Synthesis and evaluation of antioxidant and antimicrobial properties of thymol containing pyridone moieties

Various derivatives of 1,2-dihydro-6-(4-hydroxy-5-isopropyl-2-methylphenyl)-2-oxo-4-arylpyridine-3-carbonitrile (IVa–m) were synthesized and characterized. Their antioxidant and antimicrobial properties were evaluated by measuring their activity in vitro. Among the newly synthesized derivatives IVg, IVh, IVi, IVj, IVk, IVl, and IVm showed good antioxidant activity. However, all derivatives show better antibacterial and antifungal properties than that of parent thymol. The probable mechanism, particularly for antioxidant properties of these compounds is proposed.     

Solid pseudo-papillary tumors of the pancreas: current update

Solid pseudo-papillary tumors are rare pancreatic tumors, which occur in females and are typically indolent neoplasms. However, atypical, aggressive variants can occur with locally advanced disease or metastases. They have characteristic imaging features, which vary according to size. This article provides a current update on the molecular biology, histopathology, clinico-radiological features, and management of these tumors.     

Roles of Salmonella enterica serovar Typhimurium encoded Peptidase N during systemic infection of Ifnγ-/- mice

Pathogen encoded peptidases are known to be important during infection; however, their roles in modulating host responses in immunocompromised individuals are not well studied. The roles of S. typhimurium (WT) encoded Peptidase N (PepN), a major aminopeptidase and sole M1 family member, was studied in mice lacking Interferon-γ (IFNγ), a cytokine important for immunity. S. typhimurium lacking pepN (ΔpepN) displays enhanced colony forming units (CFU) compared to WT in peripheral organs during systemic infection in C57BL/6 mice. However, Ifnγ(-/-) mice show higher CFU compared to C57BL/6 mice, resulting in lower fold differences between WT and ΔpepN. Concomitantly, reintroduction of pepN in ΔpepN (ΔpepN/pepN) reduces CFU, demonstrating pepN-dependence. Interestingly, expression of a catalytically inactive PepN (ΔpepN/E298A) also lowers CFU, demonstrating that the decrease in CFU is independent of the catalytic activity of PepN. In addition, three distinct differences are observed between infection of C57BL/6 and Ifnγ(-/-) mice: First, serum amounts of TNFα and IL1β post infection are significantly lower in Ifnγ(-/-) mice. Second, histological analysis of C57BL/6 mice reveals that damage in spleen and liver upon infection with WT or ΔpepN is greater compared to ΔpepN/pepN or ΔpepN/E298A. On the other hand, Ifnγ(-/-) mice are highly susceptible to organ damage by all strains of S. typhimurium used in this study. Finally, greater survival of C57BL/6, but not Ifnγ(-/-) mice, is observed upon infection with ΔpepN/pepN or ΔpepN/E298A. Overall, the roles of the host encoded IFNγ during infection with S. typhimurium strains with varying degrees of virulence are highlighted.     

Carcinoid tumours: predicting the location of the primary neoplasm based on the sites of metastases

Objectives

To predict the primary neuroendocrine tumour of the gastrointestinal tract site based on observed metastatic sites.

Methods

We studied data from the radiology database of a single, large cancer centre on 250 patients with pathologically confirmed neuroendocrine tumours. Primary tumour sites and the locations of metastases were collected from pathologic and radiologic reports of all available imaging modalities, such as computed tomography (CT), positron emission tomography (PET/CT), magnetic resonance imaging (MRI) and octreotide scans in the database. A nominal regression model was used to predict primary tumour site using the observed metastatic sites. Regression coefficients that were not statistically significant at the 5 % level were eliminated from the model in a stepwise procedure.

Results

Lung and liver metastases were not statistically significant predictors of the location of primary tumours (p?=?0.86 and 0.074, respectively); whereas, lymph node, bone, and peritoneal metastases were significant predictors (p?<?0.0001, 0.0004, and 0.014, respectively).

Conclusions

Metastatic neuroendocrine tumours to the lymph nodes, bone, and peritoneum can be used to predict the primary neuroendocrine site; however, metastases in the lung and liver alone cannot predict the site of the primary tumour site.

Key Points

? Imaging helps one to diagnose the location of primary neuroendocrine neoplasm and the associated metastases. ? Diffuse metastatic disease often makes identification of the primary difficult. ? A prediction model developed may help identification of the primary in this setting. ? It may also help identify occult metastases and thereby assist in management.     

