Atrophy and Inflammatory Changes in Salivary Glands Induced by Oxidative Stress after Exposure to Drugs and Other Chemical Substances: A Systematic Review.

Background and Objectives: Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. Materials and Methods: A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. Results: Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. Conclusions: Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.

A Retrospective Clinical Trial Regarding Oral Rehabilitation Diagnosis Strategies Based on Stomatognathic System Pathology.

INTRODUCTION: Orofacial pain is a common occurrence in daily dental practice; it is frequently attributed to temporomandibular dysfunction, one of its major causes, followed by pathology of the salivary glands, without avoiding interference at the level of the pain pathways caused by complications of periodontal pathology. The main objective of this study is to identify an important cause of pain in the oral-maxillofacial territory by quantifying the changes at the salivary glandular level using stereological methods. The secondary objective of the present research is to identify the implications of periodontal changes as a consequence of salivary quantitative and qualitative changes, quantified using periodontal indices, on the balance of the temporomandibular joint, dysfunction of it being an important cause of facial pain and having a profound impact on the complex oral rehabilitation algorithm of each clinical case, a condition evaluated with the analysis of the results of the Souleroy questionnaire. MATERIAL AND METHODS: In a retrospective study, we evaluated the clinical results obtained after applying complex rehabilitation treatment to 35 subjects, 20 women and 15 men with salivary and TMJ dysfunctions, selected between 2020 and 2021 from the Clinic of Maxillofacial Surgery, Iasi. RESULTS AND DISCUSSION: The most common symptoms of temporomandibular disorders (TMDs) that were identified through the Souleroy questionnaire were pain and different types of damage to the masticatory muscles. The most significant changes in elders are reported in the case of serous cells, which reduced their percentage volume from 46.7% to 37.4%. CONCLUSION: As regards stereological analysis in conjunction with histological images, there were significant changes in diameters, perimeters, and longitudinal axes in the adult patients as opposed to the elderly patients, which were also influenced by the type of pathology at this level. The scores recorded on the diagnostic Souleroy scale indicated a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3.

A male-derived nonribosomal peptide pheromone controls female schistosome development.

Schistosomes cause morbidity and death throughout the developing world due to the massive numbers of eggs female worms deposit into the blood of their host. Studies dating back to the 1920s show that female schistosomes rely on constant physical contact with a male worm both to become and remain sexually mature; however, the molecular details governing this process remain elusive. Here, we uncover a nonribosomal peptide synthetase that is induced in male worms upon pairing with a female and find that it is essential for the ability of male worms to stimulate female development. We demonstrate that this enzyme generates ß-alanyl-tryptamine that is released by paired male worms. Furthermore, synthetic ß-alanyl-tryptamine can replace male worms to stimulate female sexual development and egg laying. These data reveal that peptide-based pheromone signaling controls female schistosome sexual maturation, suggesting avenues for therapeutic intervention and uncovering a role for nonribosomal peptides as metazoan signaling molecules.

Alpha1a-Adrenoceptor Genetic Variant Triggers Vascular Smooth Muscle Cell Hyperproliferation and Agonist Induced Hypertrophy via EGFR Transactivation Pathway.

α1a Adrenergic receptors (α1aARs) are the predominant AR subtype in human vascular smooth muscle cells (SMCs). α1aARs in resistance vessels are crucial in the control of blood pressure, yet the impact of naturally occurring human α1aAR genetic variants in cardiovascular disorders remains poorly understood. To this end, we present novel findings demonstrating that 3D cultures of vascular SMCs expressing human α1aAR-247R (247R) genetic variant demonstrate significantly increased SMC contractility compared with cells expressing the α1aAR-WT (WT) receptor. Stable expression of 247R genetic variant also triggers MMP/EGFR-transactivation dependent serum- and agonist-independent (constitutive) hyperproliferation and agonist-dependent hypertrophy of SMCs. Agonist stimulation reduces contractility Using pathway-specific inhibitors we determined that the observed hyperproliferation of 247R-expressing cells is triggered via ß-arrestin1/Src/MMP-2/EGFR/ERK-dependent mechanism. MMP-2-specific siRNA inhibited 247R-triggered hyperproliferation indicating MMP-2 involvement in 247R-triggered hyperproliferation in SMCs. ß-arrestin1-specific shRNA also inhibited 247R-triggered hyperproliferation but did not affect hypertrophy in 247R-expressing SMCs, indicating that agonist-dependent hypertrophy is independent of ß-arrestin1. Our data reveal that in different cardiovascular cells the same human receptor genetic variant can activate alternative modulators of the same signaling pathway. Thus, our findings in SMCs demonstrate that depending on the type of cells expressing the same receptor (or receptor variant), different target-specific inhibitors could be used to modulate aberrant hyperproliferative or hypertrophic pathways in order to restore normal phenotype.

