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1.
Mol Med Rep ; 19(4): 2611-2619, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720108

RESUMO

Selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants worldwide, which have been reported to exert potential detrimental effects on bone mineral density and increase the risk of developing fractures. The present study aimed to investigate the pathways underlying the negative effects of fluoxetine on bone using mesenchymal stem cells (MSCs) derived from rat adipose tissue as a source of osteoprogenitor cells. MSCs were harvested from adipose tissue using a collagenase enzyme digestion method and were allowed to differentiate into osteoprogenitor cells. Various concentrations of fluoxetine were added to the cells, which were harvested and analyzed by flow cytometry to detect apoptotic markers Annexin V and caspase­3, in order to assess the levels of apoptosis. The levels of endogenous serotonin released in the extracellular matrix were measured using a serotonin ELISA kit. The underlying molecular pathways associated with the effects of fluoxetine on bone were investigated with reverse transcription­quantitative polymerase chain reaction. The results of the present study revealed a significant dose­dependent increase in apoptosis in response to increasing doses of fluoxetine, which was independent of serotonin levels in the culture supernatant. These findings indicated that fluoxetine exerted a direct inhibitory effect on bone cells via an apoptosis­dependent pathway. Furthermore, the expression levels of serotonergic genes, including serotonin 1B receptor, serotonin 2A receptor (HTR2A), serotonin 2B receptor and serotonin transporter, were down regulated; of these genes, HTR2A exhibited the highest expression levels. Further in vitro and in vivo studies are required to verify this association and to determine the molecular pathways involved in fluoxetine­induced bone loss. Fluoxetine­induced apoptosis of osteoprogenitor cells may be the mechanism underlying the increased incidence of bone loss observed in patients treated with fluoxetine.


Assuntos
Fluoxetina/farmacologia , Células-Tronco Mesenquimais/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Serotonina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Expressão Gênica , Imunofenotipagem , Masculino , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Ratos
2.
Int J Womens Health ; 9: 441-447, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28670143

RESUMO

OBJECTIVE: Attempting in vivo healing of cyclophosphamide-induced ovarian insufficiency in a mouse model using bone marrow mesenchymal stem cells (BMMSCs). METHODS: Female BALB/c white mice were used to prepare a model for premature ovarian failure by single intraperitoneal injection of cyclophosphamide (80 mg/kg). Ten mice were injected with BMMSCs and then sacrificed after 21 days for morphometric evaluation of the ovaries. Hormonal profile was evaluated while mice were being sacrificed. Another 10 mice were left for natural breeding with male mice, and 5 of these were injected with BMMSCs. Oocyte-like structures were obtained from 3 mice and were subjected to in vitro fertilization/intracytoplasmic sperm injection. RESULTS: Morphometric analysis of the ovaries demonstrated the presence of newly formed primordial follicles. Contribution of MSCs to the formation of these follicles was proven by a labeling technique. There was a drop in estradiol and rise in follicle-stimulating hormone levels, followed by resumption of the hormonal levels to near normal 21 days after MSCs therapy. The 5 mice that were injected with MSCs became pregnant after natural breeding. Fertilization and further division was reported in 5 oocytes subjected to intracytoplasmic sperm injection, but division did not continue. CONCLUSION: From this proof-of-concept trial, we can say that healing of damaged ovaries after chemotherapy in mice is possible using in vivo therapy with BMMSCs. This should open the gate for a series of animal studies that test the possibility of in vitro maturation of germinal epithelium of the ovary into mature oocytes.

3.
Int J Stem Cells ; 9(1): 79-89, 2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27426089

RESUMO

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI. METHODS: A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined. RESULTS: MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters. CONCLUSIONS: Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.

4.
Int J Stem Cells ; 9(1): 145-51, 2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27426096

RESUMO

BACKGROUND: In severe chronic stages of emphysema the only treatment is lung transplantation. SO, an urgent need exists for the development of effective treatments. Stem cells therapy arises as a new therapeutic approach. AIM OF THE WORK: To investigate whether bone marrow mononuclar cells (BMMNCs) can promote lung regeneration and decrease apoptosis in lipopolysaccharide (LPS) induced pulmonary emphysema in C57Bl/6 mice. MATERIAL AND METHODS: 14 weeks old female mice (C57Bl/6), weighing around 25 g were used in this study. The mice were divided into 4 groups (10 in each group): group A: mice received no treatment, group B: mice received intranasal instillation of LPS with no further treatment, group C: mice received intranasal instillation of LPS then given a dose of BMMNCs and evaluated 21 days later and group D: the mice that received intranasal instillation of LPS then given a dose of Dulbecco's Modified Eagle's Medium (DMEM) and evaluated 21 days later. Imaging analysis was done using imagej program. To measure apoptotic index, Anti-caspase 3 polyclonal antibody staining was done. RESULTS: Analysis of the mean of airspace equivalent diameters (D0) and its statistical distribution (D1) for the different groups allowed to observe that group treated with BMMNCs (group C) showed the significant improvement in D0 and D1 than the group received LPS only (group B). Analysis of apoptotic index showed significant difference between BMMNCs treated group (group C) and that received LPS only (group B). CONCLUSIONS: BMMNCs effectively promote lung regeneration and reduction of apoptosis in pulmonary emphysema.

5.
Anticancer Agents Med Chem ; 16(5): 621-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26373394

RESUMO

An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Compostos Organosselênicos/farmacologia , Peptídeos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Oxirredução/efeitos dos fármacos , Peptídeos/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
6.
Int Urol Nephrol ; 48(2): 287-97, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26660954

RESUMO

OBJECTIVES: To study the effects of darbepoetin-α (DPO-α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats. METHODS: Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 µg/kg bw) once weekly for 12 weeks. By the end of experiment hemoglobin (Hb) content, serum creatinine, BUN, albumin, triglycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialdehyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done. RESULTS: DPO-α significantly improved the animal survival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues. CONCLUSION: Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb content, hyperlipidemia, enhancement of endogenous antioxidants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane.


Assuntos
Darbepoetina alfa/administração & dosagem , Glomérulos Renais/ultraestrutura , Túbulos Renais/ultraestrutura , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Hematínicos/administração & dosagem , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia
7.
Eur J Med Chem ; 97: 190-201, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25969171

RESUMO

Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans (C. albicans) fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure-activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.


Assuntos
Antineoplásicos , Antioxidantes , Ácidos Carboxílicos/química , Cianatos/síntese química , Desenho de Drogas , Compostos Organosselênicos/química , Compostos de Selênio/síntese química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cianatos/química , Cianatos/farmacologia , Células Hep G2 , Humanos , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/farmacologia , Oxirredução , Compostos de Selênio/química , Compostos de Selênio/farmacologia
8.
Exp Biol Med (Maywood) ; 240(12): 1572-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25825359

RESUMO

Cisplatin, Cis-diamminedichloroplatinum (CDDP), is a platinum-based chemotherapy drug, and its chemotherapeutic use is restricted by nephrotoxicity. Inflammatory and apoptotic mechanisms play a central role in the pathogenesis of CDDP-induced acute kidney injury (AKI). The aim of this study was to compare the therapeutic potential of candesartan, angiotensin II receptor blocker, versus bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of CDDP-induced nephrotoxicity. Adult male Wistar rats (n = 40) were divided into four groups; Normal control: received saline injection, CDPP group: received CDDP injection (6 mg/kg single dose), Candesartan group: received candesartan (10 mg/kg/day) for 10 days + CDDP at day 3, and Stem cells group: received CDDP + BM-MSCs intravenously one day after CDDP injection. The rats were sacrificed seven days after CDDP injection. Significant elevation in serum creatinine and urea, renal levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1, renal expressions of nuclear factor kappa B (NF-κB), p38-mitogen-activated protein kinase (MAPK), caspase-3 and Bcl-2-associated x protein (Bax) were found in CDDP-injected rats when compared to normal rats. Both candesartan and BM-MSCs ameliorated renal function and reduced significantly the inflammatory markers (TNF-α , NF-κB, p38-MAPK and MCP-1) and apoptotic markers (caspase-3 and Bax) in renal tissue after CDDP injection. Candesartan as well as BM-MSCs have anti-inflammatory and anti-apoptotic actions and they can be used as nephroprotective agents against CDDP-induced nephrotoxicity. BM-MSCs is more effective than candesartan in amelioration of AKI induced by CDDP.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Apoptose/fisiologia , Benzimidazóis/uso terapêutico , Inflamação/fisiopatologia , Transplante de Células-Tronco Mesenquimais , Tetrazóis/uso terapêutico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Animais , Nitrogênio da Ureia Sanguínea , Caspase 3/análise , Quimiocina CCL2/análise , Cisplatino/toxicidade , Creatinina/sangue , Citometria de Fluxo , Rim/química , Rim/efeitos dos fármacos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , NF-kappa B/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/análise , Proteínas Quinases p38 Ativadas por Mitógeno/análise
9.
Can J Physiol Pharmacol ; 92(9): 733-43, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25093892

RESUMO

OBJECTIVES: To study the effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on adriamycin (ADR)-induced chronic nephropathy in rats. METHODS: 60 male Sprague-Dawley rats were distributed among 3 groups (20 rats each): (i) the negative control group, which was normal rats that received saline (vehicle); (ii) the positive control (ADR) group, which was rats that received 2 intravenous injections of ADR into the penile vein at 14 day intervals without treatment, and (iii) the MSC group, which were rats treated as for the ADR group that were also given 2 intravenous injections of MSCs (5 days after each ADR injection). RESULTS: ADR caused a significant reduction in animal body mass, survival rate, hemoglobin (Hb) content, serum albumin, and renal GSH, and significantly increased serum levels of triglycerides, cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1), renal MDA, as well as caspase-3 expression and glomerular and tubulointerstitial damage compared with the negative control group. MSC treatment failed to improve animal survival rate, body mass, Hb level, proteinuria, or hypoalbuminemia; however, it mildly improved the serum BUN, hyperlipidemia, caspase-3 expression, urinary levels of KIM-1, renal oxidative stress markers, and glomerular and tubulointerstitial damage score. CONCLUSION: administration of BM-MSCs during induction of ADR nephropathy provides partial protection, which could be due to improvements in the levels of of endogenous antioxidants, reduction of apoptosis, and maintenance of the integrity of the glomerular membrane.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Transplante de Medula Óssea , Doxorrubicina/efeitos adversos , Transplante de Células-Tronco Mesenquimais , Insuficiência Renal Crônica/terapia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia
10.
Tumour Biol ; 35(10): 9941-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25004806

RESUMO

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols' wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC50 = 30.4 µM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol's SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol's cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Catecóis/química , Sobrevivência Celular/efeitos dos fármacos , Álcoois Graxos/química , Humanos , Células MCF-7 , Relação Estrutura-Atividade
11.
Anat Cell Biol ; 47(2): 83-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24987544

RESUMO

Mesenchymal stem cells (MSCs) offer significant promise as a multipotent source for cell-based therapies and could form the basis for the differentiation and cultivation of tissue grafts to replace damaged tissue. However, no gene expression follow up analysis has been undertaken to characterize the in vitro adipogenic differentiated MSCs. The main goal of this study was to focus on MSCs and to analyze their differentiation capacity. To achieve this aim, bone marrow MSCs from sprague dawely rats were isolated, expanded in monolayer culture and characterized with respect to their cluster of differentiation (CD) and ability for adipogenic differentiation capacity. The expression of CD44, CD45, CD29, CD34, and CD90 on bone marrow derived MSCs was characterized using flow cytometry. Adipogenesis was determined by staining with oil-red O and reverse transcription polymerase chain reaction assessments of lipoprotein lipase, leptin, adiponectin and adipocyte genes at different time intervals, after 4, 7, 14, and 21 days. Our results revealed that the pattern of CD marker expression was highly positive significant with CD29, CD44, and CD90 when compared with CD34 and CD45. MSCs showed proliferative potential and were capable of adipogenic differentiation characterized by reddish brown-droplets following staining with oil-red O and expression of molecular bands of genes. These results demonstrate, at the morphological, immunophenotyping and gene expression levels, the multipotency of MSCs and thus highlight their potential therapeutic value for cell-based tissue engineering.

12.
Gen Physiol Biophys ; 33(2): 205-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24968414

RESUMO

Hepatic injury secondary to renal I/R injury has been documented in several studies. This study aimed to investigate the role of NO in hepatic injury secondary to renal I/R in rat model. Sprague-Dawley rats (n = 48) were divided into 4 equal groups; sham-operated, I/R injury group (45 min of bilateral renal ischemia), L-arginine group (I/R with 300 mg/kg L-arginine, 20 min before ischemia), L-NAME group (I/R with 50 mg/kg L-NAME, 20 min before ischemia). L-NAME (NO synthase inhibitor) caused significant elevation in serum creatinine, BUN, liver enzymes, liver histopathological damage score (p ≤ 0.05) and MDA production (p ≤ 0.001); on the other hand significantly decreased NO and GSH levels (p ≤ 0.05). L-arginine significantly decreased serum creatinine, BUN and GSH (p ≤ 0.05) and caused significant elevation in liver enzymes and NO (p ≤ 0.05), and also in MDA levels (p ≤ 0.001) in liver tissues. We conclude that endogenous NO might have protective effect against hepatic injury induced by renal I/R injury and inhibition of this endogenous NO by L-NAME or exogenous administration of NO (by L-arginine) might be harmful.


Assuntos
Rim/lesões , Fígado/lesões , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/complicações , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Rim/patologia , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley
13.
Exp Clin Transplant ; 9(4): 247-51, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21819369

RESUMO

OBJECTIVES: The effect of basiliximab induction therapy on long-term patient and graft survival is not clear. We sought to evaluate if there is any advantage to routine basiliximab induction on the long-term outcome of living-related donor kidney transplants. MATERIALS AND METHODS: One hundred adult recipients with their first kidney allograft were randomized into 2 treatment groups; 1 group received basiliximab, and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine, microemulsion, and azathioprine). We followed them for 10 years. RESULTS: Basiliximab reduced the proportion of patients who experienced an acute rejection in the first year (18/50) when compared with the control group (31/50) (P = .009), and in 10 years (28/50) when compared with controls (37/50) (P = .059). The cumulative steroid dosage used throughout the study was significantly lower in the basiliximab group. The overall incidence of posttransplant complications was comparable among the 2 groups. There was no significant difference in patient and graft survival; 10-year patient and graft survival were 92% and 76% for basiliximab and 90% and 68% for the control group. CONCLUSIONS: Routine basiliximab induction significantly reduces the incidence of acute rejection without any noticeable effects on the long-term renal transplant outcome.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim , Doadores Vivos , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Basiliximab , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Egito , Feminino , Rejeição de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/imunologia , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Arab J Urol ; 9(4): 235-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26579304

RESUMO

OBJECTIVES: To assess the predictive importance of ultrasonic grade 1 hyperechogenicity in potential live related kidney donors in the absence of urinary abnormalities and with perfect renal function. SUBJECTS AND METHODS: The study included 34 potential living related kidney donors with this abnormality; their mean (SD, range) age was 32.7 (8.45, 23-48) years. Ten matched healthy donors with normal ultrasonographic appearance of the kidneys were studied as controls. All cases were thoroughly investigated, including measuring glomerular filtration rate by isotopic scintigraphy. The renal reserve was estimated by dopamine and amino-acid infusion in all subjects (study and control groups). A percutaneous renal biopsy was taken from 17 subjects in the abnormal echogenicity group and open renal biopsy was taken from eight of the control subjects. RESULTS: The renal reserve was comparable in both groups. Abnormal histopathological changes were found in seven subjects (41%) of the abnormal echogenicity group, i.e. partial glomerulosclerosis in one, mesangial thickening in two, interstitial fibrosis in one, focal tubular atrophy in one, immunoglobulin (Ig M) immune deposits in three and IgA in one. Only one subject in the control group showed mild mesangial thickening. CONCLUSION: Grade 1 echogenicity might be a sign of unrecognized kidney disease. Renal biopsy is mandatory when such related donors are the only available ones. Abnormal histopathology contraindicates donation.

15.
Perit Dial Int ; 30(3): 269-73, 2010 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20424195

RESUMO

BACKGROUND: Despite the well-known advantages of continuous ambulatory peritoneal dialysis (CAPD), it continues to be grossly underutilized in many developing countries. However, some developing countries, such as Mexico, use the modality very effectively. In view of this, we started the first CAPD program in Egypt. METHODS: Since its start in 1997, our program has treated 33 patients. Straight double-cuffed Tenckhoff catheters were surgically placed in all patients. Twin-bag systems were used. All patients underwent monthly clinical and biochemical assessment and measurement of Kt/V urea. Peritonitis and exit-site infection rates were monitored. RESULTS: Most treated patients were adult and female. Mean age was 31.7 years and mean follow-up duration was 18 months. Peritonitis rate was 1 episode /21.3 months and was easily managed in most patients. Staphylococcus aureus was the most commonly isolated organism (24%) but 49% of cases were culture negative. There were no exit-site infections. Mean weekly Kt/V urea was 1.78 +/- 0.23. CONCLUSION: We report the successful development of a small CAPD program in Egypt, made possible by well-established financial support, a motivated team of doctors and nurses, and good patient selection and training.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/estatística & dados numéricos , Adulto , Pessoas com Deficiência , Egito/epidemiologia , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Peritonite/epidemiologia , Peritonite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
16.
Clin Exp Nephrol ; 14(1): 68-74, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19876703

RESUMO

AIM: Persistent or de novo left ventricular hypertrophy (LVH) is a risk factor for cardiovascular diseases and congestive heart failure following renal transplantation (RT). Our aim was to determine the associations and impact of persistent LVH on RT outcome. MATERIALS AND METHODS: We included 72 live-donor renal allograft recipients with mean age of 28.5 years who had evidence of LVH at time of transplantation and had stable functioning grafts 1 year after transplantation. Cardiac status of all recipients was assessed before transplantation and at 1 year after transplantation by echocardiography. Recipients were subdivided into two groups according to persistence or regression of LVH 1 year after transplantation. The first group included 33 patients who had persistent LVH. The second group included 39 patients in whom LVH had regressed (control group). Both groups were closely followed for 10 years. RESULTS: Univariate analysis showed that persistent LVH 1 year after RT was significantly associated with high serum creatinine, higher incidence of medical infection, and acute and chronic rejection. Chronic rejection and infection were the only valid associations on multivariate logistic regression analysis. Patient and graft survival were significantly lower in the persistent LVH group (P = 0.012). CONCLUSION: Persistent LVH may be associated with higher incidence of medical infection and chronic rejection that worsen the prognosis for renal transplant recipients.


Assuntos
Hipertrofia Ventricular Esquerda/complicações , Transplante de Rim/efeitos adversos , Adulto , Creatinina/sangue , Ecocardiografia , Feminino , Rejeição de Enxerto/etiologia , Humanos , Infecção/etiologia , Doadores Vivos , Modelos Logísticos , Masculino , Prognóstico , Estudos Prospectivos
17.
Clin Exp Nephrol ; 12(5): 376-381, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18327678

RESUMO

BACKGROUND/AIMS: The effect of basiliximab induction therapy on long-term patient and graft survival is not yet clear. We aimed to evaluate if there is any advantage of routine basiliximab induction on the long-term outcome of living related donor kidney transplantation. METHODS: One hundred adult recipients with their first kidney allograft were randomized into two treatment groups, one group received basiliximab and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine (CsA) micro-emulsion and azathioprine) and were followed up thoroughly for 7 years. RESULTS: Basiliximab significantly reduced the proportion of patients who experienced acute rejection in the first year (18/50) when compared to the control group (31/50), and in 7 years (28/50) when compared to (37/50) in controls. The cumulative steroid dose used throughout the whole study period was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable among the two treatment groups. There was no significant difference in patient or graft survival; 7 years patient and graft survival were 92, 76% for basiliximab and 92, 80% for the control group, respectively. CONCLUSION: Routine basiliximab induction significantly reduced the incidence of acute rejection without any noticeble beneficial effect on the long-term renal transplantation outcome.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Doadores Vivos , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Anticorpos Monoclonais/efeitos adversos , Azatioprina/uso terapêutico , Basiliximab , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Estudos Longitudinais , Masculino , Estudos Prospectivos , Proteínas Recombinantes de Fusão/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento
18.
Pediatr Nephrol ; 23(11): 2067-73, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18071759

RESUMO

Our objective was to study the complications of chronic renal failure (CRF) among pediatric live-donor kidney transplant recipients. Between March 1976 and December 2005, 1,785 live-donor kidney transplantations were carried out at our center. Of the recipients, 292 were 20 years old or younger (mean age 12.8 years, ranging from 4 years to 20 years). Clinical and laboratory parameters of these 292 patients were analyzed retrospectively. They were 182 boys and 110 girls. Patients who had received transplants before 1988 were treated with prednisolone and azathioprine as combined therapy. From 1988 to 1998, a triple regimen comprising prednisolone, azathioprine and cyclosporine A (CsA) was administered. Tacrolimus and mycophenolate mofetil (MMF) were introduced as primary therapy in 1998. Growth, anemia, infections, and surgical, cardiac, neurologic, bone and other medical complications were assessed. Triple-drug immunosuppression (prednisone + CsA + azathioprine) was used in 68.2% of transplants. Acute rejection rate was 47.6%; chronic rejection rate was 31%. Hypertension (62%) was the commonest complication. Anemia was diagnosed in 61%. A substantial proportion of patients (48%) were short, with height standard deviation scores (SDSs) of less than -1.88. The overall infection rate was high, and the majority (54%) was bacterial. Malignancy was diagnosed in eight (3%) patients. The incidence of urological complications was 14%, and that of vascular complications was 1%. Cardiac complications included left ventricular hypertrophy (LVH) in 47.9% of patients, left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). Neuropathic changes were found in 19% of our cases, with the distal muscles of lower limbs more affected. Other complications included avascular bone necrosis in 8% (all of them in the hip joint) and bone loss in 60% of patients. We concluded that, despite the long-term success of pediatric renal transplantation in a developing country, there is a risk of significant morbidity.


Assuntos
Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Doadores Vivos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Doenças Ósseas Metabólicas/epidemiologia , Criança , Pré-Escolar , Egito/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Hipertensão Renal/epidemiologia , Transplante de Rim/estatística & dados numéricos , Masculino , Fatores de Risco , Adulto Jovem
19.
Int Urol Nephrol ; 39(3): 979-81, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17541722

RESUMO

The value of intravenous immunoglobulin (IVIG) and simvastatin as potential modalities for the treatment of sensitized patients was evaluated by testing the efficacy of these agents on a relatively large cohort of adult hemodialysis patients (11) who were waiting for renal allotransplantation at our center. The patients had persistently positive crossmatches with their living related donors and a panel reactive antibody titer of more than 20%. All patients received IVIG (500 mg/kg per day on alternate days for a total of six doses); panel reactive antibody (PRA) titer and crossmatch testing were carried out after each dose and before each subsequent one. Two months after the last dose, eight patients received simvastatin (20 mg/day) for a period of 2 months; PRA titer and crossmatch testing were carried out every two weeks. Only four patients showed an insignificant reduction of PRA activity (P = 0.36); no patient attained a negative crossmatch. Simvastatin also resulted in an insignificant reduction of anti-human leukocyte antigen (HLA) antibodies in three patients (P = 0.32). We propose that IVIG or simvastatin alone can not effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials on the use of IVIG and simvastatin with other modalities of treatment to desensitize these patients may be warranted.


Assuntos
Dessensibilização Imunológica/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Transplante de Rim/imunologia , Sinvastatina/uso terapêutico , Resistência a Medicamentos , Teste de Histocompatibilidade , Humanos
20.
Int Urol Nephrol ; 39(2): 635-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17347908

RESUMO

Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation.Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 +/- 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 +/- 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall's correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.


Assuntos
Desenvolvimento Infantil , Crescimento , Falência Renal Crônica/fisiopatologia , Transplante de Rim , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino
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