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BACKGROUNDS & AIM: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats. MATERIALS AND METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1ß (IL-1ß), and cleaved caspase-3 immuno-expressions were also evaluated. RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1ß and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1ß), and apoptotic (caspase-3) parameters. CONCLUSION: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1ß signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.
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Acetatos , Ciclofosfamida , Ciclopropanos , Interleucina-1beta , Antagonistas de Leucotrienos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placenta , Quinolinas , Ratos Wistar , Transdução de Sinais , Sulfetos , Animais , Feminino , Gravidez , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Ciclofosfamida/toxicidade , Ciclofosfamida/efeitos adversos , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Acetatos/uso terapêutico , Acetatos/farmacologia , Interleucina-1beta/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Placenta/metabolismo , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ratos , Fator de Crescimento Placentário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamassomos/metabolismo , Apoptose/efeitos dos fármacosRESUMO
The Aja and Salma mountains in the Hail region are home to a variety of indigenous wild plants, some of which are used in Bedouin folk medicine to treat various ailments. The purpose of the current study was to unveil the chemical, antioxidant and antibacterial properties of Fagonia indica (Showeka) grown widely in these mountains, as data on the biological activities of this plant in this remote area are scarce. XRF spectrometry indicated the presence of some essential elements, which were in the order of Ca > S > K > AL > CL > Si > P > Fe > Mg > Na > Ti > Sr > Zn > Mn. Qualitative chemical screening revealed the presence of saponins, terpenes, flavonoids, tannins, phenols and cardiac glycosides in the methanolic extract (80% v/v). GC-MS showed the presence of 2-chloropropanoic acid 18.5%, tetrahydro-2-methylfuran 20.1%, tridecanoic acid 12-methyl-, methyl ester 2.2%, hexadecanoic acid, methyl ester 8.6%, methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate 13.4%, methyl linoleate 7.0%, petroselinic acid methyl ester 15%, erucylamide 6.7% and diosgenin 8.5%. Total phenols, total tannins, flavonoids, DPPH, reducing power, -carotene and ABTS IC50 (mg/mL) scavenging activity were used to measure the antioxidant capabilities of Fagonia indica, which exhibited prominent antioxidant properties at low concentrations when compared to ascorbic acid, butylate hydroxytoluene and beta-carotene. The antibacterial investigation revealed significant inhibitory effects against Bacillus subtilis MTCC121 and Pseudomona aeruginosa MTCC 741 with inhibition zones of 15.00 ± 1.5 and 12.0 ± 1.0 mm, respectively. The MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) ranged between 125 to 500 µg/mL. The MBC/MIC ratio indicated possible bactericidal efficacy against Bacillus subtilis and bacteriostatic activity against Pseudomona aeruginosa. The study also showed that this plant has anti-biofilm formation activity.
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Aim: Protein-bound uremic toxins (PBUTs) may displace drugs from the plasma proteins and render them more liable to clearance. This study aims to investigate the possible interplay between PBUTs and directly acting antivirals (DAAs). Methods: PBUT plasma protein binding was compared to those of paritaprevir (PRT), ombitasivir (OMB) and ritonavir (RTV) in silico to assess the possible competitive displacement. The three drugs were LC-MS/MS determined in seven patients across dialysis and non-dialysis days and results were compared. Results & conclusion: Results showed that the PBUT exhibited a lower binding than DAA reducing the liability of their competitive displacement. This was echoed by an unaltered plasma concentration across dialysis days. Results may indicate that PBUT accumulation may have limited effect on disposition of DAA.
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Toxinas Biológicas , Uremia , Humanos , Antivirais , Cromatografia Líquida , Uremia/metabolismo , Espectrometria de Massas em Tandem , Diálise Renal/métodos , Proteínas Sanguíneas/metabolismo , Toxinas Biológicas/metabolismoRESUMO
BACKGROUND: Liver IR is a frequent clinical complication with high morbidity and mortality. The present study evaluated the possible protective effect of sodium hydrosulfide (NaHS), a H2S donor, in IR-induced hepatic injury and explored the mechanisms of actions of the investigated drug. METHODS: Male albino rats (200-230 g) were divided into the following groups: group 1:Sham-operated non treated rats, group 2: IR non treated rats, group 3: L-NNA + IR rats, group 4: NaHS + IR rats, group 5: L-NNA + NaHS + IR rats. Blood samples were collected for ALT determination. Liver tissue samples were used for the assessment of GPx, catalase, SOD, MDA, total nitrites and TNF- α. Parts from the liver were fixed in 10% formalin solution for histopathological examination and immunohistochemical examination of iNOS, eNOS and caspase-3. RESULTS: NaHS protected the liver against IR. This hepatoprotection was associated with normalization of antioxidant enzyme activity and decrease in hepatic MDA, TNF-α and expression of caspase- 3 and iNOS. CONCLUSION: NaHS is hepatoprotective in IR injury. The hepatoprotective effects of NaHS are associated with antioxidant, anti-inflammatory and antiapoptotic effects. These effects are probably mediated via NO modulation.
