Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancer Chemother Pharmacol ; 85(2): 331-343, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31989218

RESUMO

One promising strategy for minimizing chemotherapeutic resistance in hepatocellular carcinoma (HCC) is the use of effective chemosensitizers. We studied the complementary multi-targeted molecular mechanisms of metformin and celastrol in mice with diethylnitrosamine-induced HCC to investigate whether metformin could augment the sensitivity of HCC tissue to the effect of celastrol. Simultaneous administration of celastrol (2 mg/kg) and metformin (200 mg/kg) improved liver function, enhanced the histological picture and prolonged survival. Additionally, combination therapy exerted anti-inflammatory activity, as indicated by the decreased levels of TNF-α and IL-6. This protective role could be attributed to inhibition of inflammasome activation. Herein, our data revealed downregulated NLRP3 gene expression, suppressed caspase-1 activity and reduced levels of the active forms of IL-1ß and IL-18. Under this condition, pyroptotic activity was suppressed. In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio. In addition to their repressive effect on the gene expression of NFκBp65, TNFR and TLR4, metformin and celastrol inhibited phosphorylation-induced activation of IκBκB and NFκBp65 and decreased IκBα degradation. Combination therapy with metformin and celastrol repressed markers of angiogenesis, metastasis and tumour proliferation, as revealed by the decreased hepatic levels of VEGF, MMP-2/9 and cyclin D1 mRNA, respectively. In conclusion, by inhibiting NLRP3 inflammasome and its prerequisite NFκB signalling, simultaneous administration of metformin and celastrol appears to have additive benefits in the treatment of HCC compared to cela monotherapy. This effect warrants further clinical investigation.

3.
J Craniofac Surg ; 31(1): 210-213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31469730

RESUMO

OBJECTIVE: The aim of the study was to assess different radiologic bony landmarks for endoscopic localization of the sphenopalatine foramen (SPF). METHODS: Paranasal computed tomography (CT) scans of adults without sinonasal pathology were included. On axial cuts, the anteroposterior distances from the SPF to maxillary line, anterior head of the middle turbinate, basal lamella of the middle turbinate, choanal arch, and posterior fontanel of the maxillary sinus ostium were measured. While on coronal cuts, the vertical distances from the SPF to the nasal floor was measured. The registered measurements were then studied and statistically analyzed. RESULTS: In 70 patients (140 sides, 840 measurements), the mean distances from the SPF to nasal floor, choanal arch, maxillary line, anterior head of the middle turbinate, basal lamella, and posterior fontanel were 25.6 ±â€Š2.4, 8.5 ±â€Š1.38, 36.4 ±â€Š2.6, 34.6 ±â€Š4.26, 8.1 ±â€Š1.27, and 13.7 ±â€Š1.7 mm, respectively, without significant differences between right and left sides. Females showed significantly shorter mean distances between SPF and the nasal floor (P = 0.0011), choanal arch (P = 0.0459), and posterior fontanel (P < 0.0001) than males. While no significant differences were detected between both sexes as regard distances from SPF to maxillary line (P = 0.5579), anterior head of middle turbinate (P = 0.8581), and basal lamella (P = 0.0638). CONCLUSION: Preoperative CT can provide multiple easily detected, reliable, and simple bony landmarks that can help SPF endoscopic localization. Thus the authors recommend adding these measurements to the preoperative CT checklist for patients scheduled for sphenopalatine artery ligation and/or excision of vascular lesions.

4.
Sci Rep ; 9(1): 19095, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836811

RESUMO

Sorafenib (SO) is a multi-kinase inhibitor that targets upstream signals in the MAPK pathway. Drug resistance and transient survival benefits are the main obstacles associated with SO treatment in Hepatocellular carcinoma (HCC) patients. Mebendazole (MBZ), an anthelmintic agent, has demonstrated activity against various cancer types. Therefore, we aimed to investigate the possible mechanisms of MBZ other than its anti-tubulin activity. MBZ (100 mg/kg/day, P.O.) was administered to N-nitrosodiethylamine-induced HCC mice as a monotherapeutic agent or in combination with SO. Our results revealed that MBZ decreased AFP levels, improved liver function and histology and increased survival in HCC mice, particularly when administered in combination with SO. MBZ also reduced hepatic inflammation and fibrogenesis as evidenced by reductions in TNF-α and TGF-ß1 levels, respectively. Increased hepatic caspases-3 and -9 and decreased BCL-2 levels suggest induced-cell death. In addition, MBZ demonstrated anti-angiogenic, anti-metastatic, and anti-proliferative effects, as indicated by reduced VEGF levels, MMP-2:TIMP-1 ratios, and reduced cyclin D1 levels and Ki67 immunostaining, respectively. Our main finding was that MBZ targeted downstream signal of the MAPK pathway by inhibiting ERK1/2 phosphorylation. Targeting downstream MAPK signalling by MBZ and upstream signalling by SO is a novel approach to minimizing resistance and prolonging survival.

5.
Naunyn Schmiedebergs Arch Pharmacol ; 392(12): 1591-1604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31367864

RESUMO

Hepatocellular carcinoma (HCC) is characterized by bad prognosis and is the second most common reason for cancer-linked mortality. Treatment with sorafenib (SRF) alone increases patient survival by only a few months. A causal link has been determined between angiotensin II (Ang-II) and HCC. However, the mechanisms underlying the tumorigenic effects of Ang-II remain to be elucidated. N-Nitrosodiethylamine was utilized to examine the effects of telmisartan (TEL) (15 mg/kg), SRF (30 mg/kg), and a combination of these two agents on HCC mice. Downregulation of NF-кBP65 mRNA expression and inhibition of the phosphorylation-induced activation of both ERK1/2 and NF-кB P65 were implicated in the anti-tumor effects of TEL and SRF. Consequent regression of malignant changes and improvements in liver function associated with reduced levels of AFP, TNF-α, and TGF-ß1 were also confirmed. Anti-proliferative, anti-metastatic, and anti-angiogenic effects of treatment were indicated by reduced hepatic cyclin D1 mRNA expression, reduced MMP-2 levels, and reduced VEGF levels, respectively. TEL, but not SRF, demonstrated agonistic activity for PPARγ receptors, as evidenced by increased PPARγ DNA binding activity, upregulation of CD36, and HO-1 mRNA expression followed by increased liver antioxidant capacity. Both TEL and SRF inhibited TAK1 phosphorylation-induced activation, indicating that TAK1 might act as a central mediator in the interaction between ERK1/2 and NF-кB. TEL, by modulating the ERK1/2, TAK1, and NF-кB signaling axis in the context of PPARγ agonistic activity, exerted anti-tumor effects and increased tumor sensitivity to SRF. Therefore, TEL is an encouraging agent for further clinical trials regarding the management of HCC.

6.
Arch Biochem Biophys ; 671: 185-195, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31326516

RESUMO

Variations in Nrf-2 and NF-κB expression profiles have been reported in ulcerative colitis (UC), in which an interplay between these two critical pathways has been identified. The therapeutic potential of angiotensin receptor blockers (ARBs) for oxidative damage and inflammation has recently received considerable attention. Dextran sodium sulfate (DSS)-induced colitis in rats closely resembles human UC and is associated with oxidative damage and the production of pro-inflammatory mediators. Therefore, we aimed to investigate the effect of orally administered telmisartan (TEL) (1.75, 3.5 and 7 mg/kg) in a rat model of DSS-induced colitis. Our study revealed that TEL, particularly at 7 mg/kg, alleviated tissue injury and inflammatory signs upon histological analysis and enhanced survival and recovery during DSS-induced colitis. The levels of colonic IL-1ß, IL-6, TNF-α and serum C-reactive protein (CRP) were downregulated, while the level of colonic IL-10 was upregulated. TEL repressed DSS-induced neutrophil infiltration and improved the colonic antioxidant defence machinery. TEL inhibited apoptotic signalling as indicated by lower caspase 3 expression, increased CD36 gene expression and exhibited PPARγ agonistic activity. In addition, TEL downregulated gene expression and inhibited phosphorylation of the NF-κB p65 subunit. On the other hand, TEL upregulated the gene expression of Nrf-2 and HO-1. We concluded that TEL, besides its PPARγ agonistic activity, acted as a modulator of Nrf-2/NF-κB interactions and exhibited anti-apoptotic activity after tissue damage and that PPARγ and CD36 might play a critical role in the pathogenesis of murine colitis. Therefore, our findings suggest that further investigations on human IBDs are warranted.

7.
Abdom Radiol (NY) ; 44(5): 1773-1784, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30603882

RESUMO

PURPOSE: We investigated the added value of diffusion-weighted imaging (DWI)/apparent diffusion coefficient (ADC) in the categorization of small hepatic observation (≤ 20 mm) detected in patients with chronic liver disease in reference to LI-RADS (liver imaging reporting and data system) classification system. METHODS: We prospectively evaluated 165 patients with chronic liver disease with small hepatic observations (≤ 20 mm) which were previously categorized as LI-RADS grade 3-5 on dynamic contrast-enhanced CT (DCE-CT). All patients were submitted to a functional MRI including DCE and DWI. Using LI-RADS v2017, two radiologists independently evaluated the observations and assigned a LI-RADS category to each observation using DCE-MRI alone and combined DCE-MRI and DWI/ADC. In the combined technique, the radiologists assigned a LI-RADS category based on a modified LI-RADS criteria in which restricted diffusion on DWI was considered a major feature of HCC. We evaluated the inter-reader agreement with Kappa statistics and compared the diagnostic performance of the LI-RADS with two imaging techniques by Fisher's exact test using histopathology as the reference standard. RESULTS: Combined technique in LI-RADS yielded better sensitivities (reader 1, 97% [65/67]; reader 2, 95.5% [64/67]) for HCC diagnosis than DCE-MRI alone (reader 1, 80.6% [54/67], p = 0.005; reader 2, 83.6% [56/67], p = 0.04). The specificities were insignificantly lower in combined technique (reader 1, 88.4% [107/121]; reader 2, 77.7% [94/121]) than in DCE-MRI alone (reader 1, 90.9% [110/121], p = 0.67; reader 2, 79.3% [96/121], p = 0.88). The inter-reader agreement of the LI-RADS scores between combined technique and DCE-MRI was good (κ = 0.765). CONCLUSION: The use of DWI/ADC as an additional major criterion, improved the sensitivity of LI-RADS in the diagnosis of HCC while keeping high specificity.

8.
Toxicol Appl Pharmacol ; 364: 120-132, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594690

RESUMO

Alteration in the expression pattern of Nrf-2 and NFκB has been reported in ulcerative colitis (UC) in which functional crosstalk between these two critical pathways has been suggested. The ameliorative potential of the AT1R blocker olmesartan (OLM) on oxidative stress and inflammatory cytokines has received considerable attention in recent years. Acetic acid (AA)-induced UC demonstrates close resemblance to human UC regarding histopathological features and cytokine profile and is associated with local intense immune response, oxidative stress and release of inflammatory cytokines. Therefore, The effect of OLM (1, 5 and 10 mg/kg) administered orally to rats subjected to intra-rectal instillation of 2 ml of 3% AA in saline solution is investigated. The study revealed that OLM ameliorated colon injury and inflammatory signs as visualized by histopathological examination. Levels of colon IL-6, TNF-α, IL-1ß, TGF-ß, and serum CRP were down-regulated, while the level of colon IL-10 was up-regulated. In a dose-dependent manner, OLM suppressed AA-induced neutrophils accumulation and improved colon anti-oxidant defense machinery. Also, OLM repressed the Bax:BCL-2 ratio and caspase3 expression. The mechanism of these protective effects was found to lay behind its ability to down-regulate gene expression and inhibit phosphorylation and nuclear translocation of p65 subunits. On the other hand, OLM up-regulated gene expression of Nrf-2 and HO-1. In conclusion, our data show that OLM is an Nrf2 activator, NFkB inhibitor and apoptosis inhibitor in an experimental model of ulcerative colitis. Overall, the study indicates that OLM shows promise as a potential therapy for the treatment of human inflammatory bowel diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/prevenção & controle , Colo/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Imidazóis/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Tetrazóis/farmacologia , Ácido Acético , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/enzimologia , Colite Ulcerativa/patologia , Colo/enzimologia , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Inibidor de NF-kappaB alfa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
9.
Int Immunopharmacol ; 64: 340-349, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30243070

RESUMO

Therapeutic interventions are still limited in the treatment of liver fibrosis even though an incredible number of publications related to silymarin are produced. This is due to the complex molecular pathogenesis. Several studies pointed to the role of renin-angiotensin system (RAS) in hepatic fibrogenesis. Therefore, the present study was designed to examine the effect of the combination of lisinopril (LIS) with silymarin (SIL) on CCl4-induced hepatic fibrosis along with an in-vitro confirmatory experiment. Rats were treated with LIS (1 mg kg-1) and SIL (30 mg kg-1) as a single agent and as combined to LIS (1 mg kg-1). Our results revealed that down-regulation of NFĸBp65 mRNA expression and inhibition of phosphorylation of NFĸBp65 (at Ser536) and NFĸBia were implicated in the anti-fibrotic effect of both LIS and SIL. Consequently lower levels of NFкB-induced TNF-α, TGF-ß1, MMP-2, TIMP-1 and VEGF compared to control group. In addition, levels of α-SMA protein expression and hydroxyproline are decreased in association with marked improvement in liver function, oxidative stress markers and histological picture. In addition, LIS augmented the inhibitory effect of SIL on NFĸB pathway at lower dose level. We concluded that LIS, via targeting NFĸB pathway, increases anti-oxidant capacity of liver tissue and exhibits anti-inflammatory, anti-fibrotic and anti-angiogenic activity and augments sensitivity to SIL. Therefore, LIS is a promising candidate for further clinical investigation in the treatment of liver fibrosis.


Assuntos
Lisinopril/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Silimarina/farmacologia , Animais , Células Cultivadas , Citoproteção , Hepatócitos/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/mortalidade , Cirrose Hepática Experimental/patologia , Masculino , NF-kappa B/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
10.
Open Access Maced J Med Sci ; 6(6): 955-960, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29983784

RESUMO

BACKGROUND: Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular carcinoma (HCC). OBJECTIVE: We aimed to investigate the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) on the survival of mice with diethylnitrosamine (DEN) induced HCC. METHODS: HCC was induced by weekly i.p. administration of DEN. Mice were treated with sorafenib (SO) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/kg), losartan (LO) (10 mg/kg), PE (1 mg/kg) + SO (30 mg/kg), FO (2 mg/kg) + SO (30 mg/kg), or LO (10 mg/kg) + SO (30 mg/kg). Survival analysis was done using the Kaplan-Meier method, and the log-rank test was used for assessing the significance of difference between groups. RESULTS: The administration of PE, FO and LO as monotherapy or as combined with SO resulted in marked improvement in the liver histologic picture with no impact on overall survival of mice. CONCLUSION: Interfering the RAS either through the inhibition of ACE or the blockade of angiotensin II type 1 (AT1) receptors has similar effects on the liver of DEN-induced HCC mice and is not associated with longer survival due to detrimental effects of DEN on other organs. Hence, repetitive administration of DEN in such models of HCC is not suitable for mortality assessment studies.

11.
Toxicol Lett ; 295: 32-40, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859236

RESUMO

Hepatocellular carcinoma (HCC) is a major global health problem. Therapeutic interventions of HCC are still limited because of its complicated molecular pathogenesis. Many reports showed that renin-angiotensin system (RAS) contributes to the development of different types of malignancies. Therefore, the present study aimed to examine the effect of RAS inhibition using perindopril (1 mg/kg), fosinopril (2 mg/kg), or losartan (10 mg/kg) on diethylnitrosamine-induced HCC compared to sorafenib (30 mg/kg). The administration of RAS inhibitors resulted in improved liver function and histologic picture with a reduction in AFP levels. These effects found to be mediated through inactivation of NFкB pathway by the inhibition of NFĸB p65 phosphorylation at the Ser536 residue and inhibition of the phosphorylation-induced degradation of NFĸBia. Consequently, expression levels of cyclin D1 mRNA were significantly lowered. In addition, NFкB-induced TNF-α and TGF-ß1 levels were reduced leading to lower levels of MMP-2 and VEGF. We concluded that RAS inhibition either through inhibiting the ACE or the blockade of AT1R has the same therapeutic benefit and that the tissue affinity of the ACEIs has no impact on its anti-tumor activity. These results suggest that ACEIs and ARBs can serve as promising candidates for further clinical trials in the management of HCC.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Dietilnitrosamina , Fosinopril/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Losartan/farmacologia , NF-kappa B/metabolismo , Perindopril/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclina D1/genética , Ciclina D1/metabolismo , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Sorafenibe , Fatores de Tempo , Fator de Transcrição RelA/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Can J Physiol Pharmacol ; 96(6): 569-576, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29425464

RESUMO

Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl4-induced liver fibrosis. Mice were treated with silymarin (30 mg·kg-1), perindopril (1 mg·kg-1), fosinopril (2 mg·kg-1), or losartan (10 mg·kg-1). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-ß1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.


Assuntos
Tetracloreto de Carbono/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/fisiopatologia , NF-kappa B/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Actinas/metabolismo , Alanina Transaminase/sangue , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroxiprolina/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Metaloproteinase 2 da Matriz/sangue , Camundongos , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangue , alfa-Fetoproteínas/metabolismo
13.
Iran J Kidney Dis ; 12(6): 331-340, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30595562

RESUMO

INTRODUCTION: Disturbances of lipid metabolism has been reported in nephrotic syndrome (NS) and may predispose to atherosclerosis. This study aimed to investigate the correlation between cardiovascular risk factors and carotid intima-media thickness (CIMT) and brachial artery flow-mediated dilatation in patients with idiopathic NS. MATERIALS AND METHODS: This case-control study included 31 patients with NS and 31 healthy individuals as the control group. All patients were subjected to full clinical examination; laboratory investigations in the form of lipid profile, kidney function tests, serum protein, serum albumin, C-reactive protein, and ferritin; carotid ultrasonography, and brachial artery flow-mediated dilatation. RESULTS: Serum cholesterol, low-density lipoprotein cholesterol, and triglyceride levels was significantly higher in the case group than the control group. High-density lipoprotein cholesterol and albumin levels were significantly lower in the case group. The absolute change in brachial artery diameter was significantly lower in the case group than that of the control group. Proportionate change in brachial artery diameter was significantly lower in the case group than that of the control group. Common carotid artery CIMT in the case group was significantly higher than that of the controls. Lastly, there were significant increases in weight and body mass index in the relapse group than the remission group. CONCLUSIONS: Patients with NS are more prone to atherosclerosis and vascular changes; CIMT was thicker in nephrotic children compared to the controls. The significantly abnormal values of flow-mediated dilatation in children with NS suggests an ongoing process of endothelial dysfunction.


Assuntos
Artéria Braquial/fisiologia , Espessura Intima-Media Carotídea , Síndrome Nefrótica/patologia , Síndrome Nefrótica/fisiopatologia , Vasodilatação/fisiologia , Aterosclerose/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores de Risco
14.
Urology ; 107: 103-106, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28456539

RESUMO

OBJECTIVE: To evaluate the role of preoperative testicular shear wave elastography (SWE) in the prediction of improvement of semen analysis parameters after subinguinal microsurgical varicocele ligation in patients with primary infertility and clinically detectable varicocele. PATIENTS AND METHODS: Testicular SWE before the surgical intervention was done. Forty-eight patients were scheduled for subinguinal microsurgical varicocele ligation as a treatment option. Computer-assisted semen analysis was repeated 6 months after the intervention. RESULTS: At a cutoff value of 4.5 kPa, the stiffness index had a sensitivity of 86.4% and a specificity of 84.2% for semen parameter improvement after varicocelectomy. Correlation between different parameters of semen analysis and SWE showed a statistically significant negative correlation between SWE stiffness index and both sperm count (million/mL) and total motility. On the other hand, a nonsignificant negative correlation was found between SWE stiffness index and percentage of normal form. CONCLUSION: Testicular SWE is a good test that can be used in the assessment of male infertility with clinically detectable varicocele, and its results may predict semen parameter improvement after varicocelectomy. Further studies on a larger number of patients are needed to verify our results.


Assuntos
Infertilidade Masculina/cirurgia , Sêmen/diagnóstico por imagem , Motilidade Espermática/fisiologia , Testículo/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Varicocele/cirurgia , Adulto , Diagnóstico por Computador , Seguimentos , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Ligadura , Masculino , Microcirurgia/métodos , Reprodutibilidade dos Testes , Fatores de Tempo , Varicocele/complicações , Varicocele/diagnóstico
15.
J Egypt Soc Parasitol ; 45(3): 511-20, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26939228

RESUMO

Schistosomiasis is a chronic disease with considerable social impact. Despite the availability of affordable chemotherapy, drug treatment has not significantly reduced the overall number of disease cases. Among other mechanisms, the parasite produces PGE2 and PGD2 to evade host immune defenses. To investigate the role of PGE2 and PGD2 in schistosomiasis, we evaluated the effects of L-161,982, Ah6809 (PGE2 receptor antagonists alone of combined with each other) and MK-0524 (PGD2 receptor antagonist) during prepatent Schistosoma mansoni infection. Drugs were administered intraperitoneally an hour before and 24 hours after infection of C57BL/6 mice with 100 Schistosoma mansoni cercariae. L-161,982, Ah6809, their combination and MK-0524 caused partial protection against pre-patent S. mansoni infection which was mediated by biasing the immune response towards Th1 phenotype. These results showed that blockade of PGE2 and PGD2 receptors confers partial protection against pre-patent S. mansoni infection in mice and that they may be useful as adjunctive therapy to current anti-schistosomal drugs or vaccines.


Assuntos
Indóis/farmacologia , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Esquistossomose mansoni/prevenção & controle , Tiofenos/farmacologia , Triazóis/farmacologia , Xantonas/farmacologia , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas de Prostaglandina/farmacologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA