Canavan disease or N-acetyl aspartic aciduria: a case report]

Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive leukodystrophy characterized by spongy degeneration of brain. The disease is an inborn error of metabolism caused by aspartoacylase deficiency resulting from accumulation of N-acetyl aspartic acid in the brain. The authors report a case in a 10-month-old boy who presented with developmental delay and megalencephaly noticeable after 4 months of age. Magnetic resonance imaging of the brain showed diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry.     

Identification of a novel frameshift mutation in the DFNB31/WHRN gene in a Tunisian consanguineous family with hereditary non-syndromic recessive hearing loss

Approximately 80% of hereditary hearing loss is non-syndromic. Non-syndromic deafness is the most genetically heterogeneous trait. The most common and severe form of hereditary hearing impairment is autosomal recessive non-syndromic hearing loss (ARNSHL), accounting for approximately 80% of cases of genetic deafness. To date, 22 genes implicated in ARNSHL have been identified. Recently a gene, DFNB31/WHRN, which encodes a putative PDZ scaffold protein called whirlin, was found to be responsible for the ARNSHL DFNB31. We found evidence for linkage to the DFNB31locus in a consanguineous Tunisian family segregating congenital profound ARNSHL. Mutation screening of DFNB31/WHRNrevealed four nonpathogenic sequence variants and a novel frameshift mutation [c.2423delG] + [c.2423delG] that changed the reading frame and induced a novel stop codon at amino acid 818 ([p.Gly808AspfsX11] + [p.Gly808AspfsX11]). To determine the contribution of the DFNB31locus in the childhood deafness, we performed linkage analysis in 62 unrelated informative families affected with ARNSHL. No linkage was found to this locus. From this study, we concluded that DFNB31/WHRN is most likely to be a rare cause of ARNSHL in the Tunisian population.     

Antiviral and Immune Stimulant Activities of Glycyrrhizin Against Duck Hepatitis Virus

This study was conducted to investigate the effect of glycyrrhizin as an immune stimulant against duck hepatitis virus (DHV). In vitro study was carried out to determine cytotoxic and antiviral effects of glycyrrhizin in VERO cells. In vivo study was performed on 40 one-day-old White Pekin ducklings. -and the birds weres divided into 4 groups: control, glycyrrhizin treated, vaccinated with live attenuated DHV vaccine and glycyrrhizin treated and vaccinated; to investigate the changes in immunity and challenge test. Blood samples were collected from each duckling for evaluation of cellular and humeral immunity. The in vitro results revealed that glycyrrhizin had antiviral and no toxic effects till 10⁶ dilutions. Higher antibody titer was observed from the 5^th week till the end of experiment in glycyrrhizin and vaccinated group. Treatment with glycyrrhizin alone or with DHV vaccine demonstrated a pronounced lymphocytic proliferation response after 4 days post-inoculation till the end of experiment, while vaccinated group revealed a pronounced proliferation response after 24 days post-inoculation. Treatment with glycyrrhizin alone or combination with DHV vaccine revealed good immune stimulant and antiviral effect against DHV.     

Variability of tropism and replicative capacity of two naturally occurring influenza A H9N2 viruses in cell cultures from different tissues

Studies carried out on cell permissivity are of great interest to understand virus replication and pathogenicity. We described the results of a comparative analysis of replication efficiency of two naturally occurring influenza A H9N2 variants isolated from poultry and wild birds, differing by only two substitutions Q226L and T384N, in the receptor-binding site of haemagglutinin and the 380 loop region of NA proteins, respectively. Considering the overall growth of both viruses, lung cultures ensured the most efficient growth of TUN12L226N384 strain with titres up to 10⁹ TCID₅₀/ml whereas small intestine culture was highly susceptible to the TUN51Q226T384 virus reaching a titre of 10⁶ TCID50/ml. The lowest replication was shown in liver cells. The addition of trypsin was essential for the replication of either virus in primary fibroblasts, but it had a marginal positive effect on virus replication in the four other culture types with maximum titres of 10⁸ TCID₅₀/ml. This means that in chicken, the proteolytic activation of the H9N2 viruses with the cleavage motif RSSR may be mediated by other endoproteases than trypsin. Further investigations should concentrate on the production of the appropriate set of viruses by a reverse genetics approach and the examination of cellular protease expression in chicken tissues. This would lead to a more complete understanding of the tropism of low-pathogenic Influenza A viruses.     

Doppler echocardiographic study of left ventricular diastolic function in hemodialysis patients

OBJECTIVES: The purpose of this study is to examine the diastolic dysfunction particularities in hemodialysis patients and to identify the parameters having the most discriminating power of diastolic dysfunction. METHODS: Conventional Doppler echocardiography study implies left ventricular diastolic function from Doppler transmitral flow (E/A), color M-mode flow propagation velocity (Vp) and combined indexes: ratio of peak E-wave velocity to Vp (ENp) and difference in duration of pulmonary venous and mitral flow at atrial contraction (Ap-Am). RESULTS: Left ventricular diastolic dysfunction is found in 86% of the 100 hemodialysis patients: abnormal relaxation pattern 52%, pseudo-normal pattern 21%, restrictive pattern 13%. Left ventricular hypertrophy is independent of blood pressure (eta2=3.386; p>0.06). Diastolic function pattern has no relation with duration of dialysis treatment (F=2.637, p>0.05) or left ventricular mass (F=4.298, p>0.06). We noted correlations with age for all parameters of transmitral Doppler flow (p<0.01), Vp and systolic fraction except combined indexes (p>0.05). Doppler parameters of which discriminating power is significant (p<0.001) are in deceasing order: isovolumic relaxation time, E/A, Vp, early filling deceleration time, Ap-Am, E/VP and systolic fraction. The parameter Vp discriminates normal filling from abnormal or pseudo-normal patterns. However it doesn't allow any discrimination between abnormal and pseudo-normal patterns or abnormal and restrictive patterns. Discriminating analysis classify correctly 100% of pseudo normal pattern patients with 2 variables (isovolumic relaxation time and Vp or VP with E/Vp). Factor analysis suggests that Vp characterizes normal pattern and E/A ratio and Ap-Am characterize restrictive pattern. CONCLUSION: Parameters of diastolic function discriminating value is different from one stage to another. VP characterizes normal pattern, combined indexes restrictive pattern. Vp and isovolumic relaxation time discriminates normal from pseudo-normal pattern.     

IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.     

Prognosis of periprosthetic regurgitation after mitral valve replacement using the Saint Jude prosthesis

Periprosthetic regurgitation (PPR) is a common complication of mitral valve replacement (MVR). The management of moderate and minor PPR remains controversial. The goal of this prospective study was to determine the incidence, predictors and outcome of PPR discovered using omniplan transoesophageal echocardiography (TEE) performed at the early postoperative period (14.7 days) of MVR with SJM prosthesis. Our study enrolled 56 patients, the mean age was 44.5 +/- 11.9 years. The incidence of PPR was 59% (33 patients). TEE showed one jet in nine patients (27%), two jets in 23 patients (70%) and three jets in one patient (3%). PPR is minor in 24 patients (63%) and moderate in nine patients (27%). No patient developed hemolytic anemia or congestive heart failure. In univariate analysis, diameter of prostheses > 27 mm, number of suture knots < 17 and diameter of prostheses/number of knot ratio > 1.7 independently predicted the presence of PPR. In multivariate analysis only a rapport diameter of protheses/number of suture knots > 1.7 mm is predictif of PPR (odd ratio = 9, P = 0.036). Ninety percent of PPR remained present at six weeks and only 29% were present after 12.5 months. CONCLUSION: Mild and minor PPR were frequent during the early postoperative period after MVR. The clinical significance and natural history is benign and they do not require any specific treatment.