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1.
Metab Eng ; 81: 144-156, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043641

RESUMO

Kynurenine pathway has a potential to convert L-tryptophan into multiple medicinal molecules. This study aims to explore the biosynthetic potential of kynurenine pathway for the efficient production of actinocin, an antitumor precursor selected as a proof-of-concept target molecule. Kynurenine pathway is first constructed in Escherichia coli by testing various combinations of biosynthetic genes from four different organisms. Metabolic engineering strategies are next performed to improve the production by inhibiting a competing pathway, and enhancing intracellular supply of a cofactor S-adenosyl-L-methionine, and ultimately to produce actinocin from glucose. Metabolome analysis further suggests additional gene overexpression targets, which finally leads to the actinocin titer of 719 mg/L. E. coli strain engineered to produce actinocin is further successfully utilized to produce 350 mg/L of kynurenic acid, a neuroprotectant, and 1401 mg/L of 3-hydroxyanthranilic acid, an antioxidant, also from glucose. These competitive production titers demonstrate the biosynthetic potential of kynurenine pathway as a source of multiple medicinal molecules. The approach undertaken in this study can be useful for the sustainable production of molecules derived from kynurenine pathway, which are otherwise chemically synthesized.


Assuntos
Escherichia coli , Cinurenina , Oxazinas , Cinurenina/genética , Cinurenina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Triptofano/genética , Triptofano/metabolismo , Glucose/genética , Glucose/metabolismo , Engenharia Metabólica , Vias Biossintéticas
2.
Med Res Rev ; 43(4): 775-828, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36710510

RESUMO

Modified and synthetic α-amino acids are known to show diverse applications. Histidine, which possesses numerous applications when subjected to synthetic modifications, is one such amino acid. The utility of modified histidines varies widely from remarkable biological activities to catalysis, and from nanotechnology to polymer chemistry. This renders histidine residue an important place in scientific research. Histidine is a well-studied scaffold and constitutes the active site of various enzymes catalyzing important reactions in the biological systems. A rational modification in histidine structure with a distinctly developed protocol extensively changes its physical and chemical properties. The utilization of modified histidines in search of potent, target selective and proteostable scaffolds is vital in the development of bioactive peptides with enhanced drug-likeliness. This review is a compilation and analysis of reported side-chain ring modifications at histidine followed by applications of ring-modified histidines in the synthesis of various categories of bioactive peptides and peptidomimetics.


Assuntos
Química Farmacêutica , Histidina , Humanos , Histidina/química , Peptídeos/farmacologia , Peptídeos/química , Descoberta de Drogas
3.
Chemistry ; 29(63): e202302499, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37584901

RESUMO

Spacious M4 L6 tetrahedra can act as catalytic inhibitors for base-mediated reactions. Upon adding only 5 % of a self-assembled Fe4 L6 cage complex, the conversion of the conjugate addition between ethylcyanoacetate and ß-nitrostyrene catalyzed by proton sponge can be reduced from 83 % after 75 mins at ambient temperature to <1 % under identical conditions. The mechanism of the catalytic inhibition is unusual: the octacationic Fe4 L6 cage increases the acidity of exogenous water in the acetonitrile reaction solvent by favorably binding the conjugate acid of the basic catalyst. The inhibition only occurs for Fe4 L6 hosts with spacious internal cavities: minimal inhibition is seen with smaller tetrahedra or Fe2 L3 helicates. The surprising tendency of the cationic cage to preferentially bind protonated, cationic ammonium guests is quantified via the comprehensive modeling of spectrophotometric titration datasets.

