Lipid profile in oral submucous fibrosis

<p>Abstract</p> <p>Background</p> <p>Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption.</p> <p>Materials and methods</p> <p>In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed.</p> <p>Results</p> <p>A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF.</p> <p>Conclusion</p> <p>The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.</p

PHYTOCHEMICAL STANDARDIZATION AND ANTIOXIDANT POTENTIAL OF AYURVEDA FORMULATION DARVYADI RASKRIYA

The study represents phytochemical standardization and antioxidant potential of ayurveda formulation Darvyadi Raskriya. The study involves development of high-performance thin-layer chromatographic (HPTLC) method for analysis of formulation. The study utilizes analysis of glycyrrhizin in formulation which is the phytoconstituent of Glycyrrhiza glabra one of the component of formulation. The sample in ethanol was applied on aluminium TLC plates using Linomat 5 spray (CAMAG). Linear ascending development was performed in twin trough glass chamber saturated with mobile phase. The mobile phase consisted of ethyl acetate-methanol-formic acid (10:5:1 v/v/v). The spectrodensitometric detection was performed at the wavelength of 254 nm. The regression analysis was found to be linear with r2=0.997 in the concentration range 5-25 ppm. The antioxidant activity of formulation was also found to be significant as compared to control. Keywords: Standardization, Glycyrrhiza glabra, Glycyrrhizin, HPTLC, Antioxidant

Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading

<p>Abstract</p> <p>Background</p> <p>Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor.</p> <p>Methods</p> <p>In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated.</p> <p>Results</p> <p>The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma.</p> <p>Conclusion</p> <p>The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.</p

Doses to internal organs for various breast radiation techniques - implications on the risk of secondary cancers and cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Breast cancers are more frequently diagnosed at an early stage and currently have improved long term outcomes. Late normal tissue complications induced by adjuvant radiotherapy like secondary cancers or cardiomyopathy must now be avoided at all cost. Several new breast radiotherapy techniques have been developed and this work aims at comparing the scatter doses of internal organs for those techniques.</p> <p>Methods</p> <p>A CT-scan of a typical early stage left breast cancer patient was used to describe a realistic anthropomorphic phantom in the MCNP Monte Carlo code. Dose tally detectors were placed in breasts, the heart, the ipsilateral lung, and the spleen. Five irradiation techniques were simulated: whole breast radiotherapy 50 Gy in 25 fractions using physical wedge or breast IMRT, 3D-CRT partial breast radiotherapy 38.5 Gy in 10 fractions, HDR brachytherapy delivering 34 Gy in 10 treatments, or Permanent Breast ¹⁰³Pd Seed Implant delivering 90 Gy.</p> <p>Results</p> <p>For external beam radiotherapy the wedge compensation technique yielded the largest doses to internal organs like the spleen or the heart, respectively 2,300 mSv and 2.7 Gy. Smaller scatter dose are induced using breast IMRT, respectively 810 mSv and 1.1 Gy, or 3D-CRT partial breast irradiation, respectively 130 mSv and 0.7 Gy. Dose to the lung is also smaller for IMRT and 3D-CRT compared to the wedge technique. For multicatheter HDR brachytherapy a large dose is delivered to the heart, 3.6 Gy, the spleen receives 1,171 mSv and the lung receives 2,471 mSv. These values are 44% higher in case of a balloon catheter. In contrast, breast seeds implant is associated with low dose to most internal organs.</p> <p>Conclusions</p> <p>The present data support the use of breast IMRT or virtual wedge technique instead of physical wedges for whole breast radiotherapy. Regarding partial breast irradiation techniques, low energy source brachytherapy and external beam 3D-CRT appear safer than ¹⁹²Ir HDR techniques.</p

Synergistic effect of stromelysin-1 (matrix metalloproteinase-3) promoter (-1171 5A->6A) polymorphism in oral submucous fibrosis and head and neck lesions

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions.</p> <p>Methods</p> <p>MMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age.</p> <p>Results</p> <p>Analysis of MMP 3 (-1171 5A->6A) polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1.22-4.20) and in controls (5A genotype frequency 0.07) as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51) and controls (5A genotype frequency = 0.07) In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26) and nearly the same in case of HNSCC (OR = 1.94) as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age.</p> <p>Conclusions</p> <p>This study concluded that the expression of MMP-3 genotype associated with the 5A alleles, it may have an important role in the susceptibility of the patients to develop OSMF and HNSCC.</p

Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in <it>NOD1 </it>gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of <it>NOD1 </it>gene in context to Indian population.</p> <p>Methods</p> <p>A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of <it>NOD1 </it>gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's χ²test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12.</p> <p>Results</p> <p>We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of <it>NOD1 </it>gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, <it>p </it>= 0.002; L349P, <it>p </it>= 0.002 and L370R, <it>p </it>= 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg²⁺binding sites. No significant association was observed within different sub phenotypes.</p> <p>Conclusion</p> <p>We propose that the location of mutations in the Exon 6 spanning the ATP and Mg²⁺binding site of NBD in <it>NOD1 </it>gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility.</p

3D Echo systematically underestimates right ventricular volumes compared to cardiovascular magnetic resonance in adult congenital heart disease patients with moderate or severe RV dilatation

<p>Abstract</p> <p>Background</p> <p>Three dimensional echo is a relatively new technique which may offer a rapid alternative for the examination of the right heart. However its role in patients with non-standard ventricular size or anatomy is unclear. This study compared volumetric measurements of the right ventricle in 25 patients with adult congenital heart disease using both cardiovascular magnetic resonance (CMR) and three dimensional echocardiography.</p> <p>Methods</p> <p>Patients were grouped by diagnosis into those expected to have normal or near-normal RV size (patients with repaired coarctation of the aorta) and patients expected to have moderate or worse RV enlargement (patients with repaired tetralogy of Fallot or transposition of the great arteries). Right ventricular end diastolic volume, end systolic volume and ejection fraction were compared using both methods with CMR regarded as the reference standard</p> <p>Results</p> <p>Bland-Altman analysis of the 25 patients demonstrated that for both RV EDV and RV ESV, there was a significant and systematic under-estimation of volume by 3D echo compared to CMR. This bias led to a mean underestimation of RV EDV by -34% (95%CI: -91% to + 23%). The degree of underestimation was more marked for RV ESV with a bias of -42% (95%CI: -117% to + 32%). There was also a tendency to overestimate RV EF by 3D echo with a bias of approximately 13% (95% CI -52% to +27%).</p> <p>Conclusions</p> <p>Statistically significant and clinically meaningful differences in volumetric measurements were observed between the two techniques. Three dimensional echocardiography does not appear ready for routine clinical use in RV assessment in congenital heart disease patients with more than mild RV dilatation at the current time.</p

Evolutionary Rate Covariation Identifies New Members of a Protein Network Required for Drosophila melanogaster Female Post-Mating Responses

Seminal fluid proteins transferred from males to females during copulation are required for full fertility and can exert dramatic effects on female physiology and behavior. In Drosophila melanogaster, the seminal protein sex peptide (SP) affects mated females by increasing egg production and decreasing receptivity to courtship. These behavioral changes persist for several days because SP binds to sperm that are stored in the female. SP is then gradually released, allowing it to interact with its female-expressed receptor. The binding of SP to sperm requires five additional seminal proteins, which act together in a network. Hundreds of uncharacterized male and female proteins have been identified in this species, but individually screening each protein for network function would present a logistical challenge. To prioritize the screening of these proteins for involvement in the SP network, we used a comparative genomic method to identify candidate proteins whose evolutionary rates across the Drosophila phylogeny co-vary with those of the SP network proteins. Subsequent functional testing of 18 co-varying candidates by RNA interference identified three male seminal proteins and three female reproductive tract proteins that are each required for the long-term persistence of SP responses in females. Molecular genetic analysis showed the three new male proteins are required for the transfer of other network proteins to females and for SP to become bound to sperm that are stored in mated females. The three female proteins, in contrast, act downstream of SP binding and sperm storage. These findings expand the number of seminal proteins required for SP's actions in the female and show that multiple female proteins are necessary for the SP response. Furthermore, our functional analyses demonstrate that evolutionary rate covariation is a valuable predictive tool for identifying candidate members of interacting protein networks. © 2014 Findlay et al

Predictors of early recurrence after resection of colorectal liver metastases

BACKGROUND: Early recurrence after resection of colorectal liver metastases (CLM) is common. Patients at risk of early recurrence may be candidates for enhanced preoperative staging and/or earlier postoperative imaging. The aim of this study was to determine if there are any risk factors that specifically predict early liver-only and systemic recurrence. METHODS: Retrospective analysis of prospective database of patients undergoing liver resection (LR) for CLM from 2004 to 2006 was undertaken. Early recurrence was defined as occurring within 18 months of LR. Patients were classified into three groups: early liver-only recurrence, early systemic recurrence and recurrence-free. Preoperative factors were compared between patients with and without early recurrence. RESULTS: Two hundred and forty-three consecutive patients underwent LR for CLM. Twenty-seven patients (11%) developed early liver-only recurrence. Dukes C stage and male sex were significantly associated with early liver-only recurrence (P < 0.05). Sixty-six patients (27%) developed early systemic recurrence. Tumour size ≥3.6 cm and tumour number (>2) were significantly associated with early systemic recurrence (P < 0.001). CONCLUSIONS: It is possible to stratify patients according to the risk of early liver-only or systemic recurrence after resection of CLM. High-risk patients may be candidates for preoperative MRI and/or computed tomography-positron emission tomography (CT-PET) scan and should receive intensive postoperative surveillance

The Neuropeptide PDF Acts Directly on Evening Pacemaker Neurons to Regulate Multiple Features of Circadian Behavior

Animals use distinct sets of clock neurons to time behaviors in the morning and evening. In this article, the direct neural targets for morning neurons and the neuropeptide pigment dispersing factor are revealed in the fruit fly