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Established Internet of Things (IoT) platforms suffer from their inability to determine whether an IoT app is secure or not. A security analysis system (SAS) is a protective shield against any attack that breaks down data privacy and security. Its main task focuses on detecting malware and verifying app behavior. There are many SASs implemented in various IoT applications. Most of them build on utilizing static or dynamic analysis separately. However, the hybrid analysis is the best for obtaining accurate results. The SAS provides an effective outcome according to many criteria related to the analysis process, such as analysis type, characteristics, sensitivity, and analysis techniques. This paper proposes a new hybrid (static and dynamic) SAS based on the model-checking technique and deep learning, called an HSAS-MD analyzer, which focuses on the holistic analysis perspective of IoT apps. It aims to analyze the data of IoT apps by (1) converting the source code of the target applications to the format of a model checker that can deal with it; (2) detecting any abnormal behavior in the IoT application; (3) extracting the main static features from it to be tested and classified using a deep-learning CNN algorithm; (4) verifying app behavior by using the model-checking technique. HSAS-MD gives the best results in detecting malware from malicious smart Things applications compared to other SASs. The experimental results of HSAS-MD show that it provides 95%, 94%, 91%, and 93% for accuracy, precision, recall, and F-measure, respectively. It also gives the best results compared with other analyzers from various criteria.
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Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.
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Células de la Médula Ósea/citología , Everolimus/farmacología , Glomérulos Renales/lesiones , Glomérulos Renales/patología , Trasplante de Células Madre , Células Madre/citología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Glomérulos Renales/efectos de los fármacos , Masculino , Proteínas de la Membrana/metabolismo , Necrosis , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
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.
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Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama , Catecoles/farmacología , Alcoholes Grasos/farmacología , Catecoles/química , Supervivencia Celular/efectos de los fármacos , Alcoholes Grasos/química , Humanos , Células MCF-7 , Relación Estructura-ActividadRESUMEN
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.
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Antibióticos Antineoplásicos/efectos adversos , Trasplante de Médula Ósea , Doxorrubicina/efectos adversos , Trasplante de Células Madre Mesenquimatosas , Insuficiencia Renal Crónica/terapia , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Riñón/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/patologíaRESUMEN
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.
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Riñón/lesiones , Hígado/lesiones , Óxido Nítrico/metabolismo , Daño por Reperfusión/complicaciones , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Catalasa/metabolismo , Creatinina/sangre , Glutatión/metabolismo , Riñón/patología , Peroxidación de Lípido , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
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.
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Hipertrofia Ventricular Izquierda/complicaciones , Trasplante de Riñón/efectos adversos , Adulto , Creatinina/sangre , Ecocardiografía , Femenino , Rechazo de Injerto/etiología , Humanos , Infecciones/etiología , Donadores Vivos , Modelos Logísticos , Masculino , Pronóstico , Estudios ProspectivosRESUMEN
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.
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Fluoxetina/farmacología , Células Madre Mesenquimatosas/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Serotonina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Biomarcadores , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Células Cultivadas , Expresión Génica , Inmunofenotipificación , Masculino , Osteoblastos/citología , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , RatasRESUMEN
The value of intravenous immunoglobulin and simvastatin as potential modalities for the treatment of sensitized patients was studied. We aimed to test their efficacy as solo agents to inhibit anti-human leukocyte antigen (HLA) antibodies. We tested samples from 11 adult hemodialysis patients who were waiting for renal allotransplantation at our center, all of whom had persistently positive crossmatches with their living related donors and panel reactive antibody titers more than 20%. All patients received intravenous immunoglobulin (500 mg/kg/day on alternate days for 6 doses). Panel reactive antibody titer measurement and crossmatch testing were carried out after each dose and before each subsequent one. Two months later, 8 patients received simvastatin (20 mg/day) for 2 months. Panel reactive antibody measurement titer and crossmatch testing were carried out every 2 weeks. Only 4 patients showed an insignificant reduction in panel reactive antibody activity (P=0.36). None of them attained a negative crossmatch. Furthermore, simvastatin also resulted in an insignificant reduction of HLA antibodies in 3 patients (P=0.32). We concluded that intravenous immunoglobulin or simvastatin alone cannot effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials of the use of intravenous immunoglobulin and simvastatin with other modalities to desensitize these patients may be warranted.
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Desensibilización Inmunológica/métodos , Antígenos HLA/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Trasplante de Riñón/inmunología , Simvastatina/uso terapéutico , Adulto , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Prueba de Histocompatibilidad , Humanos , Isoanticuerpos/análisis , Isoanticuerpos/efectos de los fármacos , Masculino , Diálisis RenalRESUMEN
BACKGROUND/AIMS: The aim of this work is to determine the long-term therapeutic benefit(s) of daclizumab induction therapy with triple immunosuppressive protocols including prednisolone, cyclosporine microemulsion (CsA), and mycophenolate mofetil (MMF) in the living related donor kidney transplantation. METHODS: Twenty-one adult recipients of their first kidney allograft were allocated to receive daclizumab with triple immunosuppressive therapy (steroids, CsA, and MMF). They were compared to 50 recipients of their first grafts who received a maintenance triple immunosuppressive therapy (steroids, CsA, and azathioprine). The patients were followed up for 5 years. RESULTS: Daclizumab group significantly experienced a marked reduction of acute rejection (7/21) when compared to the control group (31/50) with subsequent significant reduction of cumulative steroids doses at the end of 5 years. The overall incidence of post-transplant complications was comparable among the two treatment groups. There was no significant difference in patients and graft survival; 5-year patient and graft survival were 95.3%, 85.7% for daclizumab and 96%, 88% for control group, respectively. CONCLUSIONS: Although prophylactic daclizumab with triple immunosuppressive protocol including MMF have drastically reduced the incidence of acute rejections, the graft and patient survival are unchanged in this long-term follow up.
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Anticuerpos Monoclonales/farmacología , Inmunoglobulina G/farmacología , Inmunosupresores/farmacología , Trasplante de Riñón , Donadores Vivos , Ácido Micofenólico/análogos & derivados , Donantes de Tejidos , Análisis Actuarial , Adulto , Anticuerpos Monoclonales Humanizados , Daclizumab , Demografía , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto/efectos de los fármacos , Humanos , Masculino , Ácido Micofenólico/farmacología , Análisis de Supervivencia , Factores de TiempoRESUMEN
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.
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Desarrollo Infantil , Crecimiento , Fallo Renal Crónico/fisiopatología , Trasplante de Riñón , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
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.
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Desensibilización Inmunológica/métodos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Trasplante de Riñón/inmunología , Simvastatina/uso terapéutico , Resistencia a Medicamentos , Prueba de Histocompatibilidad , HumanosRESUMEN
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.
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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.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Compuestos de Organoselenio/farmacología , Péptidos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Candida albicans/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli/efectos de los fármacos , Células Hep G2 , Humanos , Células MCF-7 , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos de Organoselenio/síntesis química , Compuestos de Organoselenio/química , Oxidación-Reducción/efectos de los fármacos , Péptidos/química , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
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.
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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.
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Darbepoetina alfa/administración & dosificación , Glomérulos Renales/ultraestructura , Túbulos Renales/ultraestructura , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Doxorrubicina/toxicidad , Hematínicos/administración & dosificación , Glomérulos Renales/efectos de los fármacos , Túbulos Renales/efectos de los fármacos , Peroxidación de Lípido , Masculino , Microscopía Electrónica , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patologíaRESUMEN
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.
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The aims of this study were to investigate the prevalence of hepatitis C virus (HCV) genotypes and serotypes in anti-HCV-positive hemodialysis patients and determine the concordance between genotyping and serotyping methods. Sixty-two hemodialysis patients were included in this study. HCV RNA was determined using polymerase chain reaction assay and genotypes using a line probe assay. HCV serotyping was performed with competitive enzyme-linked immunosorbent assay. Genotype 4 (52 patients) was the most predominant genotype, followed by type 1 (10 patients). The most prevalent HCV serotype was type 4 (41 patients), followed by serotype 1 (6 patients). We detected multiple serotypes in 4 patients and untypeable strains in 11. The overall sensitivity of serotyping assay was 82% for the study patients. According to the genotyping results, the sensitivity of serotyping was 60% and 86.5% for HCV types 1 and 4, respectively. There was a 100% concordance between results of serotyping and genotyping in the identification of HCV type 1 and 91% concordance in HCV type 4. Serological typing method may be of great value in microbiology laboratories that require a simple assay for identification of HCV genotypes, although the sensitivity of this assay may be limited by the immunocompetence of infected hemodialysis patients.
