Search

Percutaneous Coronary Intervention (PCI) has revolutionized the management of Coronary Artery Disease and has become the preferred modality of revascularization in a majority of cases. Nevertheless, situations are encountered frequently where device deliverability to coronary lesions entails technical difficulties due to varied anatomies and lesional complexities like tortuosity, calcifications, length of lesions and vessel morphology. While continuous technological refinements are occurring in PCI hardware armamentarium and stent designs, a number of techniques and their modifications and variations have evolved to increase the applicability of PCI to difficult lesions. : The present article envisages a thorough review of all aspects of improving successful device deliverability in complex PCI with prominent emphasis on increasing the backup support of Guide Catheters which is the primary factor of success in difficult coronary lesions.

Identification of potential drug compounds and drug–target interactions are fundamental steps in the drug-designing process. However, the conventional process of drug discovery is expensive, time consuming, and insufficient to explore novel interactions and activity predictions. Thus arises the need for in silico chemoinformatics approaches with improved strategies that are useful to elevate predictive performance in drug designing. The objective of this study is to discuss the current approaches and major chemoinformatics tools available to perform data extraction, structure-based virtual screening, designing of new molecule identification using quantitative structure–activity relationship (QSAR), and applications of machine learning (ML) in biological or chemical evaluation. Recently, a large amount of research has been done and considered for applications of chemoinformatics in drug discovery. Reviewing various tools and techniques, the chapter mainly discusses different aspects such as (1) compound databases/libraries, (2) important tools of structure-based and ligand-based virtual screening, including molecular docking and pharmacophore-designing tools, (3) different toolkit and ML algorithms with a strong emphasis on QSAR modeling, and (4) future challenges and directions in the present state. This study would likely provide insights into advanced approaches in utilizing effective strategies and the generation of favorable bioprediction methods in drug designing.

The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.

Radiation induced skin wound/dermatitis is one of the common side effects of radiotherapy or interventional radiobiology. In order to combat impaired healing of radiation wounds, alternative therapy to use sildenafil citrate (SC) topical hydrogel as a therapeutic option was proposed that has known to enhance nitric oxide in wounds. Our aim was to develop a radiation induced skin wound model and to investigate the wound healing efficacy of 5% SC hydrogel formulation in Sprague-Dawley rats. In the present study, the radiation wound inducing dose was optimized using a multi-dose localized γ-radiation trail with 10-55Gy range (15Gy interval). Optimal irradiation dose for wound induction was selected based on radiation skin damage assessment criteria followed the relative change from35Gy or55Gy showed significant variation and median 45Gy γ-dose was selected for studying acute effects of radiation on wound healing. Significant (p0.05) higher wound contraction (88±1.02%), skin damage reduction (81±0.82%), tensile strength (45±1.61%), nitric oxide and protein recovery (53±0.72%) at dermal level prove the wound healing efficacy of 5% SC hydrogel formulation as compared to Rad 45Gy control. In addition, the dose modifying factor (DMF) for SC hydrogel treatment was found to be 1.83 and 1.57 with respect to total wound area contraction and skin damage reduction. Skin histopathology in treated tissues showed improved granulation tissue formation, less inflammatory infiltrates and mature collagen fibres in the dermis. Thus, the modality could help to improve delayed wound healing in irradiated skin tissues.

Encountering a coronary subclavian steal syndrome phenomenon is a rare opportunity. We came across three such cases. Article describes unique cases of two elderly males and one female who underwent CABG few years ago and presented with recurrent chest pain symptoms.

Chemical emergencies involving hazardous chemicals are not uncommon in India. More than 25 incidents have been identified in National Disaster Management Guidelines – Chemical (Industrial) Disaster Management, released in May 2007. In a recent occurrence on the morning of 14 July 2010, nearly at 3:00 a.m., chlorine leak was reported from a gas cylinder referred as turner, weighing about 650 kg, corroding with time at the Haji Bunder hazardous cargo warehouse in Mumbai Port Trust, Sewri, affecting over 120 people in the neighborhood, including students, laborers, port workers and fire fighters, of whom 70 were reported critical. It has been observed to be a blatant case of ignorance and negligence as well as contraventions to the safety and environmental safeguard requirements under existing statues as well as non-maintenance of failsafe conditions at the site requisite for chlorine storage. The analysis revealed significant gaps in the availability of neutralization mechanism and the chlorine stored in open increased the possibility of formation of ingress mixture due to busting of chlorine filled tankers. The Government of India has institutionalized emergency preparedness framework at national, state and district level as envisaged in Disaster Management Act, 2005, to prepare the nation to mitigate such incidences, if all the preventive safety provisions fail. Ministry of Environment and Forests (MoEF) is preparing National Action Plan-Chemical (Industrial) Disaster Management based on National Guidelines to implement all the mechanisms of capacity development across the country.

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

We evaluated the bactericidal activity of nutraceuticals against multidrug resistant Pseudomonas aeruginosa. The nutritionally valued herbs were screened on the basis of a matrix modeling approach and molecular docking based validation analysis.The database of 38 herbs developed earlier using fuzzy logic based scoring analysis was subjected to molecular docking based validation. The molecular docking (Hex 6.12) analyses of predominant phytoligands (∼10 per herb) against exoenzyme S of P. aeruginosa filtered potent herbs were selected. The preauthenticated bacterial inoculum (10(8) CFU/mL) was added to the sterile nutrient broth impregnated with standardized aqueous-alcoholic herbal extracts (1-1600 μg/mL). After overnight incubation at 37°C, antibacterial activity was evaluated in terms of minimum inhibitory and minimum bactericidal concentrations.Five herbs were selected on the basis of fuzzy set scoring, an herbal informatics model, and validation analysis based on energy of docking (i.e., Evalue of 380) phytoligands with maximum scoring obtained by Glycyrrhiza glabra. Among the 5 nutraceuticals, G. glabra showed maximum bactericidal activity significantly (P 0.05) higher than Amikacin, a standard antibiotic, which was in consonance with in silico bioprospection. Zingiber officinale, despite a low Evalue, showed considerably higher inhibition attributed to its higher flavonoid content as compared to other herbs.G. glabra (licorice), a flavoring agent; Z. officinale (ginger), a condiment; and Mentha piperita (mint), a fragrance component, showed significant therapeutic potential against multidrug resistant strains of P. aeruginosa.

We report a case of gastrointestinal histoplasmosis in a 45-year-old HIV positive man who was misdiagnosed as a case of colonic cancer. The patient presented with low-grade fever, pain in lower abdomen, anorexia and weight loss of six months duration. On examination a lump in the left iliac fossa was detected. Colonoscopy revealed stricture and ulcerated growth in the sigmoid colon. Radiological investigations suggested malignant/inflammatory mass in the sigmoid colon with luminal compromise. Patient was operated and ulcerated tissue was sent for histopathological examination, which revealed numerous intracellular, 2-4 μm, oval, narrow-based budding yeast cells suggestive of Histoplasma capsulatum . Subsequently, the patient developed fluffy opacities on X-ray chest. Examination of sputum revealed presence of acid-fast bacilli and yeast forms of H. capsulatum . Patient was started on amphotericin B but died on the seventeenth postoperative day. The diagnosis of histoplasmosis was made retrospectively. Atypical presentation and rarity of the disease led to this diagnostic pitfall. To the best of our knowledge this is the first report of gastrointestinal histoplasmosis presenting as colonic pseudotumour from India.

Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner. Electronic supplementary material The online version of this article (doi:10.1186/2251-6581-12-35) contains supplementary material, which is available to authorized users.

The present study was carried out to evaluate the role of apoptotic proteins in REC-2006-mediated radiation protection in hepatoma cell lines. REC-2006 treatment 2 h before irradiation strongly inhibited the cleavage of ATM and PARP-1 in HepG2 cells. The expression of nuclear apoptosis inducing factor (AIF) was found to be more inhibited (~17%) in HepG2 cells in REC-2006 + radiation-treated group. More inhibition (~33%) of cytochromecwas observed in HepG2 cells upon REC-2006 treatment 2 h prior irradiation. Similarly, significantly more (P<.05) inhibition of Apaf-1, caspase-9 and caspase-3 was observed in REC-2006 + radition-treated group in HepG2 cells. REC-2006 treatment restored the expression of ICAD in HepG2 cells; however, no restoration was observed in Hep3B cells. Lower nuclear to cytoplasmic CAD ratio was observed in HepG2 cells (~0.6) as compared with Hep3B cells (~1.2) in REC-2006 + radiation-treated group. In conclusion, REC-2006 rendered higher protection in HepG2 cells by inhibiting the expression and translocation of AIF, inhibiting the cleavage of ATM and PARP-1, restoring the expression of ICAD, inhibiting the release of cytochromecand thus modulating the expression of Apaf-1 caspase-9 and activity of caspase-3.

Nuclear and radiological emergencies (NREs) occurred globally and recent incidences in India are indicating toward the need for comprehensive medical preparedness required both at incident site and hospitals. The enhanced threat attributed toward insurgency is another causative factor of worry. The response capabilities and operational readiness of responders (both health and non-health service providers) in contaminated environment need to be supported by advancement in R & D and technological efforts to develop prophylactics and radiation mitigators. It is essential to develop phase 1 alternatives of such drugs for unseen threats as a part of initial preparedness. At the incident site and hospital level, external decontamination procedures need to be standardized and supported by protective clothing and Shudika kits developed by INMAS. The medical management of exposure requires systematic approach to perform triage, resuscitation and curative care. The internal contamination requires decorporation agents to be administered based on procedural diagnostics. Various key issues pertaining to policy decisions, R & D promotion, community awareness, specialized infrastructure for NREs preparedness has been discussed. The present review is an attempt to provide vital information about the current status of various radiation countermeasures and future perspective(s) ahead.

The emergence of novel H1N1 has posed a situation that warrants urgent global attention. Though antiviral drugs are available in mainstream medicine for treating symptoms of swine flu, currently there is no preventive medicine available. Even when available, they would be in short supply and ineffective in a pandemic situation, for treating the masses worldwide. Besides the development of drug resistance, emergence of mutant strains of the virus, emergence of a more virulent strain, prohibitive costs of available drugs, time lag between vaccine developments, and mass casualties would pose difficult problems. In view of this, complementary and alternative medicine (CAM) offers a plethora of interesting preventive possibilities in patients. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing pandemic flu. Potentially active herbs can serve as effective anti influenza agents. The role of CAM for managing novel H1N1 flu and the mode of action of these botanicals is presented here in an evidence-based approach that can be followed to establish their potential use in the management of influenza pandemics. The complementary and alternative medicine approach deliberated in the paper should also be useful in treating the patients with serious influenza in non pandemic situations.

The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed.

Background . In off-pump coronary bypass grafting (CABG), invasiveness is reduced but technically perfect anastomosis is jeopardized by cardiac motion and the need to hurry to reduce the time of ischemia. Also, a major cause of postoperative morbidity and mortality is ungrafted circumflex coronary artery disease. We have devised a means of overcoming these shortcomings and performing multivessel CABG. The objective of this study was to assess the safety and efficacy of our technique. Methods . One hundred patients with severe triple-vessel disease underwent multivessel off-pump CABG. For cardiac stabilization, a combination of local pericardial stabilization sutures and lifting and rotating the heart by means of posterior pericardial sutures were used. For myocardial perfusion, a technique of retrograde coronary sinus perfusion by arterial blood from the ascending aorta was used. Results . Each patient received an average of 3.8 grafts (range 3 to 5). Complications included conversion to cardiopulmonary bypass (CPB) in 1 patient and a perioperative myocardial infarction in the same patient. In all other patients we were able to perform a satisfactory grafting in all territories with no operative mortality. Rapid recovery allowed 95% of our patients to resume normal activity within 1 month. A predischarge graft angiogram in 35 patients showed 97.8% patency. Conclusions . These results suggest that off-pump CABG with our techniques is effective and safe. Early clinical outcome and excellent patency rates suggest its more widespread use in selected cases.

In recent years, a lot of interest has been generated world over in the area of radioprotection for first responders going to work in the hot zones at the incident site. A large number of molecular drugs have been screened for radioprotective efficacy, but with little success. The requirement of differential radioprotection necessitates a holistic approach, which can be realized using herbs in view of their multifaceted mode of action. Our earlier studies showed the radioprotective potential of Rhodiola imbricata, a Himalayan high-altitude plant. In this study, our focus has been to compare the pro-oxidant/antioxidant activities of three fractionated extracts of R. imbricata. The aqueous fraction exhibited significant (P < 0.05) pro-oxidant activity (up to 100 mg/ml) under metal ion-induced stress ± flux [transition metal (Fe/Cu) ± 0.25 kGy]. A decrease in the dielectric constant of the solvent system utilized for extraction, exhibited a significant (P < 0.05) negative correlation (−0.955) with mean protection potential of lipid against radiation flux. Such an effect was visualized as a significant shift from pro-oxidant to antioxidant activity in methanolic fraction (dielectric constant = 33), as compared to aqueous fraction (dielectric constant = 80). Aqueous fraction is predominantly pro-oxidant at maximal concentrations, indicating its anticancer potential. The presence of transition metals modulates such a biphasic activity differentially in various fractions, i.e., the conversion of Fe(III) or Cu(II) to Fe(II) or Cu(I), respectively, due to the presence of certain bioactive constituents (electron donation at lower concentrations), favors pro-oxidant activity. On the other hand, certain other active constituents involved in metal ion chelation contributed to the overall antioxidant activity. The methanolic fraction exhibited significant antioxidant activity up to 250 mg/ml, which contributed to its radioprotective efficacy. The aquo-methanolic fraction exhibited (disparate properties), i.e., concentration-dependant cytotoxicity (up to 250 mg/ml) and cytoprotection at 1000 mg/ml. R. imbricata, in general, exhibited a significant solvent-dependant variation in radioprotective efficacy. In conclusion, solvent extraction and dose are crucial in bioactivity modulation and R. imbricata could be developed as a potential prophylactic radiation countermeasure for use in nuclear and radiological emergencies.

We describe a case of mucormycosis of median sternotomy wound caused by Rhizopus arrhizus . The patient, a known diabetic and a case of coronary artery disease underwent coronary artery bypass surgery. In the postoperative period, patient developed infection of the median sternotomy wound, from which R. arrhizus was isolated on culture. Patient succumbed in spite of being treated with surgical debridement and amphotericin B. To the best of our knowledge, this is the first reported case of mucormycosis of median sternotomy wound from India.

Patient initials or identifier number SS ### Relevant clinical history and physical exam 85 Years old male presented with complain of recurrent TIA'SAS right hemiparesis. Carotid angiogrphy reveled 80% lesion of left internal carotid artery and 99% lesion of left external carotid artery. We