DFT and molecular docking studies on biological active acridines: the interaction with bovine serum albumin

Acridine derivatives, especially 1,8-dioxo-9-aryl-decahydroacridine represent significant scaffolds in medicinal chemistry. Given the biological properties of such products which are used in drug development, they need to have appropriate carrier. Proteins are generally used as helpful tools in drug delivery. Consequently, molecular docking between these compounds and bovine serum albumin [BSA] has been taken into account. Furthermore, in order to achieve better results, the suggested compounds have been optimized using Gaussian 03 software

characteristics of rare codon clusters in the genome and proteins of hepatitis C virus; a bioinformatics look

Recent studies suggest that rare codon clusters are functionally important for protein activity. Here, for the first time we analyzed and reported rare codon clusters in Hepatitis C Virus [HCV] genome and then identified the location of these rare codon clusters in the structure of HCV protein. This analysis was performed using the Sherlocc program that detects statistically relevant conserved rare codon clusters. By this program, we identified the rare codon cluster in three regions of HCV genome; NS2, NS3, and NS5A coding sequence of HCV genome. For further understanding of the role of these rare codon clusters, we studied the location of these rare codon clusters and critical residues in the structure of NS2, NS3 and NS5A proteins. We identified some critical residues near or within rare codon clusters. It should be mentioned that characteristics of these critical residues such as location and situation of side chains are important in assurance of the HCV life cycle. The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins. Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins. This information is helpful in development of new avenues for vaccine and treatment protocols

Clinical and Para clinical findings in the children with tyrosinemia referring for liver transplantation

Hereditary tyrosinemia type 1 [HT1] is a rare autosomal recessive inborn error of metabolism caused by deficiency of fumarylacetoacetate hydrolase enzyme. This disease manifests with severe liver and kidney impairment and is associated with an increased risk of liver cancer. The aim of this study was to evaluate clinical, laboratory, imaging, and histopathologic characteristics in the children with HT1 who had referred for liver transplantation. The present retrospective study was conducted on 45 children with HT1 who had referred to Organ Transplantation Center affiliated to Shiraz University of Medical Sciences between March 2005 and March 2010. There were 64.4% boys and 35.6% girls with mean age of 3.75 +/- 1.28 year [ranges from 2 months to 13 years]. The most first clinical presentation was hepatic [80%] and the most prevalent physical findings were hepatomegaly [57.8%], splenomegaly [51.1%], ascites [42.2%], and jaundice [37.9%]. The most relevant laboratory parameters were the high serum succinylacetone, alpha-fetoprotein, and tyrosine levels. The most common findings in the patient's abdominal ultrasonography were multiple hepatic nodules [75.6%] and inhomogeneous parenchymal echogenicity of liver [48.9%], while hyper and hypo attenuated nodules [60%] and non-homogeneous pattern of liver parenchyma [53.3%] were the most prevalent findings in abdominal computed tomography scan. In the histopathology of the liver, the most important finding was cirrhosis in all the patients. In this study, 14 patients [31.1%] received Nitisinone [2-[2-nitro- 4-trifluoromethylbenzoyl]-1,3-cyklohexanedione; NTBC]. This study described clinical and laboratory findings in the children with HT1 who had referred for liver transplantation because of end-stage liver disease from all over country, which indicates delay in diagnosis and treatment of this disease. Considering the results of this study, newborn screening for this disease is highly suggested

Etiology and complications of liver cirrhosis in children: report of a single center from southern Iran

Liver cirrhosis is one of the major causes of hospitalization and mortality in children. A wide spectrum of disorders including developmental abnormalities, infections, metabolic and genetic disorders can lead to liver cirrhosis in pediatric patients. Determination of its etiology is important for treatment modality, prevention of progressive liver damage, family counseling and prioritizing liver transplantation. The aim of this study is to evaluate the causes of liver cirrhosis in children in Southern Iran. We included all cirrhotic children aged less than 18 years who referred to an outpatient Pediatric Gastroenterology Clinic affiliated with Shiraz University of Medical Sciences between March 2009 and September 2010 in this cross-sectional study. The etiology of cirrhosis was determined according to clinical findings, laboratory tests, radiographic evaluation such as ultrasonography or computed tomography scan, hepatobiliary scintigraphy and histopathologic examination of the liver biopsy. Cirrhosis with unknown etiology was considered as cryptogenic. A total of 106 cirrhotic children aged between 5 months to 18 years old with a mean age of 8.24 +/- 6.12 years that included 60 boys [56.6%] and 46 girls [43.4%] were enrolled in the study. The most common causes of liver cirrhosis were Wilson disease [n=22; 20.7%], biliary atresia [n=19; 17.9%], and cryptogenic cirrhosis [n=14; 13.2%]. Other causes were autoimmune hepatitis [n=12; 11.3%], idiopathic neonatal hepatitis [n=10; 9.4%], hepatorenal tyrosinemia [n=9; 8.5%], glycogen storage disease [n=6; 5.7%], and progressive familial intrahepatic cholestasis [n=4; 3.8%].Considering the most common etiology of liver cirrhosis in children in this part of Iran we suggest testing for Wilson disease in all cirrhotic children

Autoimmune hepatitis in children: experiences in a tertiary center

Autoimmune hepatitis [AIH] is a necroinflammatory liver disease of unknown etiology that occurs in the children of all ages. The present study aimed to evaluate the clinical and paraclinical presentations, including pattern of autoantibodies, response to treatment, mortality, and liver transplantation outcome in the Iranian children with AIH. The medical records of 87 children [56 girls and 31 boy] diagnosed with AIH between 2001 and 2010 were retrospectively analyzed for clinical and paraclinical profiles and also treatment outcome. The mean age of the patients was 10.1 +/- 4.5 years [64.4% females]. The most common clinical findings were jaundice [70.1%], splenomegaly [67.8%], and hepatomegaly [51.7%]. Antinuclear, anti-smooth muscle, and anti LKM antibodies were positive in 14/62, 22/53 and 6/40 patients, respectively [36 patients had type 1 AIH, 6 patients had type 2 AIH, 26 patients were seronegative, and autoantibodies were not available in 19 cases]. The most common histological finding in the liver biopsies was chronic hepatitis with interface activity that was seen in 65 [74.7%] patients. The complete response was seen in 52 [59.8%] patients and 24 [27.6%] patients underwent liver transplantation. One-year and five-year survival rates were 87.5% and 80% in the transplanted patients. AIH should be kept in mind in the differential diagnosis of both acute and chronic liver diseases in the children and treatment with combination of corticosteroids and azathioprine is a good treatment option. In the patients with end stage liver cirrhosis that did not respond to medical therapy, liver transplantation is the treatment of choice

Etiology of portal hypertension in children: a single center's experiences

All conditions that interfere with blood flow at any level within the portal system can lead to portal hypertension. For better management of this disorder, it is important to determine the underlying cause. In previous studies, extra-hepatic disorders have been reported as the main cause of portal hypertension in children. In this study, we investigate the underlying causes of portal hypertension in children. This prospective, descriptive study investigated the etiology of 45 children with portal hypertension who referred to Nemazee Hospital Pediatric Gastroenterology Ward from 2005 to 2007. The underlying causes of portal hypertension were determined by liver biopsy, abdominal sonography, abdominal computed tomography scan, and liver Doppler sonography. In this study, 42 of 45 patients [93.3%] developed portal hypertension due to intrahepatic diseases. Extra-hepatic portal hypertension was detected in 3 [6.7%] patients with portal vein thrombosis. Intrahepatic diseases were the most common etiology of portal hypertension among children who referred to our center.