Diversity of clinical, radiographic and genealogical findings in 41 families with amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. OBJECTIVE: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. MATERIAL AND METHODS: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. RESULTS: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. CONCLUSION: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.

Diversity of clinical, radiographic and genealogical findings in 41 families with amelogenesis imperfecta

Abstract Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. Objective: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. Material and Methods: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. Results: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. Conclusion: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.

Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism.

Melatonin, an endogenous hormone, is used as an antioxidant drug in doses quite higher than the endogenous circulating levels of this hormone. Hepatic endoplasmic reticulum contains the cytochrome P450 (CYP450) system, which catalyzes one biotransformation pathway of melatonin; this organelle is also one of the main sources of reactive oxygen species in cells. Therefore, we proposed that the antioxidant activity of this hormone may have a biological relevance in the organelle where it is biotransformed. To evaluate this postulate, we used Fe(3+)/ascorbate, an oxygen free radical generating system that leads to lipid peroxidation, loss of protein-thiol content, and activation of UDP-glucuronyltransferase in rat liver microsomes. We found that mM concentrations of melatonin prevented all these oxidative phenomena. We also found that Fe(3+)/ascorbate leads to structural alterations in the CYP450 monooxygenase, the enzyme that binds the substrate in the CYP450 system catalytic cycle, probably through direct oxidation of the protein, and also inhibited p-nitroanisole O-demethylation, a reaction catalyzed by the CYP450 system. Notably, melatonin prevented both phenomena at microM concentrations. We provide evidence suggesting that melatonin may be oxidized by oxygen free radicals. Thus, we postulate that melatonin may be acting as an oxygen free radical scavenger, and Fe(3+)/ascorbate-modified melatonin would be directly protecting the CYP450 system through an additional specific mechanism. Pharmacological relevance of this phenomenon is discussed.

Comparative effects of superoxide anion and hydrogen peroxide on microsomal and cytosolic glutathione S-transferase activities of rat liver.

Glutathione S-transferases (GSTs) are isoenzymes occurring in the cytoplasm and as integral membrane proteins. In addition to their role in drug metabolism by conjugating electrophilic and lipophilic compounds with glutathione (GSH), these enzymes display multiple functions in cells, including antioxidant action. It has been generalized that reactive oxygen species (ROS) inhibit cytosolic GSTs and activate microsomal GSTs; some evidence shows, however, that different ROS-generating systems can inhibit microsomal GST activity. We therefore tested the effect of Fe3+/ascorbate, another ROS-generating system, on cytosolic and microsomal GST activities from rat liver cytosol and microsomes, respectively, and compared it to that of hydrogen peroxide (H2O2). We found that, while both agents displayed similar inhibitory effects on cytosolic GST activity, they promoted opposite effects on microsomal GST activity. Using specific antioxidant enzymes, we corroborated that the effect of Fe3+/ascorbate involves generation of O2(.-) without dismutation into H2O2. Since these ROS have physicochemical properties and redox potentials that are very distinct, their reactivity is different, and their oxidative action is likely to have different targets. We discuss how these properties are related with the oxidative potency of ROS, especially those of O2(.-) and H2O2.

DPPH and oxygen free radicals as pro-oxidant of biomolecules.

Numerous investigations exist about the alterations that oxygen free radicals can provoke on biomolecules; these modifications can be prevented and/or reversed by different antioxidants agents. On the other hand, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), a stable nitrogen synthetic radical, is used to evaluate the antioxidant capacity of medicinal herbal products; however, the structural changes that this radical provoke on the herbal active principles are not clear yet. In this work, we compared the redox reactivity of oxygen free radicals and DPPH radical on phospholipids and protein thiol groups present in rat liver microsomes. Cu2+/ascorbate was used as generator system of oxygen free radical and as antioxidant, an extract of Buddleja globosa's leaves. Cu2+/ascorbate provoked microsomal lipid peroxidation, microsomal thiols oxidation and oxygen consumption; all of these phenomena were inhibited by B. globosa extract. On the other hand, DPPH was bleached in different extension by the herbal extract and phosphatidyl choline; beside, DPPH decreased microsomal thiols content, but this phenomenon were not prevented by the herbal extract. Furthermore, DPPH did not induce oxygen consumption and neither modified the oxygen consumption induced by Cu2+/ascorbate. Distinct redox mechanisms may explain the differences between the reactivity of DPPH and oxygen free radicals on biomolecules, which is discussed.

Nitroaryl-1,4-dihydropyridines as antioxidants against rat liver microsomes oxidation induced by iron/ascorbate, nitrofurantoin and naphthalene.

1,4-Dihydropyridines (DHPs) used in the treatment of cardiovascular diseases, are calcium channel antagonists and also antioxidant agents. These drugs are metabolized through cytochrome P(450) oxidative system, majority localized in the hepatic endoplasmic reticulum. Several lipophilic drugs generate oxidative stress to be metabolized by this cellular system. Thus, DHP antioxidant properties may prevent the oxidative stress associated with hepatic biotransformation of drugs. In this work, we tested the antioxidant capacity of several synthetic nitro-phenyl-DHPs. These compounds (I-IV) inhibited the microsomal lipid peroxidation, UDPGT oxidative activation and microsomal thiols oxidation; all phenomena induced by Fe(3+)/ascorbate, a generator system of oxygen free radicals. As the same manner, these compounds inhibited the oxygen consumption induced by Cu(2+)/ascorbate in the absence of microsomes. Furthermore, compound III (2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridin-3,5-ethyl-dicarboxylate) and compound V (N-ethyl-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridin-3,5-methyl-dicarboxylate) inhibited the microsomal lipid peroxidation induced by Nitrofurantoin and naphthalene in the presence of NADPH. Oxidative stress induced on endoplasmic reticulum may alter the biotransformation of drugs, so, modifying their plasmatic concentrations and therapeutic effects. When drugs which are activated by biotransformation are administered together with antioxidant drugs, such as DHPs, oxidative stress induced in situ may be prevented.