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways.

The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition. We demonstrate that constitutive, synergistic activation of EGFR, Src and ERK kinases is the potential molecular mechanism of this transition. We also demonstrate that 247R triggers two distinct EGFR transactivation-dependent signaling pathways: 1) constitutive Gq-independent ß-arrestin-1/Src/MMP/EGFR/ERK-dependent hyperproliferation and 2) agonist-induced Gq- and EGFR/STAT-dependent hypertrophy. Interestingly, in cardiomyoblasts agonist-independent hyperproliferation is MMP-dependent, but in fibroblast-like cells it is MMP-independent, suggesting that expression of α1aAR genetic variant in cardiomyocytes may trigger extracellular matrix remodeling. Thus, these novel findings demonstrate that EGFR transactivation by α1aAR-247R leads to hyperproliferation, hypertrophy and alterations in cardiomyoblasts, suggesting that these unique genetically-mediated alterations in signaling pathways and cellular function may lead to myocardial fibrosis. Such extracellular matrix remodeling may contribute to the genesis of arrhythmias in certain types of heart failure.

Blood plasma and saliva levels of magnesium and other bivalent cations in patients with parotid gland tumors.

The plasma and saliva cations in parotid malignant tumors of stages II-III were studied in 31 patients before surgical therapy and in 27 control group volunteers. The magnesium (t-Mg), calcium (t-Ca), copper (t-Cu) and zinc (t-Zn) concentrations in plasma were determined, and t-Mg and t-Ca in saliva. Our results showed that salivary and plasma t-Mg concentrations were significantly higher in patients with parotid malignant tumors in comparison to control group (saliva: 0.25 +/- 0.04 mmol/L versus 0.14 +/- 0.03/L, p < 0.01; plasma: 1.05 +/- 0.06 mmol/L versus 0.86 +/- 0.05 mmol/L, p < 0.05). The t-Ca plasma concentrations were lower for patients with parotid malignant tumors by 20-22% in comparison to the control group (p < 0.05). Plasma and salivary t-Mg/t-Ca molar ratios are respectively 0.38 and 0.12 for control group, and respectively 0.61 and 0.31 for patients with parotid gland tumors. The t-Zn plasma concentration for patients with parotid malignant tumors (0.017 +/- 0.010 mmol/L) was significantly lower (p < 0.05) in comparison to control group (0.024 +/- 0.011 mmol/L). Plasma t-Cu/t-Zn molar ratio is respectively 0.68 for control group and 1.12 for patients with parotid gland tumors. The mechanism responsible for the increase of salivary magnesium as a consequence of the development of tumoral tissue needs to be clarified.

[Oral modifications during menopause]. / Modificari orale la menopauza.

The menopause, a physiological process specific to elderly women (>50 years) is defined by various involutive phenomena occurred at general level and particularly in the stomatognatic system elements. The authors followed the influence of the oral contraceptives in changes of oral tissues during menopause. The study was carried on 148 elderly women during menopause split in two groups: group I (study group) who have used oral contraceptives in earlier years, group II (control group) without contraceptive therapy. The evaluation of the results was made using clinical exams and complementary investigations (X-ray, cytological, histopathological, mycological, salivary rate exams) and index quantification. The results showed the importance of the apparition of changes in to the oral tissues during menopause increased in comparison to the control group. Corresponding prevention strategies are the basis of oral health management in women at menopause.