Evaluation of maternal serum levels of cell adhesion molecules and endothelial inflammatory markers in normal pregnancy, gestational hypertension and pre-eclampsia

Background: Hypertensive disorders complicate 5 to 10% of all pregnancies. Despite the still unexplained pathogenesis, endothelial dysfunctions and inflammatory mediators are thought to be responsible for the pathogenesis gestational hypertension and pre-eclampsia. Aims and objective of the study was to determine the serum levels of cell adhesions molecules - VCAM-1 and ICAM-1 and endothelial inflammatory markers TNF-α and homocysteine in normal pregnancies, Gestational Hypertension and in Pre-eclampsiaMethods: The cross-sectional study was carried out in Department of Obstetrics and Gynecology and Biochemistry, ESI-PGIMSR, New Delhi between October 2013-April 2015. 150 patients who gave informed written consent were enrolled and were divided equally in three groups of 50 each (normotensive, gestational hypertensive and pre-eclamptic patients). Three groups have been compared in terms of variables such as age, BMI, gestational age, systolic and diastolic blood pressure, platelet count, AST, ALT, mode of delivery, neonatal weight, VCAM-I, ICAM-I, homocysteine and TNF-alpha concentrations.Results: We found the higher concentrations of vascular cell adhesions molecules (VCAM-1 and ICAM-1) and inflammatory mediators (homocysteine and TNF α) in gestational hypertensive patients and in pre-eclamptic patients. Out of four markers, concentrations of ICAM-1 was found in largest proportions and it was also statistical significant. P value was <0.001. Though in our study concentration VCAM-1, homocysteine and TNF-α were also high in gestational hypertensive groups as compared with normotensive patients, but they were not statistical significant.Conclusions: We conclude that higher concentrations of vascular cell adhesions molecules and inflammatory mediators may be responsible for hypertensive disorders of pregnancy suggesting the role of endothelial dysfunction as a central pathogenic feature in development of preeclampsia

Tissue engineering applications in periodontics: Alternate god

"Tissue engineering" also referred as regenerative medicine indicates a new interdisciplinary initiative, which has the goal of growing tissues or organs directly from a single cell taken from an individual. Originally coined to denote the construction in the laboratory of a device containing viable cells and biologic mediators in a synthetic or biologic matrix that could be implanted in patients to facilitate regeneration. However, the term has crept into clinical armory of periodontists and has attained certain halo and glamour even when used in mundane and prosaic situations. Thus, this paper critically evaluates its role and application in clinical scenario

Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision

Identification of Ser/Thr kinase and Forkhead Associated Domains in <i>Mycobacterium ulcerans:</i> Characterization of Novel Association between Protein Kinase Q and MupFHA

<div><p>Background</p><p><i>Mycobacterium ulcerans</i>, the causative agent of Buruli ulcer in humans, is unique among the members of <i>Mycobacterium</i> genus due to the presence of the virulence determinant megaplasmid pMUM001. This plasmid encodes multiple virulence-associated genes, including <i>mup011</i>, which is an uncharacterized Ser/Thr protein kinase (STPK) PknQ.</p><p>Methodology/Principal Findings</p><p>In this study, we have characterized PknQ and explored its interaction with MupFHA (Mup018c), a FHA domain containing protein also encoded by pMUM001. MupFHA was found to interact with PknQ and suppress its autophosphorylation. Subsequent protein-protein docking and molecular dynamic simulation analyses showed that this interaction involves the FHA domain of MupFHA and PknQ activation loop residues Ser¹⁷⁰ and Thr¹⁷⁴. FHA domains are known to recognize phosphothreonine residues, and therefore, MupFHA may be acting as one of the few unusual FHA-domain having overlapping specificity. Additionally, we elucidated the PknQ-dependent regulation of MupDivIVA (Mup012c), which is a DivIVA domain containing protein encoded by pMUM001. MupDivIVA interacts with MupFHA and this interaction may also involve phospho-threonine/serine residues of MupDivIVA.</p><p>Conclusions/Significance</p><p>Together, these results describe novel signaling mechanisms in <i>M. ulcerans</i> and show a three-way regulation of PknQ, MupFHA, and MupDivIVA. FHA domains have been considered to be only pThr specific and our results indicate a novel mechanism of pSer as well as pThr interaction exhibited by MupFHA. These results signify the need of further re-evaluating the FHA domain –pThr/pSer interaction model. MupFHA may serve as the ideal candidate for structural studies on this unique class of modular enzymes.</p></div

Docking analysis of PknQ with MupFHA domain.

<p>(<b>A</b>) Homology modeling derived structural models showing docking of wild-type PknQ (stick diagram) with the wild-type FHA domain variable loop region of MupFHA (green ribbon diagram). Phosphate group (orange) has been added to Ser¹⁷⁰ and Thr¹⁷⁴ of PknQ and the phosphorylated residues have been renamed as Sep170 and Tpo174, respectively. The red encircled region of interaction has been enlarged in (<b>B</b>). The residues Arg⁴¹, Arg⁵³, Ser⁵⁵, Arg⁵⁶ and Ser⁷⁵ of MupFHA show stable interactions with the PknQ activation loop and form H-bonds with the negatively charged pSer¹⁷⁰ (Sep170) and pThr¹⁷⁴ (Tpo174). (<b>C</b>) Enlarged region of interaction between PknQ-pThr¹⁷⁴ and MupFHA. Canonical interaction of pThr¹⁷⁴ is observed showing H-bonds with Arg⁵³, Ser⁵⁵ and Ser⁷⁵ of MupFHA (see text). (<b>D</b>) Enlarged region of interaction between PknQ-pSer¹⁷⁰ and MupFHA. PknQ-pSer¹⁷⁰ is shown to be anchored by the residues Arg⁴¹ and Arg⁵⁶ of MupFHA. (<b>E</b>) Region of interaction between PknQ-pThr¹⁷⁴ and MupFHA^S55A (in red stick). (<b>F</b>) Region of interaction between PknQ-pSer¹⁷⁰ and MupFHA^R41A (in red stick). Both (E) and (F) show the loss of H-bond network and thus destabilized interaction between PknQ and MupFHA.</p

<i>In silico</i> analysis of <i>M. ulcerans</i> STPKs.

<p>(<b>A</b>) Genomic alignment of <i>M. ulcerans</i> STPKs showing conserved patterns (NCBI). Genetic patterns show twelve STPKs present in the chromosome in addition to one STPK, PknQ, which is encoded by the virulence-associated plasmid pMUM001. (<b>B</b>) Phylogenetic analysis of all <i>M. ulcerans</i> STPKs. The phylogenetic tree was generated using protein FASTA sequences of <i>M. ulcerans</i> STPKs in Phylip. PknQ clearly belongs to the PknF/PknI/Mul_2200 clade.</p