PURPOSE: The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. MATERIALS AND METHODS: Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. RESULTS: We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. CONCLUSION: In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.
Adenosine Triphosphate ; Carcinoma, Squamous Cell* ; Cytokines ; Epithelial Cells* ; Follow-Up Studies ; Head* ; Humans ; Models, Molecular ; Neck* ; p38 Mitogen-Activated Protein Kinases ; Protein Isoforms* ; Protein Kinases ; Surface Plasmon Resonance

BACKGROUND/AIMS: The prevalence of irritable bowel syndrome (IBS) varies from 4% to 20% in different Asian nations. Prevalence of IBS in native North Indian community is not known. METHODS: Between November 2008 to December 2009, we estimated the prevalence of IBS in a rural community of Ballabgarh block, located in Haryana state. A structured questionnaire based on Rome III module was used to collect symptoms related to IBS from all the participants in a door to door survey. A Rome III criterion was used for diagnosis of IBS. IBS was further classified based on predominance of symptoms as constipation predominant, diarrhea predominant, mixed and unspecified based on Rome III module. RESULTS: There were 4,767 participants (mean age 34.6 +/- 10.8, males 50%). Overall, 555 (11.6%; 95% CI, 10.7-12.5) had constipation, 542 (11.4%; 95% CI, 10.5-12.3) diarrhea and 823 (17.3%; 95% CI, 16.2-18.4) abdominal pain. The overall prevalence of IBS was 4% (95% CI, 3.5-4.6). The prevalence of constipation predominant IBS was 0.3% (95% CI, 0.16-0.49), diarrhea predominant IBS 1.5% (95% CI, 1.18-1.90), mixed IBS 1.7% (95% CI, 1.35-2.11) and unsubtyped IBS 0.5% (95% CI, 0.32-0.75). The prevalence of IBS was significantly higher in females compared with males (4.8% vs 3.2%, P = 0.008). However, there was no significant difference between males and females in the prevalence of different subtypes of IBS. The prevalence increased with age. CONCLUSIONS: The prevalence of IBS in a North Indian community is 4%. IBS poses a significant burden on the rural adults.
Abdominal Pain ; Adult ; Asia ; Asian Continental Ancestry Group ; Constipation ; Diarrhea ; Female ; Humans ; India ; Irritable Bowel Syndrome ; Male ; Prevalence ; Surveys and Questionnaires ; Rome ; Rural Population

BACKGROUND/AIMS: To study the prevalence of somatic and psychiatric co-morbidities in the patients of irritable bowel syndrome (IBS) and to assess the quality of life (QOL) of these patients. METHODS: One hundred and eighty-four IBS patients and 198 controls were included. Diagnosis of IBS, its sub-classification and assessment of other functional gastrointestinal disorders (FGIDs) was made on basis of Rome III criteria. Severity of IBS was assessed using IBS severity scoring system. Psychiatric evaluation was done using Patient Heath Questionnaire. QOL was evaluated using WHO QOL-BREF. RESULTS: One hundred and forty-seven (79.9%) and 158 (85.9%) patients with IBS had at least one other FGID or at least one somatic co-morbidity, respectively. Higher number of patients had at least one psychiatric co-morbidity compared to controls (79.9% vs 34.3%; P < 0.001). Major depressive syndrome (47.3% vs 5.1%; P < 0.001), somatoform disorder (50% vs 14.6%; P < 0.001) and panic syndrome (44% vs 11.6%; P < 0.001) were more common in IBS than controls. Only 14 (7.6%) patients were receiving drug treatment for their psychiatric illness. Severe IBS symptoms were present in significantly higher number of patients with constipation predominant IBS than diarrhea predominant IBS. Those with severe disease had higher prevalence of psychiatric (95.1%) and somatic (96.7%) co-morbidities compared with mild disease. QOL of IBS patients was significantly lower in all four domains compared to controls. Presence of at least one other FGID was significantly associated with presence of one or more psychiatric co-morbidity (P < 0.001). CONCLUSIONS: Majority of IBS patients presenting to a tertiary care center had associated psychiatric, somatic co-morbidities and reduced QOL. Very few of them received specific psychiatric treatment.
Anxiety Disorders ; Constipation ; Depression ; Depressive Disorder ; Diarrhea ; Gastrointestinal Diseases ; Humans ; Irritable Bowel Syndrome ; Panic ; Prevalence ; Quality of Life ; Surveys and Questionnaires ; Rome ; Somatoform Disorders ; Tertiary Care Centers ; Tertiary Healthcare