Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
Chem Biol Interact ; 369: 110276, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36414029

RESUMO

Myocardial infarction (MI) is a progressive myocardial necrosis that can lead to a number of life-threatening complications. MiRNAs have a crucial role in the pathogenesis of many cardiovascular diseases. Remarkably, miR-122 targets the sirtuin-6 (Sirt-6) gene, which is an essential regulator of cardiovascular function and is considered a partial angiotensin converting enzyme 2 (ACE2) activator. Modulation of this axis is supposed to contribute to MI pathogenesis. The current study aims to investigate the cardioprotective effects of xanthenone through targeting the miR-122/Sirt-6/ACE2 axis on experimentally-induced MI in rats. Xanthenone was administered for 14 days and isoprenaline was injected in the last 2 days of the experiment. Xanthenone treatment resulted in a significant downregulation of miR-122, which further upregulated Sirt-6 and thus activated the adenosine monophosphate-activated protein kinase (AMPK). AMPK increases ACE2 levels and results in a decrease in the level of its substrate angiotensin II resulting in the normalization of the inflammatory cytokines and the cardiac biomarkers. Finally, by targeting the miR-122/Sirt-6/AMPK/ACE2 axis, xanthenone has the potential to be a promising cardioprotective agent against MI.


Assuntos
MicroRNAs , Infarto do Miocárdio , Ratos , Animais , Enzima de Conversão de Angiotensina 2/genética , Peptidil Dipeptidase A/genética , Proteínas Quinases Ativadas por AMP , Infarto do Miocárdio/tratamento farmacológico , MicroRNAs/genética
2.
Front Oncol ; 12: 1045016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439420

RESUMO

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor (areg/egf). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients.

3.
Front Oncol ; 12: 969429, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147914

RESUMO

Sickle cell disease (SCD) is a serious global health problem, and currently, the only curative option is hematopoietic stem cell transplant (HCT). However, myeloablative total body irradiation (TBI)-based HCT is associated with high mortality/morbidity in SCD patients. Therefore, reduced-intensity (2-4 Gy) total body radiation (TBI) is currently used as a conditioning regimen resulting in mixed chimerism with the rescue of the SCD disease characteristic features. However, donor chimerism gradually reduces in a few years, resulting in a relapse of the SCD features, and organ toxicities remained the primary concern for long-term survivors. Targeted marrow irradiation (TMI) is a novel technique developed to deliver radiation to the desired target while sparing vital organs and is successfully used for HCT in refractory/relapsed patients with leukemia. However, it is unknown if TMI will be an effective treatment for a hematological disorder like SCD without adverse effects seen on TBI. Therefore, we examined preclinical feasibility to determine the tolerated dose escalation, its impact on donor engraftment, and reduction in organ damage using our recently developed TMI in the humanized homozygous Berkley SCD mouse model (SS). We show that dose-escalated TMI (8:2) (8 Gy to the bone marrow and 2 Gy to the rest of the body) is tolerated with reduced organ pathology compared with TBI (4:4)-treated mice. Furthermore, with increased SCD control (AA) mice (25 million) donor BM cells, TMI (8:2)-treated mice show successful long-term engraftment while engraftment failed in TBI (2:2)-treated mice. We further evaluated the benefit of dose-escalated TMI and donor cell engraftment in alleviating SCD features. The donor engraftment in SCD mice completely rescues SCD disease features including recovery in RBCs, hematocrit, platelets, and reduced reticulocytes. Moreover, two-photon microscopy imaging of skull BM of transplanted SCD mice shows reduced vessel density and leakiness compared to untreated control SCD mice, indicating vascular recovery post-BMT.

4.
Phys Med Biol ; 67(19)2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36084625

RESUMO

Objective.Intensity-modulated radiotherapy (IMRT) is widely used in clinical radiotherapy, treating varying malignancies with conformal doses. As the test field for clinical translation, preclinical small animal experiments need to mimic the human radiotherapy condition, including IMRT. However, small animal IMRT is a systematic challenge due to the lack of corresponding hardware and software for miniaturized targets.Approach.The sparse orthogonal collimators (SOC) based on the direct rectangular aperture optimization (RAO) substantially simplified the hardware for miniaturization. This study investigates and evaluates a significantly improved RAO algorithm for complex mouse irradiation using SOC. Because the Kronecker product representation of the rectangular aperture is the main limitation of the computational performance, we reformulated matrix multiplication in the data fidelity term using multiplication with small matrices instead of the Kronecker product of the dose loading matrices. Solving the optimization problem was further accelerated using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA).Main results.Four mouse cases, including a liver, a brain tumor, a concave U-target, and a complex total marrow irradiation (TMI) case, were included in this study with manually delineated targets and OARs. Seven coplanar-field SOC IMRT (sIMRT) plans were compared with idealistic fluence map based IMRT (iIMRT) plans. For the first three cases with simpler and smaller targets, the differences between sIMRT plans and iIMRT plans in the planning target volumes (PTV) statistics are within 1%. For the TMI case, the sIMRT plans are superior in reducing hot spots (also termedDmax) of PTV, kidneys, lungs, heart, and bowel by 20.5%, 31.5%, 24.67%, 20.13%, and 17.78%, respectively. On average, in four cases in this study, the sIMRT plan conformity is comparable to that of the iIMRT's with lightly increased R50 and Integral Dose by 2.23% and 2.78%.Significance.The significantly improved sIMRT optimization method allows fast plan creation in under 1 min for smaller targets and makes complex TMI planning feasible while achieving comparable dosimetry to idealistic IMRT with fluence map optimization.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Algoritmos , Animais , Humanos , Camundongos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
5.
Front Oncol ; 12: 941814, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924145

RESUMO

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image-guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)-based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI-based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI.

6.
Front Mol Biosci ; 9: 864839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651814

RESUMO

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with chronic hepatitis C virus (HCV) infection as a major risk factor of HCC. Circulating microRNAs are deregulated in HCC and are candidate biomarkers. The aim of this study was to explore the expression profile of miRNA-122, miR-483, and miR-335 in the serum of HCV-related hepatocellular carcinoma (HCC). 90 HCV-related hepatocellular carcinoma (HCC) patients, 90 non-malignant HCV patients, and 60 healthy controls were included. Serum microRNAs were measured by a qRT-PCR custom array. The expression levels of miR-122 and miR-483 were upregulated in HCC patients, while the miR-335 expression level was downregulated versus controls and HCV groups. Receiver-operating characteristic (ROC) curve analysis was created to examine miRNAs. miR-483 presented the best diagnostic potential because it showed the highest diagnostic accuracy for distinguishing HCV-related HCC patients from controls (AUC = 0.98) with 100% sensitivity. Moreover, there was obvious prognostic power in distinguishing HCV from HCC (AUC = 0.95) with 88% sensitivity. In conclusion, studied microRNAs (miR-122, miR-483, and miR-335) could serve as potential non-invasive early diagnostic biomarkers for HCC, and we identified a panel of three serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

7.
J Enzyme Inhib Med Chem ; 37(1): 118-124, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34894966

RESUMO

Hepatic stellate cells activation (HSCs) plays a crucial role in the pathogenesis of liver fibrosis. Specific microRNAs have been suggested to affect the activation of HSCs via various signalling pathways including TGF-ß/smads and Wnt/ß-catenin pathways. Dasatinib is a multitarget inhibitor of many tyrosine kinases has recently studied for its anti-fibrotic effects in a variety of fibrous diseases. This study investigated the role of modulation of miRNA-378 and miRNA-17 in the pathogenesis of liver fibrosis through altering Wnt/ß-catenin and TGF-ß/smads pathways and evaluated the beneficial effect of the tyrosine kinase inhibitor, dasatinib, in thioacetamide-induced liver fibrosis model in mice. Treatment with dasatinib down-regulated miRNA-17 expression, leading to the restoration of WiF-1 and smad-7 which cause the inhibition of both Wnt/ß-catenin and TGF-ß/smads signalling. In addition, it upregulated miRNA-378 leading to the decrease of Wnt-10 which contributes to the suppression of activated HSCs.


Assuntos
Dasatinibe/farmacologia , Cirrose Hepática/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Proteína Smad7/metabolismo , Tioacetamida/antagonistas & inibidores , Animais , Dasatinibe/química , Relação Dose-Resposta a Droga , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Camundongos , MicroRNAs/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
8.
Arch Physiol Biochem ; 128(5): 1181-1187, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32421395

RESUMO

MicroRNAs (miRNAs) have critical roles in colorectal cancer (CRC) tumorigenesis and development. It has been reported that Eph receptor A7 (EphA7) was a potential target of miR-944 which is transcriptionally activated in cancer. The aim of this study was to explore the expression profile of miR-944 and its target gene EPHA7 in the serum of Egyptian CRC patients. 150 CRC patients, 50 adenomatous polyps (AP) patients, and 100 healthy controls were included. Serum miR-944 was downregulated (0.304 ± 0.0512) while serum EPHA7 was upregulated (3.163 ± 0.610) in CRC and AP patients versus controls and discriminated aganst these groups by Receiver operating characteristic curve (ROC) analysis. miR-944 presented the highest diagnostic accuracy for CRC patients from control (AUC = 0.90). Moreover obvious prognostic power in distinguishing AP from CRC (AUC = 0.87). In conclusion, miR-944 and EPHA7 are potential genetic markers of CRC predisposition and novel potential non-invasive diagnostic biomarkers for CRC.


Assuntos
MicroRNA Circulante , Neoplasias Colorretais , MicroRNAs , Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , MicroRNAs/genética , Receptor EphA1/genética , Receptor EphA7
9.
Front Mol Biosci ; 8: 754098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778375

RESUMO

Liver fibrosis is characterized by a series of events including activation of quiescent hepatic stellate cells (HSCs) into proinflammatory, contractile, and fibrogenic myofibroblasts, which is the primary trigger for the fibrogenesis process. HSC activation involves many signaling pathways such as the TGF-ß/smads pathway. Specific microRNAs have been identified to play a crucial role in the activation of HSCs via various signaling pathways. Piperine has recently been studied as a promising anti-fibrotic agent against pancreatic fibrosis through altering the TGF-ß1/Smad pathway. Hence, the current study evaluated the beneficial effects of piperine in thioacetamide-induced liver fibrosis in mice through the modulation of miRNA-17 and TGF-ß/smads pathways. Mice were allocated into three groups randomly. Thioacetamide was used to induce liver fibrosis for 6 weeks. Starting from the fourth week of the experiment, mice were treated with piperine daily for 21 days. Piperine treatment resulted in a significant downregulation of miRNA-17 expression, leading to the restoration of smad-7 accompanied with marked inhibition of TGF-ß/smads signaling with further suppression of the activated HSCs and collagen deposition in the hepatocytes. In conclusion, piperine has the potential to be a promising therapeutic drug for the treatment of liver fibrosis through inhibiting the TGF-ß/smads pathway.

10.
Cent European J Urol ; 74(4): 595-600, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35083082

RESUMO

INTRODUCTION: Although it is apparently simpler to perform unstented tubularized incised plate (TIP) repair for distal hypospadias repair, consensus on feasibility of the use of unstented repair is still a matter of debate. Evidence reporting that unstented repair outcome is comparable to stented repair, especially in the long-term, is still weak due to reporting outcome inconsistencies, different study designs, inclusion of more than one technique, and inherent variability in meatal locations. Thus, we need a continuous and evolving assessment of the outcome of unstented repair to compile adequate evidence on the advantage of unstented TIP repair in distal hypospadias entity. The aim of this article was to review our long-term results with tubularized incised plate urethroplasty for distal hypospadias repair without a postoperative stent to determine its outcome which might justify its use. MATERIAL AND METHODS: After a review of 154 patients with distal penile hypospadias, who underwent repair in Minia Urology & Nephrology University Hospital in the period between June 2015 and February 2018, we excluded cases who underwent MAGPI repair, redo cases and patients who failed to complete follow-up. We chose 72 patients who had only 1st time TIP repair and whom we could contact. A total of 44 out of 72 cases with stented repair were assigned to Group A, while 28 cases with unstented repair were assigned to Group B. Success was assessed based on Hypospadias Objective Penile Evaluation (HOPE) score by three separate senior pediatric urology consultants, independent of the surgeon and in the absence of high post-void residual urine (PVR). Average rate was calculated to be compared between both study groups. RESULTS: There was no statistically significant difference regarding preoperative meatal location and age at repair and short-term complications. In the long-term; there was no statistically significant difference between the occurrence of urethrocutanous fistula (UCF, 4 vs 2 cases in Group A & B, respectively) and complete disruption (2 cases in each group) with need for redo repair. Results of total mean of HOPE score calculated showed no statistically significant differences between study groups and also failed to showed statistical significance on individual domains of HOPE score. CONCLUSIONS: Unstented TIP repair showed a similar outcome to stented TIP repair of distal hypospadias especially in the long-term despite a more troublesome early postoperative period.

