Response of letter to the editor on Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy.

In a letter to the editor, Raineri SM et al. have given an insight of another dimension of procalcitonin (PCT) use as a diagnostic tool in invasive candidiasis. But based on our preliminary information, PCT is reported as unconventional modes of diagnosis approach which yet to prove its stand-alone biomarker properties for invasive candidiasis.

Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy.

BACKGROUND: Sepsis is a global healthcare problem, characterized by whole body inflammation in response to microbial infection, which leads to organ dysfunction. It is becoming a frequent complication in hospitalized patients. Early and differential diagnosis of sepsis is needed critically to avoid unnecessary usage of antimicrobial agents and for proper antibiotic treatments through the screening of biomarkers that sustains with diagnostic significance. MAIN BODY OF ABSTRACT: Current targeting conventional markers (C-reactive protein, white blood cell, tumour necrosis factor-α, interleukins, etc.) are non-specific for diagnosing sepsis. Procalcitonin (PCT), a member of the calcitonin super family could be a critical tool for the diagnosis of sepsis. But to distinguish between bacterial versus viral infections, procalcitonin alone may not be effective. Rapid elevation in the concentration of procalcitonin and other newly emerging biomarkers during an infection and its correlation with severity of illness makes it an ideal biomarker for bacterial infection. Beside this, the procalcitonin levels can be used for monitoring response to antimicrobial therapy, diagnosis of secondary inflammations, diagnosis of renal involvement in paediatric urinary tract infection, etc. The present article summarizes the relevance of procalcitonin in the diagnosis of sepsis and how it can be useful in determining the therapeutic approaches. CONCLUSION: Further studies are needed to better understand the application of PCT in the diagnosis of sepsis, differentiating between microbial and non-microbial infection cases and determining the therapeutic approaches for sepsis.

Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome.

The population of India harbors one of the world's most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs.

Association of genetic variants of mannan-binding (MBL) lectin-2 gene, MBL levels and function in ulcerative colitis and Crohn's disease.

Ulcerative colitis and Crohn's disease are the two major forms of inflammatory bowel disease (IBD). A series of reports have hypothesized interplay of genetic and environmental factors in the pathogenesis of IBD. Polymorphism in the mannan-binding lectin-2 (MBL-2) gene is known to affect the structural assembly and function thereby predisposing subjects to various diseases. The present study was designed to evaluate effect of MBL-2 gene polymorphism on MBL levels and function in IBD patients. Genomic DNA was isolated from blood samples collected from 157 ulcerative colitis, 42 Crohn's disease and 204 control subjects. Genotyping for different polymorphic sites at exon1 of MBL-2 gene was performed by refractory mutation system-PCR and amplification followed by restriction digestion (PCR-RFLP). Serum MBL concentration and C4 deposition levels were estimated using ELISA. Mannan-binding lectin-2 genotypic variants were calculated in IBD and healthy controls. The frequency of single nucleotide polymorphisms at codon 54 was significantly higher in ulcerative colitis patients than controls (P < 0.0001). Ulcerative colitis patients with 'codon 54'-variation showed low serum MBL concentrations coupled with altered MBL function compared to controls. In conclusion, single nucleotide polymorphism in the MBL-2 gene is an important risk factor significantly affecting MBL levels and function in the development of ulcerative colitis among Indians.

Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome

The population of India harbors one of the world's most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs.

Antibacterial and ulcer healing effects of organoselenium compounds in naproxen induced and Helicobacter pylori infected Wistar rat model.

Aim of the present study was to evaluate in vitro toxicity and in vivo antibacterial, anti-inflammatory, antiulcer, and antioxidant activities of two organoselenium compounds, selenocystine (SeCys) and ebselen (Ebs). The study was conducted in experimentally induced ulcers in rodent model infected with Helicobacter pylori (H. pylori). In vitro toxicological studies on normal splenic lymphocytes revealed that SeCys and Ebs were non-toxic to the cells even at 100 µM concentration. Antibacterial activity was observed at 500 µg/mL concentration of either of the compounds against H. pylori. In vivo studies after treatment with SeCys and Ebs (500 µg/kg/day) resulted in significant reduction in ROS production and inhibition of lipid peroxidation in gastric tissue. The antioxidant and anti-inflammatory activities of both the compounds were also confirmed by their ability to lower GSH reduction, to induce the expression of antioxidant genes such as GPx-4, and MnSOD and to suppress inflammatory genes namely COX-2, TNF-α and TGF-ß. In addition, the immunomodulatory activity of both the compounds was evident by enhance of the CD4 levels and maintenance of the IgG, IL-6 and IL-10 levels. Persistent treatment (500 µg/kg, for 28 days) with both the compounds showed considerable (p<0.05) ulcer healing property supporting its role in gastro protection. In conclusion, the results of our study suggest that both SeCys and Ebs possess broad spectrum of activities without any potential toxicity.

Relevance of Helicobacter pylori genotypes in gastric pathology and its association with plasma malondialdehyde and nitric oxide levels.

Persistent infection with Helicobacter pylori confers an increased risk of peptic ulceration and gastric adenocarcinoma. Reactive oxygen and nitrogen species play a crucial role in the progression from normal gastric mucosa to cancer. The aim of the present study was to investigate the plasma malondialdehyde and nitric oxide levels in H. pylori related gastroduodenal diseases and associate their levels with gastric pathology and genotypes of H. pylori. Malondialdehyde and nitric oxide levels in plasma samples of 250 subjects were spectrophotometrically determined. Subsequently, genotypic and histopathological assessment was performed in gastric biopsies obtained during endoscopy. The levels of MDA and NO exceeded in subjects infected with genotype-1 of Hp than those with other genotypes suggesting more precise interaction of highly virulent strains of Hp in eliciting severe tissue damage. In conclusion, the study demonstrates close relationship between the plasma malondialdehyde and nitric oxide levels, gastric histopathology and genotypes of H. pylori.