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1.
Langmuir ; 40(16): 8418-8426, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38588383

RESUMO

Degradation of dyes under natural light sources is one of the most active research areas in basic science for greener technology. In this context, the photocatalytic activity of semiconductors has received massive attention in solving water treatment-related issues as these possess enormous potential for degrading organic impurities. Here, we report that barium aluminate (BaAl2O4, BAO), which has been extensively studied for photoluminescence applications, is found to be a highly potent candidate for photocatalytic activities. We have explored the degradation of dyes (meant for water purification) by using the photocatalytic properties of pure and Dy- and Yb-codoped BAO. Crystal structure, electron microscopy, and Raman analysis of the autocombustion-synthesized pure and codoped BAO samples revealed significant morphological changes such as increased particle size and stabilization of rod-like structures. UV-vis absorbance measurements confirm the presence of multiple bandgaps in the BAO samples, which is substantiated by X-ray absorption spectroscopy measurements. Photocatalytic degradation studies of methylene blue (MB) dye (with different catalyst concentrations, dopings, and MB dye concentrations) have been carried out by using BAO. The kinetics of the photocatalytic degradation measurements has been explained by the Boltzmann distribution function, and the fastest (in less than 40 min), with more than 99% degradation of MB impurity, is reported here for the first time in BAO compounds. Synthesized BAO samples show excellent cyclic stability, which is essential for their potential applications in environmental remediation. The trade-off between the enhancement of surface area and increased particle size is considered the key parameter for controlling the photocatalytic performance of the BAO catalyst after Dy and Yb codopings.

2.
PeerJ Comput Sci ; 10: e1854, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435573

RESUMO

Named Data Networking (NDN) has emerged as a promising network architecture for content delivery in edge infrastructures, primarily due to its name-based routing and integrated in-network caching. Despite these advantages, sub-optimal performance often results from the decentralized decision-making processes of caching devices. This article introduces a paradigm shift by implementing a Software Defined Networking (SDN) controller to optimize the placement of highly popular content in NDN nodes. The optimization process considers critical networking factors, including network congestion, security, topology modification, and flowrules alterations, which are essential for shaping content caching strategies. The article presents a novel content caching framework, Popularity-aware Caching in Popular Programmable NDN nodes (PaCPn). Employing a multi-variant vector autoregression (VAR) model driven by an SDN controller, PaCPn periodically updates content popularity based on time-series data, including 'request rates' and 'past popularity'. It also introduces a controller-driven heuristic algorithm that evaluates the proximity of caching points to consumers, considering factors such as 'distance cost,' 'delivery time,' and the specific 'status of the requested content'. PaCPn utilizes customized DATA named packets to ensure the source stores content with a valid residual freshness period while preventing intermediate nodes from caching it. The experimental results demonstrate significant improvements achieved by the proposed technique PaCPn compared to existing schemes. Specifically, the technique enhances cache hit rates by 20% across various metrics, including cache size, Zipf parameter, and exchanged traffic within edge infrastructure. Moreover, it reduces content retrieval delays by 28%, considering metrics such as cache capacity, the number of consumers, and network throughput. This research advances NDN content caching and offers potential optimizations for edge infrastructures.