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Óxido Nítrico , Traumatismo por Reperfusão , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fígado/patologia , Masculino , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Sulfetos , Fator de Necrose Tumoral alfaRESUMO
The spread of infectious diseases with significantly high mortality rates can wreak devastating damage on global health systems and economies, underscoring the need for better disease diagnostic platforms. Solid-phase polymerase chain reaction (SP-PCR) potentially combines the advantages of conventional PCR-based diagnostics with the capability of multiplexed detection, given that the spatial separation between primers circumvents unwanted primer-primer interactions. However, the generally low efficiency of solid-phase amplification results in poor sensitivity and limits its use in detection schemes. We present an SP-PCR-based, multiplexed pulldown fluorescence assay for the detection of Mycobacterium tuberculosis (MTB), utilizing highly fluorescent oligonucleotide-functionalized CdSe/CdS and CdSe1-xSx/CdS nanorods (NRs) as multicolor hybridization probes. The large surface area of the NRs allows for their easy capture and pulldown, but without contributing significantly to the interparticle photon reabsorption when clustered at the pulldown sites. The NR nanoprobes were specifically designed to target the hotspot regions of the rpoB gene of MTB, which have been implicated in resistance to standard rifampicin treatment. The implementation of the semiconductor NRs as photostable multicolor fluorophores in a multiplexed SP-PCR-based detection scheme allowed for the identification of multiple hotspot regions with sub-picomolar levels of sensitivity and high specificity in artificial sputum. While this work demonstrates the utility of semiconductor NRs as highly fluorescent chromophores that can enable SP-PCR as a sensitive and accurate technique for multipathogen diagnostics, the flexible surface chemistry of the NRs should allow them to be applicable to a wide variety of detection motifs.
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DNA Bacteriano/análise , Corantes Fluorescentes/química , Mycobacterium tuberculosis/isolamento & purificação , Nanotubos/química , Reação em Cadeia da Polimerase/métodos , Proteínas de Bactérias/genética , Compostos de Cádmio/síntese química , Compostos de Cádmio/química , Códon , RNA Polimerases Dirigidas por DNA/genética , Corantes Fluorescentes/síntese química , Limite de Detecção , Nanopartículas Metálicas/química , Mycobacterium tuberculosis/química , Compostos de Selênio/síntese química , Compostos de Selênio/química , Sensibilidade e Especificidade , Sulfetos/síntese química , Sulfetos/químicaRESUMO
The present study aimed to evaluate the protective effects of selenium (Sel) administration against tacrolimus (Tac) - induced lung toxicity and to assess the relation between heme oxygenase 1 (HO-1) and these effects. The study was conducted on 36 Wistar male albino rats equally divided into four groups: (i) normal control; (ii) Sel (0.1 mg/kg per day p.o. for four weeks); (iii) TAC 3 mg/mL as single oral dose on 27th day; and (iv) Tac + Sel. Lung tissues, lung homogenate, and bronchoalveolar lavage of the sacrificed animals were investigated biochemically and histopathologically, by immunohistochemistry or by PCR. The Tac group showed significantly lower expression of HO-1. Administration of Sel was associated with increased HO-1 expression. Oxidative (malondialdehyde, reduced glutathione, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity) and nitrosative stress (nitric oxide) markers and markers of inflammation (interleukin 1ß (IL-1ß), IL-6, and IL-10) showed changes corresponding to HO-1 levels in rat groups. Tac group showed the highest expression of caspase-3. Sel exerted a protective role against Tac-induced lung toxicity.
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Lesão Pulmonar Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Selênio/farmacologia , Tacrolimo/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Interações Medicamentosas , Heme Oxigenase (Desciclizante)/genética , Imunossupressores/toxicidade , Interleucina-10/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Activation of hepatic stellate cells is a central event in hepatic fibrogenesis that offers multiple potential sites for therapeutic interventions. Peroxisome proliferator-activated receptors are implicated in liver fibrosis. We aimed to evaluate the effect of bezafibrate and pioglitazone on a thioacetamide (TAA) rat model of liver fibrosis and to clarify the possible underlying mechanisms. Rats received intraperitoneal injections of TAA for 6 weeks. Daily oral treatments with bezafibrate or pioglitazone were started with the first day of TAA intoxication. Serum liver function tests, hepatic malondialdehyde (MDA), total nitrite and nitrate (NOx), superoxide dismutase, and hepatic histopathology were assessed to evaluate hepatic damage. Alpha smooth muscle actin (α-SMA) and tissue inhibitor metalloproteinase-1 (TIMP-1) and caspase-3 were also assessed. The TAA group experienced significant deterioration of liver functions, increased oxidative stress, and increased liver tissue NOx. Administration of bezafibrate or pioglitazone resulted in significant improvement of all liver functions and reduced oxidative stress in hepatic tissues. Only administration of bezafibrate significantly reduced NOx levels. Liver tissues from the TAA-treated group showed disrupted normal architecture. Administration of bezafibrate or pioglitazone attenuated this picture. Stronger α-SMA expression was detected in the TAA group. Treatment with bezafibrate or pioglitazone decreased the α-SMA expression.
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Bezafibrato/uso terapêutico , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Pioglitazona/uso terapêutico , Actinas/biossíntese , Animais , Células Estreladas do Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Masculino , Malondialdeído/sangue , Nitritos/sangue , Ratos , TioacetamidaRESUMO
INTRODUCTION: Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the formation of collagen fibrils in dentin, leading to morphological and structural changes that affect the strength and appearance of teeth. However, there is still a lack of understanding regarding the nanoscale characterization of the disease, in terms of collagen ultrastructure and mechanical properties. Therefore, this research presents a qualitative and quantitative report into the phenotype and characterization of OIDI in dentin, by using a combination of imaging, nanomechanical approaches. METHODS: For this study, 8 primary molars from OIDI patients and 8 primary control molars were collected, embedded in acrylic resin and cut into longitudinal sections. Sections were then demineralized in 37% phosphoric acid using a protocol developed in-house. Initial experiments demonstrated the effectiveness of the demineralization protocol, as the ATR-FTIR spectral fingerprints showed an increase in the amide bands together with a decrease in phosphate content. Structural and mechanical analyses were performed directly on both the mineralized and demineralized samples using a combination of scanning electron microscopy, atomic force microscopy, and Wallace indentation. RESULTS: Mesoscale imaging showed alterations in dentinal tubule morphology in OIDI patients, with a reduced number of tubules and a decreased tubule diameter compared to healthy controls. Nanoscale collagen ultrastructure presented a similar D-banding periodicity between OIDI and controls. Reduced collagen fibrils diameter was also recorded for the OIDI group. The hardness of the (mineralized) control dentin was found to be significantly higher (p<0.05) than that of the OIDI (mineralized) dentine. Both the exposed peri- and intratubular dentinal collagen presented bimodal elastic behaviors (Young's moduli). The control samples presented a stiffening of the intratubular collagen when compared to the peritubular collagen. In case of the OIDI, this stiffening in the collagen between peri- and intratubular dentinal collagen was not observed and the exposed collagen presented overall a lower elasticity than the control samples. CONCLUSION: This study presents a systematic approach to the characterization of collagen structure and properties in OIDI as diagnosed in dentin. Structural markers for OIDI at the mesoscale and nanoscale were found and correlated with an observed lack of increased elastic moduli of the collagen fibrils in the intratubular OIDI dentin. These findings offer an explanation of how structural changes in the dentin could be responsible for the failure of some adhesive restorative materials as observed in patients affected by OIDI.
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Colágeno/metabolismo , Dentinogênese Imperfeita/metabolismo , Osteogênese Imperfeita/metabolismo , Dentina/metabolismo , Dentina/ultraestrutura , Dentinogênese Imperfeita/diagnóstico por imagem , Elasticidade , Dureza , Humanos , Dente Molar , Osteogênese Imperfeita/diagnóstico por imagem , Fenótipo , Radiografia Interproximal , Espectroscopia de Infravermelho com Transformada de Fourier , Desmineralização do DenteRESUMO
AIM OF THE STUDY: Non-alcoholic fatty liver disease (NAFLD) is a challenging health problem. Hyperuricemia is a key player in the pathogenesis of NAFLD. This study investigated the effect of allopurinol (uric acid synthesis inhibitor) in combination with metformin and vitamin E in prevention of fructose induced-fatty liver in rats. MATERIAL AND METHODS: Rats were divided into 7 groups: control group, fructose group (model group of NAFLD), allopurinol-treated group, metformin-treated group, vitamin E-treated group, metformin plus vitamin E-treated group and a combination group (received allopurinol plus metformin plus vitamin E). Development of NAFLD was assessed biochemically by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as by histopathological examination. Oxidative stress parameters [reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA)], and the inflammatory mediators tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) were assessed, along with serum levels of uric acid and triglyceride (TG). RESULTS: Combination of allopurinol plus metformin plus vitamin E significantly attenuated fatty changes compared to their respective monotherapy. Interestingly, though all treated groups showed significant attenuation in the oxidative stress markers, TNF-α level and iNOS immunostaining in hepatic tissue, along with a significant decrease in the levels of uric acid and TG, the combination group showed a further significant decrease in the serum level of uric acid and iNOS immunostaining compared to other treated regimens. CONCLUSIONS: Allopurinol synergistically increases the protective effect of metformin and vitamin E in treatment of NAFLD, namely via reduction of uric acid synthesis and iNOS expression.
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BACKGROUND: To evaluate the level of knowledge regarding warning signs, presenting symptoms and risk factors associated with coronary heart disease (CHD) among population of Dubai and Northern Emirates in UAE. MATERIALS AND METHODS: A cross sectional survey of 1367 residents of Dubai and Northern Emirates was conducted using a self-administered questionnaire. RESULTS: Respondents were classified into two groups: Young Adult Population (YAP; 18-24 years of age) and General Population (GP; 25 years and older). Majority of participants were males (56.7%) and of South Asian (57.5%) or Middle-Eastern (30.8%) ethnicity. Regarding presenting symptoms of CHD, chest pain was identified by around 80% of population, whereas pain in the left shoulder was recognized by 61% of GP and 44% of YAP. Atypical symptoms were poorly identified. Regarding risk factors, only one-fourth population knew that males were at higher risk compared to premenopausal females. Few knew that the risk increases in females after menopause and that the risk is higher for females who smoke and use oral contraceptives. 62% knew that the survivors of a heart attack are at high risk of recurrences. Except for tobacco smoke, hypercholesterolemia and hypertension, knowledge of other risk factors was not satisfactory. Older adults and females had comparatively higher level of knowledge. CONCLUSION: Knowledge level of many of the symptoms and risk factors of CHD is unsatisfactory. There is, therefore, a need to increase the awareness in the population of UAE. The knowledge gaps identified through this study can be addressed through health campaigns to increase the awareness about warning signs, symptoms and modifiable risk factors. .
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Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization-remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.
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Osso e Ossos/fisiologia , Calcificação Fisiológica/fisiologia , Desmineralização do Dente/fisiopatologia , Remineralização Dentária , Dente/fisiologia , Cálcio/análise , Humanos , Fosfatos/análiseRESUMO
Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p < 0.05) decrease in serum levels of alanine transferase (ALT) and aspartate transferase (AST) and alkaline phosphatase (ALP) enzymes; hepatic malondialdehyde (MDA) and total nitrites and nitrates (NOx) levels; as well as a significant increase in hepatic superoxide dismutase (SOD) activity. In addition, there was a remarkable improvement in the histopathological features and a significant reduction in the expression of COX-2, iNOS and caspase-3 enzymes as compared with the MTX group. We recommend considering captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols.
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Apoptose/efeitos dos fármacos , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Captopril/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Metotrexato/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Animais , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Captopril/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclo-Oxigenase 2/biossíntese , Imuno-Histoquímica , Testes de Função Hepática , Masculino , Óxido Nítrico Sintase Tipo II/biossíntese , Substâncias Protetoras/administração & dosagem , Ratos , TelmisartanRESUMO
INTRODUCTION: Rotavirus is the major cause of acute gastroenteritis (AGE) in infants and young children all over the world. The objective of the study was to compare different methods for detecting rotavirus and to assess the burden of rotavirus as a causative agent for AGE in children younger than five. METHODS: This case control study included 65 children with AGE and 35 healthy control children. They were chosen from the Pediatric Department of Zagazig University Hospitals from October 2014 to March 2015. Stool samples were obtained and assayed for rotavirus by the immunochromatography test (ICT), enzyme linked immunosorbent assay (ELISA) and quantitative real time RT-PCR (qr RT-PCR). RESULTS: Fifty out of the 65 patients (76.9%) were positive for qr RT-PCR. Forty-five (69.2%) and 44 (67.7%) were positive for ICT and ELISA, respectively. There was a significant association between the severity of the disease as determined by the Vesikari score and rotavirus infection. CONCLUSION: This study demonstrated that ICT is a useful method for the rapid screening of group A rotavirus in fecal specimens, because it is rapid, inexpensive, easy to perform, and requires very little equipment. In addition, this study highlights the substantial health burden of rotavirus AGE among children less than five.
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Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions.
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Citoproteção/efeitos dos fármacos , Etanercepte/farmacologia , Guanidinas/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Metotrexato/efeitos adversos , Animais , Biomarcadores/metabolismo , Caspase 3/metabolismo , Rim/citologia , Rim/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: Ischemia-reperfusion (IR) injury represents an important pathological process of liver injury during major hepatic surgery. The role of cyclooxygenase (COX) enzymes in the pathogenesis of ischemia-reperfusion (IR)-induced liver injury is not clear. This study investigated the effect of a selective COX-2 inhibitor, celecoxib, versus non-selective, indomethacin, on hepatic IR injury in rats. MATERIALS AND METHODS: Hepatic IR was induced in adult male rats. The animals were divided into 4 groups: normal control (sham group), IR non-treated group; IR-indomethacin-treated group; and IR-celecoxib-treated group. Liver injury was evaluated by serum alanine aminotransferase (ALT) and a histopathological examination of liver tissues. Hepatic tissue content of oxidative stress parameters glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, malondialdehyde (MDA), nitric oxide (NO) and the inflammatory marker, tumor necrosis factor-alpha, (TNF-α) were measured. Moreover, the immunohistochemical detection of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and caspase-3 in the hepatic tissue was performed. KEY FINDINGS: Celecoxib, but not indomethacin, significantly attenuated hepatic IR injury as evidenced by reduction in serum ALT as well as by improvement in the histopathological scoring. Such effect was associated with attenuation in oxidative stress and TNF-α, along with modulation of immunohistochemical expression of eNOS, iNOS and caspase-3 in the hepatic tissue. SIGNIFICANCE: The present study concluded that selective COX-2 inhibition (but not non-selective), is hepatoprotective against liver IR injury; indicating a differential role of COX-1 versus COX-2. Modulation of iNOS, eNOS and caspase-3 might participate in the protective effect of selective COX-2-inhibitors.
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Inibidores de Ciclo-Oxigenase 2/farmacologia , Indometacina/farmacologia , Hepatopatias/tratamento farmacológico , Pirazóis/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Sulfonamidas/farmacologia , Alanina Transaminase/sangue , Animais , Caspase 3/metabolismo , Celecoxib , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/patologia , Masculino , Malondialdeído/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Ratos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Non-adherence to prescription is common among hemodialysis (HD) patients and has been associated with significant morbidity. At least 50% of HD patients are believed to be non-adherent to some part of their treatment. We aimed to assess the prevalence of non-adherence to dialysis prescription among 100 chronic HD patients. We explored the relationship between non-adherence on one hand and socioeconomic profile, depression scores and cognitive function on the other hand. The impact of patients' non-adherence on nutritional status, quality of life and dialysis adequacy was also assessed. The mean age of the study group was 50.51 ± 12.0 years. There were 62 females and 38 males in the study. Thirty-six patients (36%) were non-compliant to their dialysis prescription. No significant differences were detected between compliant and non-compliant patients in their education level and employment status. Inter-dialytic weight gain, serum phosphorus and depression scores were significantly higher in non-compliant patients compared with compliant patients, whereas body weight, serum albumin, serum calcium, quality of life scores and nutrition scores were significantly higher in compliant patients (P <0.05). In conclusion, non-adherence is highly prevalent among chronic HD patients and is associated with poor quality of life, depression and malnutrition.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Cooperação do Paciente , Pacientes/psicologia , Diálise Renal/psicologia , Insuficiência Renal Crônica/terapia , Adulto , Biomarcadores/sangue , Cognição , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Depressão/epidemiologia , Depressão/psicologia , Egito/epidemiologia , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Desnutrição/psicologia , Pessoa de Meia-Idade , Estado Nutricional , Prescrições , Prevalência , Qualidade de Vida , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/psicologia , Fatores de Risco , Fatores SocioeconômicosRESUMO
INTRODUCTION: Hypertension affects more than a quarter of the global adult population. Studies conducted worldwide suggest an overall small, yet useful, role of omega-3 PUFAs in reducing blood pressure in hypertensive patients. However there is no substantial data in this regard from population based in Middle East and Asia. OBJECTIVES: To determine the effects of (omega-3) PUFA supplementation on the blood pressure of hypertensive patient. To identify if male and female hypertensive patients respond differently to PUFA. To identify if response of hypertensive patients to PUFA varies with the duration of hypertension and co-existence of diabetes/dyslipidemia. MATERIALS AND METHODS: This observational study was conducted among hypertensive patients visiting OPD of the Gulf Medical College Hospital, Ajman, UAE, during the period Jan-Dec 2012. A total of 100 hypertensive patients on treatment with their antihypertensive medications, 50 of whom were taking n-3 PUFA supplementation, were followed up for a period of 3 months. Comparisons were drawn between the BP recordings at the time of enrollment in the study and their follow up values 3 months after enrollment. RESULTS: There was a statistically significant reduction in both the systolic and diastolic blood pressures after 3 months of PUFA therapy. The BP lowering effect of PUFA was more in males. A statistically significant reduction in BP was noted in non-diabetic patients and patients with long standing hypertension. CONCLUSION: Findings of the study suggest that omega-3 PUFA dietary supplements augment the benefits of pharmacotherapy in hypertension.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Hipertensão/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Emirados Árabes UnidosRESUMO
Ischemia-reperfusion injury (IRI) is an important cause of liver damage in many clinical situations. Levosimendan is a promising therapy for prevention of IRI. The present work investigated the possible contribution of nitric oxide (NO), cyclooxygenase (COX) enzymes, and adenosine triphosphate sensitive potassium channel (K-ATP) in the protective effect of levosimendan in liver IRI in rats. Rats were divided into 7 groups. Sham-operated group (negative control group); IR-nontreated group (positive control group), levosimendan-treated group (treated with levosimendan); indomethacin, nonselective COX inhibitor,+levosimendan group (cotreated with indomethacin+levosimendan); celecoxib (selective COX-2 inhibitor)+levosimendan group; L-NNA (Nitro- ω-L-arginine, nonselective NO synthase inhibitor)+levosimendan group; and glibenclamide (K-ATP blocker)+levosimendan group. Liver injury was evaluated biochemically (by serum level of alanine aminotransferase (ALT)) as well as by histopathology. Hepatic tissue content of oxidative stress markers, tumor necrosis factor-alpha (TNF-α), along with immunohistochemical expression of induced NO synthase (iNOS), endothelial NO synthase (eNOS), and caspase-3 in hepatic tissue were assayed. The study showed that levosimendan attenuated liver IRI as evidenced by a decrease in serum ALT level and confirmed by histopathology. The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-α, iNOS, eNOS, and caspase-3. The hepatoprotective effect of levosimendan was partially attenuated by pretreatment by either nonselective COX inhibitor, NOS inhibitor, or K-ATP channel blocker; indicating that the hepatoprotective effect of levosimendan was attributed, at least in part to activation of COX-1, modulation of NO, and opening of K-ATP channel.
Assuntos
Hidrazonas/uso terapêutico , Fígado/efeitos dos fármacos , Inibidores de Fosfodiesterase/uso terapêutico , Piridazinas/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Hidrazonas/farmacologia , Fígado/metabolismo , Fígado/patologia , Masculino , Inibidores de Fosfodiesterase/farmacologia , Piridazinas/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , SimendanaRESUMO
Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.
RESUMO
Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor- α , and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury.