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OBJECTIVE: This study was designed to investigate the effect of camel milk and Tarangabin (manna of Alhagi maurorum) combination therapy in addition to conventional treatments in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Forty-four patients of 15 to 70 years old, with CKD due to hypertension or diabetes, and estimated glomerular filtration rate (eGFR) of 15-60 ml/min per 1.73 m2, were enrolled in this trial. The patients were randomized to receive either 400 cc of camel milk with 10 cc of Tarangabin syrup orally in two divided daily doses for 3 months plus conventional therapy or conventional therapy alone. The conventional treatment included diabetes medications and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. RESULTS: The baseline characteristics of patients were similar in the two groups. Serum levels of creatinine (p=0.01), blood levels of urea nitrogen (p=0.0001), triglyceride (p=0.02), and potassium (p=0.05), and diastolic blood pressure (p=0.0001) decreased, while eGFR (p=0.001) improved in intervention group significantly. CONCLUSION: It seems that the therapeutic protocol used in this study can improve renal function in patients with CKD through regulating glucose and anti-inflammatory, laxative, and immunostimulatory properties.
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Background: A human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector (LV) pseudotyped by a variant of rabies envelope glycoprotein, FUG-B2, has previously been prepared and used in transfection of hippocampal CA1 ("Cornu Ammonis" area 1) neurons. This study aimed to verify reactive gliosis and neuronal damage after injection of the vector into the rat hippocampus. Methods: HEK 293T cells were transfected with transfer (fck-Jaws-GFP-ER2), envelope (FUG-B2), and packaging (pMDLg/pRRE, pRSV-Rev) plasmids, and the vector was injected into CA1 of the rat hippocampus. After one week, transduction efficiency, and the number of neuronal and astroglial cells were determined in CA1 and CA3 by double staining of the brain slices. Results: Hippocampal cells were successfully transfected as 92.7% of CA1 and 95.8% of CA3 neuronal cells expressed GFP. The frequency of neuronal and astroglial cells in CA1 and CA3 of the vector-injected rats remained unchanged compared to those in the control and the saline-injected rats. Furthermore, no morphological change was found in hippocampal astrocytes and neuronal cells. Conclusion: The HIV-1-based LV pseudotyped by FUG-B2 is safe and does not cause neuroinflammation and neuronal loss once directly delivered into the rat hippocampus.
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Vectores Genéticos/metabolismo , Gliosis/patología , Glicoproteínas/metabolismo , Hipocampo/patología , Lentivirus/metabolismo , Degeneración Nerviosa/patología , Rabia/metabolismo , Animales , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Masculino , Ratas WistarRESUMEN
BACKGROUND: The trisynaptic circuit (entorhinal cortex-dentate gyrus-CA3-CA1) is a key unidirectional network in the hippocampus. Damage to the hippocampus interrupts this circuit and causes neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest with respect to treating trisynaptic circuit pathologies. METHODS: We generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG-B2. The efficiency of the vector in the retrograde transduction of the rat hippocampal neurons (i.e. the entorhinal cortex from the dentate gyrus, the dentate gyrus from CA3, and CA3 from CA1) was examined by direct injection of the vector into the dentate gyrus, CA3 and CA1. To distinguish transduction of the neuronal and glial cells, as well as selective retrograde gene transfer, double-staining of the green fluorescent protein (GFP) expressing cells with the specific neuron biomarker NeuN (neuronal nuclear protein) and the specific glia biomarker GFAP (glial fibrillary acidic protein) was performed across the network. RESULTS: The transgene was successfully introduced into the circuit. More than 80% of the neuronal and glial cells at the injection sites preserved GFP expression during the 2-month period after vector injection. Importantly, GFP was expressed selectively in almost 80.0% of the presynaptic neuronal cells by retrograde axonal transport of the vector. CONCLUSIONS: The FUG-B2-based vector system can efficiently introduce the transgene into the rat hippocampal neurons both directly and indirectly through retrograde monosynaptic movement. This efficient and long-lasting gene delivery might provide a tool for treating neurological disorders originating in hippocampal circuits.
