Prolonged hospitalization and exposure to third generation cephalosporins are reported to facilitate the acquisition and colonization of Vancomycin Resistant Enterococci (VRE). Though VRE is not uncommon in India, urinary tract infection with a vanA genotype is a cause of serious concern as VRE co-exhibit resistance to aminoglycosides. In India, majority of the VRE isolates recovered from hospitalized patients include Enterococcus faecium. We report a case of catheter associated urinary tract infection by an endogenous, multidrug resistant E. faecalis of vanA genotype following prolonged hospitalization, ICU stay, catheterisation and exposure to 3G cephalosporin and metronidazole. The patient responded to linezolid therapy.
High level aminoglycoside resistance (HLAR); Multidrug resistance; Vancomycin resistant Enterococci (VRE)
Porokeratosis, a keratinization disorder, is probably a group of unrelated conditions with same distinctive histological appearance, featuring cornoid lamellae. A case of punctate porkeratosis in a 24 year old male patient is reported for its rarity.
Cornoid lamella; keratinization disorder; porokeratosis
A car-borne survey was carried out in Kerala, India to estimate external dose. Measurements were made with a 3-in × 3-in NaI(Tl) scintillation spectrometer from September 23 to 27, 2013. The routes were selected from 12 Panchayats in Karunagappally Taluk which were classified into high level, mid-level and low level high background radiation (HBR) areas. A heterogeneous distribution of air kerma rates was seen in the dose rate distribution map. The maximum air kerma rate, 2.1 μGy/h, was observed on a beach sand surface. 232Th activity concentration for the beach sand was higher than that for soil and grass surfaces, and the range of activity concentration was estimated to be 0.7–2.3 kBq/kg. The contribution of 232Th to air kerma rate was over 70% at the measurement points with values larger than 0.34 μGy/h. The maximum value of the annual effective dose in Karunagappally Taluk was observed around coastal areas, and it was estimated to be 13 mSv/y. More than 30% of all the annual effective doses obtained in this survey exceeded 1 mSv/y.
This study was designed to evaluate the efficiency of microwave sterilization of orthodontic instruments and molar bands immersed in plain distilled water with and without oral rinse, and to ascertain the minimum time of exposure required to sterilize.
Materials and Methods:
The orthodontic instruments (hinged and nonhinged), molar bands and mouth mirrorsused in the patient 's mouth were selected for the study. The instruments were divided into two groups – Group I with oral rinse-set A (0.01% chlorhexidine gluconate) and set B (0.025% betadine) and Group II (included sets C and D without oral rinse). The instruments of set A, B and C were microwaved at 2,450 MHz, 800 W for 5 min, whereas, set D was microwaved for 10 min at the same above mentioned specifications. The efficacy of sterilization was assessed by stab inoculation of the instruments onto trypticase soya agar plates. The plates were checked for bacterial growth following incubation at 37 °C for 24 h. For sterility control,Geobacillus stearothermophilus (MTCC 1518) was included.
No growth was observed in the plates that were inoculated with the microwaved orthodontic instruments of sets A, B and D, whereas scanty bacterial growth was observed in the plates inoculatedwith the microwaved set C instruments.
Effective sterilization was achieved when the orthodontic instruments and molar bands were immersed in distilled water without oral rinse and microwaved for 10 min as also for those that were immersed in distilled water with oral rinse and microwaved for 5 min.
Biological indicator; microwave sterilization; molar bands; orthodontic pliers
In order to develop non-ATP competitive CDK2/cyclin A inhibitors, the REPLACE strategy has been applied to generate fragment alternatives for the N-terminal tetrapeptide of the cyclin binding motif (HAKRRLIF) involved in substrate recruitment prior to phosphotransfer. The docking approach used for the prediction of small molecule mimics for peptide determinants was validated through reproduction of experimental binding modes of known inhibitors and provides useful information for evaluating binding to protein-protein interaction sites. Further to this, potential arginine isosteres predicted using the validated LigandFit docking method were ligated to the truncated C-terminal peptide, RLIF using solid phase synthesis and evaluated in a competitive binding assay. After testing, identified fragments were shown to represent not only appropriate mimics for a critical arginine residue but also to interact effectively with a minor hydrophobic pocket present in the binding groove. Further evaluation of binding modes was undertaken to optimize the potency of these compounds. Through further application of the REPLACE strategy in this study, peptide-small molecule hybrid CDK2 inhibitors were identified that are more drug-like and suitable for further optimization as anti-tumor therapeutics.
Exploring innovative ways to ensure healthy aging of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine) that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements, and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of pomegranate (Punica granatum L.), a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly) model. Supplementation of standard corn meal with 10% (v/v) pomegranate juice (PJ) extended the life-span of male and female flies by 18 and 8%, respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8). MSD for control and resveratrol (RV) groups was at 20.8 and 23.1 days, respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced) and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in human beings.
pomegranate; anti-aging; rasayana; ayurveda; Drosophila
The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.
To assess bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) patients and its relation, if any, to clinical, hormonal and metabolic factors.
Materials and Methods:
A prospective evaluation of 194 T2DM patients (97 men and 97 women) was carried out. BMD was done with dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Physical activity, nutritional intake and sunlight exposure were calculated. Biochemical and hormonal tests included serum 25 hydroxy vitamin D [25(OH) D], parathyroid hormone, estrogen, testosterone and urinary calcium-creatinine ratio. Glycosylated hemoglobin and complete lipid profiles were done in patients with diabetes. Five hundred and seventy one non-diabetic controls (262 males and 309 females) were evaluated for BMD alone.
BMD was normal (Z score > -2) in 156 (80.5%) and low (Z score ≤ -2) in 38 (19.5%) patients in the diabetes study group. BMD in the diabetes group was significantly higher than the control group in both sexes at the hip and spine. The difference was no longer significant on analysis of a BMI matched control subgroup. Weight and BMI showed significant correlation to BMD. Duration of T2DM, degree of glycemic control, use of drugs like statins and thiazolidinediones, 25(OH) D levels, calcium intake, sunlight exposure and physical activity did not significantly affect BMD in this cohort of individuals with diabetes.
Bone mineral density of Asian Indian T2DM subjects was similar to that of healthy volunteers in this study.
Asian Indian; bone mineral density; obesity; type 2 diabetes mellitus; vitamin D deficiency
Myxoid tumors are a heterogeneous group of lesions characterized by a marked abundance of extra cellular mucoid (myxoid) matrix. The term aggressive emphasizes the often infiltrative nature of the tumor and its frequent association with recurrence. A case of aggressive angiomyxoma arising from the vagina in a 55-year-old woman is reported for its rarity.
Aggressive; angio myxoma; Carney complex
A major challenge in drug discovery is to develop and improve methods for targeting protein-protein interactions. Further exemplification of the REPLACE strategy for generating inhibitors of protein-protein interactions demonstrated that it can be used to optimize fragment alternatives of key determinants, to combine these in an effective way and was achieved for compounds targeting the CDK2 substrate recruitment site on the cyclin regulatory subunit. Phenylheterocyclic isosteres replacing a critical charge-charge interaction provided new structural insights for binding to the cyclin groove. In particular, these results shed light onto the key contributions of a H-bond observed in crystal structures of N-terminally capped peptides. Furthermore the structure-activity relationship of a bisarylether C-terminal capping group mimicking dipeptide interactions, was probed through ring substitutions, allowing increased complementarity with the primary hydrophobic pocket. This study further validates REPLACE as an effective strategy for converting peptidic compounds to more pharmaceutically relevant compounds.
Endophytes are microorganisms (bacteria or fungi or actinomycetes) that dwell within robust plant tissues by having a symbiotic association. They are ubiquitously associated with almost all plants studied till date. Some commonly found endophytes are those belonging to the genera Enterobacter sp., Colletotrichum sp., Phomopsis sp., Phyllosticta sp., Cladosporium sp., and so forth. Endophytic population is greatly affected by climatic conditions and location where the host plant grows. They produce a wide range of compounds useful for plants for their growth, protection to environmental conditions, and sustainability, in favour of a good dwelling place within the hosts. They protect plants from herbivory by producing certain compounds which will prevent animals from further grazing on the same plant and sometimes act as biocontrol agents. A large amount of bioactive compounds produced by them not only are useful for plants but also are of economical importance to humans. They serve as antibiotics, drugs or medicines, or the compounds of high relevance in research or as compounds useful to food industry. They are also found to have some important role in nutrient cycling, biodegradation, and bioremediation. In this review, we have tried to comprehend different roles of endophytes in plants and their significance and impacts on man and environment.
This study investigates the effects of surfactants and drug loading on the drug release rate from ethylene vinyl acetate (EVA) copolymer. The release rate of nystatin from EVA was studied with addition of non-ionic surfactants Tween 60 and Cremophor RH 40. In addition, the effect of increasing drug load on the release rates of nystatin, chlorhexidine diacetate and acyclovir is also presented.
Polymer casting solutions were prepared by stirring EVA copolymer and nystatin (2.5 wt %) in dichloromethane. Nystatin and surfactants were added in ratios of (1:1), (1:2) and (1:3). Drug loading was studied with 2.5, 5.0, 7.5, and 10.0% wt. proportions of nystatin, chlorhexidine diacetate and acyclovir incorporated into a separate polymer. Three drug loaded polymer square films (3cm × 3cm × 0.08 cm) were cut from dry films to follow the kinetics of drug release at 37°C. 10 ml of either distilled water or PBS was used as the extracting medium that was replaced daily. PBS was used for nystatin release with addition of surfactants and water was used for the study on drug loading and surfactant release. The rate of drug release was measured by UV-spectrophotometer. The amount of surfactant released was determined by HPLC.
The release of nystatin was low in PBS and its release rate increased with the addition of surfactants. Also, increasing surfactant concentrations resulted in increased drug release rates. The release rates of chlorhexidine diacetate (p<0.0001), acyclovir (p<0.0003) and nystatin (p<0.0017) linearly increased with increasing drug loads. The amount of surfactants released was above the CMC.
This study demonstrates that the three therapeutic agents show a sustained rate of drug release from EVA copolymer over extended periods of time. Nystatin release in PBS is low owing to its poor solubility. Its release rate is enhanced by addition of surfactants and increasing the drug load as well.
Drug delivery; EVA matrix; nystatin; surfactants; chlorhexidine diacetate; acyclovir; drug loading
Crohn's disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn's disease (CCD) is synonymous with metastatic Crohn's disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity.
Cutaneous crohn's disease; metastatic crohn's disease; non caseating granulomas
The Enterococcus faecalis biofilm in the root canal makes it difficult to be eradicated by the conventional irrigants with no toxicity to the tissues. Hence, plant products with least side effects are explored for their use as irrigants in the root canal therapy.
To evaluate and compare the antibacterial efficacy of Mangifera indica L. kernel (mango kernel) and Ocimum sanctum L. leaves (tulsi) extracts with conventional irrigants (5% sodium hypochlorite (NaOCl) and 2% chlorhexidine) against E. faecalis dentinal biofilm.
Materials and Methods:
Agar diffusion and broth microdilution assay was performed with the herbal extracts and conventional irrigants (2% chlorhexidine and 5% NaOCl) against E. faecalis planktonic cells. The assay was extended onto 3 week E. faecalis dentinal biofilm.
Significant reduction of colony forming units (CFU)/mL was observed for the herbal groups and the antibacterial activity of the herbal groups was at par with 5% NaOCl.
The antibacterial activity of these herbal extracts is found to be comparable with that of conventional irrigants both on the biofilm and planktonic counterparts.
Antibacterial activity; Enterococcus faecalis biofilm; mango kernel; root canal; tulsi leaves
From among a cohort of 65,553 men aged 30–84 in Karunagappally Taluk, Kerala, India, 52 hypopharyngeal cancer cases and 85 laryngeal cancer cases were identified by the Karunagappally Cancer Registry during the period between 1990 and 2009.
We conduct Poisson regression analysis of grouped data, taking into account age and education.
This study showed that the incidence rates of cancers of the hypopharynx and the larynx were strongly related to the number of bidis smoked a day (P<0.001 for both hypopharyngeal and laryngeal cancers) and duration of bidi smoking (P=0.009; P<0.001). Laryngeal cancer risk was significantly increased by bidi smoking (P<0.001), cigarette smoking (P=0.013) and regular alcohol use (P=0.005).
The present study, the first cohort study to examine the association of hypopharyngeal and laryngeal cancer incidence rates with bidi smoking in South Asia, clearly showed dose–response relationships between those cancer risks and bidi smoking; larger amounts of bidi smoked a day and longer durations of bidi smoking increased the incidence rates of those cancers. Tobacco chewing was found not related to the risk of hypopharynx or larynx cancer.
Microarray experiments can simultaneously identify thousands of genes that show significant perturbation in expression between two experimental conditions. Response networks, computed through the integration of gene interaction networks with expression perturbation data, may themselves contain tens of thousands of interactions. Gene set enrichment has become standard for summarizing the results of these analyses in terms functionally coherent collections of genes such as biological processes. However, even these methods can yield hundreds of enriched functions that may overlap considerably.
We describe a new technique called Markov chain Monte Carlo Biological Process Networks (MCMC-BPN) capable of reporting a highly non-redundant set of links between processes that describe the molecular interactions that are perturbed under a specific biological context. Each link in the BPN represents the perturbed interactions that serve as the interfaces between the two processes connected by the link.
We apply MCMC-BPN to publicly available liver-related datasets to demonstrate that the networks formed by the most probable inter-process links reported by MCMC-BPN show high relevance to each biological condition. We show that MCMC-BPN’s ability to discern the few key links from in a very large solution space by comparing results from two other methods for detecting inter-process links.
MCMC-BPN is successful in using few inter-process links to explain as many of the perturbed gene-gene interactions as possible. Thereby, BPNs summarize the important biological trends within a response network by reporting a digestible number of inter-process links that can be explored in greater detail.
Molecular interaction networks; Gene expression data; Networks of biological processes; Data integration; Markov chain Monte Carlo
It takes about 2 weeks for the onset of antidepressant action of drugs while electroconvulsive therapy though faster, is a cumbersome procedure requiring an anaesthetist and at least a minor operation theatre. Recent studies have shown that Ketamine, when given to severely depressed patients in the dose of 0.5 mg/kg as a slow intravenous infusion over 40 minutes, brought about acute relief from depression and amelioration of suicidal risk within a few hours. The improvement, however, was transient and lasted for up to a week but could be sustained by further weekly or biweekly injections. As the dose of ketamine administered was found to be safe, it was now tried in the intramuscular route in two severely depressed patients with similar rapid improvement. The cases are reported here which pave way for an easier mode of treating acute depression.
Acute depression; intramuscular ketamine; suicidality
Apart from the degree of stenosis, the morphology of carotid atherosclerotic plaques and presence of neovascularization are important factors that may help to evaluate the risk and ‘vulnerability’ of plaques and may also influence the choice of treatment. In this article, we aim to describe the techniques and imaging findings on CTA, high resolution MRI and contrast enhanced ultrasound in the evaluation of carotid atherosclerotic plaques. We also discuss a few representative cases from our institute with the related clinical implications.
Carotid; magnetic resonance imaging; stenosis; ultrasound; vulnerable plaque
A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented.
Bromocriptine; pregnancy; prolactinoma
Lichen sclerosus (LS) is a chronic inflammatory disorder of an unknown aetiology most commonly affecting the anogenital area. However, extragenital involvement also occurs uncommonly. A case of extra-genital LS involving the areolae of both breasts, in a 15-year-old boy, is reported for its rarity.
An alternative strategy for inhibition of the cyclin dependent kinases in anti-tumor drug discovery is afforded through the substrate recruitment site on the cyclin positive regulatory subunit. Critical CDK substrates such as the Rb and E2F families must undergo cyclin groove binding before phosphorylation and hence inhibitors of this interaction also block substrate specific kinase activity. This approach offers the potential of generating highly selective and cell cycle specific CDK inhibitors and to reduce the inhibition of transcription mediated through CDK7 and 9, commonly observed with ATP competitive compounds. While highly potent peptide and small molecule inhibitors of CDK2/cyclin A, E substrate recruitment have been reported, little information has been generated on the determinants of inhibitor binding to the cyclin groove of the CDK4/cyclin D1 complex. CDK4/cyclin D is a validated anti-cancer drug target and continues to be widely pursued in the development of new therapeutics based on cell cycle blockade. We have therefore investigated the structural basis for peptide binding to its cyclin groove and have examined the features contributing to potency and selectivity of inhibitors. Peptidic inhibitors of CDK4/cyclin D of pRb phosphorylation have been synthesized, and their complexes with CDK4/cyclin D1 crystal structures have been generated. Based on available structural information, comparisons of the cyclin grooves of cyclin A2 and D1 are presented and provide insights into the determinants for peptide binding and the basis for differential binding and inhibition. In addition, a complex structure has been generated in order to model the interactions of the CDKI, p27KIP1, with cyclin D1. This information has been used shed light onto the endogenous inhibition of CDK4 and also to identify unique aspects of cyclin D1 and which can be exploited in the design of cyclin groove based CDK inhibitors. Peptidic and non-peptidic compounds have been synthesized in order to explore structure-activity relationship for binding to the cyclin D1 groove which to date has not been carried out in a systematic fashion. Collectively, the data presented provides new insights into how compounds can be developed that function as chemical biology probes to determine the cellular and anti-tumor effects of CDK inhibition. Furthermore, such compounds will serve as templates for structure-guided efforts to develop potential therapeutics based on selective inhibition of CDK4/cyclin D activity.
The layer-by-layer assembly of sequentially adsorbed, alternating polyelectrolytes has become increasingly important over the past two decades. The ease and versatility in assembling polyelectrolyte multilayers (PEMs) has resulted in numerous wide ranging applications of these materials. More recently, PEMs are being used in biological applications ranging from biomaterials, tissue engineering, regenerative medicine, and drug delivery. The ability to manipulate the chemical, physical, surface, and topographical properties of these multilayer architectures by simply changing the pH, ionic strength, thickness, and postassembly modifications render them highly suitable to probe the effects of external stimuli on cellular responsiveness. In the field of regenerative medicine, the ability to sequester growth factors and to tether peptides to PEMs has been exploited to direct the lineage of progenitor cells and to subsequently maintain a desired phenotype. Additional novel applications include the use of PEMs in the assembly of three-dimensional layered architectures and as coatings for individual cells to deliver tunable payloads of drugs or bioactive molecules. This review focuses on literature related to the modulation of chemical and physical properties of PEMs for tissue engineering applications and recent research efforts in maintaining and directing cellular phenotype in stem cell differentiation.