Inhaled anti-tubercular therapy: Dry powder formulations, device and toxicity challenges

The thesis is comprised of a series of studies that characterise the potential of inhaled therapy for treatment of TB using rifapentine as a model. Novel inhalable dry powder formulations containing efflux pump inhibitors (verapamil or thioridazine) and rifapentine were successfully formulated. These powders demonstrated excellent aerosol performance and enhanced in vitro activity against intracellular growth of M. tuberculosis compared to single drug treatments. Alternatively, rifapentine-PLGA particles regardless of monomer and molecular weight showed good aerosol performance and higher affinity for macrophage uptake. In the following study, a modified Aerolizer® as a low-cost generic device demonstrated promising results for delivery of rifapentine up to a maximum dose of 100 mg in a single capsule. Finally, it was found that intratracheal delivery of rifapentine (20 mg/kg) triggered a transient neutrophil influx in the lungs which resolved by 7 days post-dosing. These findings suggest that the inhaled rifapentine is more suitable for periodic dosing (i.e. weekly) and as an adjunct to the standard oral anti-TB drug regimen

Blow out fracture A Novel Management Modality

Blow out fracture of orbit involves fracture of orbital floor without fracture of infraorbital rim. This injury is common from frontal blow to orbit. Frontal blow to orbit causes increased intraorbitaltension causing fracture of floor of the orbit (weak point) with prolapse of orbital content into the maxillary sinus cavity. This causes enophthalmos and diplopia. Infraorbital rim is not involved in pure blow out fracture, it is also involved then it should be considered as an impure blow out fracture [3]. Entrapment of inferior rectus muscle between the fracture fragments will causediplopia in these patients. This article discusses a novel endoscopic internal reduction of fractured fragments. Main advantage of endoscopic approach is the lack of facial skin incision. It iscosmetically acceptable.

Studies On The Activity Of Isoniazid Derivatives And Their Combinations With Other Anti-TB Drugs On Mycobacterium Tuberculosis

The low permeability of the cell envelope against hydrophilic anti-tuberculosis (TB) drugs especially isoniazid (INH), is one of the crucial factors that contribute to the intrinsic resistance in Mycobacterium tuberculosis. Previous studies have floated the idea that the anti-mycobacterial activity of INH can be enhanced by augmenting the hydrophilic INH into a hydrophobic/lipophilic compound. Therefore, a series of 13 derivatives with different hydrophobicity were synthesized by adding different hydrophobic acyl chain to the parent compound, INH

Outcome of Glansectomy and Skin Grafting in the Management of Penile Cancer

Purpose. To report outcome data for patients with penile cancer treated surgically with glansectomy and skin grafting. Materials and Methods. We retrospectively reviewed data on all patients undergoing surgical management of penile cancer by a single surgeon between 1998 and 2008. Outcomes in patients who underwent glansectomy and skin grafting were analysed. Results. Between 1998 and 2008 a total of 25 patients with a mean age 60 (39–83) underwent glansectomy and skin grafting. Six patients had carcinoma in situ (CIS); the stage in the remaining patients ranged from T1G1 to T3G3. Mean followup for patients was 28 months (range 6–66). Disease specific survival was 92% with 2 patients who had positive nodes at lymph node dissection developing groin recurrence. One patient developed a local recurrence requiring a partial penectomy. Conclusions. Penile preserving surgery with glansectomy and skin grafting is a successful technique with minimal complications for local control of penile carcinoma arising on the glans. Careful followup to exclude local recurrence is required

Clinical Study Outcome of Glansectomy and Skin Grafting in the Management of Penile Cancer

properly cited. Purpose. To report outcome data for patients with penile cancer treated surgically with glansectomy and skin grafting. Materials and Methods. We retrospectively reviewed data on all patients undergoing surgical management of penile cancer by a single surgeon between 1998 and 2008. Outcomes in patients who underwent glansectomy and skin grafting were analysed. Results. Between 1998 and 2008 a total of 25 patients with a mean age 60 (39-83) underwent glansectomy and skin grafting. Six patients had carcinoma in situ (CIS); the stage in the remaining patients ranged from T1G1 to T3G3. Mean followup for patients was 28 months (range 6-66). Disease specific survival was 92% with 2 patients who had positive nodes at lymph node dissection developing groin recurrence. One patient developed a local recurrence requiring a partial penectomy. Conclusions. Penile preserving surgery with glansectomy and skin grafting is a successful technique with minimal complications for local control of penile carcinoma arising on the glans. Careful followup to exclude local recurrence is required

Effect of storage temperature on the stability of spray dried bacteriophage powders

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2–0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106–107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.The University of Sydney; Australian Research Council; National Institute of Allergy and Infectious Diseases of the National Institutes of Health; National Health and Medical Research Council Centre of Research Excellence in Tuberculosis Contro

Fusidic acid/tea-tree oil nanoemulsions : a potentially safe and effective anti MRSA/MSSA topical agent for chronic wound healing

Fusidic acid (FA) is clinically used as an antibacterial agent for the treatment of Gram-positive bacterial infections. It interferes with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G on the ribosome. In the present work, oil-in-water nanoemulsion (NE) was developed as a carrier for the transdermal delivery of FA. Different oils, surfactants and co-surfactants were screened. The solubility of FA, the emulsifying capacity of the surfactants and phase diagrams for each oil and surfactant mix were constructed. From the analysis, eight stable NE formulations were chosen, and their physicochemical properties were further evaluated. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were also evaluated, and cytotoxicity was conducted on HS-27 cell line to determine the safety of the formula. It was found that the NE produced from tea tree oil has the most optimal stability with promising antibacterial activity against MRSA as compared to a commercially available product. The safety profile of the NE was also comparable to the commercial product; thus, the formulated FA-NE is promising for clinical use

Design, characterization, in vitro antibacterial, antitubercular evaluation and structure–activity relationships of new hydrazinyl thiazolyl coumarin derivatives

Herein, we describe the synthesis of 11new thiazolyl coumarin derivatives and evaluation of their potential role as antibacterial and antituberculosis agents. The structures of the synthesized compounds were established by extensive spectroscopic studies (Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, 2D-nuclear magnetic resonance and liquid chromatography–mass spectrometry) and elemental analysis. All synthesized compounds were assayed for their in vitro antibacterial activity against a few gram positive and gram negative bacteria and antituberculosis activity against Mycobacterium tuberculosis H37Rv ATCC 25618 by using colorimetric microdilution assay method. Nine derivatives showed moderate anti-bacterial and anti-tuberculosis activities against all the tested strains. The highest activity against all the pathogens including Mycobacterium tuberculosis was observed by compound 7c with MIC values ranging between 31.25–62.5 μg/mL, indicating that coumarin skeleton could indeed provide useful scaffold for the development of new anti-microbial drugs

Neck space infections our experience

This article is about the cases of neck space infections presented to the department of E.N.T and HEAD & NECK surgery of Govt.stanley medical college, during a two month period of 15thNovember 2011to 15th January 2012. Out of the 8 cases presented to the department, 2 cases were of tuberculous cold abscess. Five cases treated with I&D of which two cases needed preliminarytracheostomy.