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Glicoproteínas/genética , Hipocampo/metabolismo , Lentivirus/genética , Red Nerviosa/metabolismo , Fragmentos de Péptidos/genética , Sinapsis/metabolismo , Proteínas Virales/genética , Animales , Células Cultivadas , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Vectores Genéticos/genética , Glicoproteínas/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/citología , Masculino , Neuronas/metabolismo , Fragmentos de Péptidos/metabolismo , Ratas Wistar , Transducción Genética/métodos , Transgenes/genética , Proteínas Virales/metabolismoRESUMEN
OBJECTIVES: Kinetic glomerular filtration rate estimation may have more power and versatility than the Modification of Diet in Renal Disease or Cockcroft-Gault formula for evaluating kidney function when plasma creatinine fluctuates rapidly. After kidney donation, glomerular filtration rate rapidly fluctuates in otherwise healthy patients. We compared 3 formulas for estimating glomerular filtration rate: kinetic, Modification of Diet in Renal Disease, and Cockcroft-Gault, for determining stages of acute kidney injury early after kidney donation. MATERIALS AND METHODS: In 42 living kidney donors, we measured serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and glomerular filtration rates before uninephrectomy and 3 days afterward. To estimate glomerular filtration rate, we used Cockcroft-Gault, Modification of Diet in Renal Disease, and kinetic equations. We sought the most accurate formula for staging acute kidney injury according to the risk, injury, failure, loss, and end-stage criteria. RESULTS: The kinetic glomerular filtration rate model found more cases of stage 3 acute kidney injury than did the Modification of Diet in Renal Disease or Cockcroft-Gault formula. Receiver operating characteristic curves showed that the kinetic glomerular filtration rate model had more sensitivity and specificity than the Cockroft-Gault formula for discriminating among risk, injury, failure, loss, and end-stage criteria stages of acute kidney injury, based on serum creatinine changes. On day 2 after donation, a more sensitive marker with a shorter half-life (serum neutrophil gelatinase-associated lipocalin) was more significantly correlated with kinetic glomerular filtration rate estimation. CONCLUSIONS: The kinetic glomerular filtration rate model was able to discriminate stages of acute kidney injury early after kidney donation according to risk, injury, failure, loss, and end-stage criteria better than the Modification of Diet in Renal Disease or Cockcroft-Gault formulas. The kinetic model detected failure-stage acute kidney injury ≥ 1 to 2 days earlier than the MDRD formula, CG formula detected no failure.
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Lesión Renal Aguda/diagnóstico , Tasa de Filtración Glomerular , Trasplante de Riñón/efectos adversos , Riñón/fisiopatología , Donadores Vivos , Modelos Biológicos , Nefrectomía/efectos adversos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Creatinina/sangre , Cistatina C/sangre , Diagnóstico Precoz , Femenino , Humanos , Trasplante de Riñón/métodos , Cinética , Lipocalina 2/sangre , Masculino , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
A nano-liposomal carrier was prepared for the anti-inflammatory drug prednisolone acetate (PA). The drug showed remarkable loading in the nano-carriers. The drug-loaded nano-liposmes with average sizes of about 186 nm and zeta potentials of -20 mV were obtained. Our drug release studies showed an apparently zero-order trend with only 18% of the drug released in the first 120 h. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no chemical interaction between the drug and carrier. Transmission electron microscopy (TEM) imaging showed near-spherical drug-containing nano-carriers. The intramuscular (IM) trial of the nanoformulation compared with the free drug showed both pharmacokinetic (lower Cmax, higher area under the curve (AUC)) and pharmacodynamic (higher and longer lasting anti-inflammatory effect, both macroscopically and biochemically) superiority for the nano-liposomal drug above the free prednisolone in rats.
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Preparaciones de Acción Retardada/química , Liposomas/química , Nanopartículas/química , Prednisolona/química , Animales , Área Bajo la Curva , Rastreo Diferencial de Calorimetría/métodos , Química Farmacéutica/métodos , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Masculino , Microscopía Electrónica de Transmisión/métodos , Tamaño de la Partícula , Prednisolona/análogos & derivados , Prednisolona/farmacocinética , Prednisolona/farmacología , Ratas , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier/métodosRESUMEN
INTRODUCTION: Hyperglycemia is common and a contributing factor to the undesirable outcomes in kidney transplant recipients. This study investigates the relationship of pretransplant blood glucose levels and the occurrence of delayed graft function among kidney transplant recipients without a diagnosis diabetes mellitus before transplantation. MATERIALS AND METHODS: Eighty-one patients on long-term hemodialysis with no history of clinically diagnosed diabetes mellitus were enrolled in this study. Correlation of the occurrence of delayed graft function with age, gender, donor source, underlying cause of kidney failure, insulin resistance, and blood glucose levels before transplantation was evaluated. RESULTS: There was a significant correlation between abnormal glucose metabolism categories and occurrence of delayed graft function (P = .004). Logistic regression analysis showed that fasting blood glucose before kidney transplantation is an independent predictor of delayed graft function immediately after transplantation (odds ratio = 1.042, P = .04). CONCLUSIONS: Hyperglycemic patients have an increased risk for delayed graft function and should be treated by more potent immune therapy and further restriction of blood glucose regulation in peritransplantation period.