Design, Facile Synthesis, and Antibacterial Activity of Hybrid 1,3,4-thiadiazole-1,3,5-triazine Derivatives Tethered via -S- Bridge

Some hybrid 1,3,4-thiadiazole-1,3,5-triazine derivatives tethered via -S- bridge were synthesized and characterized with the aid of spectroscopic and elemental analysis. These hybrid conjugates were then investigated for their antibacterial activity against selected Gram-positive and Gram-negative bacteria. Excellent to moderate antibacterial activity was presented by the target compounds.     

Helicobacter pylori: past,current and future treatment strategies with gastroretentive drug delivery systems

Helicobacter pylori have been subject to intense investigation since its discovery from gastric biopsy in 1982. This gastropathogen has been regarded as serious public health problem due to its association with dyspepsia, gastritis, gastroduodenal ulcers, mucus-associated lymphoid tissue lymphoma and gastric carcinoma. In vivo eradication of established H. pylori infections is difficult due to several factors such as gastric niche, coccoid form due to sub-minimum inhibitory concentration of antimicrobials, bacterial load, primary antibiotic resistance, patient compliance and stability of therapeutics in gastric acid secretion. Considering these factors, a logical way to improve the outcome of the treatment is to develop dosage forms which are able to deliver the anti-helicobacter agents in the gastric niche for both local and systemic actions, simultaneously taking care of stability of therapeutics in acidic environment. Such dosage forms, which are popularly known as gastro retentive drug delivery systems (GRDDS), have the immense potential to effectively counter the problem of high bacterial load; prevent induction of coccoid bacteria thereby improving treatment outcome and compliance. This review describes efficacy of various therapeutic agents, treatment strategies and status of different GRDDS until now.     

Single Miniplate Fixation for Mandibular Symphysis and Parasymphysis Fracture as a Viable Alternative to Conventional Plating Based on Champy’s Principles: A Prospective Comparative Clinical Study

To compare long term and short term outcomes of fixing mandibular symphysis and parasymphysis fractures with single mini plate and conventional fixation using two mini plates. Study design: in this prospective clinical comparative study, 30 patients with fracture in study region were randomly divided into two groups. Group A patients received single 2.5 mm titanium miniplate and Group B patients received two 2 mm titanium miniplates as per Champy's lines of osteosynthesis. Patients were followed up at intervals of 1, 12 and 24 weeks. Parameters assessed were: duration of surgery, fracture stabilization, paresthesia, occlusion and wound dehiscence. Statistically significant difference was observed in mean duration of surgery and wound dehiscence (P < 0.05). No significant difference was observed with respect to other parameters. Single 2.5 mm miniplate for mandibular symphysis and parasymphysis fractures is a time saving and cost effective technique with post-operative outcomes similar to conventional 2 plate fixation.     

Presurgical Nasoalveolar Molding (PNAM) for a Unilateral Cleft Lip and Palate: A Clinical Report

Cleft lip and palate deformity is a congenital defect of the middle third of the face. Incidence varies from 1:500 to 1:2500 live births. Etiology depends upon hereditary and environmental factors. Restoration of these defects is important not only for functional and esthetic reasons, but also because there may be a positive psychological impact for the patient and parents. The goal of primary closure of the lip for unilateral cleft lip is to ensure a normal and symmetrical lip and nose. Presurgical infant orthopedics has been employed since the 1950s as an adjunctive neonatal therapy for the correction of cleft lip and palate. Presurgical nasoalveolar molding (PNAM) represents a paradigm shift from the traditional methods of presurgical infant orthopedics. PNAM consists of active molding of the alveolar segments as well as the surrounding soft tissues. This clinical report describes a new approach of PNAM therapy for an infant with complete unilateral cleft lip and palate showing significant reduction in cleft defect size and improved contour and topography of deformed surrounding soft tissues.     

Ophthalmic Complication Following Posterior Superior Alveolar Nerve Block for Tooth Extraction! A Rare Occurrence

One of the most commonly asked question by a patient who comes for extraction especially in the rural areas is whether the procedure will cause problems to the eye!! In reality however, ophthalmic complications following routine maxillary molar extractions are practically unheard of. When they occur they can be extremely unnerving not just to the patient but also to the surgeon. Patients generally panic which makes it tougher for the clinician to assess the situation. We present a case of a 26 year old female patient developing ophthalmic complication following local anesthesia administration during extraction of upper left maxillary third molar. In this article, ophthalmic complications arising from posterior superior alveolar nerve block are discussed and management guidelines are highlighted.     

Limb lead interchange in thorough QT/QTc studies

The investigators analyzed 85,133 electrocardiograms (ECGs) recorded in 484 subjects from 5 thorough QT/QTc studies (3 using Holter devices, 2 using 12-lead ECGs) for inadvertent limb lead interchanges using a dedicated quality control process in a central ECG laboratory. Limb lead interchanges were present in 2919 (3.4%) ECGs in 17.9% of subjects and were more frequent with Holter devices (7.5% vs 0.8%, P < .0001), where leads remain connected for prolonged periods, affecting data from several time points. Left arm-left leg interchange was seen in 54% of 12-lead ECGs and right arm-left arm interchange in 38%. The ECG device itself could identify 21.7% of interchanges, whereas experienced readers blinded to subject and visit identified 79% of interchanges; 21% of interchanges were identified only during the quality control process. If correctly identified, QT measurement could be performed in a precordial lead. If undiagnosed, incorrect QT interval measurements and morphological diagnosis may confound results.     

Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1

Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal fibroblasts - a natural target cell for HSV-1 infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after creating additional oxygen vacancies under UV-light illumination. Our results provide a novel insight into the significance of ZnO MNSs as the potent HSV-1 inhibitor and rationalize their development as a novel topical agent for the prevention of HSV-1 infection.     

Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.     

Bioavailability Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine,a Polyhydroxy Base,as a Novel Ternary Component

The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-β-cyclodextrin (HPβCD). The molecular inclusion of DRF-4367 with HPβCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPβCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubility enhancement were investigated by using phase solubility and thermodynamic parameters. The complexation of DRF-4367 with HPβCD is thermodynamically favored because the Gibbs free energies of transfer of the drug to the cyclodextrin cavity are negative. The solubilization efficiency and stability were further improved while retaining the favorable Gibbs free energies of transfer with the addition of meglumine. Inclusion ternary complex of DRF-4367 with HPβCD and meglumine showed significant improvement in dissolution compared with uncomplexed drug and binary system. Moreover, the phenomena of reprecipitation observed with binary system during dissolution could be avoided with meglumine as an enabling ternary component. This improved physicochemical behavior of ternary complex with the novel inclusion of a polyhydroxy base translated into an enhanced oral bioavailability of DRF-4367 compared with either uncomplexed drug or nanosuspension.     

Perforation of the gall bladder following typhoid fever-induced ileal perforation.

Gall bladder perforation is a potentially life-threatening condition. Spontaneous perforation is infrequent and rarely seen in the absence of gallstones but gall bladder perforation is an occasional complication of typhoid fever. If such perforations are not treated in time, mortality rates are very high. We report a case of gall bladder perforation complicating typhoid fever following enteric perforation of the ileum necessitating sequential laparotomies during the same admission.