In vitro Dissolution Testing of Rifampicin Powder Formulations For Prediction of Plasma Concentration-Time Profiles After Inhaled Delivery.

PURPOSE: The purpose of this study was to evaluate the in vitro lung dissolution of amorphous and crystalline powder formulations of rifampicin in polyethylene oxide (PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and to predict the in vivo plasma concentration-time profiles using the in vitro data. METHODS: The in vitro dissolution and permeation profiles of respirable rifampicin particles were studied using a custom-made dissolution apparatus. Data from the in vitro dissolution test were used to estimate the parameters to be used as the input for the simulation of in vivo plasma concentration-time profiles using STELLA® software. For prediction of in vivo profiles, a one-compartment model either with a first order elimination or with a Michaelis-Menten kinetics-based elimination was used. RESULTS: Compared to the crystalline formulation, the amorphous formulation showed rapid in vitro dissolution suggesting their possible faster in vivo absorption and higher plasma concentrations of rifampicin following lung delivery. However, the simulations suggested that both powder formulations would result in similar plasma-concentration time profiles of rifampicin. CONCLUSIONS: Use of an in vitro dissolution test coupled with a simulation model for prediction of plasma-concentration time profiles of an inhaled drug was demonstrated in this work. These models can also be used in the design of inhaled formulations by controlling their release and dissolution properties to achieve desired lung retention or systemic absorption following delivery to the lungs.

Aqueous electrolyte-mediated reversible K+ ion insertion into graphite.

Herein, reversible K+ ion insertion into graphite in an aqueous electrolyte is illustrated. It is shown that more facile diffusion of K+ ions is possible in natural graphite than in pyrolytic graphite.

Investigation of reversible metal ion (Li+, Na+, Mg2+, Al3+) insertion in MoTe2 for rechargeable aqueous batteries.

In this work, we report the electrochemical reactivity of MoTe2 for various metal ions with special emphasis on Al3+ ion storage in aqueous electrolytes for the first time. A stable discharge capacity of 100 mA h g-1 over 250 cycles at a current density of 1 Ag-1 could be obtained for the Al3+ ion, whereas inferior storage capacities were shown for other metal ions.

Fabrication of ultra-high numerical aperture GeO2-doped fiber and its use for broadband supercontinuum generation: publisher's note.

This publisher's note serves to correct Appl. Opt.56, 9315 (2017)APOPAI0003-693510.1364/AO.56.009315.

An electrochemical study on LiMn2O4 for Al3+ ion storage in aqueous electrolytes.

Herein, we report the possibility of electrochemical Al3+ ion insertion in LiMn2O4 in aqueous electrolytes. LiMn2O4 exhibits a discharge potential plateau of 1.5 V and a discharge capacity of 65 mA h g-1 is achieved at a current rate of 800 mA g-1 at the 75th cycle with the pre-addition of low-valence Mn ions in an aqueous AlCl3 electrolyte.

Noise-like pulse generation around 1.3-µm based on cascaded Raman scattering.

Based on cascaded Raman scattering, near-infrared (NIR) noise-like pulses (NLPs) were successfully demonstrated using a Yb-doped fiber amplifier system. Through a nonlinear fiber amplifier using a germanium-zirconia-silica Yb3+-doped single mode fiber as a gain fiber, the fourth-order Stokes wave (4th-SW) can be excited to extend the emission peak of approximately 1.2-µm and a 3-dB bandwidth of approximately 130 nm. To further shift the wavelength more efficiently toward 1.3 µm, filtered NLPs with an emission peak at 1075 nm were adopted as seeded pulses to excite the fifth-order Stokes wave (5th-SW) because of the better conversion efficiency of stimulated Raman scattering without gain competition with Yb-doped fiber. The generated NIR NLPs were shown to be an excellent light source for the photoluminescence emission from three photon absorption of perovskite to illustrate the red shift of the emission peak owing to the reabsorption effect.

