Wagdi Elkashef

CXCL10 antagonism and plasma sDPPIV correlate with increasing liver disease in chronic HCV genotype 4 infected patients

Egypt has the highest prevalence of hepatitis C virus infection worldwide. CXCL10 is a potent chemoattractant that directs effector lymphocytes to sites of inflammation. It has been reported that plasma CXCL10 is processed by dipeptidylpeptidase IV (DPPIV) thus leading to the generation of an antagonist form. Using Luminex-based immunoassays we determined the concentration of different forms of CXCL10 (total, agonist, and antagonist). We also evaluated plasma soluble DPPIV (sDPPIV) concentration and plasma dipeptidylpeptidase (DPP) activity. Using flow cytometry and immunohistochemistry, we analyzed the distribution of lymphocyte subsets. Plasma CXCL10 was elevated in chronic HCV patients, however the agonist form was undetectable. Increased sDPPIV concentration and DPP activity supported the NH2-truncation of CXCL10. Finally, we demonstrated an increased frequency of CXCR3(+) cells in the peripheral blood, and low numbers of CXCR3(+) cells within the lobular regions of the liver. These findings generalize the observation of chemokine antagonism as a mechanism of immune modulation in chronic HCV patients and may help guide the use of new therapeutic immune modulators.

Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity

The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evaluation of the potential protective efficacy of tranilast against acute and subacute CP-induced lung and kidney injuries in male Swiss Albino mice. Intraperitoneal CP significantly impaired oxidant/anti-oxidant balance and increased inflammatory cell count in bronchoalveolar lavage fluid, serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) levels, with significant impairment of lung and kidney architectures. Tranilast taken orally for 8 and 14 days significantly enhanced mice anti-oxidant defense mechanisms; it increased lung and kidney SOD activity, GSH content and reduced lipid peroxidation. Tranilast significantly reduced serum creatinine and BUN. Furthermore, it decreased accumulation of inflammatory cells in the lungs. Serum TNF-α, LDH, total lung and kidney protein contents significantly declined as well. Histopathological examination revealed concomitant significant tissue recovery. Such results show a significant protective potential of tranilast against deleterious lung and kidney damage induced by CP, probably by enhancing host antioxidant defense mechanism, decreasing cytotoxicity, and decreasing expression of inflammatory cytokines.

Tranilast ameliorates impaired hepatic functions in Schistosoma mansoni-infected mice

The ability of tranilast, a mast cell stabilizer and anti-transforming growth factorβ (TGFβ) to improve impaired hepatic functions in Schistosoma mansoni (S. mansoni)-infected mice, was investigated, providing the first evidence on the ability of tranilast to improve hepatic impairment due to schistosomal infection. Tranilast had significant beneficial effects against progression of hepatic fibrosis in S. mansoni-infected mice treated with praziquantel and those untreated. Different aspects of drug activity were investigated. Its effect on serum liver functions was evaluated by estimating: alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and albumin. Its effect on the extent of liver fibrosis, through estimation of hepatic hydroxyproline and hepatic collagen content in liver hydrolysates, was also evaluated. Also, the expression of profibrogenic mediators, such as serum TGFβ1, was estimated. Finally, the effect on S. mansoni infection itself was studied, via histopathological examination of liver specimens stained with both hematoxylin–eosin and Masson’s trichome stains. Tranilast ameliorated the harmful effects of S. mansoni infection on the liver. Such action was manifested in its significant ability to improve impaired hepatic functions, reduce histopathological changes, lower hepatic collagen content and finally reduce serum TGFβ1 levels. The beneficial effect of tranilast may be in part due to its ability to reduce the production of profibrogenic mediators in the infected animals by improving the host immune response or by interfering with critical steps in the fibrogenic cascade.

Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model

Abstract Allergic asthma is a chronic respiratory disease with a prevalent T helper (Th2)‐mediated immune reaction. Crocin, the major bioactive constituent of saffron, has been reported in multiple studies to have numerous pharmacological activities, including prominent anti‐oxidant activities. In the current study, the anti‐asthmatic potential of crocin was evaluated. Adult male Swiss Albino mice were administered 10 mg of ovalbumin (OVA) mixed with 1 mg of aluminum hydroxide intraperitoneally on days 0 and 7 and were administered crocin (25 mg/kg) orally daily for 16 days. Asthma progression was associated with significant increase in the lung/body weight index, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung total protein content, and serious index of lung permeability, indicating pulmonary edema with accumulation of serous fluids within the lungs. Serum lactate dehydrogenase (LDH) activity and lung malondialdehyde (MDA) content were significantly increased, while lung superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and serum and lung catalase activities were significantly decreased. These changes reflect significant pulmonary inflammation with concomitant disturbance of oxidant/antioxidant homeostasis. Moreover, tumor necrosis factor (TNF)‐&agr;, interleukin (IL)‐4, and IL‐13 contents in the lung were also significantly high after OVA sensitization. Crocin treatment significantly alleviated the OVA‐induced allergic asthma‐associated alterations in inflammatory and oxidative stress biomarkers. Crocin enhanced anti‐oxidant defenses, reduced the incidence of oxidative stress, and restored pro‐inflammatory cytokines to normal levels. Histopathological analysis showed significant lung improvement in crocin‐treated mice. In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associated with down‐regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis. HighlightsCrocin ameliorates allergic asthma‐induced pulmonary damage.Crocin decreases inflammatory cells recruitment and edema.Crocin decreases pulmonary MDA and increases SOD, GSH and catalase.Crocin modulates IL‐4/IL‐13 signaling.Crocin reduces lung TNF‐&agr; content.

Endoscopic ultrasound of isolated gastric corrosive stricture mimicking linitis plastica

Isolated gastric outlet obstruction after 1 month of asymptomatic ingestion of corrosive is a rare phenomenon and rarely reported. In this type of cases, diagnosis is very difficult due to no symptoms at the time of poisoning, and biased history. We report a case of a young male presented with isolated gastric outlet obstruction after 1 month of asymptomatic ingestion of toilet cleaner, which was known to us later, mimicking linitis plastica. On upper endoscopy, the stomach was grossly edematous, antrum edematous and inflamed with reduced distensibility and narrow pyloric canal. Endoscopic ultrasound of the stomach revealed diffuse thickening of the gastric wall, mainly the antrum, involving submucosa and muscularis propria. We propose corrosive injury to be in the differential diagnosis of gastric linitis plastica.

Bilharzial endocervical polyp.

Schistosomiasis still represents a major threat to womens health in many developing countries. The frequency in developed countries is increasing among immigrants and tourists who have a history of freshwater exposure in endemic areas. This is a case of 43-year-old immunocompetent Egyptian woman presented by abnormal vaginal bleeding. The gynecological examination revealed an endocervical polyp measuring 3 x 2 x 1 cm. Polypectomy was done. Histopathological examination revealed several granulomas containing viable eggs of Schistosoma hematobium. Schistosomiasis is rarely presented with endocervical polyp. In developing countries, schistosomiasis may be considered in differential diagnosis of patient with endocervical polyp.

Tadalafil reduces airway hyperactivity and protects against lung and respiratory airways dysfunction in a rat model of silicosis

Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage. BALF content of inflammatory cells, lung total protein, MDA, nitrite/nitrate, tumor necrosis factor α (TNFα), transforming growth factor β1 (TGFβ1) and collagen contents significantly declined with concomitant reduction in serum LDH activity; confirming reduction of silica-induced oxidative stress and inflammation. Meanwhile, lung SOD activity and GSH content significantly increased; confirming restoration of anti-oxidant defenses. Immunohistochemical analysis of lung TGFβ1 expression was correlated with observed biochemical improvements. There was a significant decline in thickness of the walls of the blood vessels and in macrophages and alveolar septal expression of TGFβ1 paralleled with reduction in collagen and extracellular matrix (ECM) components deposition. Ultimately, biochemical and histopathological improvements were accompanied by restoration of normal respiratory functions and reduction in airway hyperactivity and responses to both of carbachol and 5-HT. In conclusion; down-regulation of inflammatory and fibrogenic cytokines expression, restoration of oxidants/antioxidant hemostasis, antioxidant boost and promotion of angiogenesis are implicated in the observed protective effect of tadalafil.

Post-splenectomy splenosis presenting as hepatocellular carcinoma in the left lateral section of the liver: A case report

INTRODUCTION Defined as heterotrophic autotransplantation of splenic tissue after splenic trauma or surgery. PRESENTATION OF CASE We present a case of 45 years old female patient with past history of splenectomy for haemolyticanaemia. Complaining of abdominal pain the patient was investigated by abdominal CT scan which revealed a focal lesion in the left lateral section of the liver suspicious to be hepatocellular carcinoma and gall bladder stones. Serum α-fetoprotein was within normal range. Exploration revealed a well encapsulated lesion completely separable from the liver and the diaphragm. Histopathological examination confirmed the diagnosis of splenosis. Although it is a rare condition, we recommend that the diagnosis of splenosis should be put in consideration in every patient with past history of splenectomy for proper management. DISCUSSION Although several cases of hepatic splenosis have been reported in the literature, supra-hepatic splenosis as our case has been rarely described. CONCLUSION Considering patients past history of splenectomy or splenic trauma should add splenosis to the list of possible differential diagnosis to avoid unnecessary surgical intervention.

Does steatosis affect the performance of diffusion-weighted MRI values for fibrosis evaluation in patients with chronic hepatitis C genotype 4?

BACKGROUND/AIMS To evaluate the effect of hepatic steatosis on the apparent diffusion coefficient (ADC) of hepatic fibrosis in patients with HCV genotype 4-related chronic hepatitis. MATERIALS AND METHODS Overall, 268 chronic hepatitis C patients (164 males and 104 females) underwent liver biopsy for fibrosis assessment by the METAVIR score and grading for hepatic steatosis. They were classified into early fibrosis stage (F1, F2) and advanced fibrosis stage (F3, F4). Diffusion-weighted MRI (DWI) of the liver was performed using 1.5-Tesla scanners, and the ADC value of the patients with and without steatosis in different stages of fibrosis was estimated and compared. RESULTS In patients with early fibrosis, the ADC value significantly decreased in patients with steatosis (1.52±0.17×10-3 mm2/s) compared to that in patients without steatosis (1.65±0.11×10-3 mm2/s) (p<0.001). In those with an advanced stage of fibrosis, the ADC value was also significantly decreased in patients with steatosis (1.07±0.16×10-3 mm2/s) compared with that in patients without steatosis (1.35±0.11×10-3 mm2/s) (p≤0.001). The cutoff value for ADC for steatosis prediction in the early fibrosis group was 1.585 according to the AUROC curve, with a sensitivity of 76.8% and a specificity of 73.5%. The cutoff value for ADC for steatosis prediction in patients with an advanced stage of fibrosis was 1.17×10-3 mm2/s, with a sensitivity of 97% and a specificity of 88.5%. CONCLUSION Histologically detected hepatic steatosis should always be considered when assessing hepatic fibrosis using diffusion-weighted MRI to avoid the underestimation of the ADC value in patients with chronic hepatitis C genotype 4.

Right adrenal gland neuroblastoma infiltrating the liver and mimicking mesenchymal hamartoma: A case report

Highlights • The right adrenal gland neuroblastoma and infiltrated the adjacent liver substance mimicking mesenchymal hamartoma of the liver.• The Presentation of fever of unknown origin in a case of right adrenal gland neuroblastoma is rare.• Neuroblastoma should be considered in differential diagnosis of abdominal mass in all infants and children.