ontology functional classification terms (BLASTX results and GO term), were retrieved for 2006 (92.0%) sequences, and 656 sequences were further annotated with 812 Enzyme Commission (EC) codes and were mapped to 108 different KEGG pathways. In addition, expression status of 830 unigenes in response to terminal drought stress was evaluated using macro-array (dot blots). The expression of few selected genes was validated by northern blotting and quantitative real-time PCR assay.</p> <p>Conclusion</p> <p>Our study compares not only genes that are up- and down-regulated in a drought-tolerant genotype under terminal drought stress and a drought susceptible genotype but also between the bulks of the selected RILs exhibiting extreme phenotypes. More than 50% of the genes identified have been shown to be associated with drought stress in chickpea for the first time. This study not only serves as resource for marker discovery, but can provide a better insight into the selection of candidate genes (both up- and downregulated) associated with drought tolerance. These results can be used to identify suitable targets for manipulating the drought-tolerance trait in chickpea.</p