Anti-thymocyte globulin induced non-cardiogenic pulmonary edema during renal transplantation

Non-cardiogenic pulmonary edema (NCPE) is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, without evidence of left atrial hypertension/congestive heart failure/fluid overload. The diagnosis of drugrelated NCPE relies upon documented exclusion of other causes of NCPE like gastric aspiration, sepsis, trauma, negative pressure pulmonary edema. We describe a 28year-old, 50 kg male with ASA risk III posted for laparoscopic renal transplantation, who developed NCPE after 4 hours of administration of rabbit anti-human thymocyte immunoglobulin (ATG). He was successfully treated with mechanical ventilatory support and adjuvant therapy. This report emphasizes that this fatal complication may occur with use of ATG.     

Microsponges based novel drug delivery system for augmented arthritis therapy

The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug–polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug–polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.     

Incidence and Pattern of Cranio-Maxillofacial Injuries: A 22 year Retrospective Analysis of Cases Operated at Major Trauma Hospitals/Centres in Pune, India

This study aims to retrospectively analyze the incidence and pattern of cranio-maxillofacial injuries in the developing world in a hope to emphasize on authorities the need of improvising infrastructural facilities, medical and other. Hospital medical records with available radiographs of 6,872 patients treated for cranio-maxillofacial injuries at major trauma centres in Pune, India over a 22 year period (from July 1989 to June 2010) were reviewed. Relevant data pertaining to patients’ age, sex, cause of injury, sites of injury, associated injuries, anaesthesia, various treatment modalities and complications were recorded and analyzed statistically. A total of 6,872 patients sustained maxillofacial injuries of which 5,936 (86.4 %) were caused by road traffic accidents (RTA), followed by fall in 608 cases. Distribution pattern of sex revealed male predominance (M:F-2.5:1) and the third decade age group (2,416) sustained maximum cranio-maxillofacial injuries. Of 12,503 cranio-maxillofacial sites involved, mandible (6,456) predominated, while there was middle third involvement in 5,024 cases. Most of the patients (4,856) were treated with open reduction and internal fixation without maxillo-mandibular fixation and complications were noted in 320 patients. In comparison to similar recent studies reported in the literature, our findings show that RTA remains the most common cause of cranio-maxillofacial injuries with male preponderance. Also RTA remains the major preventable etiological factor of cranio-maxillofacial injuries, which should prompt authorities to take “Herculean effort” to implement rules and educate people.     

Isolated gastric Crohn’s disease

Crohn’s disease (CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterized by segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and account for 40% of cases and involvement of small intestine in about 30%. The stomach is rarely the sole or predominant site of CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. Isolated stomach involvement is very unusual presentation accounting for less than 0.07% of all gastrointestinal CD. The diagnosis is difficult to establish in cases of atypical presentation as in isolated gastroduodenal disease. In the absence of any other source of disease and in the presence of nonspecific upper GI endoscopy and histological findings, serological testing can play a vital role in the diagnosis of atypical CD. Recent studies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and anti-Saccharomycescervisia antibody may be used as additional diagnostic tools. The effectiveness of infliximab in isolated gastric CD is limited to only a few case reports of adult patients and the long-term outcome is unknown.     

A cohort study to evaluate cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients attending orthopedic department of a tertiary care hospital

Background:

Cyclooxygenase-2 inhibitors (COX-2-Is) have recently been concerned in the occurrence of adverse cardiovascular (CV) events. Rofecoxib and valdecoxib has been withdrawn from the market, but celecoxib, etoricoxib and parecoxib continues to be used. Other nonsteroidal anti-inflammatory drugs (NSAIDs) may also increase the risk of CV events. However, clinical trial databases for COX-2-Is had created lots of controversies regarding cardiovascular safety of selective and nonselective cyclooxygenase inhibitors (COX-Is). This study was, conducted to assess and compare the CV risk of COX-Is in arthritic patients over a period of time.

Materials and Methods:

In this prospective cohort study adult arthritics of either sex those were freshly diagnosed or taking COX-Is for < 3 months; were included. Patients were grouped into nonselective and selective COX-2-I groups with reference to treatment they received. The CV risk factors like blood pressure (BP), blood sugar level (BSL), lipid profile, body mass index (BMI) were assessed and compared; demography of CV risk factors was also studied. Data obtained was analysed using Student''s ‘t’-test of OpenEpi statistical software.

Results:

Study clearly revealed that all NSAIDs exhibit variable CV risk; however, selective COX-2-Is found to exhibit more CV risk. BMI, BP and lipid profile; the potential CV risk factors, showed significant impairment in selective COX-2-Is group; P < 0.01, P < 0.001 and P < 0.05, respectively, compared to baseline and P < 0.05 vs. nonselective COX-Is for BMI.

Conclusions:

This study portrays the potential CV risk of selective COX-2-Is; confirms and re-evaluate the results of earlier studies in this regard.