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Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C/diagnóstico , Diálisis Renal , Adulto , Egipto/epidemiología , Femenino , Genotipo , Hepatitis C/sangre , Hepatitis C/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Muestreo , Sensibilidad y Especificidad , SerotipificaciónRESUMEN
BACKGROUND: The potential benefit of pre-transplant treatment of chronic hepatitis C on long-term evolution after renal transplantation is not clear. METHODS: Fifty successive renal transplant candidates had their sera positive for HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received a standard course of interferon-alpha2b (IFN; 3 MU three times weekly after hemodialysis sessions for 6 months). RESULTS: IFN was discontinued in 2 patients (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the treatment group and in none of the control group. Two patients of the IFN group had a virological relapse post-transplantation. Post-transplant follow-up periods were 41.5 +/- 15 and 50 +/- 16 months for the treated and control groups respectively. Transaminases remained normal in all patients of the IFN group after transplantation. In contrast, biochemical evidence of acute and chronic hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) patients, respectively, of the control group. Logistic regression analysis identified non-receiving IFN before transplantation as a risk factor for post-transplant hepatic dysfunction (odds ratio = 11.7, p = 0.003) and for chronic allograft nephropathy (odds ratio = 11.6, p = 0.02). CONCLUSIONS: IFN-treated patients had a significantly better post-transplant hepatic function and significantly lower rates of chronic allograft nephropathy.
Asunto(s)
Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Trasplante de Riñón , Diálisis Renal , Adulto , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/mortalidad , Hepatitis C Crónica/fisiopatología , Hepatitis C Crónica/virología , Humanos , Terapia de Inmunosupresión , Interferón alfa-2 , Interferón-alfa/efectos adversos , Trasplante de Riñón/efectos adversos , Hígado/fisiopatología , Masculino , Proteinuria/etiología , ARN Viral/sangre , Proteínas Recombinantes , Trasplante HomólogoRESUMEN
BACKGROUND: Adequate dialysis cannot be ascertained on the sole base of a normal or even a high Kt/V(urea) so the impetus of this study was to use the neurophysiologic studies as a marker of the biologic status of the hemodialysis patients to assess the optimum level of Kt/V(urea). METHODS: This study was carried out on 20 patients (15 men and 5 women) on maintenance hemodialysis; their ages ranged from 18 to 66 years. Initially, the patients were subjected to thorough clinical and laboratory investigations, and their dialysis adequacy was assessed by studying their urea kinetic modeling and neurophysiologic studies (Phase I). Dialysis was optimized to achieve a target Kt/V(urea) of 1.3 in Phase II and 1.5 in Phase III. The duration of each phase was six months at the end of which all patients were thoroughly reevaluated. Nutrition was not manipulated during the study. RESULTS: A neurophysiologic study showed a significant improvement of polyphasicity pattern of both proximal and distal muscles of the upper and lower limbs concomitant with improvement of quality of life on achieving a Kt/V(urea) of 1.5 (p < 0.001). There was no significant change of the duration and amplitude of all studied muscles, however. CONCLUSION: Achieving a Kt/V(urea) of 1.5 is a more suitable target for hemodialysis patients because it may be an avenue for improving the neuromuscular functions of these patients.
Asunto(s)
Enfermedades Neuromusculares/terapia , Diálisis Renal/normas , Urea/farmacocinética , Adolescente , Adulto , Anciano , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Modelos Biológicos , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/etiología , Diálisis Renal/efectos adversosRESUMEN
BACKGROUND: Glomerular crescent formation is a feature of the most severe forms of human glomerulonephritis. The postinfectious form of rapidly progressive glomerulonephritis with crescents is a form of immune complex glomerulonephritis which seem to have a better prognosis. A relatively poorer prognosis for crescentic postinfectious glomerulonephritis in South Africa has been reported. In the present study, we have tried to determine the mode of presentation, and the prognostic factors for renal and patient outcome for cases with postinfectious crescentic glomerulonephritis (CGN). METHODS: Between 1990 and 2000 a total number of 128 patients with CGN were managed at our center, among them 23 cases were diagnosed as postinfectious CGN. They were followed-up for a mean period of 40.1 +/- 28.9 months. Among them 12 were males and 11 were females. The median age was 12.35 years (range 4-55 years). The median serum creatinine at presentation was 7.24 mg/dl (range 1.3-14.5 mg/dl). We studied the clinical, laboratory and histopathological data .of our cases and their impact on the renal and patient outcome. RESULTS: By univariate study the risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors. The risk factors that significantly affected patient mortality were hypertension and serum creatinine at last follow-up. CONCLUSION: postinfectious CGN is a severe form of glomerulonephritis that usually presents with rapidly progressive renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction.