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In the presence of cyanide and various respiratory substrates (succinate or pyruvate + malate) addition of high concentrations of lucigenin (400 μM; Luc2+) to rat liver mitochondria can induce a short-term flash of high amplitude lucigenindependent chemiluminescence (LDCL). Under conditions of cytochrome oxidase inhibition by cyanide the lucigenininduced cyanide-resistant respiration (with succinate as substrate) was not inhibited by uncouplers (FCCP) and oligomycin. Increase in transmembrane potential (Δϕ) value by stimulating F0F1-ATPase functioning (induced by addition of MgATP to the incubation medium) caused potent stimulation of the rate of cyanide-resistant respiration. At high Δϕ values (in the presence of MgATP) cyanide resistant respiration of mitochondria in the presence of succinate or malate with pyruvate was insensitive to tenoyltrifluoroacetone (TTFA) or rotenone, respectively. However, in both cases respiration was effectively inhibited by myxothiazol or antimycin A. Mechanisms responsible for induction of LDCL and cyanide resistant mitochondrial respiration differ. In contrast to cyanide-resistant respiration, generation of LDCL signal, that was suppressed only by combined addition of Complex III inhibitors, antimycin A and myxothiazol, is a strictly potential-dependent process. It is observed only under conditions of high Δϕ value generated by F0F1-ATPase functioning. The data suggest lucigenin-induced intensive generation of superoxide anion in mitochondria. Based on results of inhibitor analysis of cyanide-resistant respiration and LDCL, a two-stage mechanism of autooxidizable lucigenin cation-radical (Luc·+) formation in the respiratory chain is proposed. The first stage involves two-electron Luc2+ reduction by Complexes I and II. The second stage includes one-electron oxidation of reduced lucigenin (Luc(2e)). Reactions of Luc(2e) oxidation involve coenzyme Q-binding sites of Complex III. This results in formation of autooxidizable Luc·+ and superoxide anion generation. A new scheme for lucigenin-dependent electron pathways is proposed. It includes formation of fully reduced form of lucigenin and two-electron-transferring shunts of the respiratory chain. Lucigenin-induced activation of superoxide anion formation in mitochondria is accompanied by increase in ion permeability of the inner mitochondrial membrane. [ABSTRACT FROM AUTHOR]

: ObjectivesOur aim was to corroborate the observed association between the deletion/deletion (DD) genotype of the insertion/deletion polymorphism in the alpha2B-adrenoceptor (AR) and increased risk for acute myocardial infarction (AMI), and to study whether this genotype also confers an increased risk for sudden cardiac death (SCD).: BackgroundVasospasm has been suggested to play a role in AMI. Alpha2-AR mediate coronary vasoconstriction in humans, and studies on mice suggest the involvement of the alpha2-AR subtype B in vasoconstriction. A deletion variant of the human alpha2B-AR has been associated with impaired receptor desensitization in vitro. In a population-based prospective study of 912 middle-aged men, the DD genotype of the alpha2B-AR conferred an increased risk for AMI.: MethodsA series of 700 unselected sudden out-of-hospital deaths of middle-aged white men subjected to medico-legal autopsy was analyzed.: ResultsGenotype information was obtained for 683 men (DD = 22%, insertion/deletion = 51%, insertion/insertion = 27%). Carriers of the DD genotype had an increased risk for SCD (n = 278, odds ratio [OR] = 2.0, p = 0.01) and fatal AMI (n = 84, OR = 2.1, p = 0.04) compared with the other two genotypes combined. The risks for SCD and fatal AMI were higher in carriers of the DD genotype who died before the age of 55 years (OR = 4.5 and 5.0, p < 0.001 for both).: ConclusionsMiddle-aged white men carrying the DD genotype of the alpha2B-AR have a significantly increased risk for SCD and AMI, especially before the age of 55 years. [Copyright &y& Elsevier]

We describe the properties of npq4-9, a new mutant of Arabidopsis thaliana (L.) Heynh. with reduced nonphotochemical quenching (NPQ) capacity that possesses a single amino acid substitution in the PsbS gene encoding PSII-S, a ubiquitous pigment-binding protein associated with photosystem II (PSII) of higher plants. Growth, photosynthetic pigment contents, and levels of the major PSII antenna proteins were not affected by npq4-9. Although the extent of de-epoxidation of violaxanthin to antheraxanthin plus zeaxanthin for leaves displaying the mutant phenotype equaled or exceeded that observed for the wild type, the relative effectiveness of de-epoxidized xanthophylls in promoting NPQ was consistently lower for the mutant. Energy partitioning in PSII was analyzed in terms of the competition for singlet chlorophyll a among the processes of fluorescence, thermal dissipation, and photochemistry. The key processes of NPQ and photochemistry in open PSII centers are represented by the relative in vivo rate constants kN and kP0, respectively. The magnitude of kP0 in normal leaves declined only slightly with increasing kN, consistent with localization of NPQ primarily in the antenna complex. Conversely, a highly significant linear decline in kP0 with increasing kN was observed for the mutant, consistent with a role for the PSII reaction center in the NPQ mechanism. Although the PSII absorption cross-section for white light was not significantly different relative to that of the wild type, PSII quantum yield was significantly lower in the mutant. The resulting lower capacity for linear electron transport in the mutant primarily affected reduction of terminal acceptors other than CO2. Parallel measurements of fluorescence and in vivo absorbance at 820 nm indicated a consistently higher steady-state level of reduction of PSII acceptors and accumulation of P700+ for the mutant. This suggests that inter-photosystem electron transport in the mutant is restricted either by a higher transthylakoid ΔpH or by diminished accessibility to reduced plastoquinone. [ABSTRACT FROM AUTHOR]

Mammalian vestibular maculae are anatomically organized for complex parallel processing of linear acceleration information. Anatomical findings in rat maculae are provided in order to underscore this complexity, which is little understood functionally. This report emphasizes that a synthetic approach is critical to understanding how maculae function and the kind of information they conduct to the brain. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to determine if there is an association of different gene polymorphisms of renin-angiotensin system and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) in St Petersburg population. Patients and methods: We examined 156 patients (the mean age 49 ±8 years) with mild-to-moderate EH recruited from the general population of the outpatient clinic. Left ventricular mass was measured by echocardiography and left ventricular mass index (LVMI) was calculated. Subjects were genotyped for I/D polymorphism of the angiotensin-converting enzyme (ACE) gene, A1166C polymorphism of renin-of the AT1 receptor gene, M235T polymorphism of angiotensinogen gene and-6G/A polymorphism of its promoter region. Results: Genotype distribution of the sample obeyed Hardy-Weinberg equilibrium and was comparable to that reported previously for hypertensive individuals. Groups of patients with II, ID and DD polymorphism of ACE gene did not differ significantly in their LVMI levels. Furthermore, neither ID ACE-gene polymorphism nor AT1-receptor gene and angiotensinogen gene polymorphism was associated with LVH. Additionally, no any significant gene-gene interactions were found to be associated with LVH in the group studied. Conclusions: In the light of these observations it seems reasonable to make a preliminary conclusion about lack of association between LVH and distinct polymorphisms of renin-angiotensin system genes in the population studied. [ABSTRACT FROM AUTHOR]

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18119 patients were screened and 15314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m[sup 2], coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease. [ABSTRACT FROM AUTHOR]

A new quantitative determination of proteins using 2-(8hydroxy-3,6-dislpho-1-naphthylazo)-1,8-dihydroxynapphthalene-3,6-disu lphonic acid (Beryllon II) by Rayleigh Light Scattering (RLS) has been developed. Under weak acidic condition (pH 3.80) proteins can enhance the weak RLS of Beryllon greatly and quantitatively at 380nm. This method is characterized with very high sensitivity, wide linear range of determination (0.10-32.40 μg m1[SUP-1] for bovine serum albumin), rapidity, and simplicity (one step and common fluorimeter). There is little or no interference from amino acids, most of the metal ions or other coexistent substances. The method was applied to the determination of protein in human plasma and the results are very close to those of the Coomassie Brilliant Blue method assay (CBB method). [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) within the brain is involved in central blood pressure regulation. Biochemical and neurophysiological studies suggest that the brain system is regulated independently of the peripheral RAS and that the system may also contribute to blood pressure control and body fluid homeostasis. In addition, circulating angiotensin II can exert some of its actions through the stimulation of angiotensin subtype 1 (AT[sub 1]) and subtype 2 (AT[sub 2]) receptors within the brain. As in peripheral tissues, the AT[sub 1] receptor mediates the central actions of angiotensin II on osmotic control and blood pressure regulation. The AT[sub 2] receptor appears to be involved in brain development and neuronal regeneration, but may also modulate some effects of central AT[sub 1] receptor stimulation. Selective non-peptide antagonists of the AT[sub 1] receptor have been shown to inhibit not only peripheral, but also central AT[sub 1] receptors after systemic application. In animal models, treatment with AT[sub 1] receptor antagonists proved to be beneficial with respect to stroke incidence and outcome. Other animal studies have shown that the AT[sub 1] receptor antagonists enable endogenous angiotensin II to stimulate nerve generation via AT[sub 2] receptors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the predictive value of Immunohistochemical p53 cut-off scores as an adjunct to routine histopathology for better diagnosis of cervical lesions., Materials and Methods: Prospective study carried out for 1 year. After ethical approval and informed consent, a total of 100 cervical tissue samples were analyzed; chronic cervicitis (CC)-15, cervical intraepithelial neoplasia (CIN)-40, and squamous cell carcinoma cervix (SCC)-45 (FIGO 2018 clinical staging). After routine processing of tissue specimen, hematoxylin and eosin (HE) staining was done. Grading of cervical precancerous lesions (CIN) was done as per World Health Organisation criteria as CIN 1,2 or 3. Broder's grading was assigned for every SCC sample., Results: Mean p53 scores of CC, CIN, and SCC cases were 0.0, 1.70, and 4.38, respectively, CIN 1, 2, and 3 were 1.07, 1.63, and 2.22, respectively. SCC was differentiated from CIN3 with p53 ≥4.5 as predictor for SCC, sensitivity and specificity were 57.8% and 88.9%, respectively. Overall diagnostic accuracy of the proposed scoring system for differentiating CC, CIN, and SCC was 61%, while the accuracy of previous methods of interpreting p53 immunoreactivity as immunoscore >2 or arbitrary cut-off of >10% cells with nuclear positivity was only 48%., Conclusion: ROC-derived immunoscore cut-offs can provide the much-needed objectivity and optimal decision thresholds to immunohistochemistry interpretation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 International Journal of Applied and Basic Medical Research.)

Expression of HLA class II molecules on thyrocytes is a characteristic feature of autoimmune thyroid disease and may lead the thyroid cells to present autoantigens to CD4+ T lymphocytes. Since HLA-DM is a critical molecule in class II-restricted antigen processing and presentation, we assessed the expression of HLA-DMB, -invariant chain (Ii), class II transactivator (CIITA) and DRA in an untransformed, pure thyrocyte strain HTV-59A. Here we report that both HLA-DMB mRNA and the protein are expressed in thyrocytes and that CIITA expression is enhanced by interferon-gamma (IFN-γ) treatment and occurs before DMB, Ii and DRA up-regulation, suggesting CIITA expression is a requirement for antigen processing in thyrocytes. These results indicate that thyrocytes are capable of antigen processing and possibly antigen presentation to T cells. [ABSTRACT FROM AUTHOR]