Paroxysmal spinal hemidystonia in neuromyelitis optica.

Paroxysmal dystonia occurs because of genetic or structural lesion in the basal ganglia or thalamus, and there is paucity of reporting in spinal pathology. We report a patient with paroxysmal hemidystonia admitted to a tertiary care hospital, India, and review the literature on spinal dystonia in neuromyelitis optica (NMO). A 19-year-old woman presented with recurrent visual loss and quadriparesis. She developed paroxysmal hemidystonia after 18 days of a second episode of quadriplegia, during which her muscle power improved to Grade 3. Magnetic resonance imaging (MRI) of her spine showed central T2 hyperintensity extending from C2 to C7 vertebral level, and a cranial MRI was normal. Tibial somatosensory evoked potentials were unrecordable. Aquaporin-4 antibody was positive in serum, confirming the diagnosis of NMO. Paroxysmal hemidystonia responded to carbamazepine 200 mg thrice daily. Paroxysmal dystonia may occur in a patient with myelitis and may respond to carbamazepine.

4-Substituted 2-amino-3,4-dihydroquinazolines with a 3-hairpin turn side chain as novel inhibitors of BACE-1.

Herein, we report the identification, design, and synthesis of a series of 4-substituted 2-amino-3,4-dihydroquinazolines with hairpin turn side chains as novel inhibitors of BACE-1. The dihydroquinazoline derivatives were rationally designed by modifying the amide group and relocating the α -hydrophobic substituent on the hairpin turn side chain of lead compound 2 to the C4-position on the 3,4-dihydroquinazoline scaffold to facilitate interactions with the S1, S2 and S1' subsites of BACE-1. Among these derivatives, two compounds exhibited potent BACE-1 inhibitory activity: 4-methyl-substituted (22a, BACE-1 CFA IC50 = 0.38 µM; BACE-1 WCA IC50 = 0.14 µM) and 4-cyclohexylmethyl-substituted (22b, BACE-1 CFA IC50 = 0.49 µM; BACE-1 WCA IC50 = 0.14 µM) 2-amino-3,4-dihydroquinazoline, each bearing a side chain of N-cyclohexyl-N-((1-methyl-1H-pyrazol-4-yl)methyl amide. The results suggest that the structural modifications maintain the hairpin turn topology similar to that of compound 2 and provide an additional interaction with the S2 subsite.

Assessment of antibacterial efficacy of a biocompatible nanoparticle PC@AgNPs against Staphylococcus aureus.

A plant, Priva cordifolia mediated silver nanoparticle was prepared and characterized by UV-Vis spectroscopy, fourier-transform infrared spectroscopy (FT-IR), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD) analysis. The minimum inhibitory concentration of the synthesized nanoparticle against Staphylococcus aureus was found to be 100 ±â€¯0.80 µg/mL with 9.38 ±â€¯0.04 mm zone of inhibition. The bactericidal activity was shown primarily due to membrane damage evident from SEM, atomic force microscopy (AFM), potassium efflux, cellular material leakage, and bio-electrochemical changes in electron transport chain data. It was also of interest to find PC@AgNPs interfering with biofilm formation by S.aureus, assessed qualitatively by SEM, confocal laser scanning microscopy (CLSM) and quantitatively by dye staining method. The bio-compatibility of PC@AgNPs was established by anti-coagulant, thrombolytic, partial thromboplastin time, thrombin-like activity and fibrinolytic activity that suggested its good maintenance of hemostatic conditions. PC@AgNPs also prevented the coagulation of rabbit plasma which as per the standard drug Dabigatran reaction was indicative of the down-regulation of virulence Coa gene expression.

Classification of Epigenetic Biomarkers with Atomically Thin Nanopores.

We use the electronic properties of 2D solid-state nanopore materials to propose a versatile and generally applicable biosensor technology by using a combination of molecular dynamics, nanoscale device simulations, and statistical signal processing algorithms. As a case study, we explore the classification of three epigenetic biomarkers, the methyl-CpG binding domain 1 (MBD-1), MeCP2, and γ-cyclodextrin, attached to double-stranded DNA to identify regions of hyper- or hypomethylations by utilizing a matched filter. We assess the sensing ability of the nanopore device to identify the biomarkers based on their characteristic electronic current signatures. Such a matched filter-based classifier enables real-time identification of the biomarkers that can be easily implemented on chip. This integration of a sensor with signal processing architectures could pave the way toward the development of a multipurpose technology for early disease detection.

