Unsuitability of fecal alpha 1- antitrypsin as a marker for differentiation of microbial and non microbial diarrhea

Alpha 1 - antitrypsin [AAT], an acute phase protein of human serum, is eliminated in the feces in some intestinal disorders, especially diarrhea and its estimation has been used as a marker for protein loss. In this study, we have investigated the possibility of using the determination of fecal A AT in the differential diagnosis of microbial and non-microbial diarrhea, which is ordinarily done by stool culture. In this case-control study, fecal A AT concentration was estimated in children hospitalized in the Pediatric department of Hajar hospital, Shahrekord, Iran. Group 1 consisted of 30 children with microbial diarrhea. Group 2 consisted of 30 children with nonmicrobial diarrhea and the control group consisted of 30 children without diarrhea. Stool samples were collected from all children. Fecal samples were subjected to stool culture and examination. Fecal AAT was estimated using radial immunodiffusion technique. The mean fecal AAT concentration was 50.0 +/- 46.2 mg/dl in group 1, 25.8 +/- 38.3 mg/dl in group 2 and 1.1 +/- 3.4 mg/dl in the control group. There was a significant difference in fecal AAT values in case of diarrhea when compared with the control group. Fecal levels of AAT were significantly higher in microbial diarrhea than in non-micro bial diarrhea and levels in both were much higher than in controls. However, A AT levels were low in some individual microbial cases making this measurement unhelpful for differential diagnosis

[Investigation of host cell protein synthesis shut-off inhibition by a Herpes simplex virus type-1 gene, ICP34.5, in a neuronal cell line, SK-N-SH]

Background and aim: the cellular response to virus infection is a complex process and includes induction of interferons [IFNs]. IFNs are key components of the host innate immunity to virus infection and act through several pathways to block virus growth and virulence. Cells infected with a variety of viruses synthesize double stranded RNA, which induces an IFN response. Protein kinase R [PKR] is induced by IFNs and is a major mediator of the cellular response to virus infection. PKR becomes activated and phosphorylates initiation factor-2alpha [eIF-2alpha]. This leads to the loss of functional eIF-2alpha, which results in inhibition of protein synthesis. In herpes simplex virus type-1 [HSV-1] infected cells, activation of the PKR pathway results in premature shut-off of host protein synthesis. However, HSV-1 encodes a gene, ICP34.5, which blocks the shut-off of the host protein synthesis. This gene is the virulence factor of this virus in the central nervous system of the mice. This gene is not essential for replication of this virus in some cell lines. However, its role in neuronal cell lines such as SK-N-SH cells following infection with recombinant mutant expressing ICP34.5 specifically, has not been investigated. The aim of this research was to investigate this role

Method: based on homologous recombination, a number of HSV-1 recombinants constructed, their DNA analyzed by using Southern blotting and they were characterized by using Western blotting and host shut-off techniques. Following infection of SK-N-SH cells, inhibition of host protein synthesis shut-off by this mutant compared with a deletion mutant lacking this gene and an HSV-1 wild type has been investigated

Results: the results showed that ICP34.5 is essential for maintenance of host protein synthesis and thus replication of HSV-1 in this cell line

Conclusion: in cells infected with HSV-1, the function of this gene is the inhibition of host protein synthesis shut-off, induced by infected cell