4.
Bioorg Chem ; 130: 106252, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379149

RESUMO

We investigated synthetic amino acid-based approach to design short peptide-based antibiotics. Tautomerically restricted, amphiphilic 1-aryl-l-histidines along with hydrophobic tryptophan were utilized to synthesize the designed peptides. l-Trp-l-His(1-biphenyl)-NHBzl (12e, IC50 = 1.91 µg/mL; MIC = 3.46 µg/mL) and l-His[1-(4-n-butylphenyl)]-l-Trp-l-His[1-(4-n-butylphenyl)]-NHBzl (16d, IC50 = 1.36 µg/mL; MIC = 2.46 µg/mL) produced potency against Cryptococcus neoformans. Peptides with moderate antibacterial activities (IC50s = 4.40-8.80 µg/mL) were also identified. The mechanism of action and cellular changes revealed that membrane disruption due to interactions of the positively charged peptides with the negatively charged membrane of the cryptococcal cells result in permeabilization, leading to pore formation. The internal localization of the peptides instigated the interactions with DNA causing fragmentation of the genetic material, which together with membrane disruption led to cell death. Flow cytometric analysis points to cells death by apoptotic pathway. Time kill kinetics and synergistic study confirmed the fungicidal nature and synergism with amphotericin B.


Assuntos
Membrana Celular , Criptococose , Cryptococcus neoformans , Peptídeos , Aminoácidos/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Criptococose/tratamento farmacológico , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Peptídeos/metabolismo
5.
Arch Pharm (Weinheim) ; 356(4): e2200576, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36592413

RESUMO

Cryptococcus neoformans, an opportunistic fungal pathogen, causes cryptococcosis in immunocompromised persons. A series of modified L-histidines-containing peptides are synthesized that exhibit promising activity against C. neoformans. Analog 11d [L-His(2-adamantyl)-L-Trp-L-His(2-phenyl)-OMe] produced potency with an IC50 of 3.02 µg/ml (MIC = 5.49 µg/ml). This peptide is noncytotoxic and nonhaemolytic at the MIC and displays synergistic effects with amphotericin B at subinhibitory concentration. Mechanistic investigation of 11d using microscopic tools indicates cell wall and membrane disruption of C. neoformans, while flow cytometric analysis confirms cell death by apoptosis. This study indicates that 11d exhibits antifungal potential and acts via the rapid onset of action.


Assuntos
Criptococose , Cryptococcus neoformans , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Antifúngicos/farmacologia , Peptídeos/farmacologia , Anfotericina B/farmacologia , Criptococose/microbiologia
6.
Drug Dev Res ; 84(3): 514-526, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36757096

RESUMO

Availability of a limited number of antifungal drugs created a necessity to develop new antifungals with distinct mode of action. Investigation on a new series of peptides led us to identify Boc-His-Trp-His[1-(4-tert-butylphenyl)] (10g) as the most promising inhibitor exhibiting IC50 value of 4.4 µg/mL against Cryptococcus neoformans. Analog 10g exhibit high selectivity to fungal cells and was nonhemolytic and noncytotoxic at its minimum inhibitory concentration. 10g produced fungicidal effect on growing cryptococcal cells and displayed synergistic effect with amphotericin B. Overall cationic character of 10g resulted in interaction with negatively charged fungal membrane while hydrophobicity enhanced penetration inside the cryptococcal cells causing hole(s) formation and disruption to the membrane as evident by the scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy analyses. Flow cytometric investigation revealed rapid death of fungal cells by apopotic pathway.


Assuntos
Aminoácidos , Antifúngicos , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Peptídeos/farmacologia , Membrana Celular , Testes de Sensibilidade Microbiana
7.
Environ Monit Assess ; 195(9): 1026, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552319

RESUMO

Groundwater is one of the important sources available for drinking, agricultural, domestic, and various other purposes in the study area. Study area is having agricultural importance and is famous for Basmati rice production in the world. In order to assess water suitability for irrigation and drinking purposes, 25 sampling sites were selected and water samples were collected from handpumps, borewells and motors from May 2022 to June 2022. Fifteen physico-chemical parameters and water quality index (WQI) was calculated to assess the drinking water suitability. The results obtained then compared with the BIS (2012) and WHO drinking water guidelines. For irrigation water suitability, irrigation water quality index (IWQI) and other indices were calculated. Heavy metal health risk assessment was also evaluated using target hazard quotient (THQ), carcinogenic risks (CR), non-carcinogenic risks, heavy metal pollution index (HPI), etc. Study found 60% of water samples under poor category of WQI. All water samples were found suitable for irrigation purposes according to different indices except for permeability index for which only 32% samples were found suitable. IWQI classifies 52%, 32%, and 12% of water samples under moderate, low, and no restriction category respectively. Groundwater of the study area found to be contaminated with copper (Cu), iron (Fe), lead (Pb), and chromium (Cr) while low contamination of zinc (Zn) and arsenic (As) was found according to heavy metal evaluation index (HEI). High contamination of chromium (HPI= 9740.8) and lead (HPI=188) was recorded as per HPI. HQ value for men, women, and children in case of zinc were found safe while HQ values for copper and lead in all population groups were found at risk. Overall, the study area was found highly contaminated with the lead, copper, and chromium concentrations. Thus, study recommends regular monitoring of the groundwater of study area as well as treatment before using this water for drinking purposes.


Assuntos
Água Potável , Água Subterrânea , Metais Pesados , Poluentes Químicos da Água , Criança , Feminino , Humanos , Qualidade da Água , Monitoramento Ambiental/métodos , Cobre , Metais Pesados/análise , Cromo , Zinco , Índia , Medição de Risco , Poluentes Químicos da Água/análise
8.
Bull Environ Contam Toxicol ; 111(1): 16, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460624

RESUMO

Chromium (Cr) occurs in several oxidation states from trivalent to hexavalent. However, hexavalent forms are more toxic and mainly produced by anthropogenic activities. A hydroponic experiment was conducted to analyse the comparative remediation of Cr by Marsilea minuta and Pistia stratiotes. Plants were exposed to four concentrations of Cr (0.5, 1.0, 1.5, and 2.0 mM) for 3 days. The highest accumulation of Cr was seen at the 1.5 mM concentration after 3 days in Marsilea (11.96 mg/g) and Pistia (18.78 mg/g). Dry weights decreased and malondialdehyde (MDA) levels increased in response to increasing Cr concentrations. Results indicate that both macrophytes are suitable candidates for Cr phytoremediation. Antioxidant-enzyme activity as a function of metal tolerance is imperative for a coherent understanding of plant physiology under metal stress.


Assuntos
Araceae , Cromo , Biodegradação Ambiental , Antioxidantes , Oxirredução
9.
Bioorg Chem ; 127: 106002, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35816873

RESUMO

The quest for new class of peptide-based antibiotics has steered this research towards the design and synthesis of short sequences possessing modified amphiphilic histidine along with hydrophobic tryptophan residues. The new structural class of dipeptides Trp-His(1-Bn)-OMe/NHBn and tripeptides His(1-Bn)-Trp-His(1-Bn)-OMe/NHBn demonstrated promising antifungal and antibacterial activities with membrane lytic action. The illustration of desirable hydrophilic-lipophilic balance appeared in the dipeptide Trp-His[1-(3,5-di-tert-butylbenzyl)]-NHBn (13d) that produced the most promising antifungal activity with IC50 value of 2.10 µg/mL and MIC = 3.81 µg/mL against C. neoformans and antibacterial activity against E. faecalis and S. aureus with identical IC50 value of 4.40 µg/mL and MIC of 8.0 µg/mL. Peptide 13d did not exhibit cytotoxicity and hemolysis at the MIC value and above. This quintessence amphiphilicity was further corroborated by the mechanistic elucidations, which revealed that, peptide act by utilizing charge and hydrophobicity as the primary characteristic tools. Owing to their fundamental affinity, the negatively charged fungal membrane is enacted upon by the positively charged peptide, whereas the intrinsic hydrophobicity of the peptide allowed penetration into the lipophillic core of the fungal cell membrane. Consequently, the integrity of cell membrane is compromised leading to increased fluidity. The membrane eventually disintegrates thereby creating a hollow pore and appearance of a doughnut into the cell when visualized under SEM. The cell death mechanism and damage to the cell wall and intracellular organelles have been elucidated with the help of flow cytometry, TEM and CLSM studies.


Assuntos
Antifúngicos , Cryptococcus neoformans , Antibacterianos/química , Antifúngicos/química , Dipeptídeos/química , Testes de Sensibilidade Microbiana , Peptídeos/química , Staphylococcus aureus
10.
Molecules ; 28(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36615282

RESUMO

Delineation of clinical complications secondary to fungal infections, such as cryptococcal meningitis, and the concurrent emergence of multidrug resistance in large population subsets necessitates the need for the development of new classes of antifungals. Herein, we report a series of ring-modified histidine-containing short cationic peptides exhibiting anticryptococcal activity via membrane lysis. The N-1 position of histidine was benzylated, followed by iodination at the C-5 position via electrophilic iodination, and the dipeptides were obtained after coupling with tryptophan. In vitro analysis revealed that peptides Trp-His[1-(3,5-di-tert-butylbenzyl)-5-iodo]-OMe (10d, IC50 = 2.20 µg/mL; MIC = 4.01 µg/mL) and Trp-His[1-(2-iodophenyl)-5-iodo)]-OMe (10o, IC50 = 2.52 µg/mL; MIC = 4.59 µg/mL) exhibit promising antifungal activities against C. neoformans. When administered in combination with standard drug amphotericin B (Amp B), a significant synergism was observed, with 4- to 16-fold increase in the potencies of both peptides and Amp B. Electron microscopy analysis with SEM and TEM showed that the dipeptides primarily act via membrane disruption, leading to pore formation and causing cell lysis. After entering the cells, the peptides interact with the intracellular components as demonstrated by confocal laser scanning microscopy (CLSM).


Assuntos
Cryptococcus neoformans , Histidina , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Peptídeos/farmacologia , Dipeptídeos , Testes de Sensibilidade Microbiana
11.
Environ Monit Assess ; 194(5): 342, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35389102

RESUMO

The present study tracked the city-wide dynamics of severe acute respiratory syndrome-corona virus 2 ribonucleic acids (SARS-CoV-2 RNA) in the wastewater from nine different wastewater treatment plants (WWTPs) in Jaipur during the second wave of COVID-19 out-break in India. A total of 164 samples were collected weekly between February 19th and June 8th, 2021. SARS-CoV-2 was detected in 47.2% (52/110) influent samples and 37% (20/54) effluent samples. The increasing percentage of positive influent samples correlated with the city's increasing active clinical cases during the second wave of COVID-19 in Jaipur. Furthermore, wastewater-based epidemiology (WBE) evidence clearly showed early detection of about 20 days (9/9 samples reported positive on April 20th, 2021) before the maximum cases and maximum deaths reported in the city on May 8th, 2021. The present study further observed the presence of SARS-CoV-2 RNA in treated effluents at the time window of maximum active cases in the city even after tertiary disinfection treatments of ultraviolet (UV) and chlorine (Cl2) disinfection. The average genome concentration in the effluents and removal efficacy of six commonly used treatments, activated sludge process + chlorine disinfection (ASP + Cl2), moving bed biofilm reactor (MBBR) with ultraviolet radiations disinfection (MBBR + UV), MBBR + chlorine (Cl2), sequencing batch reactor (SBR), and SBR + Cl2, were compared with removal efficacy of SBR + Cl2 (81.2%) > MBBR + UV (68.8%) > SBR (57.1%) > ASP (50%) > MBBR + Cl2 (36.4%). The study observed the trends and prevalence of four genes (E, RdRp, N, and ORF1ab gene) based on two different kits and found that prevalence of N > ORF1ab > RdRp > E gene suggested that the effective genome concentration should be calculated based on the presence/absence of multiple genes. Hence, it is imperative to say that using a combination of different detection genes (E, N, RdRp, & ORF1ab genes) increases the sensitivity in WBE.


Assuntos
COVID-19 , Vigilância Epidemiológica Baseada em Águas Residuárias , Biofilmes , Reatores Biológicos , COVID-19/epidemiologia , Cloro , Monitoramento Ambiental , Humanos , RNA Viral , RNA Polimerase Dependente de RNA , SARS-CoV-2 , Águas Residuárias
12.
J Food Sci Technol ; 59(3): 898-908, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35153320

RESUMO

Ellagic acid (EA) is a polyphenolic bioactive with a wide range of pharmacological activities. Regrettably, it possesses poor solubility, stability and permeability (in the gastrointestinal tract); and first-pass metabolism. Therefore, to address these challenges, the present research was aimed to encapsulate EA in cyclodextrin nanosponges (CDNS). Herein, the melt method and microwave-assisted technique have been employed for crafting CDNS. EA was loaded in CDNS via freeze-drying, followed by appropriate characterization. EA-CDNS were also assessed for encapsulation, particle size, zeta potential, and polydispersity index, which presented satisfactory results. In vitro, antioxidant activity was conducted using the DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. The solubilization efficacy of EA was analyzed in distilled water and compared with CDNS, which demonstrated ten folds augmentation for the selected batch. A remarkable improvement in the photostability of EA was also observed after its inclusion. In nutshell, the results demonstrated the superiority of the melt method in terms of solubility, entrapment, photostability, and antioxidant potential.

