Dyslipidaemia and inflammatory markers as the risk predictors for cardiovascular disease in newly diagnosed premenopausal hypothyroid women

BackgroundHypothyroidism can predispose systolic and diastolic cardiac dysfunction, increased peripheral vascular resistance, endothelial dysfunction, altered coagulopathy, and dyslipidemia resulting in atherosclerosis. Thyroid hormones can influence homocysteine metabolism by regulating the methylenetetrahydrofolate reductase (M THR). So, this study aimed to compare the markers homocysteine, high sensitive C-reactive protein (hs-CRP), and Atherogenic Indices (AI) between newly diagnosed hypothyroid and euthyroid premenopausal women.Methods80 Female patients between 20 and 45 years were enrolled in this study and were equally divided into cases and controls group. Laboratory tests included: i) Serum T3, T4, TSH was measured using electrochemiluminescence, ii) lipid profile, homocysteine, and hs-CRP were measured for all the participants. Atherogenic indices: Castelli risk indices I&II, Atherogenic coefficient (AEC), and Atherogenic Index of Plasma (AIP) were calculated using formulas. A comparison between the study groups was made by using the Independent t-test and Mann-Whitney U test. p-value < 0.05 was considered significant.ResultsThe hypothyroid group had significantly higher levels of homocysteine (p= 0.014), and hs-CRP (hs-CRP> 3.0 mg/L, 70% of participants have intermediate to high risk for a cardiovascular event) and elevated BMI compared to participants in the euthyroid group. Atherogenic indices (p< 0.001) was significantly increased in the hypothyroid participants'' group. TC, TG , and LDL were significantly elevated in the hypothyroid group but did not show any association with systolic and diastolic blood pressure.ConclusionsPremenopausal women with hypothyroidism have a greater predisposition for cardiovascular disease compared to euthyroid     

Matrix-Metalloproteinase Inhibitory Study of Novel Tetrahydroisoquinoline-4-carboxylates: Design,Synthesis, and Molecular Docking Studies

The design, molecular docking, synthesis and structure-activity relationship (SAR) of a series of novel methyl 1-oxo-2-(propan-2-yl)-3-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylates, were investigated for antiproliferative and cytotoxic studies by screening against cancer cell lines of different origin by MTT, LDH and Trypan Blue Assay. Irrespective of cell lines, among the synthesized nonpeptido-mimetic analogs 5a – e , 5c has executed potent bio-potency with IC₅₀ value of 7.00 to 7.21 μM, which further expressed in-vivo anti-tumor activity against murine T-cell lymphoma cell lines (Daltons Lymphoma-DLA) by regressing tumor growth. The formation of neovessels from the vasculogenesis was diminished reflecting the antitumor activity. The neovessel formation is directly relied on expression of matrix meteloproteases (MMP's) level which was drastically reduced by 5c treatment as evaluated by immonoblot assays. This is further supported by in-silico ADMET studies performed by ACD I-Lab 2.0 were in agreement with Lipinski rule of five. Reporting results were assessed as a positive parameter for further validation of the compound for therapeutic potential of cancer by 5c for preclinical studies in near future.     

Structural,Morphological and Photoluminescence Studies of Pure ZrO2 and ZrO2: Eu+3 Nanophosphors Synthesised by Microwave-Assisted Hydrothermal Technique

The luminescence properties of pure and ZrO₂: Eu⁺³ nanophosphors with different concentration of the Eu⁺³ is synthesised and studied. A novel and environment benign microwave-induced hydrothermal process is used to synthesise the nanoparticles. As-formed pure ZrO₂ nanoparticles were X-ray amorphous, and upon calcination at higher temperatures, they crystallise to a combination of both cubic and tetragonal phases. However, the ZrO₂: Eu⁺³ nanophosphors prepared through the same technique under similar conditions yield exclusively cubic ZrO_2, and it entirely depends on the concentration of Eu⁺³ as revealed by XRD studies. The nanoparticles are found to be spherical, non-porous and agglomerated as observed by SEM. The surface area of the nanoparticles of pure ZrO₂ is found to be 30 m²/g for as-formed samples and 130 m²/g for calcined samples by BET studies. The increase in the surface area for calcined sample is due to the escaping of the adsorbed hydroxyl groups from the surface of the nanoparticles. The photoluminescence properties of the pure and Eu⁺³-doped ZrO₂ nanoparticles were measured under 251 nm excitation wavelength. Under this excitation, pure ZrO₂ gives the emissions at 394 nm, whereas Eu⁺³-doped nanoparticles gives the emissions at 613 nm, which corresponds to inter-f-f transition from ⁵D₀ ➔⁷F₂ (613 nm) and is arising due to electronic dipole in the Eu⁺³ activator ion. CIE colour space (x, y) coordinates corresponding to 613 nm in the CIE chromaticity diagram is 0.680, 0.319.

Graphical Abstract

     

Accelerated Evolution and Molecular Surface of Venom Phospholipase A2 Enzymes

Multiple phospholipase A₂ (PLA₂) isoenzymes found in a single snake venom induce a variety of pharmacological effects. These multiple forms are formed by gene duplication and accelerated evolution of exons. We examined the amino acid sequences of 127 snake venom PLA₂ enzymes and their homologues to study in which location most natural substitutions occur. Our data show that hot spots of amino acid substitutions in this group of proteins occur mostly on the surface. A logistic model correlating the substitution rates of each amino acid residue with their surface accessibility indicates that the probability of natural substitutions occurring in the fully exposed residue is 2.6–3.5 times greater than that of substitutions occurring in buried residues. These surface substitutions play a significant role in the evolution of new PLA₂ isoenzymes by altering the specificity of targeting to various tissues or cells, resulting in distinct pharmacological effects. Thus natural substitutions in PLA₂ enzymes, in contrast to popular belief, are not random substitutions but appear to be directed toward modifying the molecular surface. Received: 11 May 1998 / Accepted: 29 June 1998