11.
Arab J Urol ; 18(4): 252-256, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-33312737

RESUMO

OBJECTIVE: To compare a modified technique using the Dormia basket vs Stone Cone for stone entrapment to avoid proximal stone migration during ureteroscopic pneumatic lithotripsy of ureteric stones. PATIENTS AND METHODS: Our study included all patients with ureteric stones of <15 mm who underwent ureteroscopic pneumatic lithotripsy from January 2015 to September 2018. The study had two arms that were conducted over two consecutive periods; the first included 72 patients in whom we used the Stone Cone (Group 1) and the second included 86 patients in whom we started to use a Dormia basket with a modification (Group 2) to guard against proximal stone migration. RESULTS: Both groups were comparable for gender, age, and stone characteristics. Lower ureteric stones were the most prevalent as they represented 62.5% and 60.5% in groups 1 and 2, respectively; while upper ureteric stones were respectively found in 16.7% and 17.4%. Chemical stone analysis revealed that calcium oxalate stones were most predominant accounting for 51.3% and 51.1% in groups 1 and 2, respectively. Most of the stones were radio-opaque stones representing 57% and 58.1% in groups 1 and 2, respectively. There was a significant difference in operative time, with a mean (SD) operative time was 50.9 (11.2) in Group 1 vs 58.3 (12.4) min in Group 2 (P < 0.001). The success rate, defined as no retropulsion of stone fragments, was 97.7% in Group 2 vs 91.7% in Group 1 (P < 0.01). Complications were minor and comparable between the groups. There was no difference in hospital stay between the groups, but the cost assessment favoured Group 2. CONCLUSION: We found that our modified-basket stone entrapment technique compared favourably with the Stone Cone to guard against stone retropulsion during ureteroscopic pneumatic lithotripsy. Our modification to the basket was found to be feasible, efficient, safe, reproducible and cost-effective in preventing proximal stone migration. This procedure is particularly suitable in cost-limited environments.

12.
World J Urol ; 38(3): 775-781, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31087123

RESUMO

PURPOSE: We compared the effect of chemical disinfection (CIDEX® OPA) and low-temperature hydrogen peroxide gas plasma (STERRAD NX) on two brand new digital flexible ureteroscope (DFU) (Flex-Xc) using subjective and objective parameters. METHODS: Over 11-month period, all flexible ureteroscopic procedures that fulfill the inclusion criteria were done by two brand new flexible ureteroscopes and were prospectively evaluated. Intraoperative data included total operative time, laser power and duration, stone criteria and subjective evaluation of the procedure as well as visibility and maneuverability scores were reported. The end point of the study was when the scope was deemed by the surgeon as unable to perform the procedure; when leak test is positive. RESULTS: A total of 88 patients were randomized either for the first flexible ureteroscope disinfected using Cidex® OPA (n = 59, 67%) or second ureteroscope sterilized with Sterrad NX (n = 29, 33%). Intraoperative, the first DFU was significantly used with a total operative time of approximately 49 h compared to the second one (p < 0.001). In the same context, laser power parameters were significantly different among the two groups (p = 0.003). The subjective evaluation of the procedure, maneuverability, visibility scores, laser duration, stone burden and post-operative infection rate were statistically insignificant between both groups. At the end point of the study, the deflection in up and downward directions for both DFU were measured. CONCLUSIONS: The durability and longevity of the DFU is strongly related to the sterilization method. Our findings suggest that CIDEX® OPA should prioritize Sterrad in sterilization of DFU.


Assuntos
Desinfetantes , Desinfecção/métodos , Contaminação de Equipamentos/prevenção & controle , Reutilização de Equipamento , Glutaral , Peróxido de Hidrogênio , Gases em Plasma , Ureteroscópios , Adulto , Idoso , Feminino , Humanos , Cálculos Renais/cirurgia , Cálices Renais/cirurgia , Pelve Renal/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Cálculos Ureterais/cirurgia , Adulto Jovem
13.
Curr Pharm Biotechnol ; 20(7): 588-594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198107

RESUMO

OBJECTIVE: Korean red ginseng was reported to have many biological effects like the antioxidant and the anti-inflammatory activities. Oxidative stress and neuro-inflammation play major roles in the pathogenesis of Parkinson's disease (PD). The current study aimed to investigate the protective effects of ginseng on rotenone-induced PD in rats. METHODS: Rats were randomly allocated into 4 groups: normal rats, rotenone control, ginseng+rotenone and ginseng only treated rats. The severity of PD was evaluated through locomotor activity perceived in the open field test, histological examination and immunohistochemical detection of amyloid-ß in brain tissues, in addition to the biochemical assessment of tyrosine hydroxylase activity in brain tissues. Moreover, the following parameters were investigated for studying the possible mechanisms of ginseng neuroprotective effect: nuclear factor-κß (NF-κß), tumor necrosis factor-alpha (TNF-α), caspase- 3, lipid peroxides and reduced glutathione (GSH). RESULTS: Ginseng exhibited potent neuroprotective effect that was reflected upon the histopathological examination, marked improvement in the locomotor activity and through its ability to suppress the amyloid- ß deposition in the cortex and striatum along with significant increase in the tyrosine hydroxylase activity. Ginseng successfully inhibited the NF-κß inflammatory pathway in brain tissues beside the inhibition of other oxidative stress and inflammatory mediators. Furthermore, it exhibited antiapoptotic effect via the inhibition of caspase-3 expression. CONCLUSION: Ginseng could be a promising treatment in PD. It can suppress dopaminergic neuron degeneration through variable mechanisms mainly via inhibition of NF-κß pathway in addition to inhibition of oxidative stress and apoptosis.


Assuntos
Caspase 3/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Panax/química , Transtornos Parkinsonianos/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Glutationa/metabolismo , Masculino , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Extratos Vegetais/isolamento & purificação , Distribuição Aleatória , Ratos Wistar , República da Coreia , Rotenona
14.
Naunyn Schmiedebergs Arch Pharmacol ; 392(3): 279-286, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30474696

RESUMO

Amitriptyline is a tricyclic antidepressant that was suggested to have antifibrotic potential. The current study aimed to investigate the modulatory effects of amitriptyline on bleomycin-induced pulmonary fibrosis in rats. Rats were randomly assigned into 4 groups: normal control, bleomycin control, amitriptyline+bleomycin, and amitriptyline only treated group. Lung injury was evaluated through the histological examination and immunohistochemical detection of α-smooth muscle actin (α-SMA) in lung tissue, in addition to the biochemical assessment of pulmonary contents of hydroxyproline and transforming growth factor beta-1 (TGF-ß1). In addition, the following parameters were investigated for studying the possible mechanisms of amitriptyline antifibrotic effect: inducible nitric oxide synthase (iNOS), nuclear factor-κß (NF-κß), tumor necrosis factor-alpha (TNF-α), serpine-1, p53, nuclear factor erythroid 2-related factor 2 (Nrf2), lipid peroxides, and reduced glutathione (GSH). Amitriptyline exhibited potent antifibrotic effect that was reflected upon the histopathological examination and through its ability to suppress all the fibrotic parameters. Amitriptyline successfully suppressed the expression of NF-κß, Nrf2, iNOS, and p53 in lung tissues besides the inhibition of other oxidative stress and inflammatory mediators. Amitriptyline could be a promising treatment to pulmonary fibrosis. Amitriptyline not only prevents the depression and its drawbacks in patients suffering from pulmonary fibrosis but also it can suppress fibrosis through variable mechanisms mainly via inhibition of NF-κß/TNF-α/TGF-ß pathway in addition to inhibition of Nrf2 and iNOS expression.


Assuntos
Amitriptilina/farmacologia , Amitriptilina/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Animais , Bleomicina , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Ratos Wistar
15.
J Obstet Gynaecol Res ; 42(5): 547-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26786750

RESUMO

AIM: To compare the efficacy and safety of the clomiphene citrate (CC) stair-step protocol with standard gonadotrophin (follicle-stimulating hormone) treatment in clomiphene-resistant polycystic ovary syndrome (PCOS) patients. The study was a prospective cohort study in a tertiary infertility center in Abu Dhabi, United Arab Emirates (UAE). METHODS: The subjects consisted of 100 PCOS CC-resistant patients who attended between January 2014 and January 2015. Fifty received CC again but in accordance with the stair-step protocol, and the other 50 received the standard gonadotrophin treatment used in the center in which the study was conducted. The primary outcome measure was dominant follicle achievement; the secondary outcome measures were (i) clinical pregnancy rate; (ii) time to ovulation measured from treatment initiation to sonographic confirmation of a dominant follicle in days; and (iii) adverse effect occurrence. RESULTS: There was no difference between the two treatment modalities concerning the ability to achieve a dominant follicle or the clinical pregnancy rate. The time to ovulation was significantly shorter with the CC stair-step protocol than with gonadotrophin treatment. Ovarian hyperstimulation syndrome and ovarian cyst formation were more likely to occur with gonadotrophin treatment. CONCLUSION: Clomiphene citrate stair-step protocol can be offered to PCOS CC-resistant patients as an alternative to gonadotrophin therapy with similar efficacy.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Foliculoestimulante/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Clomifeno/administração & dosagem , Clomifeno/efeitos adversos , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/efeitos adversos , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Foliculoestimulante/efeitos adversos , Humanos , Infertilidade Feminina/complicações , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
J Pediatr Urol ; 12(2): 97.e1-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26468014

RESUMO

INTRODUCTION: Intravesical foreign bodies (FBs) are rare and have interesting pathology for urologists. There has been an increase in reports of intravesical FBs in the last few decades, but they are still considered to be rare in children, especially young girls. Here we present our experience in the assessment and management of intravesical self-inserted sharp objects in children. PATIENTS AND METHODS: We reviewed the records of children with self-introduced intravesical FBs admitted to our hospital during the last 10 years. Twenty-four cases were included in this study (20 girls and 4 boys). The presenting symptoms and methods of diagnosis and treatment were reviewed. RESULTS: The ages of the patients ranged from 4 to 12 years. In all cases, foreign bodies were self-inserted. All patients were subjected to KUB (kidney, ureter, bladder radiograph) and abdominal ultrasonography. Based on the KUB findings, the FBs in girls were found to be metal pins in 12, a hair clip in four, and a wooden pencil in three (Figure). In boys, a coiled electric wire was found in three, with a urinary calculus formed over one of them. There were small metallic objects in two cases (1 boy and 1 girl). Endoscopic removal of FBs was done successfully in 19 cases (18 girls and 1 boy), and open cystostomy was performed in four cases (3 boys and 1 girl). DISCUSSION: Intravesical FBs are important considerations in the differential diagnosis of pathological lower urinary tract symptoms. They represent significant challenges to urologists. Among children, the reasons for self-insertion of FBs might reflect psychiatric disorders. Routine psychiatric evaluations should be offered to all patients with intentional FB insertion to avoid missing any underlying psychiatric disorders. In our study, psychiatric evaluations have been advised for all the affected children and their parents. Self-inserted FBs are commonly seen in adults and are rarely encountered in children. To our knowledge, this is the largest reported series of children with self-inflicted intravesical FBs. In addition, all of the FBs in this study had one or more sharp edges that made their endoscopic extraction more difficult without causing bladder or urethral damage. In children, removal of intravesical FBs represents a great challenge, as the size of the pediatric urethra may hinder safe transurethral removal. Endoscopic handling of intravesical FBs is mostly unsuccessful in boys because of the long and narrow urethra, and open cystostomy might be the treatment of choice to save the urethra. In contrast, the short female urethra renders the endoscopic removal of intravesical FBs more successful. In this study, endoscopic removal of FBs was done successfully in 19 cases (18 girls and 1 boy), and open cystostomy was performed in four cases (3 boys and 1 girl). CONCLUSIONS: Although FBs in the urinary tract of children are very rare, they need to be considered during any evaluation of pathological lower urinary tract symptoms. Endoscopic management is feasible for most of these patients. The size, number, nature of foreign bodies, and any associated urinary calculi determine the treatment modality.


