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1.
Saudi Pharm J ; 30(6): 649-654, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35812147

RESUMEN

Basic expectation from graduates of any pharmacy program is to be able to provide pharmaceutical care at both patients and community levels, be able to solve problems arising during practice, be able to improve quality and outcomes of the services provided continuously and be able to respond effectively to patients and community changing needs. Pharmacy education in Saudi Arabia established in 1959 by founding the first college in Riyadh (King Saud University) followed by establishing two pharmacy colleges in Jeddah (King Abdulaziz University, 2001) and Abha (King Khalid University, 2001), then a college in Al Ahsa (King Faisal University, 2002), followed by four colleges three-years later in each of Buraydah (Qassim University, 2005), Madinah (Taibah University, 2005), Taif (Taif University, 2005) and Makkah (Umm Al-Qura University, 2005). Up to date the number of pharmacy colleges offering basic degrees in pharmacy are 21 governmental and eight privates. This review describes pharmacy education in Saudi Arabia, the historical perspective, current situation, and the important features. The report focuses on the changes during the last two decades covering three main aspects (1) Clinical education and training, (2) Research output, and (3) Quality and accreditation.

2.
Infect Drug Resist ; 15: 3801-3814, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35875614

RESUMEN

Background and Aims: Reports examine quinolone resistance mechanisms among Pseudomonas spp. are sporadic in the Kingdom of Saudi Arabia (KSA). We previously examined the genetic bases of plasmid-mediated quinolone resistance among Pseudomonas spp. clinical isolates. This study investigated chromosomally mediated quinolone resistance mechanisms via investigation of the mutations in the gyrA and parC genes. Methods: The minimum inhibitory concentration (MIC) to different quinolones was determined. Twenty-nine quinolone resistant Pseudomonas spp. clinical isolates were included. The gyrA and parC genes were sequenced by Sanger capillary electrophoresis. Multiple sequence alignment for the translated gyrA and parC genes was performed to identify mutation sites. Results: Of the 29 isolates, 27 isolates were P. aeruginosa and two were P. putida. The cluster analysis of the quinolone susceptibility pattern revealed seven susceptibility phenotypes (A-G) based on susceptibility patterns rather than the MIC values. Also, 22 different susceptibility phenotypes were detected based on MIC values. All isolates exhibited a missense mutation at position 83 (S83I/T/F) of the gyrA gene in addition to six missense mutations at positions outside the QRDR of this gene. In addition, 82.8% (24/29) of the isolates harbored a missense mutation in the parC gene at position 87 (S87L), along with six novel mutations outside the QRDR of the parC gene. Haplotyping of the gyrA, parC, and the overall QRDR revealed six, 10, and 13 different haplotypes, respectively. Conclusion: This study documents the incidence of the commonly reported mutations in the gyrA and parC genes in addition to novel mutations in these genes among Pseudomonas spp. clinical isolates recovered from KSA. Together with our previous findings, these data provide an insight into the genetic background of quinolone resistance among Pseudomonas spp. clinical isolates in KSA.

3.
Infect Drug Resist ; 14: 4739-4756, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34795490

RESUMEN

BACKGROUND: Acinetobacter baumannii (A. baumannii) is one of the most important nosocomial pathogens responsible for a wide range of infections. AIM: This study aimed to investigate the existence of the plasmidic genes encoding for aminoglycoside modifying enzymes (AMEs), 16S rRNA methyltransferases (RMT), and the altered dihydropetroate synthase (DHPS) encoded by the sul1 gene among A. baumannii clinical isolates collected from Taif, Kingdom of Saudi Arabia (KSA). The mutations in aac(6')-Ib and sul1 genes were also investigated. METHODS: Forty A. baumannii clinical isolates were investigated for their susceptibility to ten antibiotics. The plasmid DNA was extracted and screened for nine genes encoding for aminoglycoside resistance in addition to the sul1 gene. The clonal relatedness was determined by random amplified polymorphic DNA (RAPD)-PCR. Mutation in aac(6')-Ib and the sul1 genes were detected by capillary electrophoresis sequencing (CES). RESULTS: All isolates were A. baumannii in which 42.5% of them exhibited a high level of aminoglycoside resistance (HLAR). The most prevalent AMEs and RMT encoding genes were aph(3')-VI, the two aac(6') gene variants [aac(6')-Ib and aac(6')-SL], ant(3'')-I, and armA in which 90%, 87.5%, 85%, and 45% of isolates tested positive, respectively. The other investigated aminoglycoside resistant encoding genes, namely aac(3)-II, aac(6')-II, and rmtB, were not detected. Only 15% of isolates harbored the sul1 gene. RAPD-PCR classified the 40 isolates into three clusters in which cluster II was the main cluster. DNA sequencing revealed that 34.29% (12/35) of isolates tested positive for aac(6')-Ib were found to harbor a common missense mutation in position 102 indicating a novel allelic variant named aac(6')-SL. Also, DNA sequencing revealed three missense mutations in the sul1 gene. CONCLUSION: This is the first Saudi study to investigate the plasmid borne aminoglycoside and sulfonamide resistance genes among A. baumannii clinical isolates. A novel allelic variant for aac(6')-Ib was detected in addition to novel mutations in the sul1 gene.

4.
J Trace Elem Med Biol ; 52: 74-82, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30732903

RESUMEN

Cadmium is an extremely toxic pollutant that reaches human body through intake of the industrially polluted food and water as well as through cigarette smoking and exposure to polluted air. Cadmium accumulates in different body organs especially the liver. It induces tissue injury largely through inflammation and oxidative stress-based mechanisms. The aim of the current study was to investigate the ability of γ glutamyl cysteine (γGC) to protect against cadmium-induced hepatocellular injury employing Wistar rats as a mammalian model. The results of the current work indicated that γGC upregulated the level of the anti-inflammatory cytokine IL-10 and downregulated the levels of the pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the cadmium-exposed rats. In addition, γGC reduced the liver tissues cadmium content in the cadmium-treated rats, suppressed the cadmium-induced hepatocellular apoptosis and oxidative modifications of cellular DNA, lipids, and proteins. Additionally, γGC enhanced the antioxidant potential of the liver tissues in the cadmium-treated rats as evidenced by a remarkable increase in the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and significant increase in the levels of the total antioxidant capacity and reduced glutathione as well as a significant reduction in oxidized to reduced glutathione (GSSG/GSH) ratio. Moreover, it effectively improved liver cell integrity in the cadmium-treated rats as demonstrated by a significant reduction in the serum activity of the liver enzymes (ALT and AST) and amelioration of the cadmium-evoked histopathological alterations. Together, these findings underscore, for the first time, the alleviating effects of γGC against cadmium-induced hepatocellular injury that is potentially mediated through reduction of liver tissue cadmium content along with modulation of both hepatocellular redox status and inflammatory cytokines.


Asunto(s)
Apoptosis/efectos de los fármacos , Cloruro de Cadmio/toxicidad , Daño del ADN , Dipéptidos/antagonistas & inhibidores , Inflamación/inducido químicamente , Hígado/efectos de los fármacos , Hígado/patología , Administración Oral , Animales , Antioxidantes/análisis , Antioxidantes/metabolismo , Biomarcadores/sangre , Cloruro de Cadmio/administración & dosificación , Cloruro de Cadmio/análisis , Dipéptidos/metabolismo , Modelos Animales de Enfermedad , Inflamación/sangre , Inflamación/patología , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar
5.
Food Funct ; 9(12): 6632-6642, 2018 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-30511081

RESUMEN

Gentamycin is an aminoglycoside antibiotic that is widely employed for controlling Gram negative bacterial infections including that caused by the antibiotic-resistant Pseudomonas species. The clinical use of gentamycin is substantially limited by its side effects particularly acute kidney injury (AKI). The aim of the current study was to investigate the protective effect of the plant flavonoid troxerutin (150 mg kg-1 day-1 for 15 days) against gentamycin-induced AKI using Wistar rats as an experimental mammalian model. The results of the present work revealed that troxerutin significantly improved renal function as demonstrated by the increase in the glomerular filtration rate and the decrease in the levels of urinary albumin, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen (p < 0.001). In addition, troxerutin significantly attenuated gentamycin-induced renal tissue injury as indicated by the decreased protein expression of the renal tubular injury marker KIM-1, the attenuation of the renal histopathological changes, and the modulation of the oxidative stress markers as reflected by the decrease in the levels of lipid and protein oxidative modifications and the increase in the levels of reduced glutathione and total antioxidant capacity (p < 0.001). Furthermore, troxerutin down-regulated the levels of inflammatory cytokines (IL-10, TNF-α, and IL-6), attenuated apoptotic cell death, and enhanced the renal tissue regenerative capacity as demonstrated by the increase in the protein expression of the proliferating cell nuclear antigen, PCNA (p < 0.001). Collectively, the results of the current study highlight, for the first time, the ameliorating effects of troxerutin against gentamycin-induced AKI in rats that is potentially mediated via the modulation of p38 MAPK signaling as well as via antioxidant, anti-inflammatory and anti-apoptotic activities.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Moléculas de Adhesión Celular/metabolismo , Gentamicinas/efectos adversos , Hidroxietilrutósido/análogos & derivados , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Animales , Apoptosis/efectos de los fármacos , Moléculas de Adhesión Celular/genética , Humanos , Hidroxietilrutósido/administración & dosificación , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Regeneración/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/genética
6.
Food Funct ; 9(5): 2661-2672, 2018 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-29667662

RESUMEN

Methotrexate (MTX) is a classical chemotherapeutic agent with nephrotoxicity as the most disturbing adverse effect. So far, its underlying molecular mechanisms, particularly PI3K/Akt/eNOS transduction, are inadequately explored. Several antioxidant modalities have been characterized to ameliorate MTX-induced renal injury. In this regard, Camel milk (CM) is a natural product with recognized antioxidant and anti-inflammatory features. Thus, the current study aimed to investigate the potential ameliorating effects of CM in MTX-induced kidney injury in rats. Renal tissues were studied in terms of renal injury markers, histopathology, oxidative stress, apoptosis and PI3K/Akt/eNOS signaling. CM was orally administered (10 ml kg-1) and the renal injury was induced by a single i.p. injection of MTX (20 mg kg-1). Interestingly, CM dose-dependently attenuated MTX-triggered increase of BUN and serum creatinine and renal Kim-1 expression and mitigated the renal histopathological changes. CM counteracted renal oxidative stress as manifested by lowering of lipid peroxides, restoration of NOX-1 levels and augmentation of the antioxidant defenses e.g., GSH, SOD, GPx and total antioxidant capacity. With respect to apoptosis, CM curbed the cleavage of PARP and caspase-3, downregulated p53, Bax and Cyt C proapoptotic signals and enhanced Bcl-2 and PCNA levels. In the same context, CM activated the prosurvival PI3K/Akt/eNOS pathway via enhancing PI3K p110, phospho-Akt and phospho-eNOS levels. Equally important, CM preconditioning did not interfere with MTX cytotoxicity in TK-10 or PC-3 cancer cells. Together, the current findings demonstrate, for the first time, the renoprotective effects of CM in MTX-induced kidney injury via activation of PI3K/Akt/eNOS signaling and combating oxidative stress and apoptosis.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Metotrexato/efectos adversos , Leche/química , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Apoptosis/efectos de los fármacos , Camelus , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Femenino , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo III/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos
7.
Cell Physiol Biochem ; 46(4): 1628-1642, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29694984

RESUMEN

BACKGROUND/AIMS: The clinical utility of 5-fluorouracil (5-FU) is limited by its nephrotoxicity. Camel milk (CM) has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. METHODS: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA. The expression of MMP-2, MMP-9, NF-κBp65, p53, Bax and PCNA were detected by Immunohistochemistry. To gain an insight into the molecular signaling mechanisms, we determined the effect of CM on MAPKs, NF-κB and PI3K/Akt/eNOS pathways by Western blotting. RESULTS: CM lowered 5-FU-triggered increase of creatinine, BUN, Kim-1 and NGAL renal injury biomarkers and attenuated the histopathological aberrations. It suppressed oxidative stress and augmented renal antioxidant armory (GSH, SOD, GPx, TAC) with restoration of NOX-1, Nrf-2 and HO-1 levels. CM also suppressed renal inflammation as indicated by inhibition of MPO, TNF-α, IL-1ß, IL-18 and MCP-1 proinflammatory mediators and downregulation of MMP-2 and MMP-9 expression with boosting of IL-10. Regarding MAPKs signaling, CM suppressed the phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 and inhibited NF-κB activation. For apoptosis, CM downregulated p53, Bax, CytC and caspase-3 proapoptotic signals with enhancement of Bcl-2 and PCNA. It also enhanced PI3K p110α, phospho-Akt and phospho-eNOS levels with augmentation of renal NO, favoring cell survival. Equally important, CM preconditioning enhanced 5-FU cytotoxicity in MCF-7, HepG-2, HCT-116 and PC-3 cells, thus, justifying their concomitant use. CONCLUSION: The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K/Akt/eNOS pathway.


Asunto(s)
Fluorouracilo/toxicidad , Riñón/efectos de los fármacos , Leche/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Camelus/metabolismo , Línea Celular Tumoral , Creatinina/análisis , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células HCT116 , Hemo-Oxigenasa 1/metabolismo , Células Hep G2 , Humanos , Riñón/lesiones , Lipocalina 2/análisis , Células MCF-7 , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , NADPH Oxidasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo
8.
Chem Biol Interact ; 285: 40-47, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29499191

RESUMEN

UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model. Rats were distributed into normal control group (NC), L-carnitine control group (LC), UVA-Exposed group (UVA), and UVA-Exposed and L-carnitine-treated group (UVA-LC). L-carnitine significantly attenuated UVA-induced elevation of the DNA damage markers 8-oxo-2'-deoxyguanosine (8-oxo-dG) and cyclobutane pyrimidine dimers (CPDs) as well as decreased DNA fragmentation and the activity of the apoptotic marker caspase-3. In addition, L-carnitine substantially reduced the levels of lipid peroxidation marker (TBARS) and protein oxidation marker (PCC) and significantly elevated the levels of the total antioxidant capacity (TAC) and the antioxidant reduced glutathione (GSH) in the skin tissues. Interestingly, L-carnitine upregulated the level of the DNA repair protein proliferating cell nuclear antigen (PCNA). Besides it mitigated the UVA-induced activation of the oxidative stress-sensitive signaling protein p38 and its downstream target c-Fos. Moreover, L-carnitine significantly downregulated the levels of the early response proinflammatory cytokines TNF-α, IL-6, and IL-1ß. Collectively, our results highlight, for the first time, the potential attenuating effects of L-carnitine on UVA-induced skin tissue injury in rats that is potentially mediated through suppression of UVA-induced oxidative stress and inflammatory responses.


Asunto(s)
Carnitina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Rayos Ultravioleta , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Citocinas/metabolismo , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Inmunosupresores/farmacología , Peroxidación de Lípido/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Piel/efectos de la radiación
9.
Cell Physiol Biochem ; 43(2): 540-552, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28930753

RESUMEN

BACKGROUND/AIMS: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. METHODS: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund's adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. RESULTS: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. CONCLUSION: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.


Asunto(s)
Antiinflamatorios/inmunología , Artritis Reumatoide/terapia , Leche/inmunología , Proteínas Quinasas Activadas por Mitógenos/inmunología , Transducción de Señal , Animales , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Experimental/terapia , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Camelus/inmunología , Interleucina-10/análisis , Interleucina-10/inmunología , Proteínas Quinasas Activadas por Mitógenos/análisis , FN-kappa B/análisis , FN-kappa B/inmunología , Óxido Nítrico Sintasa de Tipo II/análisis , Óxido Nítrico Sintasa de Tipo II/inmunología , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunología
10.
Int J Microbiol ; 2017: 8050432, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28638412

RESUMEN

Inappropriate use of antibiotics in clinical settings is thought to have led to the global emergence and spread of multidrug-resistant pathogens. The goal of this study was to investigate the prevalence of genes encoding aminoglycoside resistance and plasmid-mediated quinolone resistance among clinical isolates of Klebsiella pneumoniae. All K. pneumoniae isolates were phenotypically identified using API 20E and then confirmed genotypically through amplification of the specific K. pneumoniae phoE gene. All isolates were genotyped by the enterobacterial repetitive intergenic consensus polymerase chain reaction technique (ERIC-PCR). Antibiotic susceptibility testing was done by a modified Kirby-Bauer method and broth microdilution. All resistant or intermediate-resistant isolates to either gentamicin or amikacin were screened for 7 different genes encoding aminoglycoside-modifying enzymes (AMEs). In addition, all resistant or intermediate-resistant isolates to either ciprofloxacin or levofloxacin were screened for 5 genes encoding the quinolone resistance protein (Qnr), 1 gene encoding quinolone-modifying enzyme, and 3 genes encoding quinolone efflux pumps. Biotyping using API 20E revealed 13 different biotypes. Genotyping demonstrated that all isolates were related to 2 main phylogenetic groups. Susceptibility testing revealed that carbapenems and tigecycline were the most effective agents. Investigation of genes encoding AMEs revealed that acc(6')-Ib was the most prevalent, followed by acc(3')-II, aph(3')-IV, and ant(3'')-I. Examination of genes encoding Qnr proteins demonstrated that qnrB was the most prevalent, followed by qnrS, qnrD, and qnrC. It was found that 61%, 26%, and 12% of quinolone-resistant K. pneumoniae isolates harbored acc(6')-Ib-cr, oqxAB, and qebA, respectively. The current study demonstrated a high prevalence of aminoglycoside and quinolone resistance genes among clinical isolates of K. pneumoniae.

11.
Microb Drug Resist ; 23(6): 703-717, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28099061

RESUMEN

The extensive use of ß-lactam antibiotics has led to emergence and spread of extended-spectrum ß-lactamases (ESBLs). This study was conducted to investigate the prevalence of 7 different ESBL genes (blaTEM, blaSHV, blaCTX-M, blaVEB, blaPER, blaGES, and blaOXA-10) and O25b-ST131 high-risk clone among 61 clinical isolates of Escherichia coli. Also, one broad-spectrum ß-lactamase (blaOXA-1) was investigated. This study was also constructed to evaluate iodometric overlay method in detection of ESBL production. Phenotypic identification of E. coli isolates using API 20E revealed 18 distinct biotypes. DNA fingerprinting using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) differentiated all isolates into 2 main phylogenetic groups with 60 distinct genetic profiles. Elevated values of minimal inhibitory concentration (MIC)50 and MIC90 for third- and fourth-generation cephalosporins were observed. Phenotypic tests revealed that 85.24% of isolates were ESBL producers. The incidence rates of blaTEM, blaSHV, blaCTX-M, blaGES, blaOXA-1, and blaOXA-10 among E. coli ESBL producer phenotype were 69.23%, 25%, 96.15%, 3.85%, 11.54%, and 48%, respectively. On the other hand, blaVEB and blaPER were not detected. Sequencing of blaTEM and blaSHV revealed that blaTEM-214 and blaSHV-11 were the most prevalent variants. Group characterization of blaCTX-M revealed that blaCTX-M-1 was the most prevalent group of blaCTX-M family. It was found that 30.77% of E. coli ESBL producers belonged to O25b-ST131 clone harboring blaCTX-M-15. This study concluded that iodometric overlay method was 100% sensitive in detection of ESBL production. To our knowledge, this is the first Egyptian study that declares the emergence of E. coli O25b-ST131 harboring blaGES.


Asunto(s)
Proteínas de Escherichia coli/genética , Escherichia coli/genética , beta-Lactamasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Niño , Preescolar , Egipto , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Adulto Joven , beta-Lactamas/farmacología
12.
Pharm Dev Technol ; 22(3): 390-398, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27470482

RESUMEN

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Lecitinas/química , Nanopartículas/química , Administración Oral , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Estabilidad de Medicamentos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Liposomas , Masculino , Ratas Wistar , Propiedades de Superficie
13.
J Microencapsul ; 33(7): 646-655, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27682805

RESUMEN

Depression is a modern world epidemic. Its main causative factor is oxidative stress, as reported in study subjects. Natural products are yet to show significant therapeutic effects in comparison with synthetic drugs. Current study deals with the preparation of brain-targeted polysorbate-80-coated curcumin PLGA nanoparticles (PS-80-CUR-NP), and their characterisation via Spectral and optical methods. PS-80-CUR-NP were evaluated against the oxidative stress-mediated depressant (OSMD) activity via Force despair, Tail suspension tests and stress biomarker assay (SOD and catalase activity). A significant reduction in immobility (p < 0.01) in force despair and tail suspension test and a significant increase (p < 0.001 and p < 0.01) in SOD and catalase activity was found and compared with stress control, which confirmed the OSMD activity of PS-80-CUR-NP at 5 mg equivalent dose. Further, AUC(0.5-15 h) curve of brain homogenates estimated the curcumin concentration of 1.73 ng/g C max at T max 3 h via HPLC technique.


Asunto(s)
Antidepresivos , Barrera Hematoencefálica/microbiología , Curcumina , Nanopartículas/química , Polisorbatos , Animales , Antidepresivos/química , Antidepresivos/farmacocinética , Antidepresivos/farmacología , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Ratones , Polisorbatos/química , Polisorbatos/farmacocinética , Polisorbatos/farmacología , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo
14.
Molecules ; 21(4): 477, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-27104506

RESUMEN

A green protocol has been applied to synthesize a novel series of 3-cyano-2-(tri-O-acetyl-ß-D-arabinopyranosylthio)pyridines in a short reaction time, in higher yields and with simpler operations, when compared with the conventional heating method. Deacetylation of the obtained acetylated arabinosides produced 2-(ß-D-arabinopyranosylthio)-3-cyanopyridines. The structures of the obtained products were confirmed on the basis of spectroscopic data (FT-IR, 1D, 2D-NMR). The synthesized compounds were screened for the antimicrobial activity against a selection of Gram positive and Gram negative bacteria.


Asunto(s)
Tecnología Química Verde/métodos , Piridinas/síntesis química , Piridinas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Microondas , Piridinas/química , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier
15.
Biol Trace Elem Res ; 173(1): 96-107, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26767370

RESUMEN

Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity.


Asunto(s)
Dipéptidos/farmacología , Enfermedades Renales , Intoxicación por Plomo , Regeneración/efectos de los fármacos , Animales , Caspasa 3/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Intoxicación por Plomo/tratamiento farmacológico , Intoxicación por Plomo/metabolismo , Intoxicación por Plomo/patología , Masculino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Wistar
16.
Arch Pharm (Weinheim) ; 348(11): 786-795, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26377573

RESUMEN

A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starting from l-tartaric acid, which was transformed into anhydride which then reacted with allylamine in xylene to afford the imide 2. The target molecules 12-15 were achieved via ring-closing metathesis with the Grubbs catalyst, followed by reduction of the carbonyl group and deprotection of hydroxyl groups. Finally, catalytic hydrogenation of the double bond afforded the title compounds 12-15. Molecular docking study of the title compounds 12-15 was carried out against neuraminidase as the target enzyme, in an attempt to understand the mechanism of action of the tested compounds as potential neuraminidase inhibitors. Molecular docking of the target compounds showed that all tested compounds bind to the active site of neuraminidase, with moderate to high binding energy. Compounds 12-15 were examined for their antiviral activity against H5N1 virus (A/chicken/Egypt/1/2008). Oseltamivir phosphate was used as a control for antiviral activity. The results show that compound 12 (EC50 = 0.016 µg/mL) exhibited potent anti-influenza (H5N1) activity, which approximately equals that of oseltamivir (EC50 = 0.012 µg/mL). Also, it had a therapeutic index similar to that of oseltamivir phosphate (∼20). The data also revealed that compounds 13, 14, and 15 had slightly lower antiviral activity and lower cytotoxicity than oseltamivir phosphate, with LD50 of 0.188, 0.162, and 0.176 µg/mL, respectively. However, 13, 14, and 15 had lower therapeutic indices than 12. In conclusion, we were able to synthesize cheap and potent anti-H5N1 compounds.

17.
Acta Pharm ; 65(2): 133-46, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26011930

RESUMEN

This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (>95% in 20 minutes) compared to pure crystalline CZ (56%). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism.


Asunto(s)
Ácidos Carboxílicos/química , Clozapina/administración & dosificación , Excipientes/química , Plastificantes/química , Antipsicóticos/administración & dosificación , Antipsicóticos/química , Antipsicóticos/farmacocinética , Rastreo Diferencial de Calorimetría , Química Farmacéutica/métodos , Clozapina/química , Clozapina/farmacocinética , Cristalización , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Soluciones Farmacéuticas , Solubilidad , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
18.
Arch Pharm (Weinheim) ; 348(7): 518-30, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25989149

RESUMEN

A series of diphenylthiazole-thiazolidinone hybrids was synthesized and evaluated in vitro and in vivo as anti-inflammatory/analgesic agents. The inhibition of cyclooxygenase (COX) enzymes was suggested as a molecular mechanism for the hybrids to exert their anti-inflammatory action. Of these compounds, 13b, 14, and 15b showed the most potent COX inhibitory activity with IC50 values between 2.03 and 12.27 µM, but with different selectivity profiles. All compounds were further evaluated in vivo for their anti-inflammatory/analgesic activities using three animal models. Interestingly, the results of the COX assay were in agreement with those of in vivo assays where the most potent COX inhibitors, 13b, 14, and 15b, exhibited the highest anti-inflammatory/analgesic activities compared to diclofenac. On the contrary, compounds 11 and 12 were the least potent ligands in vitro and in vivo as well.


Asunto(s)
Inhibidores de la Ciclooxigenasa/síntesis química , Diseño de Fármacos , Tiazoles/síntesis química , Animales , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Edema/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Ratones , Simulación del Acoplamiento Molecular , Unión Proteica , Tiazoles/química , Tiazoles/farmacología
19.
PLoS One ; 10(3): e0122417, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25821971

RESUMEN

Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.


Asunto(s)
Antiulcerosos/administración & dosificación , Diosmina/administración & dosificación , Etanol/efectos adversos , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/farmacología , Diosmina/farmacología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Sucralfato/administración & dosificación , Factor de Necrosis Tumoral alfa/metabolismo
20.
Food Chem Toxicol ; 69: 294-302, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24788059

RESUMEN

Current treatment strategies for inflammatory bowel diseases (IBD) are associated with several adverse effects, and thus, the search for effective agents with minimal side effects merits attention. Camel's milk (CM) is endowed with antioxidant/anti-inflammatory features and has been reported to protect against diabetes and hepatic injury, however, its effects on IBD have not been previously explored. In the current study, we aimed to investigate the potential alleviating effects of CM against TNBS-induced colitis in rats. CM (10 ml/kg b.i.d. by oral gavage) effectively suppressed the severity of colon injury as evidenced by amelioration of macroscopic damage, colon weight/length ratio, histopathological alterations, leukocyte influx and myeloperoxidase activity. Administration of CM mitigated the colonic levels of TNF-α and IL-10 cytokines. The attenuation of CM to colon injury was also associated with suppression of oxidative stress via reduction of lipid peroxides and nitric oxide along with boosting the antioxidant defenses through restoration of colon glutathione and total anti-oxidant capacity. In addition, caspases-3 activity, an apoptotic marker, was inhibited. Together, our study highlights evidences for the promising alleviating effects of CM in colitis. Thus, CM may be an interesting complementary approach for the management of IBD.


Asunto(s)
Colitis/tratamiento farmacológico , Citocinas/metabolismo , Leche , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/metabolismo , Camelus , Caspasa 3/metabolismo , Inhibidores de Caspasas/farmacología , Colitis/inducido químicamente , Colitis/patología , Regulación hacia Abajo/efectos de los fármacos , Interleucina-10/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/patología , Peroxidasa/metabolismo , Ratas Wistar , Ácido Trinitrobencenosulfónico/toxicidad , Factor de Necrosis Tumoral alfa/metabolismo
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