Etiopathogenesis Of Several Diseases Research Articles

Optimization of a Monobromobimane (MBB) Derivatization and RP-HPLC-FLD Detection Method for Sulfur Species Measurement in Human Serum after Sulfur Inhalation Treatment.

(1) Background: Hydrogen sulfide (H2S) is a widely recognized gasotransmitter, with key roles in physiological and pathological processes. The accurate quantification of H2S and reactive sulfur species (RSS) may hold important implications for the diagnosis and prognosis of diseases. However, H2S species quantification in biological matrices is still a challenge. Among the sulfide detection methods, monobromobimane (MBB) derivatization coupled with reversed phase high-performance liquid chromatography (RP-HPLC) is one of the most reported. However, it is characterized by a complex preparation and time-consuming process, which may alter the actual H2S level; moreover, a quantitative validation has still not been described. (2) Methods: We developed and validated an improved analytical protocol for the MBB RP-HPLC method. MBB concentration, temperature and sample handling were optimized, and the calibration method was validated using leave-one-out cross-validation and tested in a clinical setting. (3) Results: The method shows high sensitivity and allows the quantification of H2S species, with a limit of detection of 0.5 µM. Finally, it can be successfully applied in measurements of H2S levels in the serum of patients subjected to inhalation with vapors rich in H2S. (4) Conclusions: These data demonstrate that the proposed method is precise and reliable for measuring H2S species in biological matrices and can be used to provide key insights into the etiopathogenesis of several diseases and sulfur-based treatments.

Resveratrol supplementation at old age reverts changes associated with aging in inflammatory, oxidative and apoptotic markers in rat heart.

Aging is known to play a critical role in the etiopathogenesis of several diseases. Among them, cardiovascular disorders are especially relevant since they are becoming the first cause of death in western countries. Resveratrol is a polyphenolic compound that has been shown to exert beneficial effects at different levels, including neuronal and cardiovascular protection. Those effects of resveratrol are related, at least in part, to its antioxidant and anti-inflammatory properties. In the current investigation we were interested in exploring whether the positive effects of resveratrol at cardiac level were taking place even when the supplementation started in already old animals. Old male rats were supplemented with resveratrol during 10weeks. Using RT-PCR, we analyzed the effects of resveratrol supplementation on the expression of different genes related to inflammation, oxidative stress and apoptosis in rat heart. Resveratrol reverted age-related changes in inflammatory, oxidative and apoptotic markers in the rat heart. Among others, the expression of two major inflammatory markers, INF-γ and TNF-α and two oxidative markers, heme oxygenase-1 and nitric oxide synthase, were increased with aging, and resveratrol supplementation reduced the level of some of these to those observed in the heart of young animals. Moreover, age-related changes in apoptotic markers in rat heart tend to be also reverted by resveratrol treatment. Our results suggest that resveratrol might exert beneficial effects as an anti-aging compound to revert age-related changes in cardiac function.

Molecular links between endocrine, nervous and immune system during chronic stress.

IntroductionThe stress response is different in various individuals, however, the mechanisms that could explain these distinct effects are not well known and the molecular correlates have been considered one at the time. Particular harmful conditions occur if the subject, instead to cope the stressful events, succumb to them, in this case, a cascade reaction happens that through different signaling causes a specific reaction named “sickness behaviour.” The aim of this article is to review the complex relations among important molecules belonging to Central nervous system (CNS), immune system (IS), and endocrine system (ES) during the chronic stress response.MethodsAfter having verified the state of art concerning the function of cortisol, norepinephrine (NE), interleukin (IL)‐1β and melatonin, we describe as they work together.ResultsWe propose a speculative hypothesis concerning the complex interplay of these signaling molecules during chronic stress, highlighting the role of IL‐1β as main biomarker of this effects, indeed, during chronic stress its increment transforms this inflammatory signal into a nervous signal (NE), in turn, this uses the ES (melatonin and cortisol) to counterbalance again IL‐1β. During cortisol resistance, a vicious loop occurs that increments all mediators, unbalancing IS, ES, and CNS networks. This IL‐1β increase would occur above all when the individual succumbs to stressful events, showing the Sickness Behaviour Symptoms. IL‐1β might, through melatonin and vice versa, determine sleep disorders too.ConclusionThe molecular links here outlined could explain how stress plays a role in etiopathogenesis of several diseases through this complex interplay.

