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.     

Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its effects in biochemical responses

1. Laboratory experiments were carried out to assess uptake and metabolism of the epilepsy drug, carbamazepine and its consequent biological responses in marine clam (Ruditapes decussatus) a model non-target organism in ecotoxicology.

2. Clams were exposed to two nominal concentrations (C1?=?30?μg/L and C2?=?50?μg/L) of CBZ for a maximum period of 14 days. Analysis of CBZ and their metabolites in clam and water after exposure to two nominal concentrations of the pharmaceutical drug were performed using UPLC-HRMS analysis. CBZ accumulation reached an average tissue concentration of 1241.59 ng/g dw and 1664.33 ng/g dw at low and high nominal concentration, respectively.

3. Furthermore, a metabolite (3-hydroxy-CBZ) was detected in tissues indicating carbamazepine translocation and metabolism inside clam, suspect screening of CBZ glucuronides was also performed by accurate mass extraction but it could not be detected.

4. Activities of antioxidant enzymes superoxide dismutase, catalase and gluthatione-S-transferase generally increased. Change in the contents of glutathione, malondialdehyde and protein carbonyl were also studied.

5. Results indicated that the bioaccumulation of CBZ resulted in the changes of the antioxidant defense system and the production of ROS with the oxidative stress, ultimately induced alteration in lipid peroxidation and protein carbonyl.     

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.     

Cutaneous metastasis of lung carcinoma: a retrospective study of 12 cases

Background The skin is a rare site of metastasis of the internal malignancies. On the contrary, lung cancer is a common primary malignancy of skin metastasis. The latter is either synchronous with the primary lung tumour or can reveal it. Objective To analyse the clinical findings and the outcome of cutaneous metastasis in patients with primary lung cancer. Methods Retrospective study including 12 cases of cutaneous metastasis of lung cancer diagnosed in our institution during 6 years. Results Our patients included three women and nine men with a median age of 59.83 years. The cutaneous metastases were unique in seven cases. They revealed the primary tumour in two cases, were discovered synchronously with the primary tumour in six cases and after the primary tumour in four cases. They appeared in patients presenting multiple metastases in 10 cases. Clinical appearance consisted on a firm nodule, sometimes ulcerated with a diameter ranging from 0.5 to 5.5 cm. The tumour was sited in the thorax, the back, the abdomen; or the upper or lower limbs. Pathological examination of bronchial biopsy revealed an adenocarcinoma in eight cases, a squamous cell carcinoma in two cases and a small cell carcinoma in two cases. In spite of lung cancer therapies, the patients with metastasis to other organs with a median follow‐up time of 4 months died. Conclusion Cutaneous metastases of lung cancer are of poor prognosis. They are most of the time associated with an advanced neoplastic process with metastasis to other organs. Median survival after skin involvement does not exceed months.     

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.     

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Low-frequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-γ and IL-6) increased. Expression of the M1 macrophage marker IL-1β also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKD-induced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.     

Effect of Rehabilitation Program on Endocrinological Parameters in Patients with COPD and in Healthy Subjects

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation and endocrinological disturbance. The aim of this study is to analyze the effect of rehabilitation program on the balance of anabolic versus catabolic hormone in patients with COPD and in healthy subjects. Methods: Nineteen patients with COPD and 16 age-matched healthy subjects undertooked exercise training 3 days/week for 8 weeks. Before and after the training program the concentration of growth hormone (GH), Insulin-Like Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3), testosterone and cortisol in serum were determined. The exercise measurements included a 6-Minute Walking Test (6MWT). Results: After 8 weeks, there was no significant change in lung function in patients with COPD and healthy subjects. Growth hormone, Insulin-like Growth Factor-1 and Insulin-like Growth Factor-Binding Protein 3 increased significantly after rehabilitation training (p < 0.01). The rehabilitation program improves the testosterone/cortisol ratio (T/C ratio) in both groups. There is a significant improvement in the 6-Minute Walking distance (6MWD) in both groups (p < 0.01). Dyspnea and heart rate at rest and at the peak of the 6-Minute Walking Test (6MWT) decreased significantly after training program (p < 0.01). Conclusion: Pulmonary rehabilitation induces an improvement of the anabolic process and reduces proteine distruction by the modifications in endocrinological factors regulating skeletal muscle in patients with COPD.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.