3.
Eur J Drug Metab Pharmacokinet ; 49(2): 239-247, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38376657

RESUMO

BACKGROUND AND OBJECTIVES: The novel tyrosine kinase inhibitor (TKI) dasatinib, a multitarget inhibitor of Bcr-Abl and Src family kinases, has been licensed for the treatment of Ph+ acute lymphoblastic leukemia and chronic myeloid leukemia. Many citrus-based foods include the flavonoid naringenin, which is commonly available. Dasatinib is a Cyp3a4, P-gp, and Bcrp1 substrate, which makes it sensitive to potential food-drug interactions. The concurrent use of naringenin may change the pharmacokinetics of dasatinib, which could result in adverse effects and toxicity. The present investigation examined the impact of naringenin on the pharmacokinetics interactions of DAS and proposes a possible interaction mechanism in Wistar rats. METHODS: Rats were provided with a single oral dose of dasatinib (25 mg/kg) with or without naringenin pretreatment (150 mg/kg p.o. daily for 7 days, n = 6 in each group). Dasatinib was quantified in plasma by UHPLC MS/MS assay. Noncompartmental analysis was used to compute the pharmacokinetic parameters, and immunoblot was used to assess the protein expression in the hepatic and intestinal tissues. RESULTS: Following 7 days of naringenin pretreatment, the plasma mean concentration of dasatinib was enhanced compared with without pretreatment. In rats that were pretreated with naringenin, the pharmacokinetics of the orally administered dasatinib (25 mg/kg) was shown to be significantly different from that of dasatinib given without pretreatment (p < 0.05). There was a significant enhancement in pharmacokinetic parameters elimination half-life (T1/2), time to maximum concentration ( Tmax), maximum concentration )Cmax), area under the concentration-time curve (AUC0-t), area under the moment curve (AUMC0-∞), and mean residence time (MRT) by 28.41%, 50%, 103.54%, 72.64%, 115.08%, and 15.19%, respectively (p < 0.05) and suppression in elimination rate constant (Kel), volume of distribution (Vd), and clearance (CL) by 21.09%, 31.13%, and 46.25%, respectively, in comparison with dasatinib alone group (p < 0.05). The enhancement in dasatinib bioavailability and systemic exposure resulted from the significant inhibition of Cyp3a2, Mdr1/P-gp, and Bcrp1 expression and suppression of the dasatinib hepatic and intestinal metabolism, which enhanced the rate of dasatinib absorption and decreased its elimination. CONCLUSION: Concurrent use of naringenin-containing supplements, herbs, or foods with dasatinib may cause serious and potentially life-threatening drug interactions. Further studies are necessary to determine the clinical significance of these findings.


Assuntos
Flavanonas , Interações Alimento-Droga , Espectrometria de Massas em Tandem , Ratos , Animais , Dasatinibe , Ratos Wistar
4.
Influenza Other Respir Viruses ; 18(2): e13262, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38387887

RESUMO

INTRODUCTION: Influenza A viruses cause global health concerns due to their high amino acid substitution rates. They are linked to yearly seasonal epidemics and occasional pandemics. This study focused on sequencing influenza A virus strains in Pakistan. MATERIALS AND METHODS: We analyzed the genetic characteristics of influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Pakistan from January 2020 to January 2023. Whole genome sequences from influenza A (n = 126) virus isolates were amplified and sequenced by the Oxford Nanopore (MinION) platform. RESULTS: The HA genes of influenza A(H1N1)pdm09 underwent amino acid substitutions at positions K54Q, A186T, Q189E, E224A, R259K, and K308R in sequenced samples. The HA genes of influenza A(H3N2) had amino acid substitutions at G53D, E83K, D104G, I140M, S205F, A212T, and K276R in the sequenced samples. Furthermore, the HA gene sequences of influenza A(H1N1)pdm09 in this study belonged to subclade 6B.1A.5a.2a. Similarly, the HA gene sequences of influenza A(H3N2) were classified under six subclades (3C.3a.1 and 3C.2a1b.2a [2, 2a.1, 2b, 2c, and 2a.3b]). Notably, amino acid substitutions in other gene segments of influenza A(H1N1)pdm09 and A(H3N2) were also found. CONCLUSION: These findings indicate influenza A(H1N1)pdm09 and A(H3N2) viruses co-circulated during the 2020-2023 influenza season in Pakistan. Continued surveillance is crucial for real-time monitoring of possible high-virulence variation and their relevance to existing vaccine strains.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Humanos , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H3N2 , Estações do Ano , Paquistão/epidemiologia , Filogenia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Evolução Molecular
5.
Heliyon ; 10(4): e26050, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404875

RESUMO

Mn-substituted Cu and Zn co-doped spinel-typed nano-crystalline ferrites having nominal composition Ni0.50-xMnxCu0.15Zn0·35Fe2O4 (x = 0.00-0.25 in 0.05 increments) have been prepared through the citric acid assisted sol-gel auto-combustion technique. From the XRD measurements, it was found that several intense peaks ensured the cubic spinel-based ferrite structure beyond the formation of any impurity peaks. The crystallite sizes varied from 20 to 28 nm for ash-burnt powders following the coalescence process that decreased the lattice defects and strain. With an increase in Mn concentration, the hopping length (LA) of the tetrahedral A-site increases, while the hopping length (LB) of the octahedral B-site decreases with enhanced lattice constant. The sintered samples' average grain sizes, as measured using the Field Emission Scanning Micrographs (FESEM), differed from around 1.40 to 5.30 µm. Incorporating Mn-ion accelerates grain growth and crystallite size with increased bulk density and reduced porosity due to heat treatment. For increasing sintering temperature along with Mn concentration, porosity drops from 42% to 3%, resulting in enhancing the magnetic induction of the prepared ferrites. The 25% Mn substituted composition displays the maximum initial permeability (µi' = 315), which is ∼7 times larger than the pristine composition. Due to the reduction of Ni content, the relative quality factor rises but the magnetic loss tangent reduces. An increased trends of µi' are accompanied by decreased resonant frequency, obeying Snoek's law. According to the experimental findings, the high spin Mn substitution in the composition causes the saturation magnetization to increase while the coercivity and Néel temperature drop with increasing grain size. Hence, the locally prepared low-cost Nano-crystalline Ni-Mn-Cu-Zn ferrites bearing excellent properties can be a good candidate for promising future applications in nanotechnology.

6.
Heliyon ; 10(1): e23096, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163161

RESUMO

A simple and inexpensive spray pyrolysis deposition (SPD) approach was used to produce TiO2 and Cr (2-8) at.%-doped TiO2 thin films. To explore the morphological features of the films, FE-SEM micrographs were used and found that 6 and 8 at.% TiO2:Cr films had fibrous patterns with diameters of 0.45 and 0.78 µm, respectively, while the remainder of the films were agglomerated particles. From X-ray diffraction investigation, it was found that the TiO2 thin films had an anatase crystal phase (tetragonal) up to 6 at.% Cr doping, while an anatase-rutile mixed crystalline phase was identified for 8 at.% Cr doping. The crystallite size of the pristine TiO2 film was 35 nm, while for TiO2:Cr films, it ranges from 35 to 46 nm. The Fizeau fringes technique was employed to measure the thickness of the TiO2 film and 165 nm was found for pristine TiO2 and 164-180 nm for TiO2:Cr films. UV-visible spectroscopy was used to study optical properties such as absorbance, refractive index, optical band gap, dielectric constant, and optical conductivity. As the Cr concentration increases, the optical band gap decreases from 3.40 eV to 2.70 eV. Using the four-point probe method, it was found that the resistivity changes with temperature and is also affected by the Cr content.

7.
Environ Sci Pollut Res Int ; 31(4): 6385-6397, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38148460

RESUMO

Pesticide application has become a mandatory requirement of the modern agricultural system, resulting in the objectionable levels of pesticide residues in the treated food commodities and posing health threats to the consumers. This study aimed at optimization and validation of an analytical method which can be reliably applied for routine monitoring of the selected eighteen widely reported pesticides in tomato and eggplant. The principle of quick, easy, cheap, effective, rugged, and safe, i.e., QuEChERS, involving the acetate-buffered extraction followed by cleanup using the primary secondary amines (PSA) was employed. The analytical method was validated at three spiking levels (0.05, 0.01, 0.005 mg/kg) using gas chromatograph-micro electron capture detector (GC-µECD). Gas chromatograph-mass spectrometric detector (GC-MSD) was also used for confirmation and quantification using selective ion monitoring (SIM) mode. The method was applied on fresh samples of tomato (n = 33) and eggplant (n = 27) collected from local markets of Khyber Pakhtunkhwa, Pakistan, in the crop season 2020-2021. Twenty-five (76%) tomato samples and fifteen (56%) eggplant samples were found positive for one or more pesticides. Though the chronic and acute health risk assessments indicate that both of these vegetables are unlikely to pose any unacceptable health threat to their consumers, yet the risks from regular intake of pesticides-contaminated food commodities should be regularly addressed for possible protection of the public health and assurance of safe and consistent agro-trade, alike.


Assuntos
Resíduos de Praguicidas , Praguicidas , Solanum lycopersicum , Solanum melongena , Resíduos de Praguicidas/análise , Paquistão , Praguicidas/análise , Contaminação de Alimentos/análise , Verduras/química
8.
Pharmaceuticals (Basel) ; 16(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38139768

RESUMO

Pterostilbene (PTS) is a naturally occurring phytoalexin. PTS displays limited water solubility, which consequently results in its diminished oral bioavailability. Therefore, a ternary inclusion complex (TIC) of PTS with ß-cyclodextrin (ßCD) in the presence of ternary substance Pluronic® F-127 (PLF) was prepared using microwave technology. The PTS-TIC was characterized by dissolution performance. Further, the prepared TIC was characterized by DSC, FTIR, NMR, XRD, and SEM analysis. Additionally, the antioxidant activity of PTS and PTS-TIC was also evaluated. Phase-solubility studies revealed that PTS's solubility in water was increased by 6.72 times when ßCD/PLF was present. In comparison with PTS, prepared PTS-TIC produced a considerable improvement in PTS release. After 1 h, 74.03 ± 4.47% of PTS was released from PTS-TIC. Outcomes of DSC, FTIR, NMR, XRD, and SEM analysis revealed that the PTS was enclosed in the ßCD cavity. In terms of antioxidant properties, the PTS-TIC formulation demonstrated superior activity compared to PTS, possibly attributed to the improved solubility of PTS resulting from the formation of TIC using microwave technology. It was concluded that microwave technology proved to be an extremely beneficial means of interacting PTS with ßCD. In addition to increasing the solubility of PTS, the findings are also expected to improve its bioavailability by increasing its solubility. As a result, this study could provide insight into potential methods for enhancing the solubility of polyphenolic substances like PTS.

9.
Sci Rep ; 13(1): 16959, 2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37807007

RESUMO

Tungsten disulfide (WS2) nanotubes exhibit various unique properties depending on their structures, such as their diameter and wall number. The development of techniques to prepare WS2 nanotubes with the desired structure is crucial for understanding their basic properties. Notably, the synthesis and characterization of multi-walled WS2 nanotubes with small diameters are challenging. This study reports the synthesis and characterization of small-diameter WS2 nanotubes with an average inner diameter of 6 nm. The optical absorption and photoluminescence (PL) spectra of the as-prepared nanotubes indicate that a decrease in the nanotube diameter induces a red-shift in the PL, suggesting that the band gap narrowed due to a curvature effect, as suggested by theoretical calculations.

10.
Pharmaceutics ; 15(10)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37896151

RESUMO

Sinapic acid (SA) is a bioactive phenolic acid; its diverse properties are its anti-inflammatory, antioxidant, anticancer, and antibacterial activities. The bioactive compound SA is poorly soluble in water. Our goal was to formulate SA-transethosomes using thin-film hydration. The prepared formulations were examined for various parameters. In addition, the optimized formulation was evaluated for surface morphology, in-vitro penetration studies across the Strat M®, and its antioxidant activity. The optimized formulation (F5) exhibited 74.36% entrapment efficacy. The vesicle size, zeta potential, and polydispersity index were found to be 111.67 nm, -7.253 mV, and 0.240, respectively. The surface morphology showed smooth and spherical vesicles of SA-transethosomes. In addition, the prepared SA-transethosomes exhibited enhanced antioxidant activity. The SA-transethosomes demonstrated considerably greater penetration across the Strat M® membrane during the study. The flux of SA and SA-transethosomes through the Strat M® membrane was 1.03 ± 0.07 µg/cm2/h and 2.93 ± 0.16 µg/cm2/h. The enhancement ratio of SA-transethosomes was 2.86 ± 0.35 compared to the control. The SA-transethosomes are flexible nano-sized vesicles and are able to penetrate the entrapped drug in a higher concentration. Hence, it was concluded that SA-transethosome-based approaches have the potential to be useful for accentuating the penetrability of SA across the skin.

11.
Nano Lett ; 23(22): 10103-10109, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37843011

RESUMO

Transition metal dichalcogenide (TMDC) nanotubes exhibit unique physical properties due to their nanotube structures. The development of techniques for synthesizing TMDC nanotubes with controlled structures is very important for their science and applications. However, structural control efforts have been made only for the homostructures of TMDC nanotubes and not for their heterostructures that provide an important platform for their two-dimensional counterparts. In this study, we synthesized heterostructures of TMDC nanotubes, MoS2/WS2 heteronanotubes, and demonstrated a technique for controlling features of their structures, such as diameters, layer numbers, and crystallinity. The diameter of the heteronanotubes could be tuned with inner nanotube templates and was reduced by using small-diameter WS2 nanotubes. The layer number and crystallinity of the MoS2 outer wall could be controlled by controlling their precursors and synthesis temperatures, resulting in the formation of high-crystallinity TMDC heteronanotubes with specific chirality. This study can expand the research of van der Waals heterostructures.

12.
Saudi Pharm J ; 31(11): 101819, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37860687

RESUMO

Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph + ) acute lymphoblastic leukemia (ALL). DAS, a known potent substrate of cytochrome (CYP) 3A, P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) and is subject to auto-induction. The dietary supplementation of sinapic acid (SA) or concomitant use of SA containing herbs/foods may alter the pharmacokinetics as well as pharmacodynamics of DAS, that may probably lead to potential interactions. Protein expression in rat hepatic and intestinal tissues, as well as the in vivo pharmacokinetics of DAS and the roles of CYP3 A2 and drug transporters Pgp-MDR1 and BCPR/ABCG2, suggested a likely interaction mechanism. The single dose of DAS (25 mg/kg) was given orally to rats with or without SA pretreatment (20 mg/kg p.o. per day for 7 days, n = 6). The plasma concentration of DAS was estimated by using Ultra-High-Performance Liquid Chromatography Mass spectrometry (UHPLC-MS/MS). The in vivo pharmacokinetics and protein expression study demonstrate that SA pretreatment has potential to alter the DAS pharmacokinetics. The increase in Cmax, AUC and AUMC proposes increase in bioavailability and rate of absorption via modulation of CYP3 A2, PgP-MDR1 and BCPR/ABCG2 protein expression. Thus, the concomitant use of SA alone or with DAS may cause serious life-threatening drug interactions.

13.
Angew Chem Int Ed Engl ; 62(40): e202308515, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37583094

RESUMO

Comprehension of chemical bonding and its intertwined relation with charge carriers and heat propagation through a crystal lattice is imperative to design compounds for thermoelectric energy conversion. Here, we report the synthesis of large single crystal of new p-type cubic AgSnSbTe3 which shows an innately ultra-low lattice thermal conductivity (κlat ) of 0.47-0.27 Wm-1  K-1 and a high electrical conductivity (1238 - 800 S cm-1 ) in the temperature range 294-723 K. We investigated the origin of the low κlat by analysing the nature of the chemical bonding and its crystal structure. The interaction between Sn(5 s)/Ag(4d) and Te(5p) orbitals was found to generate antibonding states just below the Fermi level in the electronic band structure, resulting in a softening of the lattice in AgSnSbTe3 . Furthermore, the compound exhibits metavalent bonding which provides highly polarizable bonds with a strong lattice anharmonicity while maintaining the superior electrical conductivity. The electronic band structure exhibits nearly degenerate valence-band maxima that help to achieve a high Seebeck coefficient throughout the measured temperature range and, as a result, the maximum thermoelectric figure of merit reaches to ≈1.2 at 661 K in pristine single crystal of AgSnSbTe3 .

14.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631084

RESUMO

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box-Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt's antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.

15.
PLoS Biol ; 21(8): e3002231, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37590294

RESUMO

Mycobacterium tuberculosis (Mtb) defends host-mediated killing by repressing the autophagolysosome machinery. For the first time, we report NCoR1 co-repressor as a crucial host factor, controlling Mtb growth in myeloid cells by regulating both autophagosome maturation and lysosome biogenesis. We found that the dynamic expression of NCoR1 is compromised in human peripheral blood mononuclear cells (PBMCs) during active Mtb infection, which is rescued upon prolonged anti-mycobacterial therapy. In addition, a loss of function in myeloid-specific NCoR1 considerably exacerbates the growth of M. tuberculosis in vitro in THP1 differentiated macrophages, ex vivo in bone marrow-derived macrophages (BMDMs), and in vivo in NCoR1MyeKO mice. We showed that NCoR1 depletion controls the AMPK-mTOR-TFEB signalling axis by fine-tuning cellular adenosine triphosphate (ATP) homeostasis, which in turn changes the expression of proteins involved in autophagy and lysosomal biogenesis. Moreover, we also showed that the treatment of NCoR1 depleted cells by Rapamycin, Antimycin-A, or Metformin rescued the TFEB activity and LC3 levels, resulting in enhanced Mtb clearance. Similarly, expressing NCoR1 exogenously rescued the AMPK-mTOR-TFEB signalling axis and Mtb killing. Overall, our data revealed a central role of NCoR1 in Mtb pathogenesis in myeloid cells.


Assuntos
Mycobacterium tuberculosis , Correpressor 1 de Receptor Nuclear , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Leucócitos Mononucleares , Células Mieloides , Serina-Treonina Quinases TOR , Correpressor 1 de Receptor Nuclear/metabolismo
16.
Saudi Pharm J ; 31(9): 101737, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37638214

RESUMO

The objective of this study was to investigate the effects of cinnamon on the pharmacodynamic (PD) & pharmacokinetic (PK) of amlodipine in hypertensive rats. The hypertensive control group of Wistar rats received L-NAME (40 mg/kg, daily, orally) only. The cinnamon group of rats was treated with cinnamon (200 mg/kg, daily, orally) along with L-NAME. Following 14 days treatment period, blood pressures of rats were monitored at designated intervals over 24 h utilizing a tail-cuff system for measuring blood pressure. To assess the oral PK; amlodipine was administered as a single oral dose of 1 mg/kg to rats and blood samples were collected at specified intervals over 24 h and analysed by UPLC-LC MS/MS. Synergistic decreased in rat's blood pressure was observed in presence of cinnamon + amlodipine. Simultaneous administration of cinnamon ameliorates the Cmax and AUC0-t of amlodipine, the Cmax and AUC0-t was 11.04 ± 1.01 ng/ml and 113.76 ± 5.62 ng h/ml for the cinnamon + amlodipine group as compared to 4.12 ± 0.49 ng/ml and 48.59 ± 4.28 ng h/ml for the amlodipine alone group. The study demonstrates that the use of cinnamon considerably decreases the blood pressure levels and enhances the PK parameters of amlodipine in hypertensive rats.

17.
Vet Anim Sci ; 21: 100297, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37275242

RESUMO

This study was conducted to investigate the diversity and antimicrobial resistance profiling of Staphylococcus species causing sub-clinical mastitis (SCM) in dairy herds in Bangladesh as well as putative risk factors associated with the infections. Individual quarter milk samples were collected from a total of 284 lactating cows from 30 dairy farms were screened by means of California mastitis test; 178 (62.7%) of them had at least of quarter affected by SCM. After conventional microbiological isolation procedures, PCR tests were used for Staphylococcus species identification and detection of antimicrobial resistance and virulence genes. S. chromogenes (65.7%) was the most predominant species followed by, S. epidermidis (20.2%), S. haemolyticus (19.1%), S. aureus (15.7%), and S. sciuri (5.6%). High levels of antimicrobial resistance to ampicillin and amoxicillin/clavulanic acid were observed in S. aureus (82.1% and 75%) and S. sciuri (80% and 70%), while resistance to cefepime was markedly higher in S. chromogenes (95.7%), S. haemolyticus (94.1%), and S. epidermidis (97.2%). Multidrug resistance isolates were identified in all five species. The mecA gene was detected in S. aureus (32.1%) and S. chromogenes (5.98%). In addition, 20% S. sciuri and 17.7% S. haemolyticus carried the cytotoxin (pvl) gene, while 14.3% S. aureus harbored the toxic shock syndrome toxin (tst) gene. Multivariable logistic regression analysis identified "Old aged" (OR [CI]: 3.5 [1-12.4]); "Early stage of lactation" (OR [CI]: 3.4 [1.2-9.7]) and, "Firm udder condition" (OR [CI]: 4.2 [1.2-14.6]) as risk factors associated with SCM caused by S. aureus, S. chromogenes, and S. haemolyticus, respectively. Moreover, "Use of antimicrobials" (OR [CI]: 10.4 [3.4-32.1] and "History of previous clinical mastitis" (OR [CI]: 4.9 [1.2-19.7] for the carriage of methicillin-resistant Staphylococcus spp.