Oxidative stress parameters in patients with prostate cancer, benign prostatic hyperplasia and asymptomatic inflammatory prostatitis: A prospective controlled study.

The imbalance between oxidant and reductant mechanisms creates a nidus for the etiopathogenesis of several diseases. In this study, we aimed to compare the oxidative stress (OS) parameters in patients who were diagnosed with prostate cancer (pCa), benign prostatic hyperplasia (BPH) or asymptomatic inflammatory prostatitis (AIP), according to the histopathologic examination of transrectal ultrasonographic prostate biopsy and transurethral prostate resection specimens. In this study, we aimed to compare oxidative stress between histologically proven prostate cancer, hyperplasia and prostatitis. According to histopathologic examinations, 97 patients were divided into 3 study groups: group 1: pCa (n = 30), group 2: BPH (n = 41), and group 3: AIP (n = 26). Finally, 30 patients were enrolled in a control group. MDA levels, CuZn-SOD, Se-GPx, CAT activities, and trace element levels were evaluated. A statistically significant difference between prostate cancer and other groups were documented in terms of MDA activity. Contrary to AIP, a statistically significant difference has also been encountered between BPH and the control group. Decreased CuZn-SOD enzyme levels were found in PCa and BPH patients without statistical significance. Increased CAT activity was also documented in PCa, BPH and AIP patients. No significant difference in GPX activity was documented between the groups, except BPH and control group. Trace element levels were low in the patients with prostate cancer and BPH when compared with the control group. Despite the data regarding OS in PCa patients, there is a paucity of data regarding BPH and especially AIP patients. Our study revealed obvious oxidative stress in BPH and PCa patients as opposed to AIP. Assessing the oxidative stress in these patients may assist in the future prevention, diagnosis and also treatment. However, the question whether the presence of OS-related parameters and drugs could be used for the diagnosis or management of prostatic diseases, needs to be addressed in future larger and better studies with a more rational basis.

Red-Emitting Ruthenium(II) and Iridium(III) Complexes as Phosphorescent Probes for Methylglyoxal in Vitro and in Vivo.

Transition-metal complexes, ruthenium(II) and iridium(III) complexes in particular, with fascinating triplet emissions are rapidly emerging as important phosphorescent dyes for application in the sensing and imaging of biological makers in live cells and organisms. In this contribution, two red-emitting transition-metal complexes, [Ru(bpy)2(DA-phen)](PF6)2 and [Ir(ppy)2(DA-phen)](PF6) (bpy = 2,2'-bipyridine, DA-phen = 4,5-diamino-1,10-phenanthroline, and ppy = 2-phenylpyridine), were designed and synthesized as phosphorescent probes for the highly sensitive and selective detection of methylglyoxal (MGO), an essential biomarker in the etiopathogenesis of several diseases. Both probes showed weak emissions in aqueous media because of the existence of an effective photoinduced-electron-transfer process, while their emissions could be remarkably enhanced upon the addition of MGO. The photophysical and electrochemical properties, as well as phosphorescent responses of the probes toward MGO, were examined. The ground- and excited-state properties of the probes and their reaction products with MGO, [Ru(bpy)2(MP-phen)](PF6)2 and [Ir(ppy)2(MP-phen)](PF6) (MP-phen = 2-methylpyrazino-1,10-phenanthroline), the sensing mechanism, and several important experimental facts were investigated and validated using density functional theory (DFT)/time-dependent DFT computations. The results indicated that the phosphorescence switch-ON is due to the elimination of electron transfer and followed the reestablishment of emissive triplet excited states. To evaluate the feasibility of [Ru(bpy)2(DA-phen)](PF6)2 and [Ir(ppy)2(DA-phen)](PF6) as bioprobes, their cytotoxicity was examined, and their applicability for visualizing intracellular and in vivo MGO was demonstrated.

