Role of tumour necrosis factor alpha and CD95 as markers of apoptosis in pathogenesis of pediatrics renal diseases

Many renal diseases are characterized by mononuclear cell infiltrate, inflammatory cells may provide factors that cause paranchymal cell apoptosis. Monocytes and macrophages release TNFalpha, Fas ligand, oxygen radicle species and nitric oxide which may stimulate or inhibit the inflammatory response. The aim of this work is to investigate the role of apoptosis in pathogenesis of renal diseases. Eighty children were studied. They divided into four groups: group; I included (20) patients, 10 of them suffering from chronic renal insufficiency (CRI) and treated conservatively, and 10 with end stage renal disease (ESRD) on regular hemodialysis. Group II include 40 patients: (30) nephrotic syndrome cases, (10) were steroid sensitive and (20) were steroid resistant (SRNS). Another (10) were acute glomuleronephritis cases. Group III include (10) cases of urinary tract infection and group IV include (10) age and sex matched healthy children. All groups were subjected to: full history, thorough clinical examination, laboratory investigation. Complete blood picture, blood urea, serum creatinine, radioactive isotope scan of the kidney, renal biopsy for SRNS cases, measurements of serum TNFalpha and CD95 as markers of apoptosis. The results of this study showed significant increase of both TNFalpha and CD95 in all patients groups in comparison with control group (P<0.001). Both TNFalpha and CD95 levels correlated significantly in all patients groups. There was a highly significant positive correlation between blood urea, serum creatinine and apoptotic markers (r=0.66, 0.67). On the other hand there was a significant negative correlation between glomerular filtration rate and apoptotic markers (r= -0.72). Significant rise of apoptotic markers was found in post dialysis than in pedialysis groups of patients (P<0.05). In conclusion apoptotic markers (TNFalpha and CD95) were significantly increased in all groups of renal diseases. So apoptosis may play a role in pathogenesis of renal diseases. Further study of each disease separately and future use of antiapoptotic and antioxidants therapy in such patients are recommended.     

Regenerative effects of umbilical cord matrix cells (UCMCs) in a rodent model of rotenone neurotoxicity

Rotenone is one of the pesticides thought to have neurotoxic effect that could potentially play a role in the development of Parkinson's disease (PD). The neurotoxic effects of rotenone have been used to induce PD model in animals that can help in testing suggested therapies. Cell replacement therapies are suggested as new promising approach for treating PD. This study was done to evaluate the regenerative effect of intrathecal administered umbilical cord matrix cells in a rotenone model of PD in mice. Thirty, male BALB/c mice were used and divided into 3 equal groups. The control group (G.1) received only carboxymethyl cellulose orally once daily at a volume of 10ml/kg. The second group was given a daily rotenone oral dose of 30mg/kg for 28days. The third group received rotenone (30mg/(kgday) orally for 28days) and in the 15th day 1×10(5) of UCMCs were given intrathecally and then they completed the rotenone course. At the 23rd day all the animals were evaluated regarding locomotor incoordination through behavioral tests for monitoring PD development. At the end of the 28days all animals were sacrificed by overdose of phenobarbital and their brain were subjected to immunohistochemical analysis for dopaminergic neurons staining for anti TH antibodies. Intrathecal UCMCs revealed regenerative effects in SNpc as evidenced by immunohistochemical staining; this was in parallel with better performance in behavioral tests. In conclusion, the results of this study revealed the regenerative capacities of UCMCs against rotenone neurotoxicity in mice.     

Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat.

Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain, such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and capsaicin-induced paw licking and in the model of acute gastric damage induced by indomethacin. The agent showed marked anti-inflammatory activity in the carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after carrageenan challenge. The agent was also active p.o. in acute inflammation caused by carrageenan. The administration of GbE with indomethacin, rofecoxib, celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin-induced hind paw licking time and was similarly effective in the hot-plate assay of nociception. In contrast, when assessed in the tail-electric stimulation test, GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical value as an anti-inflammatory and analgesic drug alone or in conjunction with NSAIDs.     

Ocular Manifestations in Egyptian Children and Young Adults with Sickle Cell Disease

In sickle cell disease (SCD), ocular lesions result from stasis and occlusion of small eye vessels by sickled erythrocytes. Vaso-occlusive disease of the retina can be responsible for nonproliferative (NPR) and proliferative retinopathy (PR). Patients are often asymptomatic until serious complications arise as, vitreous hemorrhage and retinal detachment. This work aimed to study the frequency and pattern of ocular manifestations in Egyptian children and young adults with SCD. In this cross-sectional study, 40 steady state patients (80 eyes) aged 2–28 years (30 children and 10 young adults) with established diagnosis of SCD (26 with homozygous SS and 14 with S/β thalassemia underwent complete ophthalmic examination with dilated fundoscopy. Fluorescein angiography was performed for patients ≥12 years old. The overall frequency of retinal lesions was 47.5 % (46.2 and 50 % of SS and S/β patients respectively). PR and NPR were evident in 32.5 and 27.5 % of all enrolled patients respectively (five patients having both). Peripheral retinal occlusion was a frequent ocular finding in both groups; the youngest patient showing PR was 15 years old. Older age, longer disease duration and splenectomy were significantly more prevalent among patients with PR. Despite lack of visual symptoms, children and young adults are at risk of PR. Frequency of retinal lesions was comparable in SS and S/β patients. Periodic ophthalmologic examination starting at the age of 12 years is recommended for timely-identification of retinal lesions thus minimizing the risk of sight threatening retinopathy.     

An intervention study for prevention of HCV infection in some hemodialysis units in alexandria

This study was conducted aiming to compare between strict adherence to the universal precautions and anti HCV seropositive patients isolation as a preventive measure. To fulfill this aim, 80 anti HCV seronegative patients and 44 staff members working in three hemodialysis units were included in the study. A predesigned questionnaire was filled for all patients that included history of hepatitis risk factors, which are related, or not to dialysis process. Another questionnaire was filled for all medical and paramedical staff in the studied units, which included their knowledge, attitude and practice (KAP) as regard HCV. Pretest was done, followed by health education program (HEP). A posttest was performed after one month and every 6 months for 18 months. An observational sheet was filled by one of the researchers to describe the hemodialysis units environment and to record the practice of the staff in the studied units. Blood samples were collected from the study subjects at baseline, every 3 months for patients and every 6 months for the staff. Sera were separated and tested for anti HCV seropositivity using enzyme linked immunosorbent assay [ELISA] test third generation. Marked increase in staff's knowledge was evident one month after HEP and decreased gradually throughout the follow up period. The attitude was slightly elevated and remained nearly unchanged throughout the follow up. Only in unit A the mean preventive score was markedly increased 6 months after HEP and remained high throughout the follow up period. The incidence rate of anti HCV seroconversion decreased in unit A from (10% to 0%), where universal precautions was applied, and in unit C from (24.4% to 10%), where isolation of anti seropositive patients was done in the first and third 6 months of the follow up period respectively. It increased in unit B, where no measure was taken, from 10.5% to 16.7%.     

HER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor

Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P > 0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank = 13.23 and P > 0.001), homologous epithelial differentiation (Log-rank = 6.01 and P = 0.04), as well as HER2/neu positive tumors (Log-rank = 6.14 and P = 0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank = 21.22, P > 0.0000) and if HER2/neu positive (Log-rank = 8.53, P = 0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.