Bilateral incyclotorsion,absent facial nerve,and anotia: Fellow travelers in Möbius sequence or oculoauriculovertebral spectrum?

We report a patient with bilateral incyclotorsion, asymmetric facial palsy, monocular depression deficiency, and unilateral Type 3 Duane syndrome, along with contralateral anotia and a midline cleft palate. A dysplastic middle ear cavity and unilateral absence of the facial nerve were noted on magnetic resonance imaging scanning. The differential diagnosis includes M?bius sequence, oculoauriculovertebral spectrum, and a congenital cranial dysinnervation disorder.     

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.     

Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1

Protozoan parasites of the genus leishmania are obligate intracellular parasites of monocytes and macrophages. These pathogens have evolved to invade the mammalian immune system and typically survive for long periods of time. Leishmania have developed a variety of remarkable strategies to prevent their elimination by both innate and acquired immune effector mechanisms. One particular strategy of interest involves manipulation of host cell regulatory pathways so as to prevent macrophage activation required for efficient microbicidal activity. These interference mechanisms are the main focus of this review. Several lines of evidence have been developed to show that the Src homology-2 domain containing tyrosine phosphatase-1 (SHP-1) becomes activated in leishmania-infected cells and that this contributes to disease pathogenesis. Recent studies aimed at understanding the mechanism responsible for the change in activation state of SHP-1 led to the identification of leishmania EF-1alpha as an SHP-1 binding protein and SHP-1 activator. This was a surprising finding given that this ubiquitous and highly conserved protein plays an essential role in protein translation in both prokaryotic and eukaryotic cells. The role of leishmania EF-1alpha as an SHP-1 activator and its contribution to pathogenesis are reviewed with particular attention to the properties that distinguish it from host EF-1alpha.     

Oxidative Stress,DNA Damage and Repair in Heart Failure Patients after Implantation of Continuous Flow Left Ventricular Assist Devices

Objective: To study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs).Materials and methods: Ten HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry, respectively. ELISA was used to measure oxidized low density lipoproteins (oxLDL) in plasma. Markers of DNA damage (γ-H2AX) and repairs (Mre11, DNA ligase IV, Ku70, and Ku80) were quantified in blood lymphocytes by immunocytochemistry.Results: Levels of ROS and oxLDL were significantly higher in HF patients with LVAD than baseline as well as the control group; moreover, SOD levels were decreased with increasing post-operative periods. All the changes indicated enhanced oxidative stress among LVAD recipients. Significantly higher γ-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. γ-H2AX foci numbers in lymphocytes were positively correlated with the ROS and oxLDL and negatively with SOD levels (p<0.0001). Expressions of DNA ligase IV, Ku70 and Ku80 proteins were highest after one week and Mre11 protein after 3 months of LVAD transplantation; indicated abnormal DNA repair.Conclusions: The study, for the first time shows that, continuous flow LVAD implanted HF patients not only exhibit elevated oxidative stress and DNA damage in blood leukocytes but also have abnormalities in DNA repair pathways.     

Nephrogenic systemic fibrosis in a gadolinium-naive renal transplant recipient

A 36-year-old woman presented with a 2-year history of multiple, raised, brown papules and indurated skin over her lower legs. She had received a renal transplant 11 years earlier, and had a history of recurrent deep vein thromboses despite a negative thrombophilic screen. The patient had no history of exposure to gadolinium. Histology at this time revealed a light perivascular lymphoid infiltrate, activated fibroblasts and prominent capillary vessels. The patient re-presented 1 year later with persistence of these lesions, in the setting of worsening renal function requiring haemodialysis. Repeat skin biopsies demonstrated increased dermal collagen and angiogenesis. The dermatopathological findings, in association with renal insufficiency and multiple deep vein thromboses, led to the diagnosis of nephrogenic systemic fibrosis.     

Comparative Analysis of Mutational Profile of Sonic hedgehog Gene in Gallbladder Cancer

Digestive Diseases and Sciences - Gallbladder cancer has high incidence in northeastern India; mortality too is high as the disease is often diagnosed late. Numerous studies have shown the role of...     

LC and LC–MS/MS study of forced decomposition behavior of anastrozole and establishment of validated stability-indicating analytical method for impurities estimation in low dose anastrozole tablets

Anastrozole tablets were subjected to different ICH prescribed stress conditions of thermal, hydrolysis, humidity, photolysis and oxidation stress. The drug was found to be stable for all the stressed conditions except for oxidation. Separation of anastrozole from its potential impurities, degradation products and five anastrozole related compounds as main impurities were achieved on Inertsil ODS-3V, 250 mm × 4.6 mm i.d, 5 μm analytical column using reversed phase high performance liquid chromatography (RP-HPLC). The elution of impurities employed time dependent gradient programmed mobile phase consisting of water as mobile phase-A and acetonitrile as mobile phase-B at column flow rates of 1 ml/min and at 215 nm UV detection. The same method was also extended to LC–MS/MS studies which were carried out to identify the degradation product. The method developed was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by a different operator. The LOQ for anastrozole related compound-A (RC-A), related compound-B (RC-B), related compound-C (RC-C), related compound-D (RC-D), related compound-E (RC-E) and anastrozole were 0.05, 0.03, 0.03, 0.06, 0.06 and 0.06 μg ml⁻¹ respectively. The linearity of the proposed method for all the above related compounds was investigated in the range of LOQ to 0.600 μg ml⁻¹ respectively. The specificity was established through peak purity testing using a photo-diode array detector. Method was validated according to ICH guidelines and statistical analysis of the data proved to be suitable for stability testing at quality control.     

Achieving autologous breast reconstruction for breast cancer patients in the setting of post-mastectomy radiotherapy

Introduction  

Breast cancer is now associated with long-term disease-free and overall survival, and in the setting of mastectomy, long term psycho-sexual health becomes an important consideration. To this end, breast reconstruction has been shown to significantly improve quality of life for mastectomy patients. With adjuvant radiotherapy often required in the setting of breast reconstruction, it is unclear what interaction the two can have.