Assuntos
Previsões , Corpos Estranhos/complicações , Comportamento Autodestrutivo , Bexiga Urinária/lesões , Transtornos Urinários/etiologia , Criança , Pré-Escolar , Cistoscopia , Feminino , Corpos Estranhos/diagnóstico , Humanos , Masculino , Bexiga Urinária/diagnóstico por imagem , Transtornos Urinários/diagnóstico , Transtornos Urinários/fisiopatologia , Urografia
17.
Arab J Urol ; 13(2): 134-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26413335

RESUMO

OBJECTIVES: To determine whether there are any significant differences in complications and success rate between adjustable transobturator tape (TOA) and ordinary transobturator tape (TOT) in the treatment of female stress urinary incontinence (fSUI), as the TOA was recently introduced for the treatment of female SUI, its advantage being the ability to adjust the tape after surgery to address over- or under-correction. PATIENTS AND METHODS: In all, 96 women with SUI (mean age 53 years, SD 10) were included in the study. Patients were randomised into two equal groups (group 1, TOA, vs. group 2, TOT). The operative duration, blood loss, intra- and post-operative complications, and the success rate, were compared between the groups. RESULTS: There was no statistically significant difference between the groups in cure rates (83% vs. 80%, groups 1 and 2, respectively) or in postoperative stay. The mean operative duration in group 2 was significantly shorter than in group 1. No intraoperative bleeding requiring a blood transfusion was recorded, and there were no bladder injuries. Postoperative adjustment of the tape was only required in three patients in group 1. CONCLUSIONS: The TOA is a safe and accurate method for treating fSUI, but with experienced surgeons there was no difference in the cure rate and postoperative outcome between TOA and TOT.

18.
Arch Gynecol Obstet ; 288(3): 673-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23494199

RESUMO

OBJECTIVE: The aim of this work was to compare the pregnancy rates during IUI cycles with or without endometrial sampling. STUDY DESIGN: A prospective, randomized study. PATIENTS AND METHODS: 150 patients were recruited. They were classified into three groups. Each comprised 50 patients. Group 1 was considered the control group and underwent IUI with no endometrial sampling. Group 2 underwent Tao Brush endometrial sampling on day 8-9 of the uterine cycle that preceded the stimulation cycle, and finally, Group 3 underwent Tao Brush endometrial sampling on day 8-9 of the same IUI cycle OUTCOME OF THE STUDY: A positive pregnancy test. RESULTS: Pregnancy percentages were 18, 38, and 36 % for group 1, group 2, and group 3, respectively. The paired t test was used to compare each two individual group means. The results show a highly significant value for the paired t test of the control group and group 2 of the patients (p = 0.001), as well as a highly significant results (p = 0.002) for the group 3 and the control group. No significant value was present between the group 2 and 3 of patients (p = 0.322). CONCLUSION: Endometrial sampling significantly increases pregnancy rates in IUI procedures when it is done in the proliferative phase of the IUI cycle, or the cycle prior to IUI, than pregnancy rates with IUI alone.


Assuntos
Endométrio/lesões , Fase Folicular/imunologia , Inseminação Artificial , Taxa de Gravidez , Adulto , Biópsia , Endométrio/imunologia , Endométrio/patologia , Feminino , Humanos , Gravidez , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA