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.
A critical hepatic function is the maintenance of optimal bile acid (BA) compositions to achieve cholesterol homeostasis. BAs are rarely quantified to assess hepatic phenotype in vitro since existing analytical techniques have inadequate resolution. We report a detailed investigation into the biosynthesis and homeostasis of eight primary rat BAs in conventional in vitro hepatocyte cultures and in an engineered liver mimic. The three-dimensional (3D) liver mimic was assembled with layers of primary rat hepatocytes and liver sinusoidal endothelial cells. A high-pressure liquid chromatography and mass spectrometry technique was developed with a detection limit of 1 ng/mL for each BA, which is significantly lower than previous approaches. Over a 2-week culture, only 3D liver mimics exhibited the ratio of conjugated cholic acid to chenodeoxycholic acid that has been observed in vivo. This ratio, an important marker of BA homeostasis, was significantly higher in stable collagen sandwich cultures indicating significant deviation from physiological behavior. The biosynthesis of tauro-β-muricholic acid, a key primary rat BA, doubled only in the engineered liver mimics while decreasing in the other systems. These trends demonstrate that the 3D liver mimics provide a unique platform to study hepatic metabolism.
Hypophosphatemic rickets is a disorder of bone mineralization caused due to defects (inherited/acquired) in the renal handling of phosphorus. This group includes varied conditions, X-linked hypophosphatemic rickets being the most common inheritable form of rickets. The other common forms are autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia. Although these conditions exhibit different etiologies, increased phosphatonins form a common link among them. Fibroblast growth factor 23 (FGF23) is the most widely studied phosphatonin. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal axis, whose mechanisms have been poorly understood so far. Newer disorders are being added as the mechanisms in this axis get discovered. This review focuses on the clinical, biochemical, genetic features and management of hypophosphatemic disorders leading to defective mineralization.
1; 25(OH)2D3; autosomal dominant hypophosphatemic rickets; fibroblast growth factor 23; hypophosphatemia; tumor-induced osteomalacia; X-linked hypophosphatemic rickets
Oxidative stress and impaired antioxidant system have been implicated in the pathophysiology of various diseases. The objective of the study was to determine the quantitative phytochemicals and invitro antioxidant activity of fresh leaves of Syzygium malaccense. The result showed that the methanolic extract exhibited strong antioxidant activity and contains a higher amount of phenolics and flavonoids when compared to aqueous extract.
Syzygium malaccense; Flavonoids and phenolics; DPPH
Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes) and non-parenchymal (liver sinusoidal endothelial, LSEC) cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs) were cultured in a layered three-dimensional (3D) configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM), which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1) demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism, detoxification and signaling pathways in vitro.
The stem bark of Carallia brachiata was studied for wound healing activity. The bark was extracted with petroleum ether, ethyl acetate and methanol successively. All the extracts were screened for wound healing activity by excision and incision models in Wistar rats. The ethyl acetate and methanol extracts were found to possess significant wound healing activity. The extracts revealed the presence of sterols or triterpenoids, flavonoids, phenols, tannins, carbohydrates, fixed oils and fats.
Carallia brachiata; Rhizophoraceae; stem bark; wound healing activity
AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.
METHODS: The study was performed on 72 Indian patients with cirrhosis (63 male, nine female; aged < 50 years). Etiology of cirrhosis was alcoholism (n = 37), hepatitis B (n = 25) and hepatitis C (n = 10). Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density (BMD) was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2.
RESULTS: Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium: protein ratio and calcium: phosphorus ratio. Vitamin D deficiency was highly prevalent (92%). There was a high incidence of hypogonadism (41%). Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor (IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low (68%) and urinary deoxypyridinoline to creatinine ratio was high (79%), which demonstrated low bone formation with high resorption.
CONCLUSION: Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.
Bone mineral density; Liver disease; Chronic disease; Cirrhosis; Bone mineral metabolism; Hepatic osteodystrophy
Tuberculosis continues to be an important public health problem and cutaneous tuberculosis constitutes a minor proportion of extra pulmonary manifestations of tuberculosis. Elephantiasis of the external genitalia, as a sequel to cutaneous tuberculosis, in a 40-year-old diabetic lady is being reported for its rarity. The patient also had lesions of healed scrofuloderma of 27 years’ duration, in both axillae, with residual pedunculated nodules.
Cutaneous tuberculosis; diabetes mellitus; elephantiasis; gumma; lupus vulgaris; scrofuloderma
Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.
Cutaneous metastases; melanoma; maignant
Lycianthes bigeminata Bitter (Solanaceae) is an important medicinal herb distributed in the sholas of Nilgiris and chiefly used for curing ulcer. It is reported that the species is present in the sholas with poor population size in comparison to other constituent species. Owing to the demand and subsequent exploitation, it is predicted that it may occupy still poor association in the sholas of Nilgiris in course of time. Hence in vitro regeneration through employing tissue culture technique is needed. The preliminary attempt in the present study reports that the MS medium supplemented with Benzyl Amino Purine (BAP) and Naphthalene Amino Acid (NAA) at 0.5 mg/l each, induced effective callus formation. However further studies on hardening is suggested to know the survivability of this species.
Lycianthes bigeminata; callus; in vitro organogenesis