13.
Biochem J ; 477(10): 1879-1892, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32285912

RESUMO

Calcium (Ca2+) signaling is involved in the regulation of diverse biological functions through association with several proteins that enable them to respond to abiotic and biotic stresses. Though Ca2+-dependent signaling has been implicated in the regulation of several physiological processes in Chlamydomonas reinhardtii, Ca2+ sensor proteins are not characterized completely. C. reinhardtii has diverged from land plants lineage, but shares many common genes with animals, particularly those encoding proteins of the eukaryotic flagellum (or cilium) along with the basal body. Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is an important effector of Ca2+ signaling in animals, while calcineurin B-like proteins (CBLs) play an important role in Ca2+ sensing and signaling in plants. The present study led to the identification of 13 novel CBL-like Ca2+ sensors in C. reinhardtii genome. One of the archetypical genes of the newly identified candidate, CrCBL-like1 was characterized. The ability of CrCBL-like1 protein to sense as well as bind Ca2+ were validated using two-step Ca2+-binding kinetics. The CrCBL-like1 protein localized around the plasma membrane, basal bodies and in flagella, and interacted with voltage-gated Ca2+ channel protein present abundantly in the flagella, indicating its involvement in the regulation of the Ca2+ concentration for flagellar movement. The CrCBL-like1 transcript and protein expression were also found to respond to abiotic stresses, suggesting its involvement in diverse physiological processes. Thus, the present study identifies novel Ca2+ sensors and sheds light on key players involved in Ca2+signaling in C. reinhardtii, which could further be extrapolated to understand the evolution of Ca2+ mediated signaling in other eukaryotes.


Assuntos
Proteínas de Ligação ao Cálcio , Chlamydomonas reinhardtii , Receptores de Detecção de Cálcio , Proteínas de Algas/genética , Proteínas de Algas/metabolismo , Calcineurina/genética , Calcineurina/metabolismo , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Calmodulina/metabolismo , Membrana Celular/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Flagelos/metabolismo , Genoma de Planta , Receptores de Detecção de Cálcio/genética , Receptores de Detecção de Cálcio/metabolismo , Estresse Fisiológico
14.
J Contemp Dent Pract ; 21(5): 494-499, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32690830

RESUMO

AIM: This study aimed to compare the effects of subgingival delivery of 2% curcumin gel and 0.2% chlorhexidine gel as an adjunct to scaling and root planing (SRP) on clinical and microbiological parameters in the management of patients with chronic periodontitis. MATERIALS AND METHODS: In total, 25 systemically healthy individuals with age group ≥30 years diagnosed with chronic periodontitis were included in the study. The study was a double-blind split-mouth randomized control clinical trial. Two sites were selected in each patient and were randomly allocated to experimental and control sites. At baseline, measurements of site-specific periodontal parameters and collection of subgingival plaque sample were done. After full-mouth SRP, subgingival delivery of 2% curcumin gel in experimental sites and 0.2% chlorhexidine gel in control sites was done. At 1 and 3 months, subgingival plaque samples were collected again and site-specific periodontal parameters were measured. RESULTS: The experimental group (2% curcumin gel) showed statistically significant improvements in periodontal [i.e., sulcus bleeding index (SBI), probing pocket depth (PPD), and relative attachment level (RAL)] and microbiologic parameters in the form of colony-forming units (CFUs) in comparison with control group (0.2% chlorhexidine gel). CONCLUSION: Subgingival delivery of curcumin has shown effective anti-inflammatory and antibacterial properties. Since it is biologically accepted by the patients and its delivery in periodontal pockets can be recommended as an adjunct to SRP therapy for the treatment of patients with localized, moderate chronic periodontitis and in patients under the periodontal maintenance phase. CLINICAL SIGNIFICANCE: Curcumin being a herbal agent may be excellent alternative to chlorhexidine. It is biologically accepted by the patients and can be recommended as an adjunct to SRP in the treatment of localized moderate chronic periodontitis and periodontal maintenance patients.


