A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Extra precision glide docking, free energy calculation and molecular dynamics studies of 1,2-diarylethane derivatives as potent urease inhibitors.

For the latter half of the twentieth century, most medical professionals considered bacterial infection to be a primary cause of gastrointestinal ulcers in human beings. In 1994, the World Health Organization (WHO) recognized Helicobacter pylori, the bacterium most closely linked to ulcer development, as a type I carcinogen. Biological research has shown that there is a positive correlation between the number of species in the Helicobacter genus and the number of medical conditions associated with Helicobacter infection, both of which are increasing rapidly. N-Benzylaniline derivatives, frequently used in industrial manufacturing, are being considered as a strong candidate for ongoing drug modeling in search of novel therapies. The basic goal behind this study was to determine the potency of experimentally proved data, and to determine favorable substituents to enhance potency, and thereafter to support this finding through theoretical modification of the existing base skeleton by addition of suitable substituents. Ligands were investigated thoroughly by paying attention to the urease-inhibitory properties present in the selected series. Initially, docking was performed on ligands with protein to produce efficient docking poses. Molecular dynamics (MD) simulations were also performed to precisely understand the interactions between ligands and proteins. Thereafter, MM-GBSA was used in order to validate the methods and results. Good interaction was observed with amino acids Arg338, Ala169, Asp223, His322, and Asn168. This study also revealed that the electron rich hydroxyl group (-OH) substituent plays an important role during bond formation. In addition, various hydrogen bonds, ionic bonds, and pi-pi stacking bonds make significant contributions towards urease inhibition. Therefore, further research utilizing electron-rich moieties may lead to novel and efficacious urease inhibitors.

In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

Study of effect of variables on particle size of telmisartan nanosuspensions using box-Behnken design.

Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent precipitation technique to improve the saturation solubility and dissolution rate of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated of which TPGS was found to provide maximum decrease in particle size and accord greater stability to the nanosuspensions. Box-Behnken design was used to investigate the effect of independent variables like stabilizer concentration, time and speed of stirring on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of the drug. Concentration of TPGS and speed of rotation were found to play an important role in particle size of the nanosuspensions whereas time of stirring displayed an exponential relationship with particle size. Freeze dried nanocrystals obtained from nanosuspension of least particle size were found to have increased saturation solubility of telmisartan in different dissolution media. The reconstituted nanosuspension was found to reduce both systolic and diastolic blood pressure without affecting pulse pressure and heart rate. Statistical tools can be used to identify key process and formulation parameters which play a significant role in controlling the particle size in nanosuspensions.

Management of cosmetic embarrassment caused by Malassezia spp. with fruticose lichen Cladia using phylogenetic approach.

During anti-Malassezia screening of plants by CLSI broth microdilution method, Cladia aggregata (Swartz) Nyl. (family Cladoniaceae), a fruticose lichen from Sikkim (northeast Himalayan region), has been found effective at minimum inhibitory concentrations (mg/mL) of 2.72, 0.63, and 1.28 against yeast-like fungi namely, M. furfur, M. globosa and M. sympodialis, respectively. These test pathogens are responsible for pityriasis versicolor (PV) and seborrheic dermatitis (SD) in humans. We tried to establish the reason for variable MICs against various Malassezia spp. using bioinformatical tools, thereby reducing the cost of the experimentation. This is the first report on anti-Malassezia activity of C. aggregata and thus can serve as a potential source for the development of cosmaceuticals.

Artificial drainage devices for glaucoma surgery: an overview.

Artificial drainage devices (ADD) create an alternative pathway for aqueous drainage from the anterior chamber of an eye through a tube to the subconjunctival bleb connected to an equatorial plate under the conjunctiva. The ADDs, both valved and non-valved, are available for end stage or refractory glaucoma. Currently, some of these devices, particularly the Express shunt, are recommended for the primary treatment of glaucoma. In this article, we highlight various ADDs, their indications and contraindications, surgical techniques and associated complications.

Pulmonary complications in the non-HIV immunocompromised patient.

The incidence of non-HIV immunocompromised patients is increasing. This is primarily due to improved immunosuppressive regimes for autoimmune diseases and also increases in stem cell transplantation. Pulmonary complications are a major cause of morbidity and mortality in these patients. Imaging is frequently used to assess these complications and to streamline therapies, as microbiological and/or pathological diagnosis can often be difficult, invasive, or protracted. This review provides the reader with a structured approach to interpret the imaging findings and differentiate between different infective and non-infective complications in these patients.

Chemical leucoderma: Indian scenario, prognosis, and treatment.

Chemical leucoderma is an industrial disorder in developed countries and the common causative chemicals are phenols and catechols. Due to stringent controls and preventive measures the incidence has come down. In the recent past various chemicals in consumer products have also been documented to produce depigmentation. In India due to lax quality control measures chemical leucoderma due to consumer items is not uncommon.The various consumer items documented to cause contact depigmentation are sticker bindis, rain shoes, plastic chappals, hair dye/ black henna(kali mehndi), alta, wallets and even mobile plastic covers.

Isolation and characterization of a Pseudomonas sp. strain IITR01 capable of degrading α-endosulfan and endosulfan sulfate.

AIM: To isolate bacteria capable of degrading endosulfan (ES) and the more toxic ES sulfate and to characterize their metabolites. METHODS AND RESULTS: A Pseudomonas sp. strain IITR01 capable of degrading α-ES and toxic ES sulfate was isolated using technical-ES through enrichment culture techniques. No growth and no degradation were observed using ß-ES. Thin-layer chromatography and gas chromatography-mass spectrum analysis revealed the disappearance of both α-ES and ES sulfate and the formation of hydroxylated products ES diol, ether and lactone. We show here for the first time the formation of aforementioned metabolites in contrast to ES hemisulfate yielded by an Arthrobacter sp. Metabolism of α-ES and endosulfate was also observed using the crude cell extract of IITR01. The molecular mass of protein induced during the degradation of α-ES and sulfate as substrate was found to be approximately 150 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION: We describe characterization of bacterium capable of degrading α-ES and ES sulfate but not ß-ES. Genetic investigation suggests that a gene nonhomologous to the reported esd may be present in the strain IITR01. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes toxic ES degradation by a Pseudomonas species that may be utilized for the bioremediation of the industrial soils contaminated with ES residues.

Studies on antidermatophytic activity of waste leaves of Curcuma longa L.

During antidermatophytic screening of some essential oils, Curcuma longa L. exhibited the strongest antifungal activity, completely inhibiting the mycelial growth of ringworm, caused by the fungi- Microsporum gypseum and Trichophyton mentagrophytes. The essential oil from leaves of Curcuma longa was fungicidal at 2.5 µl/ml at which it tolerated heavy doses of inoculum. The fungicidal activity of the oil was thermostable up to 80 °C and self life up to 24 months in storage. The oil also showed a broad fungitoxic spectrum, inhibiting the mycelial growth of other fungi, viz., Epidermophyton floccosum, M. nanum, T. rubrum, T. violaceum. Moreover, up to 5 % concentration it did not exhibit any adverse effect on mammalian skins. The oil has been formulated in the form of an ointment, 1 % w/v and subjected to topical testing on patients of the Out Patient Department (OPD) at Moti Lal Nehru Medical College, Allahabad. Patients were selected on the basis of KOHpositive results and diagnosed tenia corporis. After the second week of treatment, all patients were KOH- negative. At the end of medication, 75 % of patients recovered completely while 15 % showed significant improvement from the disease. The ointment thus, can be exploited commercially after ongoing successful clinical trials. Relationship of the dermatophytes to the toxicity of the oil vis-a-vis phylogeny using molecular data of the pathogens have also been discussed.

In Vitro Anticancer Activity of the Root, Stem and Leaves of Withania Somnifera against Various Human Cancer Cell Lines.

Withania Somnifera Dunal know as Ashwagandha belong Solanaceae family. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. The current study, evaluate in vitro cytotoxicity in 50% ethanol extract of root, stem and leaves of Withania Somnifera against five human cancer cell lines of four different tissues i.e. PC-3, DU-145 (prostrate), HCT-15 (colon), A-549 (lung) and IMR-32 (neuroblastoma). Root, stem and leaves extracts showed cytotoxicity activity ranging 0-98% depending on the cell lines but maximum activity was found in 50% ethanol extract of leaves of Withania Somnifera. Ethanol extract of leaves obtained from treatments T2, T3, T4 and T5 showed strong activity against PC-3 and HCT-15 with 80-98% growth inhibition, while the 50% ethanol extract of leaves from T1 treatment showed a minimum of 39% and T3 treatment showed a maximum of 98% growth inhibition against HCT-15. This investigation is the first report of the anticancer activity in various parts of Withania Somnifera cultivated in fly ash amended soil.

Autowart injection therapy for recalcitrant warts.

BACKGROUND: Warts are caused by various strains of Human Papilloma Virus. They involve the epithelium of the skin and mucus membrane. Various treatment options are available, but extensive and recalcitrant warts not only cause distress to the patient cosmetically and psychologically but also pose a therapeutic challenge to the treating dermatologist. AIM: To evaluate the efficacy of autowart injection as a treatment option for extensive and recalcitrant warts. MATERIALS AND METHODS: Autowart injection was prepared by removing 3 to 4 mm size wart with radiocautery which was crushed under aseptic condition and injected in the gluteal region by suspending in water for injection. RESULT: Results were evaluated in 53 available patients who turned up for follow-up; 35 patients (66.03%) had complete resolution in 2 months time, 12 patients (22.64%) showed partial improvement, whereas six patients (11.32%) had no improvement. CONCLUSION: Autowart injection is suggested as an effective and noninvasive therapeutic option in extensive and recalcitrant warts where most of the available therapies are inconvenient for both patient and treating dermatologist.

Management of difficult urticaria.

Chronic urticaria, a major health problem causing patient's distress, induces often physicians' dilemma while dealing with its etiology, investigations and management. Clinical approach of such cases should include apart from clinical history and physical examination laboratory investigations like routine blood test, thyroid profile, etc. as well as sometimes special test like autologous serum skin test. Management includes reassurance, avoidance of precipitating factors, treatment of underlying disorders, and non-pharmacological approach along with pharmacotherapy. First line drug therapy comprises non-sedative and sedative antihistamines, second line doxepin, nifedipine, leukotriene-inhibitors, sulfasalazine, etc. and third line cyclosporine, dapsone, colchicin, etc.

In situ forming polymeric drug delivery systems.

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost.

Autologous serum therapy in chronic urticaria: old wine in a new bottle.

BACKGROUND: Chronic urticaria (CU) is one of the most challenging and frustrating therapeutic problems faced by a dermatologist. A recent demonstration of abnormal type 1 reactions to intradermal autologous serum injections in some CU patients has led to the characterization of a new subgroup of "autoimmune chronic urticaria". This has rekindled interest in the age-old practice of autologous blood injections as a theoretically sound treatment option in these patients. AIMS: To evaluate the efficacy of repeated autologous serum injections (ASIs) in patients with recalcitrant chronic urticaria. METHODS: A cohort of 62 (32 females) CU patients with a positive autologous serum skin test (ASST) (group 1) was prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a postintervention follow-up of 12 weeks. Another group of 13 (seven females) CU patients with negative ASST (group 2) was also treated similarly. In both groups, six separate parameters of disease severity and activity were recorded. RESULTS: Demographic and disease variables were comparable in both groups. The mean duration of disease was 1.9 +/- 0.3 years (range = 3 months to 32 years) in group 1 and 1.5 +/- 0.2 years (range = 3 months to 10 years) in group 2. In the ASST (+) group, 35.5% patients were completely asymptomatic at the end of the follow-up while an additional 24.2% were markedly improved. In the ASST (-) group, these figures were 23 and 23% respectively. The intergroup difference for complete subsidence was statistically significant (P < 0.05). In both groups, the most marked reduction was seen in pruritus and antihistamine use scores followed by the size and frequency of the wheals. CONCLUSION: Autologous serum therapy is effective in a significant proportion of ASST (+) patients with CU. A smaller but still substantial number of ASST (-) patients also benefited from this treatment.

A novel metered dose transdermal spray formulation for oxybutynin.

The objective of the present work was to develop a metered dose spray formulation for transdermal delivery of oxybutynin and to carry out the in vitro characterization of the optimized formulation. Oxybutynin release from a series of ethanol/acetone/methylal based formulations was assessed in vitro and the developed formulation was used for delivery from a metered dose spray. Various qualitative and quantitative parameters like spray pattern, particle size distribution, pH, evaporation time, pump seal efficiency test, average weight per metered dose, content per spray and content uniformity were evaluated. The different film forming agents were assessed and carbopol (0.5%) and lutrol (0.1%) were found to give good clarity of solution, evaporation rate, spray pattern and tackiness of the film. Diffusion studies of the optimized formulations through the semipermeable membrane showed the release of drug to the extent of almost 50% over a period of 24 h. Stability studies were conducted as per ICH guidelines and indicated that formulations were stable. Skin irritation studies were performed using rabbit as an animal model. The results obtained show that the metered dose transdermal spray formulation can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Patch testing experience with 1000 patients.

BACKGROUND: Patch testing is a definitive tool for diagnosing allergic contact dermatitis (ACD). It reveals the prevalence and trends of contact sensitization in the community, thereby paving the way for better standard series. There is paucity of large series of patch-tested patients from India. AIM: To report the 9-year patch-test data from a single general dermatology centre in North India. METHODS: Consecutive patients presenting with signs/symptoms of suspected ACD were patch tested from May 1997 to April 2006. The Indian Standard Series was used. Parthenium was tested only in selected patients and cetrimide and chloroxylenol were added to the series. RESULTS: In total, records of 1000 patients (566 male, 434 female) were analyzed, yielding 1155 positive reactions in 590 (59%) patients. Footwear dermatitis was the commonest suspected diagnosis, followed by ACD to medicaments, cosmetic dermatitis and plant dermatitis. Out of the allergens that were tested in all the patients, positivity to nickel was the commonest (12.9%), followed by potassium dichromate (11.1%) neomycin (7%), mercaptobenzthiazole (6.6%), nitrofurazone (6%), colophony (5.7%), fragrance mix (5.5%) and cobalt chloride (5.4%). However, parthenium was the commonest allergen based on the proportion of patients tested with it (14.5%). In men, potassium dichromate (30%) was the commonest sensitizer and in women, nickel (43%) was the commonest to show patch-test positivity. CONCLUSION: Our study revealed higher prevalence of footwear and medicament dermatitis in comparison to existing data. Allergy to antiseptics is significant in our patients. Further collaborative studies involving patients from other parts of India are required to have an overall view of ACD in India.