18.
Int J Surg Case Rep ; 107: 108357, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37276758

RESUMO

INTRODUCTION AND IMPORTANCE: Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Secretory carcinoma (SC) of the salivary gland has been recently added in fourth edition of the head and neck world health organization. Most of these tumors are located on the parotid gland with very few cases reported in the minor salivary glands of the buccal mucosa. This work has been reported in line with the SCARE criteria. PRESENTATION OF CASE: A 42 years old hypertensive male, shop keeper by occupation, with no prior addiction history, no dental extraction or trauma, presented with complaint of nodular lesion on left buccal mucosa for five years. On Clinical examination, adequate mouth opening, dentulous patient with 2.4 × 2 cm well circumscribed, nodular, non-tender, benign looking lesion was observed on left buccal mucosa near upper alveolus. Overlying mucosa appeared normal with no clinically palpable cervical lymphadenopathy. Histopathology revealed salivary gland neoplasm favoring secretory carcinoma. MRI scan showed lobulated enhancing nodular lesion arising from left buccal mucosa of size 2.3 ∗ 1.3 ∗ 1.7 cm, close to left superior alveolus without involving any cortical areas of marrow infiltration, with bilateral symmetrical level IIa reactive cervical nodes. Wide local excision and ipsilateral selective neck dissection [level 1, 2, 3] was done. Post-operative period was smooth with no complain of paresthesia observed. The final histopathology report showed secretory carcinoma. Two out of six lymph nodes from level I were positive for metastatic carcinoma with no extra nodal extension. Final stage of the tumor was pT1N2bMx. Patient underwent post-operative adjuvant radiotherapy for period of 6 weeks, received total 30 fractions and total dose of 6000 centigray. CLINICAL DISCUSSION: SC behaved clinically an indolent being painless and having long duration of symptoms with normal overlying mucosa. But histopathologically there was cervical node metastasis. That changed final staging and added adjuvant treatment for this patient. The discrepancy in clinical and pathological diagnosis might be due to the indolent clinical behavior of SC arising in the minor salivary gland of buccal mucosa. In the present case, the absence of zymogen granules and presence of microcytic pattern with eosinophilic cytoplasm and eosinophilic secretory material were suggestive of SC. CONCLUSION: This case report represents a rare case of SC of minor salivary glands of buccal mucosa, which was indolent as per clinical presentation but on final histopathological report it had cervical nodal metastasis that changed the final stage of the disease, for which adjuvant radiotherapy was needed. Although Secretory carcinomas are generally considered having a favorable prognosis and are regarded as low- grade carcinomas with limited number of recurrence and cervical nodal metastasis, but sometimes they do metastasize to cervical nodes for which accurate and timely intervention in the form of neck dissection may be performed to establish final staging and start additional treatment modality if required for better outcome of the disease.

19.
J Clin Orthop Trauma ; 41: 102171, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37303497

RESUMO

Introduction: Supraspinatus muscle atrophy is commonly associated with shoulder disease, but the effect of ageing on atrophy is not well understood. It was the aim of this study to investigate this effect using MRI scans in older patients. Methods and materials: A retrospective review of MRI scans in patients aged >70 years was performed between Jan 2016-Dec 2018.Both normal and abnormal scans were included in the analysis which included quantifying muscle atrophy of the supraspinatus using Thomazeu's occupation ratio. Results: There were 39 normal shoulder MRI scans with a mean age of 75 years (range: 70-88) and 163 abnormal scans with a mean age of 77 years (range: 70-93). The mean supraspinatus occupation ratio for normal MRI scans was 0.57 (range: 0.33-0.86) and abnormal scans 0.35 (range: 0.17-0.90). Occupation ratio was maintained with advancing until the age of 85 years before undergoing a significant declin following this. Conclusion: This study has shown that the occupation ratio is significantly reduced with shoulder disease, but normal shoulders do not undergo significant atrophy of supraspinatus tendon with increasing age. An occupation ratio of <0.32 is unlikely to occur in normal shoulders and this awareness may be useful when planning shoulder surgery, specifically shoulder arthroplasty.

20.
Cells ; 12(12)2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37371089

RESUMO

Niemann-Pick disease type C1 (NP-C) is a prematurely lethal genetic lysosomal storage disorder with neurological and visceral pathology resulting from mutations in the NPC1 gene encoding the lysosomal transmembrane protein NPC1. There is currently no cure for NP-C, and the only disease modifying treatment, miglustat, slows disease progression but does not significantly attenuate neurological symptoms. AAV-mediated gene therapy is an attractive option for NP-C, but due to the large size of the human NPC1 gene, there may be packaging and truncation issues during vector manufacturing. One option is to reduce the size of DNA regulatory elements that are essential for gene expression, such as the promoter sequence. Here, we describe a novel small truncated endogenous NPC1 promoter that leads to high gene expression both in vitro and in vivo and compare its efficacy to other commonly used promoters. Following neonatal intracerebroventricular (ICV) injection into the CNS, this novel promoter provided optimal therapeutic efficacy compared to all other promoters including increased survival, improved behavioural phenotypes, and attenuated neuropathology in mouse models of NP-C. Taken together, we propose that this novel promoter can be extremely efficient in designing an optimised AAV9 vector for gene therapy for NP-C.


Assuntos
Terapia Genética , Peptídeos e Proteínas de Sinalização Intracelular , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C , Animais , Camundongos , Terapia Genética/métodos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação , Proteína C1 de Niemann-Pick/genética , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/terapia , Doença de Niemann-Pick Tipo C/metabolismo , Vetores Genéticos , Regiões Promotoras Genéticas/genética
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