Assuntos
Anti-Infecciosos Locais , Periodontite Crônica , Curcumina , Clorexidina , Raspagem Dentária , Humanos , Aplainamento Radicular
15.
Water Sci Technol ; 80(4): 665-674, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31661446

RESUMO

Granular activated carbon was doped with iron (Fe-AC) and was used to study the removal of Safranin O (SO) using the Fe-AC/H2O2 system for reactive adsorption and Fe-AC for adsorption. Fe-AC and H2O2 doses were optimized to obtain maximum removal of SO. Maximum removal was found to be 96.1% after 5 h using 1.0 g/L Fe-AC and 5.0 mM hydrogen peroxide doses for 10 mg/L initial SO concentration. Kinetic study suggested the suitability of the pseudo-first-order model for reactive adsorption. The Langmuir isotherm explained well the sorption of SO onto Fe-AC. Parallel-pore-reactive adsorption model was applied and validated. By fitting the experimental data to the model, it is observed that the surface reaction rate coefficient, kr, was found to be five times that of the apparent rate constant, kapp. Parameters such as the external liquid film mass transfer coefficient, macro-pore and micro-pore diffusivities were estimated by regression analysis. Pore diffusion and surface reaction were found to be rate controlling for adsorption and reactive adsorption, respectively. An oxidative degradation of SO took place via hydroxylation and ring cleavage processes.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Fenazinas
16.
Bioorg Med Chem Lett ; 28(10): 1776-1780, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29678464

RESUMO

A series of cationic lipo-benzamide compounds with varying lengths of hydrocarbon chains (C2M-C18M) were evaluated for anti-Candida activity. Four compounds harbouring 8-11 hydrocarbon chains demonstrated concentration-dependent inhibition of fungal cell growth with Minimum Inhibitory Concentration (MIC) of ≤6.2 µg ml-1. The most active compound (C9M) inhibited growth of both Candida albicans and non-albicans strains and is equally active against pairs of azole sensitive and resistant clinical isolates of C. albicans. Compound C9M also inhibited different stages of Candida biofilms. Scanning Electron Microscopy (SEM) of Candida cells after C9M treatment was also done and no significant cell lysis was observed. Hemolysis assay was performed and only 2.5% haemolysis was observed at MIC concentration.


Assuntos
Alcanos/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Alcanos/química , Antifúngicos/síntese química , Antifúngicos/química , Benzamidas/síntese química , Benzamidas/química , Benzamidas/farmacologia , Candida albicans/citologia , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
17.
Pharm Res ; 34(9): 1857-1871, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28608139

RESUMO

OBJECTIVE: To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. METHOD: Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability. Biodistribution studies were conducted to showcase their effective accumulation in tumor hypoxic regions where tumor associated macrophages (TAMs) are preferentially recruited. RESULTS: ChiNPs modulated TAMs differentiation resulting in decrement of CD206 positive population. This immunotherapeutic action was furnished by enhanced expression of Th1 specific cytokines. ChiNPs also facilitated an anti-angiogenetic effect which further reduces the possibility of tumor progression and metastasis.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Fatores Imunológicos/uso terapêutico , Nanopartículas/química , Zimosan/uso terapêutico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Mama/efeitos dos fármacos , Mama/imunologia , Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos , Feminino , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacocinética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Polietilenoimina/química , Eletricidade Estática , Distribuição Tecidual , Zimosan/administração & dosagem , Zimosan/farmacocinética
18.
Emerg Radiol ; 24(1): 39-45, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27620896

RESUMO

Subdural hematomas (SDHs) comprise a significant percentage of missed intracranial hemorrhage on axial brain CT. SDH detection rates could be improved with the addition of reformatted images. Though performed at some centers, the potential additional diagnostic sensitivity of reformatted images has not yet been investigated. The purpose of our study is to determine if the addition of coronal and sagittal reformatted images to an axial brain CT increases the sensitivity and specificity for detection of acute traumatic SDH. We retrospectively reviewed consecutive brain CTs acquired for acute trauma that contained new SDHs. An equivalent number of normal brain CTs served as control. Paired sets of images were created for each case: (1) axial images only ("axial only") and (2) axial, coronal, sagittal images ("reformat added"). Three readers interpreted both the axial only and companion reformat added for each case, separated by 1 month. Reading times and SDH detection rates were compared. One hundred SDH and 100 negative examinations were collected. Sensitivity and specificity for the axial-only scans were 75.7 and 94.3 %, respectively, compared with 88.3 and 98.3 % for reformat added. There was a 24.3 % false negative (missed SDH) rate with axial-only scans versus 11.7 % with reformat added (p = <0.001). Median reader interpretation times were longer with the addition of reformatted images (125 versus 89 s), but this difference was not significant (p = 0.23). The addition of coronal and sagittal images in trauma brain CT resulted in improved sensitivity and specificity as well as a reduction in SDH false negatives by greater than 50 %. Reformatted images substantially reduce the number of missed SDHs compared with axial images alone.


Assuntos
Hematoma Subdural/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Software
19.
J Nanosci Nanotechnol ; 16(4): 4180-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27451784

RESUMO

Although curcumin (Cur), has been poised to be an anticancer boon for quite some, its progress from bench to bed has been strained due to various pharmaceutical hurdles. Consequently curcumin has been entrapped in methoxy poly ethylene glycol and linoleic acid conjugated polymeric micelles (PMs) to not only tackle the routine issues but to also provide a synergetic effect against MCF-7 breast cancer cells. Optimized PMs of Cur had size 186.53 ± 12.10 nm with polydispersity index 0.143 ± 0.031 and zeta potential -30.1 ± 3.2 mV. Developed formulation (Mpeg-Cla-Cur PMs) was hemocompatible and had high cytotoxicity (IC50 55.80 ± 4.63 µ/mL) against MCF-7 cells in comparison to pure Cur suspension (IC50 75.05 ± 5.75 µg/mL). As postulated cell cycle arrest and apoptosis studies revealed synergetic effect of Mpeg-Cla-Cur PMs with higher cell population in G1 phase in addition to high apoptosis of MCF-7 cells as compared to pure Cur suspension and con- trol group. Pharmacokinetic studies also show PMs enhanced MRT and T1/2 of Cur indicating its longer retention time in body. Mpeg-Cla-Cur PMs might become as an excellent chemotherapeutic alternative candidate for treatment of breast cancer with higher commercial value.


Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Ácido Linoleico/química , Nanocápsulas/química , Polietilenoglicóis/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Curcumina/química , Difusão , Sinergismo Farmacológico , Humanos , Células MCF-7 , Nanocápsulas/administração & dosagem
20.
Int J Nurs Pract ; 22(3): 217-23, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26617329

RESUMO

The use of peripherally inserted central catheters (PICCs) provides important central venous accesses for clinical treatments, tests and monitoring. Compared with the traditional methods, intracardiac electrocardiogram (ECG)-guided method has the potential to guide more accurate tip positioning of PICCs. This study aimed to clinically evaluate the effectiveness of an intracardiac ECG to guide the tip positioning by monitoring characteristic P-wave changes. In this study, eligible patients enrolled September 2011 to May 2012 according to the inclusion and exclusion criteria received the catheterization monitored by intracardiac ECG. Then chest radiography was performed to check the catheter position. The results revealed that, with 117 eligible patients, all bar one patient who died (n = 116) completed the study, including 60 males and 56 females aged 51.2 ± 15.1 years. Most (n = 113, > 97%) had characteristic P-wave changes. The intracardiac ECG-guided positioning procedure achieved correct placement for 112 patients (96.56%), demonstrating 99.12% sensitivity and 100% specificity. In conclusion, the intracardiac ECG can be a promising technique to guide tip positioning of PICCs. However, since the sample size in this study is limited, more experience and further study during clinical practice are needed to demonstrate achievement of optimal catheterization outcomes.


Assuntos
Cateterismo Periférico/normas , Eletrocardiografia/métodos , Adulto , Idoso , Cateterismo Periférico/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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