Acute vascular rejection after kidney transplantation outcome and effect of different therapeutic modalities

Background: Steroid resistant acute vascular rejection (AVR) is a great obstacle in successful renal transplantation (KTx). The aim of this work was to evaluate the outcome of histologically confirmed acute vascular rejection - which occurred in severe aggressive form in 39 patients following kidney transplantation as well as to study the outcome of therapy. These cases were chosen from 1000 renal allograft recipients who underwent kidney transplantation in the period between March, 1976 and April 1997 in Urology-Nephrology Center, Mansoura, Egypt.Methods: Statistical analysis of risk factors leading to AVR was carried out. The outcome of different rescue therapies used for AVR as well as graft survival functions were also analyzed.Results: Survival analysis for grafts with AVR revealed 60%, 53%, 30 %, 0% graft survival at 1, 2, 5, 10 yrs respectively after Tx. A statistically significant difference was found in comparison to patients who only experienced acute cellular rejection (90%, 84%, 71%, 46% graft survival at 1, 2, 5, 10 years post- KTx respectively) or patients who passed without rejection in their post-transplantation follow up (95%, 91.3%, 83.3%, 65.5% graft survival at 1, 2, 5, 10 yrs respectively). No statistically significant difference on the overall graft survival between the different modalities of therapy was noted. Steroid pulses + plasma exchange were given for 14 patients with AVR, whereas ATG, MAB ± plasma exchange were added to steroid resistant cases (25 patients). Logistic regression analysis of these data showed that prior blood transfusion, donor-recipient consanguinity, retransplantation are the most significant variables related to occurrence of AVR after kidney transplantation. At last follow up, 14 patients 35.9%) were living with functioning grafts, 16 patients (41%) were living on dialysis, 5 patients died with functioning grafts (12.8%) and 4 patients (10.25%) died with failed grafts.In conclusion: AVR remains a major obstacle for renal transplantation as it markedly impaired graft survival and responded poorly to therapy. Prior blood transfusion decreased the incidence of AVR whereas retransplantation and unrelated donation account significantly to the occurrence of AVR after renal Tx

Protein Kinases Mediate Anti-Inflammatory Effects of Cannabidiol and Estradiol Against High Glucose in Cardiac Sodium Channels

Background: Cardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of the cardiac voltage-gated sodium channel (Nav1.5) that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, are not well understood. We hypothesized that inflammation could mediate the high glucose-induced biophyscial changes on Nav1.5 through protein phosphorylation by protein kinases A and C. We also hypothesized that this signaling pathway is, at least partly, involved in the cardiprotective effects of cannabidiol (CBD) and 17β-estradiol (E2). Methods and Results: To test these ideas, we used Chinese hamster ovarian (CHO) cells transiently co-transfected with cDNA encoding human Nav1.5 α-subunit under control, a cocktail of inflammatory mediators or 100 mM glucose conditions (for 24 h). We used electrophysiological experiments and action potential modeling. Inflammatory mediators, similar to 100 mM glucose, right shifted the voltage dependence of conductance and steady-state fast inactivation and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. We also used human iCell cardiomyocytes derived from inducible pluripotent stem cells (iPSC-CMs) as a physiologically relevant system, and they replicated the effects produced by inflammatory mediators observed in CHO cells. In addition, activators of PK-A or PK-C replicated the inflammation-induced gating changes of Nav1.5. Inhibitors of PK-A or PK-C, CBD or E2 mitigated all the potentially deleterious effects provoked by high glucose/inflammation. Conclusion: These findings suggest that PK-A and PK-C may mediate the anti-inflammatory effects of CBD and E2 against high glucose-induced arrhythmia. CBD, via Nav1.5, may be a cardioprotective therapeutic approach in diabetic postmenopausal population

Impetigo herpetiformis during the puerperium triggered by secondary hypoparathyroidism: a case report