Role of LRRK2 variant p.Gly2019Ser in patients with Parkinsonism.

Background & objectives: Parkinsonian disorder, including Parkinson's disease (PD), is an aetiologically complex neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in an autosomal dominant form of PD with variable penetrance. The identification of a common LRRK2 variant (p.Gly2019Ser) in dementia with Lewy bodies indicated its potential role in Parkinsonian disorder. The current study was aimed to identify the p.Gly2019Ser variant in Indian patients with Parkinsonian disorder. Methods: The patient group consisting of 412 classical PD patients, 107 PD patients with cognitive impairment, 107 patients with Parkinson plus syndrome and 200 unrelated controls were recruited from eastern part of India. The allele representing p.Gly2019Ser variant was screened by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results: The p.Gly2019Ser variant was identified in an East Indian young-onset female PD patient in a heterozygous state having several motor and autonomic problems without disturbed cognition. Her younger brother, sister and elder son harbouring the same mutation were asymptomatic carriers for the variant. However, the influence of DNM3 on decreased disease onset in this family was not clear. Interpretation & conclusions: Identification of the p.Gly2019Ser variant in only one patient among a large number of Indian patients (n=626) with Parkinsonian disorder in our study suggests a limited role of the LRRK2 variant towards disease pathogenesis.

Dopamine ß hydroxylase (DBH) polymorphisms do not contribute towards the clinical course of Wilson's disease in Indian patients.

BACKGROUND: Wilson's disease (WD) is a rare copper metabolism disorder with hepatic and neurological symptoms. Dopamine ß hydroxylase (DBH) encodes a copper-dependent mono-oxygenase that converts dopamine to norepinephrine, thereby regulating the endogenous dopamine content in the neurons. Polymorphisms of DBH have been reported to be associated with several neurological diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia and attention-deficit hyperactivity disorder, which have overlapping neurological symptoms with WD. The present study aimed to assess the role of DBH polymorphisms on the clinical course of WD. METHODS: In total, 141 WD patients from India were included in the present study. Three polymorphisms of DBH (rs1611115 in the promoter, rs1108580 in exon 2 and rs129882 in 3'-UTR) were screened for their association with the clinical attributes (hepatic and neurological features) and age of onset of WD using a polymerase chain reaction-restriction fragment length polymorphsm method and sequencing approach. The distribution of genotype or allele frequencies was tested using 2 × 2 contingency chi-squared and logistic regression analysis (additive, dominant and recessive model). RESULTS: The genotypic and allelic frequencies of these single nucleotide polymophisms did not vary significantly along with the clinical symptoms (hepatic and neurological) or the age of onset of WD. No significant association was observed when we analyzed our samples with respect to harboring different kinds of ATP7B mutations (nonsense/in-del and missense). CONCLUSIONS: The data obtained in the present study suggest that the selected DBH variants are unlikely to have any significant contribution towards modifying the clinical symptoms of Indian WD patients.

Regenerated grating produced in a multimaterial glass-based photosensitive fiber with an ultrahigh thermal regeneration ratio.

This work demonstrates thermal regeneration of gratings inscribed in a new type of multi-material glass-based photosensitive fiber. And isothermal annealing procedure has been carried out on a type-I seed grating (SG) imprinted in erbium-doped zirconia-yttria-alumina-germanium (Er-ZYAG) silica glass-based fiber, which is initiated from room temperature of 25°C up to 900°C. The findings show that the created regenerated grating (RG) has an ultrahigh thermal regeneration ratio with a value of 0.72.

Catalytic Reduction of Nitriles by Polymethylhydrosiloxane Using a Phenalenyl-Based Iron(III) Complex.

The reduction of nitriles to primary amines using an inexpensive silane such as polymethylhydrosiloxane (PMHS) is an industrially important reaction. Herein we report the synthesis of an earth-abundant Fe(III) complex bearing a phenalenyl-based ligand that was characterized by mass spectroscopy, elemental analysis, cyclic voltammetry, and single-crystal X-ray diffraction. The complex showed excellent catalytic activity toward reduction of aromatic, heteroaromatic, aliphatic, and sterically crowded nitriles to produce primary amines using polymethylhydrosiloxane (PMHS).

Nanosecond pulse laser generation at 1.55 and 2 µm regions by integrating a piece of newly developed chromium-doped fiber-based saturable absorber.

This paper demonstrated the nanosecond pulse laser operation at 1.55 and 2 µm wavelength regions using a newly develop chromium-doped fiber (CrDF) as a saturable absorber (SA) to convert efficiently continuous-wave laser operation to nanosecond pulse laser operation. The laser uses an erbium-doped fiber (EDF) and thulium-doped fiber as the gain medium. A piece of 10 cm long CrDF was integrated into both laser cavities to generate nanosecond pulse laser operation. In 1.55 region generation, an additional single-mode fiber (SMF) 100 m long was added into the EDF laser cavity. Stable pulse generation occurred at a repetition rate of 1 MHz with a pulse width of 432 ns and a signal-to-noise ratio (SNR) of 66 dB. The highest peak power of 24 mW was obtained at 142 mW pump power. In 2 µm region generation, the obtained repetition rate was 10 MHz with a pulse width and SNR of 59 ns and 41 dB, respectively. The highest peak power was only 8.3 mW. By looking into the findings, the newly developed CrDF SA has a potential to be further enhanced toward better generation of ultrashort pulse fiber lasers.

The influence of storage relative humidity on aerosolization of co-spray dried powders of hygroscopic kanamycin with the hydrophobic drug rifampicin.

The purpose of this study was to investigate the influence of storage humidity on in vitro aerosolization and physicochemical properties of co-spray dried powders of kanamycin with rifampicin. The powders were stored for one-month in an open Petri dish at different relative humidities (RHs) (15%, 43%, and 75%) and 25 ± 2 °C. The in vitro aerosolization (fine particle fraction, FPF) of the powders was determined by a next generation impactor (NGI). The moisture content, particle morphology and crystallinity of the powders were determined by Karl Fischer titration, scanning electron microscopy, and X-ray powder diffractometry, respectively. At all RH, the FPF of hydrophobic rifampicin-only powder was unaffected but the FPF of hygroscopic kanamycin-only powder significantly decreased even at 43% RH. The kanamycin-only particles fused together, crystallized and formed hard cakes at 75% RH. The aerosolization of kanamycin and rifampicin in the combination powders remained unaffected at 15% and 43% RH, but aerosolization significantly decreased at 75% RH. Enrichment of the surface of the particles with hydrophobic rifampicin did not protect the combination powders from moisture uptake but it prevented particle agglomeration up to 43% RH. At 75% RH, the moisture uptake led to agglomeration of the particles of the combination powder particles and consequently an increase in aerodynamic diameter. Further studies are required to investigate how rifampicin enrichment prevents particle agglomeration, the possible mechanisms (e.g. particle interactions due to capillary forces or electrostatic forces) for the changes in the aerosolization and changes in surface composition during storage.

Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis.

This study aimed to develop a combination dry powder formulation of ethionamide and moxifloxacin HCl as this combination is synergistic against drug-resistant Mycobacterium tuberculosis (Mtb). L-leucine (20% w/w) was added in the formulations to maximize the process yield. Moxifloxacin HCl and/or ethionamide powders with/without L-leucine were produced using a Buchi Mini Spray-dryer. A next generation impactor was used to determine the in vitro aerosolization efficiency. The powders were also characterized for other physicochemical properties and cytotoxicity. All the spray-dried powders were within the aerodynamic size range of <5.0 µm except ethionamide-only powder (6.0 µm). The combination powders with L-leucine aerosolized better (% fine particle fraction (FPF): 61.3 and 61.1 for ethionamide and moxifloxacin, respectively) than ethionamide-only (%FPF: 9.0) and moxifloxacin-only (%FPF: 30.8) powders. The combination powder particles were collapsed with wrinkled surfaces whereas moxifloxacin-only powders were spherical and smooth and ethionamide-only powders were angular-shaped flakes. The combination powders had low water content (<2.0%). All the powders were physically stable at 15% RH and 25 ± 2 °C during 1-month storage and tolerated by bronchial epithelial cell-lines up to 100 µg/ml. The improved aerosolization of the combination formulation may be helpful for the effective treatment of drug-resistant tuberculosis. Further studies are required to understand the mechanisms for improved aerosolization and test the synergistic activity of the combination powder.

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease.

Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests diverse neurological and hepatic phenotypes and different age of onset, even among the siblings, with same mutational background suggesting complex nature of the disease and involvement of other candidate genes. In that context, Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be potential candidates for modifying the WD phenotype and age of onset. This study aims to identify the contribution of APOE and PRNP polymorphisms on the variable phenotypic expression of Indian WD patients. A total of 171 WD patients and 291 controls from Indian population were included in this study. Two APOE cSNPs (rs429358 and rs7412) resulting in three isoforms and M129V (rs1799990) polymorphism of PRNP were examined for their association with WD and its clinical phenotypes. The APOE ԑ4 allele was found to be significantly overrepresented in WD patients compared to controls. However, the frequency of the APOE ԑ3 allele and ԑ3/ԑ3 genotype was significantly higher in WD patients without cognitive behavior impairment compared to the ones with the impairment. On the contrary, the PRNP allele representing Val129 was found to be present in higher proportion in WD patients with cognitive behavioral decline. Our data suggest that the APOE ԑ4 allele could act as a potential risk for the pathogenesis of WD. Also, APOE and PRNP might contribute toward the cognitive behavioral decline in a section of WD patients.

Neurological Emergencies in Pregnancy.

On one side, pregnancy is a bliss, a beautiful journey for most women while on other, it increases the risk of several diseases which may cause considerable morbidity and mortality in young women in the most productive period of their lives. Neurological emergencies in pregnancy often have grave prognosis and so, must be promptly diagnosed and treated. This article reviews the clinical features and management of some of the common severe neurological emergencies in pregnancy.

Graphene: A Cathode Material of Choice for Aluminum-Ion Batteries.

The pairing of an aluminum anode with a cathode of high energy and power density determines the future of aluminum-ion battery technology. The question is-"Is there any suitable cathode material which is capable of storing sufficiently large amount of trivalent aluminum-ions at relatively higher operating potential?". Graphene emerges to be a fitting answer. Graphene emerged in the research arena of aluminum-ion battery merely three years ago. However, research progress in this front has since been tremendous. Outperforming all other known cathode materials, several remarkable breakthroughs have been made with graphene, in offering extraordinary energy density, power density, cycle life, thermal stability, safety and flexibility. The future of the Al-graphene couple is indeed bright. This Minireview highlights the electrochemical performances, advantages and challenges of using graphene as the cathode in aluminum-ion batteries in conjugation with chloroaluminate based electrolytes. Additionally, the complex mechanism of charge storage in graphene is also elaborated.

Water Molecules Gating a Photoinduced One-Electron Two-Protons Transfer in a Tyrosine/Histidine (Tyr/His) Model of Photosystem†II.

We investigate a biomimetic model of a TyrZ /His190 pair, a hydrogen-bonded phenol/imidazole covalently attached to a porphyrin sensitizer. Laser flash photolysis in the presence of an external electron acceptor reveals the need for water molecules to unlock the light-induced oxidation of the phenol through an intramolecular pathway. Kinetics monitoring encompasses two fast phases with distinct spectral properties. The first phase is related to a one-electron transfer from the phenol to the porphyrin radical cation coupled with a domino two-proton transfer leading to the ejection of a proton from the imidazole-phenol pair. The second phase concerns conveying the released proton to the porphyrin N4 coordinating cavity. Our study provides an unprecedented example of a light-induced electron-transfer process in a TyrZ /His190 model of photosystem II, evidencing the movement of both the phenol and imidazole protons along an isoenergetic pathway.

Epidemiology of dementia and its burden in the city of Kolkata, India.

OBJECTIVES: Increase in aging population is expected to lead to increasing prevalence of dementia in India. In this study, we aimed to determine prevalence, incidence, and mortality of dementia and its subtypes and assess dementia burden in terms of disability-adjusted life years (DALY). METHODS: A community study was conducted over 5 years (2003-2008) in Kolkata, India, on 100,802 (males 53,209) randomly selected subjects to assess prevalence and capture data on incident cases and deaths. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, based on Global Burden of Disease 2010 approach. RESULTS: During 2003-2004, there were 103 (men 55) cases of dementia. The prevalence was 1.53% (age adjusted 1.12%) at age ≥65 years. In those ≥55 years age, average annual incidence rate of dementia was 72.57 per 100,000. All-cause standardized mortality ratio in dementia cases was 4.74 (men 6.19, women 3.03). The burden of dementia in 2007-2008 revealed that overall YLL was 47.13 per 100,000 and YLD ranged from 1.87 to 16.95 per 100,000 depending on the clinical severity of dementia. The overall DALY lost per 100,000 due to dementia for the year 2007-2008 was 74.19. CONCLUSIONS: This community study revealed a low prevalence and incidence of dementia with consequent low DALY-derived burden of illness compared with many industrialized nations. YLL formed major component of DALY indicating premature mortality to be an outcome of dementia burden. Copyright © 2016 John Wiley & Sons, Ltd.

Fabrication of ultra-high numerical aperture GeO2-doped fiber and its use for broadband supercontinuum generation.

We report the fabrication, characterization, and application (broadband supercontinuum [SC] generation) of ultra-high numerical-aperture heavily (50 mol. %) GeO2-doped optical fiber, obtained through a modified chemical vapor deposition process and rod-in-tube method. The formation of Ge-related diamagnetic defect centers, such as germanium oxygen defect centers (GeODC) with nonbridging lone electron pairs, confirmed by x-ray photoelectron spectroscopy and optical absorption studies, inducing hypolarizable local dipoles, may be responsible in boosting the nonlinear effects and enhancing stimulated Raman scattering at pumping with high-power pulses, culminating in generation of broadband SC generation. The SC spans toward the Stokes side up to 2.4 µm, under the action of ns-range pulses launched from a smartly Q-switched erbium-doped fiber laser with operation wavelength (1.56 µm) matching the zero-dispersion wavelength of the high GeO2-doped fiber.

Prevalence, burden, and risk factors of migraine: A community-based study from Eastern India.

BACKGROUND: Headache is common in communities; however, epidemiological research regarding its prevalence is infrequent in India. AIM: We planned to study the prevalence of migraine, its disease burden, and the associated risk factors. SETTING AND DESIGN: This is an urban community study conducted in Kolkata with a cross-sectional and nested case-control design. MATERIALS AND METHODS: The criteria to study headache among a representative sample (aged 20-50 years) was based on the International Classification of Headache Disorders-II. Sex- and age-matched controls without headache were evaluated for putative risk factors. The disease burden was measured as disability adjusted life years (DALY). RESULTS: Screening of 2421 individuals revealed that the 1-year prevalence of migraine was 14.12%. Education, environmental exposure, travel, and oral contraceptives determine approximately 75% of the underlying risks. DALY showed maximum burden among women in the age range of between 30 and 34 years. CONCLUSION: The community-based prevalence of migraine in India is similar to that observed in other countries except Africa. The burden was maximum among women. The risk factors responsible for migraine should be addressed and institution of public health measures are warranted.