Archaea prevalence in inflamed pulp tissues.

Archaea have been detected in several ecological niches of the human body such as the large intestine, skin, vagina as well as the oral cavity. At present, archaea are recognized as nonpathogenic microorganisms. However, some data indicate that they may be involved in the etiopathogenesis of several diseases, including intestinal diseases as well as oral diseases: periodontitis, peri-implantitis and endodontitis. In this study, on the basis of 16S rRNA gene sequence analysis, we examined whether archaea might be present in inflamed pulp tissues and contribute to the development of endodontic infection. In comparison, we also determined selected bacterial species associated with endodontitis. We detected archaea in 85% of infected endodontic samples. In addition, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola were present in inflamed pulp tissue samples and Treponema denticola occurred with the highest frequency (70%). Further analysis revealed the presence of methanogenic archaea in analyzed samples. Direct sequencing of archaeal 16S rRNA gene PCR products indicated the occurrence of methanogenic archaea in inflamed pulp tissues; phylogenetically most similar were Methanobrevibacter oralis and Methanobrevibacter smithii. Therefore, our results show that methanogenic archaea are present in inflamed pulp tissues and may participate in the development of endodontic infection.

139 Genetic Association Study of the IgE Immunodeficiency in Mexican Population

BackgroundPrimary immunodeficiencies (PID) are genetic diseases in which one or multiple components of the immune system, including cells (i.e. B cells, T cells, natural killer cells, phagocytes, complement components) or molecules (cytokines, chemokines, etc) are affected, leading to a low capacity to eliminate microorganisms and a high susceptibility to infection diseases. Most of the PID are multifactorial entities were the environmental and multiple genetic factor are involved. The single nucleotide polymorphisms (SNPs) analysis in case and control groups has been increasing the knowledge of the etiopathogenesis of several diseases and the opportunity to identify molecular markers useful in the clinical diagnosis.MethodsWe performed a case control study including 19 pediatric patients with IgE deficiency (5 U/mL), and 180 healthy controls. 25 SNPs distributed in the IL-13, IL-10, IL-5, IL4, FCER1B, INF γ, GM-CSF, STAT 3, GATA 3 and TIK-2 were analyzed. Genotyping was performed using sondas TaqMan. Hardy-Weinberg Equilibrium (HWE) and statistical significance were evaluated using FINETTI and STATCAL software.ResultsAll genotypes, both in cases and controls were in HWE. We documented statistically significant differences in the distribution of the SNPs located in IL-4 rs4986964, P = 0.018, OR = 14.74, IL-4R, rs18005010, P = 0.018, OR = 2.22, FCER-1B, rs556917, P = 0.00001, OR = 16.9, GM-CSF, STAT-3 and GATA-3 genes: GMFCS-130 (P = 4986964, OR = 0.22), STAT-3 rs2293152 (P = 5.06 × 10−9, OR = 6.18), GATA-3 rs2229360 (P = 0.005, OR = 13.52). The highest difference was found in the T allele of rs556917, which was more frequent in cases than controls (42.1 and 1.5%, respectively, P = 0.00001 OR = 16.907, 95% CI, 5.02-54.93). Interestingly, the C allele of 4986964 (IL-4) increased significantly in homozygote genotype (C: OR = 14.74, 95% CI, 2.38-91.234, P = 0.018 to CC OR = 29.4, 95% CI, 1.154-749.32, P = 0.002).ConclusionsOur results suggest that SNPs located in the genes involved in the IgE production are risk genetic factor to IgE immunodeficiency. Increasing of the sample size is currently to get solid conclusions.