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1.
AAPS PharmSciTech ; 25(1): 14, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191830

RESUMO

Vemurafenib (VMF) is a practically insoluble (< 0.1 µg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug.


Assuntos
Cromatografia de Fase Reversa , Polissorbatos , Disponibilidade Biológica , Vemurafenib , Solubilidade
2.
AAPS PharmSciTech ; 24(5): 130, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291443

RESUMO

Chemotherapy of multi-drug-resistant tuberculosis (TB) requires prolonged administration of multiple drugs. We investigated whether pulmonary delivery of minute doses of drugs, along with reduced oral doses of the same agents, would affect preclinical efficacy. We prepared dry powder inhalation (DPI) formulations comprising sutezolid (SUT), the second-generation pretomanid analog TBA-354 (TBA), or a fluorinated derivative of TBA-354 (32,625) in a matrix of the biodegradable polymer poly(L-lactide). We established formulation characteristics, doses inhaled by healthy mice, and preclinical efficacy in a mouse model of TB. Oral doses of 100 mg/kg/day or DPI doses of 0.25-0.5 mg/kg/day of drugs SUT, TBA-354, or 32,625 administered over 28 days were sub-optimally effective in reducing lung and spleen burden of Mycobacterium tuberculosis (Mtb) in infected mice. The addition of 0.25-0.5 mg/kg/day of SUT, TBA-354, or 32,625 as DPI to oral doses of 50 mg/kg/day was non-inferior in clearing Mtb from the lungs of infected mice. We concluded that adjunct therapy with inhaled second-line agents has the potential to reduce the efficacious oral dose.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Animais , Camundongos , Antituberculosos , Preparações Farmacêuticas , Redução da Medicação , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Administração por Inalação , Pós
3.
Pharm Res ; 39(10): 2621-2633, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35962268

RESUMO

BACKGROUND: It is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D3, i.e., 1, 25-dihydroxy vitamin D3 (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb). METHODS: We optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT). RESULTS: The DPI with or without concomitant ATT markedly improved the morphology of the lungs and mitigated histopathology in both the lungs and the spleens. The number of nodular lesions on the lung surface decreased from 43.7 ± 3.1 to 22.5 ± 3.9 with the DPI alone and to 9.8 ± 2.5 with DPI + ATT. However, no statistically significant induction of host antimicrobial peptide cathelicidin or reduction in bacterial burden was seen with the DPI alone. DPI + ATT did not significantly reduce the bacterial burden in the lungs compared to ATT alone. CONCLUSIONS: We concluded that HDT using the low dose calcitriol DPI contributed markedly to mitigation of pathology, but higher dose may be required to evoke significant induction of bactericidal host response and bactericidal activity in the lung.


Assuntos
Calcitriol , Tuberculose , Administração por Inalação , Animais , Antituberculosos/farmacologia , Calcitriol/farmacologia , Inaladores de Pó Seco , Camundongos , Pós , Tuberculose/tratamento farmacológico
5.
Appl Opt ; 55(8): 1996-2001, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26974794

RESUMO

The accuracy of the resonant frequency servo loop is a major concern for the high-performance operation of a resonant fiber optic gyro. For instance, a bias error as large as tens or even hundreds of degrees/hour has been observed at the demodulated output of the resonant frequency servo loop. The traditional frequency servo mechanism is not an efficient tool to address this problem. In our previous work, we proposed a novel method to minimize the laser frequency noise to the level of the shot noise by refractive index modulation by a thermally tunable resonator. In this paper, we performed the parameter optimization for the resonator coil, multifunction integrated-optics chip, and couplers by the transition matrix using the Jones matrix methodology to minimize the polarization error. With the optimized parameter values, we achieved the bias value of the resonator fiber optic gyro to 1.924°/h.

6.
Opt Lett ; 39(10): 2924-7, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24978238

RESUMO

Long-distance quantum communication relies on storing and retrieving photonic qubits in orthogonal field modes. The available degrees of freedom for photons are polarization, spatial-mode profile, and temporal/spectral profile. To date, methods exist for decomposing, manipulating, and analyzing photons into orthogonal polarization modes and spatial modes. Here we propose and theoretically verify the first highly efficient method to carry out analogous operations for temporally and spectrally overlapping, but field-orthogonal, temporal modes. The method relies on cascaded nonlinear-optical quantum frequency conversion.

7.
Drug Discov Today ; 29(7): 104049, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38830505

RESUMO

Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising. Bacteriophages and their gene products have garnered interest as potential therapeutic options for bacterial infections. Here, we have compiled information on bacteriophages and their products that can kill Mycobacterium tuberculosis or NTM. We summarize the mechanisms whereby viable phages can access macrophage-resident bacteria and not elicit immune responses, review methodologies of pharmaceutical product development containing mycobacteriophages and their gene products, mainly lysins, in the context of drug regulatory requirements and we discuss industrially relevant methods for producing pharmaceutical products comprising mycobacteriophages, emphasizing delivery of mycobacteriophages to the lungs. We conclude with an outline of some recent case studies on mycobacteriophage therapy.


Assuntos
Micobacteriófagos , Humanos , Animais , Tuberculose/tratamento farmacológico , Mycobacterium tuberculosis , Terapia por Fagos/métodos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/terapia , Infecções por Mycobacterium/terapia , Infecções por Mycobacterium/tratamento farmacológico
8.
Int J Pharm ; 658: 124192, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38703931

RESUMO

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.


Assuntos
Administração Oftálmica , Sistemas de Liberação de Medicamentos , Oftalmopatias , Nanopartículas , Animais , Humanos , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Olho/metabolismo , Olho/efeitos dos fármacos , Oftalmopatias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
9.
Heliyon ; 10(5): e26746, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495155

RESUMO

This study examined the influence of fireworks on atmospheric aerosols over the Southern Indian city of Hyderabad during festival of Diwali using mass closure, stable carbon isotopes and the EPA-PMF model. Identification of chemical species in day and night time aerosol samples for 2019 and 2020 Diwali weeks showed increased concentrations of NH4+, NO3-, SO42-, K+, organic carbon (OC), Ba, Pb and Li, which were considered as tracers for fireworks. PM10 source apportionment was done using inorganic (trace elements, major ions) and carbonaceous (organic and elemental carbon; OC & EC) constituents, along with stable isotopic compositions of TC and EC. K+/Na+ ∼1 and K+nss/OC > 0.5 indicated contribution from fireworks. High NO3-, NH4+, Na+, Cl- and SO42- suggested the presence of deliquescent salts NaCl, NH4NO3 and (NH4)2SO4. TAE/TCE >1 suggested H+ exclusion, indicating possible presence of H2SO4 and NH4HSO4 in the aerosols. Ba, Pb, Sb, Sr and Fe increased by 305 (87), 12 (11), 12 (3), 3 (2) and 3 (4) times on Diwali nights, compared to pre-Diwali of 2019 (2020), and are considered as metallic tracers of fireworks. δ13CTC and δ13CEC in aerosols closely resembled that of diesel and C3 plant burning emissions, with meagre contribution from firecrackers during Diwali period. The δ13CEC was relatively depleted than δ13CTC and δ13COC. For both years, δ13COC-EC (δ13COC - δ13CEC) were positive, suggesting photochemical aging of aerosols during long-range transport, while for pre-Diwali 2019 and post-Diwali 2020, δ13COC-EC were negative with high OC/EC ratio, implying secondary organic aerosols formation. High toluene during Diwali week contributed to fresh SOA formation, which reacted with precursor 12C, leading to 13C depletions. Eight-factored EPA-PMF source apportionment indicated highest contribution from residue/waste burning, followed by marine/dust soil and fireworks, while least was contributed from solid fuel/coal combustion.

10.
Microbes Infect ; 26(3): 105282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38135025

RESUMO

Mycobacterium tuberculosis (Mtb) infection leads to upregulation of Suppressors of Cytokine signaling (SOCS) expression in host macrophages (Mϕ). SOCS proteins inhibit cytokine signaling by negatively regulating JAK/STAT. We investigated this host-pathogen dialectic at the level of transcription. We used phorbol-differentiated THP-1 Mϕ infected with Mtb to investigate preferential upregulation of some SOCS isoforms that are known to inhibit signaling by IFN-γ, IL-12, and IL-6. We examined time kinetics of likely transcription factors and signaling molecules upstream of SOCS transcription, and survival of intracellular Mtb following SOCS upregulation. Our results suggest a plausible mechanism that involves PGE2 secretion during infection to induce the PKA/CREB axis, culminating in nuclear translocation of C/EBPß to induce expression of SOCS1. Mtb-infected Mϕ secreted IL-10, suggesting a mechanism of induction of STAT3, which may subsequently induce SOCS3. We provide evidence of temporal variation in SOCS isoform exspression and decay. Small-interfering RNA-mediated knockdown of SOCS1 and SOCS3 restored the pro-inflammatory milieu and reduced Mtb viability. In mice infected with Mtb, SOCS isoforms persisted across Days 28-85 post infection. Our results suggest that differential temporal regulation of SOCS isoforms by Mtb drives the host immune response towards a phenotype that facilitates the pathogen's survival.


Assuntos
Mycobacterium tuberculosis , Humanos , Animais , Camundongos , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Macrófagos/microbiologia , Interleucina-12 , Isoformas de Proteínas/metabolismo
11.
Biomater Adv ; 158: 213773, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38277903

RESUMO

Despite being an approved antiemetic for more than five decades, the clinical usefulness of prochlorperazine is limited by its low solubility and inconsistent absorption in the gastrointestinal tract, which presents challenges for nanotherapeutic interventions. Here, we report the preparation of a highly soluble and permeable nanofiber formulation of prochlorperazine using the Quality-by-Design approach. The final nanofiber formulation with drug entrapment of 88.02 ± 1.14 % was obtained at 20.0 kV, with a flow rate of 0.5 ml/h and tip-to-collector distance of 19.9 cm. Physio-mechanical properties, such as thickness (0.42 ± 0.02 mm), pH resistance (7.04 ± 0.08), folding endurance (54 ± 5), and tensile strength (0.244 ± 0.02 N.mm-2), were appropriate for packaging and application to oromucosal surfaces. The content uniformity (93.48-106.63 %) and weight variation (<1.8 mg) of the optimal nanofiber formulation were within the permissible limits prescribed for orodispersible films. Microscopical investigations confirm a randomly deposited and dense network of woven nanofibers with an average diameter of 363 ± 5.66 nm. The drug particles were embedded homogeneously on the fiber in the nanoform (4.27 ± 1.34 nm). The spectral analysis using TEM-EDS shows diffraction peaks of sulfur and chlorine, the elemental constituents of prochlorperazine. The drug was amorphized in the nanofiber formulation, as led by the decline of the crystallinity index from 87.25 % to 7.93 % due to electrostatic destabilization and flash evaporation of the solvent. The enthalpy of fusion values of the drug in the nanofiber mat decreased significantly to 23.6 J/g compared to its pristine form, which exhibits a value of 260.7 J/g. The nanofibers were biocompatible with oral mucosal cells, and there were no signs of mucosal irritation compared to 1 % sodium lauryl sulfate. The fiber mats rapidly disintegrated within <1 s and released ≈91.49 ± 2.1 % of the drug within 2 min, almost 2-fold compared to the commercial Stemetil MD® tablets. Similarly, the cumulative amount of the drug permeated across the unit area of the oromucosal membrane was remarkably high (31.28 ± 1.30 µg) compared to 10.17 ± 1.11 µg and 13.10 ± 1.79 µg from the cast film and drug suspension. Our results revealed these nanofiber formulations have the potential to be fast-dissolving oromucosal delivery systems, which can result in enhanced bioavailability with an early onset of action due to rapid disintegration, dissolution, and permeation.


Assuntos
Nanofibras , Proclorperazina , Solubilidade
12.
Tuberculosis (Edinb) ; 148: 102536, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38976934

RESUMO

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb.


Assuntos
Antituberculosos , Calcitriol , Modelos Animais de Doenças , Pulmão , Macrófagos , Mycobacterium tuberculosis , Animais , Calcitriol/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Macrófagos/imunologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Feminino , Administração por Inalação , Catelicidinas , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/imunologia , Poliésteres , Interações Hospedeiro-Patógeno , Fatores de Tempo , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Baço/microbiologia , Baço/patologia , Baço/imunologia , Quimioterapia Combinada , Peptídeos Catiônicos Antimicrobianos/farmacologia , Camundongos
13.
Opt Express ; 21(11): 13840-63, 2013 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-23736638

RESUMO

We explore theoretically the feasibility of using frequency conversion by sum- or difference-frequency generation, enabled by three-wave-mixing, for selectively multiplexing orthogonal input waveforms that overlap in time and frequency. Such a process would enable a drop device for use in a transparent optical network using temporally orthogonal waveforms to encode different channels. We model the process using coupled-mode equations appropriate for wave mixing in a uniform second-order nonlinear optical medium pumped by a strong laser pulse. We find Green functions describing the process, and employ Schmidt (singular-value) decompositions thereof to quantify its viability in functioning as a coherent waveform discriminator. We define a selectivity figure of merit in terms of the Schmidt coefficients, and use it to compare and contrast various parameter regimes via extensive numerical computations. We identify the most favorable regime (at least in the case of no pump chirp) and derive the complete analytical solution for the same. We bound the maximum achievable selectivity in this parameter space. We show that including a frequency chirp in the pump does not improve selectivity in this optimal regime. We also find an operating regime in which high-efficiency frequency conversion without temporal-shape selectivity can be achieved while preserving the shapes of a wide class of input pulses. The results are applicable to both classical and quantum frequency conversion.

14.
Environ Geochem Health ; 35(4): 439-54, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23475496

RESUMO

Chronic kidney disease (CKD) has been reported in a few coastal regions of Srikakulam district and Chimakurthy mandal (~30-40 km away from the coast) in the Prakasham district of Andhra Pradesh, India. Some medical experts and the local population have apprehensions that the drinking water is the sole reason for this disease in these areas. As the source of drinking water for these two regions is only groundwater, major ions and trace elements were measured on waters from different sources to identify the causative element(s), if any. Comparison of hydrochemical data of both the areas indicates that groundwater in Srikakulam coastal region is less mineralized than that of the Prakasham region, which may be due to geological, hydrological and climatic reasons. However, the concentrations of various inorganic chemicals are within the permissible limits of drinking water. Hence, for the inorganic chemicals to cause ill health, including CKD, is unlikely or is ruled out in the study areas.


Assuntos
Água Potável/análise , Exposição Ambiental , Água Subterrânea/análise , Insuficiência Renal Crônica/induzido quimicamente , Poluentes Químicos da Água/análise , Ânions/análise , Cátions/análise , Cromatografia por Troca Iônica , Monitoramento Ambiental , Humanos , Índia/epidemiologia , Espectrometria de Massas , Insuficiência Renal Crônica/epidemiologia , Oligoelementos/análise
15.
Indian Pediatr ; 60(1): 55-62, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36639971

RESUMO

INTRODUCTION: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. METHODS: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0-18 years, and the English language. RESULTS: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. CONCLUSION: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India.


Assuntos
Hepatite C Crônica , Hepatite C , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Ribavirina/uso terapêutico , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Quimioterapia Combinada , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/induzido quimicamente , Interferons/uso terapêutico , Genótipo , Resultado do Tratamento
16.
Tuberculosis (Edinb) ; 134: 102198, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35344918

RESUMO

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, 'heals the host; ' but does not 'kill the bug.'


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Antituberculosos/uso terapêutico , Modelos Animais de Doenças , Terapia Genética , Interferon gama/genética , Pulmão/microbiologia , Camundongos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
17.
Adv Exp Med Biol ; 696: 505-13, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21431591

RESUMO

In this chapter, various block-based adaptive filter structures are presented, which estimate the deterministic components of the electrocardiogram (ECG) signal and remove the noise. The familiar Block LMS algorithm (BLMS) and its fast implementation, Fast Block LMS (FBLMS) algorithm, is proposed for removing artifacts preserving the low frequency components and tiny features of the ECG. The proposed implementation is suitable for applications requiring large signal-to-noise ratios with fast convergence rate. Finally, we have applied these algorithms on real ECG signals obtained from the MIT-BIH database and compared its performance with the conventional LMS algorithm. The results show that the performance of the block-based algorithms is superior than the LMS algorithm.


Assuntos
Algoritmos , Artefatos , Eletrocardiografia/estatística & dados numéricos , Biologia Computacional , Simulação por Computador , Bases de Dados Factuais , Humanos , Movimento/fisiologia , Músculos/fisiologia , Processamento de Sinais Assistido por Computador
18.
Environ Monit Assess ; 174(1-4): 481-92, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20443136

RESUMO

Nitrate is one of the common contaminants in the present day groundwaters resulting from increased population associated with poor sanitary conditions in the habitat area and increased agricultural activity. The hydrochemical measurements on water samples from a virgin watershed, situated in the basaltic geo-environment, have become necessary as the groundwater is the only source of drinking water for the villagers of the area. High preferential recharge conditions prevail in the area due to fractures in the solid basaltic lava flows. Instead of dilution due to fresh recharge, the post-monsoon hydrochemical concentrations in the groundwater are observed to have increased probably due to fast migration of pollutants to the aquifer through preferential recharge. As a result, the deep aquifer waters are more contaminated with hazardous nitrate than the shallow waters. Further, the village environ wells are more polluted with nitrate than the agriculture areas which could be attributed to the unhygienic sanitary conditions and livestock waste dump pits in the villages. This study suggests proper management of the sewage system and creation of suitable dump yard for the livestock and household waste to minimize the level of nitrate pollution in the well waters of village environs.


Assuntos
Nitratos/análise , Poluentes Químicos da Água/análise , Índia , Silicatos , Abastecimento de Água
19.
Environ Monit Assess ; 171(1-4): 561-77, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20069449

RESUMO

The groundwater of Nalgonda district is well known for its very high fluoride content for the past five decades. Many researchers have contributed their scientific knowledge to unravel causes for fluoride enrichment of groundwater. In the present paper, an attempt has been made to relate the high fluoride content in the groundwater to hydrogeochemical characterization of the water in a fracture hard rock terrain--the Wailpally watershed. Groundwater samples collected from all the major geomorphic units in pre- and post-monsoon seasons were analyzed for its major ion constituents such as Ca(2+), Mg(2+), Na(+), K(+), CO3-, HCO3-, Cl(-), SO4(-2), NO3-, and F(-). The groundwaters in the watershed have the average fluoride content of 2.79 mg/l in pre-monsoon and 2.83 mg/l in post-monsoon. Fluoride concentration in groundwater does not show perceptible change neither with time nor in space. The ionic dominance pattern is in the order of Na(+) > Ca(2+) > Mg(2+) > K(-) among cations and HCO3- Cl(-) > SO4(-2) NO3- F(-) among anions in pre-monsoon. In post-monsoon, Mg replaces Ca(2+) and NO3- takes the place of SO4(-2). The Modified Piper diagram reflect that the water belong to Ca(+2)-Mg(+2)-HCO3- to Na(+)-HCO3- facies. Negative chloralkali indices in both the seasons prove that ion exchange between Na(+) and K(+) in aquatic solution took place with Ca(+2) and Mg(+2) of host rock. The interpretation of plots for different major ions and molar ratios suggest that weathering of silicate rocks and water-rock interaction is responsible for major ion chemistry of groundwater in Wailpally watershed. Chemical characteristics and evolution of this fluoride-contaminated groundwater is akin to normal waters of other hard rock terrain; hence, it can be concluded that aquifer material play an important role in the contribution of fluoride in to the accompanying water. High fluoride content in groundwater can be attributed to the continuous water-rock interaction during the process of percolation with fluoride-bearing country rocks under arid, low precipitation, and high evapotranspiration conditions.


Assuntos
Fluoretos/análise , Água Doce/química , Poluentes Químicos da Água/análise , Abastecimento de Água/análise , Cálcio/análise , Tempestades Ciclônicas , Monitoramento Ambiental , Geologia , Humanos , Índia , Magnésio/análise , Estações do Ano
20.
Nanoscale Adv ; 2(9): 4125-4132, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36132780

RESUMO

Fluorescent silicon nanoparticles (SiNPs) might be one of the excellent candidates for use as optical markers in biological profiling and diagnostic applications. To exploit this perspective, they ought to be essentially synthesized from any green precursor rich in silicon. Stable dispersibility in water along with prolonged luminescence under different conditions is also desired. Moreover, one of the main challenges is to produce such optically (photoluminescence) stable and water-dispersible SiNPs. In our present work, we have reported the synthesis of a highly stable silicon nanoparticle aqueous suspension via a single-step microwave-assisted facile green route. Our as-prepared SiNPs exhibit inherent stable dispersibility, strong fluorescence, and photo-stable behavior. The experimental results demonstrate that the synthesized SiNPs are highly suitable for the detection of Fe(iii) ions. This optical sensing study opens a new avenue for use of SiNPs as a valuable optical probe in chemosensory applications. Our results provide a single-step methodology for the synthesis of highly stable SiNPs from a biological precursor, which can be used as a promising tool for various chemical and biological applications.

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