A 38-year-old multiparous woman with post thyroidectomy hypoparathyroidism developed pruritic erythematous patches with multiple pustules on its margins on her thighs and groin accompanied by fever few days after delivery by caesarean section. Impetigo herpetiformis was diagnosed based on the typical clinicopathological findings. The patient was treated with intravenous fluids, calcium, Calcitrol and corticosteroids. The correction of hypocalcaemia was accompanied with rapid improvement of her skin disease and general condition. Our case is the fourth case of impetigo herpetiformis initially presented during puerperium and the first case of puerperal impetigo herpetiformis that is precipitated by secondary hypoparathyroidism. The awareness of the possible occurrence of impetigo herpetiformis during the puerperium allows early diagnosis, treatment and prevention of maternal complications

Differential Effects of Low-Dose Erythropoietin in Rat Model of Diabetic Nephropathy: Submitted: Jan 3, 2018 Accepted: Feb 26, 2018 Published online: Mar 3, 2018

Background. Previous reports on the renoprotective effect of erythropoietin (EPO) in the setting of chronic kidney disease (CKD) have yielded conflicting results. The aim of this study is to clarify the effect of low, non-hematopoietic dose of EPO on the evolution of diabetic nephropathy (DN) in rat model. Methods. Low dose of recombinant human EPO (150 U/kg, s.c. three times/week) was given to streptozotocin (STZ)-induced diabetic rats in two schedules; in the first one, EPO was given from day 2 after STZ injection till the end of the study (28 weeks) as prophylactic treatment; and in the other schedule EPO was given after development of DN (last 8 weeks) as therapeutic treatment. Albuminuria, blood pressure, creatinine clearance, renal venous oxygen tension (vPO2), plasma EPO, hematocrit and renal histopathology were assessed. Results. Unexpectedly, 28 weeks administration of EPO to diabetic rats led to aggravation of albuminuria and worsening of histopathological damage in spite of partial correction of renal hypoxia. Contrary to this, terminal 8 weeks EPO therapy of DN reduced albuminuria and demonstrated some favorable effects on biochemical changes and histologic picture. Conclusion. Low dose EPO exerted differential effects in rat model of DN according to treatment duration. In addition, findings of the present study warrants further investigations of the exact renoprotective role of EPO in diabetic patients with CKD who receive EPO therapy for long periods

Avascular bone necrosis of the femoral head after renal transplantation: Is it avoidable?

Background: Avascular osteonecrosis (AVN) is a seriousosseous complication after renal transplantation (RT). Itsprevalence clearly decreased from 20% to 4% possiblydue to the use of calcinurin inhibitors (CNI), reduction ofsteroid doses and use of steroid free regimens. The aimof our study was to evaluate the frequency of AVNamong our kidney transplant recipients and to determinethe risk factors for its occurrence.Patients and methods: Among 1785 kidney transplantrecipients who received renal allografts between March1976 and December 2005, 40 patients (2.24%) developedAVN with a mean age of 31.3 10.2 years. Eightykidney transplant recipients without AVN were selectedto be a matched control group. The localization of AVNwas the femoral head in all cases.Results: AVN was diagnosed at a mean of 20.4 monthsafter transplantation. The following risk factors werestatistically significant; sirolimus-based regimen,hypercholesterolemia, overweight with body mass index(BMI)>26 and those with HLA A9, HLA B35 and DRB15.Conclusions: We concluded that the proper managementof hypercholesterolemia, maintenance of ideal bodyweight as well as avoidance of sirolimus-basedimmunosuppressive regimen in genetically predisposedpatients may be an effective preventive strategy to avoidAVN

High resolution computed tomography and pulmonary function tests in childhood systemic lupus erythematosus and juvenile rheumatoid arthritis

Background: Alveolar and airway injury represent one of the most common features of rheumatological diseases and is believed to have a significant impact on the course of these diseases. Objective: This work aimed at evaluating airway and alveolar involvement in children with systemic lupus erythematosus (SLE) and juvenile rheumatoid arthritis (JRA). Methods: Thirty four children (21 with SLE and 13 with JRA) were assessed by pulmonary function tests (PFTs) namely spirometry and carbon monoxide diffusion capacity (DLCO) in comparison to 10 healthy controls, as well as by plain roentgenography and high resolution computed tomography (HRCT) of the chest. Results: The studied patients had significantly lower mean PFT values as compared to controls. A restrictive pattern of PFTs was more common as it was detected in 62% of patients with SLE and 23% of those with JRA whereas an obstructive pattern was detected in 14% and 8% respectively. Significantly lower FEF 25-75% values were detected in symptomatic patients. Low values of DLCO (less than 80% of predicted) were recorded in 60% of the studied patients. Chest HRCT was abnormal in 68% of studied patients. In SLE, ground glass appearance and pleural irregularity were the most common findings whereas in JRA, bronchial wall thickening, mosaic appearance and air trapping were prominent. Abnormal findings were detected in 5/9 of asymptomatic patients. Conclusion: airway and alveolar abnormalities are frequently encountered in children with SLE (95%) and JRA (85%) even if they are asymptomatic. HRCT and pulmonary function tests including diffusion studies are recommended as useful tools for the diagnosis and early detection of pulmonary involvement in these patients.Keywords: JRA, SLE, HRCT, PFTs, DLCOEgypt J Pediatr Allergy Immunol 2004; 2(1): 8-1

Induction of antibacterial metabolites by co-cultivation of two Red-Sea-sponge-associated actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49

Liquid chromatography coupled with high resolution mass spectrometry (LC-HRESMS)-assisted metabolomic profiling of two sponge-associated actinomycetes, Micromonospora sp. UR56 and Actinokineospora sp. EG49, revealed that the co-culture of these two actinomycetes induced the accumulation of metabolites that were not traced in their axenic cultures. Dereplication suggested that phenazine-derived compounds were the main induced metabolites. Hence, following large-scale co-fermentation, the major induced metabolites were isolated and structurally characterized as the already known dimethyl phenazine-1,6-dicarboxylate (1), phenazine-1,6-dicarboxylic acid mono methyl ester (phencomycin; 2), phenazine-1-carboxylic acid (tubermycin; 3), N-(2-hydroxyphenyl)-acetamide (9), and p-anisamide (10). Subsequently, the antibacterial, antibiofilm, and cytotoxic properties of these metabolites (1&ndash;3, 9, and 10) were determined in vitro. All the tested compounds except 9 showed high to moderate antibacterial and antibiofilm activities, whereas their cytotoxic effects were modest. Testing against Staphylococcus DNA gyrase-B and pyruvate kinase as possible molecular targets together with binding mode studies showed that compounds 1&ndash;3 could exert their bacterial inhibitory activities through the inhibition of both enzymes. Moreover, their structural differences, particularly the substitution at C-1 and C-6, played a crucial role in the determination of their inhibitory spectra and potency. In conclusion, the present study highlighted that microbial co-cultivation is an efficient tool for the discovery of new antimicrobial candidates and indicated phenazines as potential lead compounds for further development as antibiotic scaffold

Reliability of Spectrum-Efficient Mixed Satellite-Underwater Systems

The combination of radio-frequency (RF) communication and underwater optical wireless communication (UOWC) plays a vital role in the underwater Internet of Things (UIoT). This correspondence proposes a dual-hop hybrid satellite underwater system that exploits non-orthogonal multiple access (NOMA) as a spectrum-efficient access technique. The RF link from the satellite to the relay on an oil platform is presumptively subject to a Shadowed-Rician (SR) fading, while the UOWC channels from the relay to the underwater destinations are suggested to follow Exponential-Generalized Gamma (EGG) distributions. The reliability of the system is characterized in terms of both underwater destinations and system outage probabilities (OPs). We derive new closed-form expressions for the OPs under imperfect successive interference cancellation (SIC) conditions. Furthermore, the asymptotic OP and the diversity order (DO) are obtained to learn more about the system’s performance. The results are verified through an extensive representative Monte-Carlo simulation. Also, we investigate the performance against the turbulence of the salty water, air bubbles level (BL), temperature gradients (TG), shadowing parameters, and satellite pointing errors due to satellite motion, even if the beam is pointed at the center of the directive antenna relay, the beam will randomly oscillate. Finally, we contrast our approach with the conventional orthogonal multiple access (OMA) scheme to demonstrate its superiority