Functionally Graded Bioactive Composites Based on Poly(vinyl alcohol) Made through Thiol-Ene Click Reaction.

Functionally graded materials (FGMs) composed of a polymer matrix embedded with calcium phosphate particles are preferred for bone tissue engineering, as they can mimic the hierarchical and gradient structure of bones. In this study, we report the design and development of a FGM based on thiolated poly(vinyl alcohol) (TPVA) and nano-hydroxyapatite (nano-HA) with graded bioactivity, cell compatibility, and degradability properties that are conducive for bone regeneration. The polymer matrix comprises crosslinked poly(vinyl alcohol) with ester and thioether linkages formed via the thiol-ene click reaction, avoiding undesired additives and byproducts. Freshly precipitated and spray-dried HA was mixed with the TPVA hydrogel, and layers of varying concentrations were cast. Upon lyophilization, the hydrogel structure yielded porous sheets of the graded composite of TPVA and nano-HA. The new FGM showed higher values of tensile strength and degradation in phosphate buffer saline (PBS) in vitro, compared to bare TPVA. The bioactive nature of the FGM was confirmed through bioactivity studies in simulated body fluid (SBF), while cytocompatibility was demonstrated with human periodontal ligament cells in vitro. Cumulatively, our results indicate that based on the composition, mechanical properties, bioactivity, and cytocompatibility, the fabricated TPVA-HA composites can find potential use as guided bone regeneration (GBR) membranes.

Optimization and production of curdlan gum using Bacillus cereus PR3 isolated from rhizosphere of leguminous plant.

Curdlan gum is a neutral water-insoluble bacterial exopolysaccharide composed primarily of linear ß-(1,3) glycosidic linkages. Recently, there has been increasing interest in the applications of curdlan and its derivatives. Curdlan is found to inhibit tumors and its sulfated derivative possess anti-HIV activity. Curdlan is biodegradable, non-toxic towards human, environment and edible which makes it suitable as drug-delivery vehicles for sustained drug release. The increasing demand for the growing applications of curdlan requires an efficient high yield fermentation production process so as to satisfy the industrial needs. In this perspective, the present work is aimed to screen and isolate an efficient curdlan gum producing bacteria from rhizosphere of ground nut plant using aniline-blue agar. High yielding isolate was selected based on curdlan yield and identified as Bacillus cereus using gas-chromatography fatty acid methyl ester analysis. B. cereus PR3 curdlan gum was characterized using FT-IR spectroscopy, SEM, XRD and TGA. Fermentation time for curdlan production using B. cereus PR3 was optimized. Media constituents like carbon, nitrogen and mineral sources were screened using Plackett-Burman design. Subsequent statistical analysis revealed that Starch, NH4NO3, K2HPO4, Na2SO4, KH2SO4 and CaCl2 were significant media constituents and these concentrations were optimized for enhancement of curdlan production up to 20.88 g/l.

Crystal structures of salen-type ligands 2-[(1E)-({1-(3-chloro-phen-yl)-2-[(E)-(2-hy-droxy-benzyl-idene)amino]-prop-yl}imino)-meth-yl]phenol and 2-[(1E)-({1-(4-chloro-phen-yl)-2-[(E)-(2-hy-droxy-benzyl-idene)amino]-prop-yl}imino)-meth-yl]phenol.

The title compounds, C23H21ClN2O2, differ from each other only by the position of the Cl atom on the corresponding benzene ring: meta relative to the central sp3 C atom for (I) and para for (II). In (I), the hy-droxy-phenyl rings are almost parallel, the dihedral angle between the mean planes being 9.2 (2)°, but in (II), the relative position of the ring is different, characterized by a dihedral angle of 48.5 (1)°. Compound (I) features intra-molecular O-H⋯N and inter-molecular C-H⋯O hydrogen bonds, while in (II), intra-molecular O-H⋯N, C-H⋯N hydrogen bonds and weak inter-molecular C-H⋯π inter-actions are observed. Compound (I) was refined as an inversion twin.

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations.

Comparison of LC-UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: application to rat pharmacokinetic study.

This study describes a comparison between LC-UV and LC-MS method for the simultaneous analyses of a few disease-modifying agents of multiple sclerosis. Quantitative determination of fampridine (FAM), teriflunomide (TFM) and dimethyl fumarate (DMF) was performed in human plasma with the recovery values in the range of 85-115%. A reversed-phase high-performance liquid chromatography (HPLC) with UV as well as MS detection is used. The method utilizes an XBridge C18 silica column and a gradient elution with mobile phase consisting of ammonium formate and acetonitrile at a flow rate of 0.5 mL min(-1) . The method adequately resolves FAM, TFM and DMF within a run time of 15 min. Owing to low molecular weights, the estimation of DMF and FAM is more versatile in UV than MS detection. With LC-UV, the detection limits of FAM, TFM and DMF were 0.1, 0.05, 0.05 µg and the quantification limit for all the analytes was 1 µg. With LC-MS, the detection and quantification limits for all of the analytes were 1 and 5 ng, respectively. The two techniques were completely validated and shown to be reproducible and sensitive. They were applied to a pharmacokinetic study in rats by a single oral dose. Copyright © 2016 John Wiley & Sons, Ltd.

A high throughput flow gradient LC-MS/MS method for simultaneous determination of fingolimod, fampridine and prednisone in rat plasma, application to in vivo perfusion study.

In this study a selective and high throughput liquid chromatography-mass spectrometry method was developed and validated for the simultaneous quantification of fingolimod (FLD), fampridine (FMP) and prednisone (PDN) in rat plasma using imipramine (IMP) as internal standard (ISTD). In this LC-MS method, following protein precipitation extraction (PPE), the analytes and ISTD were run on XBridge C18 column (150×4.6mm, 5µm) using gradient mobile phase consisting of 5mM ammonium formate in water (pH 9.0) and acetonitrile in a flow gradience program. The drug precursor and product ions were monitored on a triple quadrupole instrument that was operated in positive ionization mode. The method was validated over a concentration range of 0.1-100ng/mL for all the three analytes with relative recoveries ranging from 69 to 82%. The intra and inter batch precision (% CV) across four validation runs were less than 13.4%. The accuracy determined at four QC levels (LLOQ, LQC, MQC and HQC) were within ±6.5% of CV values. The method proved to be highly reproducible and sensitive that was successfully applied in a pharmacokinetic study after single dose oral administration to the rats and also in perfusion study sample analysis.

Crystal structure of (E)-1-([1,1'-biphen-yl]-4-yl)-3-(3-nitro-phen-yl)prop-2-en-1-one.

In the title compound, C21H15NO3, the mol-ecule has an E conformation about the C=C bond, and the C-C=C-C torsion angle is -178.24 (18)°. In the mol-ecule, the planes of the terminal rings are twisted by an angle of 42.19 (10)°, while the biphenyl part is not planar, with a dihedral angle between the rings of 39.2 (1)°. The dihedral angle between the nitro-phenyl ring and the inner benzene ring is 5.56 (9)°. The 3-nitro group is approximately coplanar with the benzene ring to which it is attached [O-N-C-C = 0.1 (3)°]. In the crystal, mol-ecules are linked via C-H⋯π inter-actions, involving the terminal benzene rings, forming corrugated layers parallel to (100).

Structural, optical, thermal and mechanical properties of Urea tartaric acid single crystals.

Urea tartaric acid (UT) an organic nonlinear optical (NLO) material was synthesized from aqueous solution and the crystals were grown by the slow evaporation technique. The single crystal X-ray diffraction (XRD) analysis revealed that the UT crystal belongs to the orthorhombic system. The functional groups of UT have been identified by the Fourier transform infrared spectral studies. The optical transparent window in the visible and near the IR regions was investigated. The transmittance of UT has been used to calculate the refractive index (n) as a function of the wavelength. The nonlinear optical property of the grown crystal has been confirmed by the Kurtz powder second harmonic generation test. The birefringence of the crystal was determined using a tungsten halogen lamp source. The laser induced surface damage threshold for the grown crystal was measured using the Nd:YAG laser. The anisotropic in mechanical property of the grown crystals was studied using Vicker's microhardness tester at different planes. The etch pit density of UT crystals was investigated. The thermal behavior of UT was investigated using the TG-DTA and DSC studies.

Crystal structure of (E)-1-(4'-meth-oxy-[1,1'-biphen-yl]-4-yl)-3-(3-nitro-phen-yl)prop-2-en-1-one.