Nutritional status of Onges of Little Andaman Island - Current state and the change over the last fifteen years.

Onges, an indigenous vulnerable tribe, inhabit the Little Andaman Island. Study undertaken during 1997, recorded high prevalence of undernutrition among children. Subsequently, food rationing was modified by Andaman and Nicobar administration. In the present study, health and nutritional status of this tribe was assessed in 2013 after a gap of 15 years. All individuals in the tribe were included. Various health parameters, viz, nutritional anthropometry, haemoglobin level, fasting sugar, lipids and intestinal parasites were investigated. Prevalence of stunted growth and underweight among children of 0-5 years was 86.4%. Severe underweight were more prevalent (40%), as compared to those recorded 15 years ago (10%), and the difference was statistically significant (P < 0.05). There has been a substantial improvement in the overall nutritional status of children in the age group of <18 years. The prevalence of wasting has halved and that of stunting and wasting has come down to one-third of that observed in 1997. Prevalence of anaemia significantly declined from 87% in 1997 to 51% 15 years later.

Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis.

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K(+) and Cl(-) efflux via activation of K(+) channels, volume-regulated anion channels (VRACs), and the K(+)-Cl(-) cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1). This results in a rapid (<10 min) and significant (>90%) reduction in intracellular K(+) content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive] pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD.

Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia.

A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-1-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyl)ureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (54) was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, respectively). Compound 54 also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound 54 also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 had a moderate pharmacokinetic profile. The mesylate salt of 54 efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (subcutaneous xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML.

Enantioselective synthesis of syn/anti-1,3-amino alcohols via proline-catalyzed sequential alpha-aminoxylation/alpha-amination and Horner-Wadsworth-Emmons olefination of aldehydes.

A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

Iterative approach to enantiopure syn/anti-1,3-polyols via proline-catalyzed sequential alpha-aminoxylation and Horner-Wadsworth-Emmons olefination of aldehydes.

Iterative use of proline-catalyzed tandem alpha-aminoxylation and HWE olefination of aldehydes provided a simple access to 1,3-polyols. The feasibility of this approach is initially studied to synthesize syn- and anti-1,3-diols and is further extended to a syn/syn-1,3,5-triol at a useful level of asymmetric induction and yield. Its usage is illustrated by the short synthesis of a hydroxylactone pheromone component, (2S,3S)-2-hydroxyhexylcyclopentanone.

Comparative study in extracorporeal shock wave lithotripsy with and without the use of local anaesthetic (Lidocaine 1%) infiltration at the shock wave site.

BACKGROUND: Extracorporeal Shock Wave Lithotripsy (ESWL) is a simple and non-invasive technique in which renal and ureteric calculi are pulverised into small fragments by shockwaves and then allowed to pass spontaneously in small fragments along with urine. Effective ESWL requires a co-operative patient who will remain immobilize on the lithotripsy table comfortably for which different anaesthetic techniques are used. Occasionally discharge of patient is delayed due to persistent sedation, nausea and vomiting. OBJECTIVE: The aim is to assess the use of local anaesthetic agent (20 ml Lidocaine 1% ) infiltration in 60 patients (Experiment Group ) and no infiltration in 60 patients ( Control Group ) on patients undergoing Extracorporeal shock wave lithotripsy (ESWL) procedure. MATERIALS AND METHODS: is a study done in 120 patients of ASA I and ASA II patients undergoing ESWL procedure. The infiltration technique is standardized so that the local anesthetic agent was infiltrated five minutes before the procedure along the line of shockwave site in Experiment Group. RESULT: In this study, the age, sex, weight, time of shockwave treatment was almost similar in both groups. The mean need of Ketamine and duration of stay after procedure was significantly more in control group than experiment group. CONCLUSION: In this study, it is concluded that the need of Ketamine and duration of stay after procedure is significantly more in control group.

Orbital lipoma: 2 cases and review of literature.

PURPOSE: Lipomas are rare benign tumors of the orbit that can resemble a variety of other orbital masses. We present 2 patients with orbital lipomas and review the literature. METHOD: Retrospective review of clinical charts, imaging studies, and pathology specimens. RESULTS: We encountered 2 patients with lipomas, both presenting with orbital swelling and a mass noted on clinical examination. A well-circumscribed lesion was seen on CT, which on excision was composed of mature fat cells arranged in lobules and surrounded by a diaphanous capsule. CONCLUSIONS: Lipomas arising in the orbit may evoke a range of clinicoradiologic differential diagnoses.