The title compound, C22H17NO4, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. Each mol-ecule exists as an E isomer with C-C=C-C torsion angles of -175.69 (17) and -178.41 (17)° in A and B, respectively. In mol-ecule A, the planes of the terminal benzene rings are twisted by an angle of 26.67 (10)°, while the biphenyl unit is non-planar, the dihedral angle between the rings being 30.81 (10)°. The dihedral angle between the nitro-phenyl ring and the inner phenyl ring is 6.50 (9)°. The corresponding values in mol-ecule B are 60.61 (9), 31.07 (8) and 31.05 (9)°. In the crystal, mol-ecules are arranged in a head-to-head manner, with the 3-nitro-phenyl groups nearly parallel to one another. The A and B mol-ecules are linked to one another via C-H⋯O hydrogen bonds, forming chains lying parallel to (-320) and enclosing R 2 (2)(10) and R 2 (2)(12) ring motifs. The meth-oxy group in both mol-ecules is positionally disordered with a refined occupancy ratio of 0.979 (4):0.021 (4) for mol-ecule A and 0.55 (4):0.45 (4) for mol-ecule B.

Crystal structure of (E)-1-(4'-methyl-[1,1'-biphen-yl]-4-yl)-3-(3-nitro-phen-yl)prop-2-en-1-one.

In the title compound, C22H17NO3, the mol-ecule has an E conformation about the C=C bond, and the C-C=C-C torsion angle is -177.7 (3)°. The planes of the terminal benzene rings are twisted by 41.62 (16)°, while the biphenyl unit is non-planar, the dihedral angle between the planes of the rings being 38.02 (15)°. The dihedral angle between the nitro-phenyl ring and the inner benzene ring is 5.29 (16)°. In the crystal, mol-ecules are linked by two weak C-H⋯π inter-actions, forming rectangular tubes propagating along the b-axis direction.

Case series of skin adnexal tumours.

BACKGROUND: Skin adnexal tumours (SATs) are a large and diverse group of benign and malignant neoplasms. They are uncommon. They can be single or multiple, sporadic or familial and they might be markers for syndromes associated with internal malignancies. Benign adnexal tumours are more common and malignant SATs are rare and are locally aggressive and have the potential for nodal involvement and distant metastasis with a poor clinical outcome.Therefore recognition of SATs and establishing a diagnosis of malignancy in SATs is important for therapeutic and prognostic reasons. AIMS AND OBJECTIVES: SATs are rare benign and malignant neoplasms. They are not commonly encountered in the routine surgical pathology practice.Hence this study aims at finding the frequency, clinical presentation and the histopathological appearances of SATS, and the differentiating features between benign and malignant tumours. MATERIALS AND METHODS: This is partly a retrospective and partly a prospective study done in a tertiary care hospital over a period of four years .All the SATs reported during this period are analysed for their clinical features, age, sex incidence and their gross and histopathological features. RESULTS: In the four years period 1,64,220 patients attended the hospital. The total number of SATS reported during this period were 21 cases (0.0128 %) Benign tumours were 19 (90.48%). Malignant tumours were 2(9.52%) The mean age for males 36.9 years and for females 35. Two years. There were 11 male patients and 10 female patients. Tumours of hair follicular differentiation were 7 (33.33%). Tumour like lesion of sebaceous origin was 1 (4.76%). Tumours of sweat gland origin were 11 (52.38%). Malignant tumours of eccrine origin were 2 (9.52%). CONCLUSION: SATs are not common. Their incidence in our study is only 0.0128 % of all cases. Eventhough benign SATs are more common than the malignant tumours, malignant SATs can occur both in young and elderly patients and they are aggressive and the SATs should be excised with wide tumour free margins.

Efficacy and tolerability of a novel herbal formulation for weight management.

OBJECTIVE: To evaluate the efficacy of an herbal blend. DESIGN AND METHODS: A randomized, double-blind, clinical trial in 60 subjects with body mass index (BMI) between 30 and 40 kg/m(2) . Participants were randomized into two groups receiving either 400 mg herbal capsules or 400 mg placebo capsules twice daily. The herbal blend comprises of extracts from Sphaeranthus indicus and Garcinia mangostana. Participants received a standard diet (2,000 kcal per day) and walked 30 min 5 days per week. RESULTS: After 8 weeks, significant net reductions in body weight (3.74 kg; P < 0.0001), BMI (1.61 kg/m(2) ; P < 0.0001), and waist circumference (5.44 cm; P < 0.05) were observed in the herbal group compared with placebo. Additionally, a significant increase in serum adiponectin concentration was found in the herbal group versus placebo (P = 0.001). Adverse events were mild and were equally distributed between the two groups. In vitro studies in the 3T3-L1 adipocyte cell line showed that the herbal extract markedly downregulated the expression of peroxisome proliferator-activated receptor gamma, adipocyte-differentiation related protein, and cluster of differentiation 36 but increased adiponectin expression. The herbal extract also reduced the expression and the recruitment of perilipin onto the membrane of lipid droplets. CONCLUSION: Supplementation with the herbal blend resulted in a greater degree of weight loss than placebo over 8 weeks.

1-Benzyl-3,5-bis-[(E)-3-thienyl-methyl-idene]piperidin-4-one.

In the title mol-ecule, C(22)H(19)NOS(2), the piperidine ring adopts an envelope conformation with the benzyl substituent in an equatorial position. Each of the olefinic double bonds has an E configuration. The dihedral angle between the two thio-phene rings is 1.55 (18)°. The thio-phene rings form angles of 72.21 (14) and 73.43 (14)° with the phenyl ring. Both thio-phene rings are disordered over two orientations [occupancy ratios of 0.799 (1):0.201 (1)] at 180° from one another. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions help to stabilize the packing.

1H and 13C NMR spectral study of some 3,5-bis[(E)-thienylmethylene]piperidin-4-ones.

(1)H and (13)C NMR spectra have been recorded for 3,5-bis[(E)-thienylmethylene]piperidin-4-one (1a), 3',3″-dimethyl-3,5-bis[(E)-thienylmethylene]piperidin-4-one (1b), 5',5″-dibromo-3,5-bis[(E)-thienylmethylene]piperidin-4-one (1c), their 1-methyl derivatives 2a-c and 3,5-bis[(E)-thienylmethylene]-2r,6c-diphenylpiperidin-4-one (3a). For selected compounds 2D spectra have been recorded. The spectral data are used to study the configuration and conformation of these molecules. The chemical shifts are discussed in light of steric, electronic and magnetic anisotropic effects. The magnetic anisotropic effects of thiophene ring and phenyl group are noteworthy. (1)H-(1)H COSY spectrum of 2b suggests that long-range (1)H-(1)H coupling, up to seven bonds, is possible in it. HMBC spectrum of 2b displays the magnetic nonequivalence of C-2 and C-6 and protons at these carbons.

Foot screening for diabetics.

INTRODUCTION: This study aims to evaluate the results of foot screening performed in a study population of 2137 diabetics (3926 feet) screened from 2006 to 2008 by the National University Hospital (NUH) multi-disciplinary team for diabetic foot problems. MATERIALS AND METHODS: A standardised protocol was designed. Foot screening consisted of detailed history taking and clinical examination including assessment for sensory neuropathy by Semmes Weinstein monofilament (SWMF) and neurothesiometer and assessment of vasculopathy by ankle-brachial index (ABI) and total body irradiation (TBI). The foot screening was performed by a trained staff nurse. All patients were classified according to King's College Classification. RESULTS: Majority of the patients were in the fifth (27.9%) and sixth (30.0%) decades of life. Two thousand sixty-four had type II diabetes, and only 73 had type I diabetes. Neuropathy was found in 1307 (33.3%) feet based on 5.07 SWMF. Vasculopathy was recorded in 510 (13.0%) and 546 (13.9%) feet based on ABI <0.8 and TBI <0.7. According to King's Classification, 1069 (50.0%) were Stage 1: Normal and 615 (28.8%) were Stage 2: At-Risk. CONCLUSION: Foot screening should be performed as early as possible to detect "At-Risk" feet and prevent the development of diabetic foot complications, thereby further reducing the risk of major amputations.

1-Methyl-3,5-bis-[(E)-(3-methyl-2-thienyl)methyl-ene]piperidin-4-one monohydrate.

In the title mol-ecule, C(18)H(19)NOS(2)·H(2)O, the piperidine ring adopts an envelope conformation with the methyl substituent in an equatorial position. Each of the olefinic double bonds has an E configuration. The dihedral angle between the two thio-phene rings is 6.04 (14)°. The water mol-ecule forms two donor inter-actions, one with the carbonyl O atom and the other to the hetero N atom. The centrosymmetric {C(18)H(19)NOS(2)·H(2)O}(2) pairs thus formed are linked into a supra-molecular chain via C-H⋯O(water) contacts.

A rare case of Guillain-Barre syndrome with pregnancy.

Guillain-Barre syndrome is a rare neuorological disorder affecting 6-24/ 1,00,000 population during pregnancy. The case involved a 29-year-old woman conceived after 14 years of marriage presenting with 16 weeks pregnancy and clinical symptoms of Guillain-Barre syndrome. It was confirmed by nerve conduction test and patient was started on intravenous immunoglobulin. She had a rapid recovery following therapy and subsequent follow-up 3 months later showed complete recovery and healthy ongoing pregnancy. Various diagnostic and treatment options are discussed.