Clock gene Per2 modulates epidermal tissue repair in vivo.

Wound healing can be influenced by genes that control the circadian cycle, including Per2 and BMAL1, which coordinate the functions of several organs, including the skin. The aim of the study was to evaluate the role of PER2 during experimental skin wound healing. Two groups (control and Per2-KO), consisting of 14 male mice each, were anesthetized by inhalation, and two 6 mm wounds were created on their dorsal skin using a punch biopsy. A silicone ring was sutured around the wound perimeter to restrict contraction. The wound healing process was clinically measured daily (closure index) until complete wound repair. On Day 6, histomorphometric analysis was performed using the length and thickness of the epithelial migration tongue, in addition to counting vessels underlying the lesion by immunofluorescence assay and maturation of collagen fibers through picrosirius staining. Bromodeoxyuridine (BrdU) incorporation and quantification were performed using the subcutaneous injection technique 2 h before euthanasia and through immunohistochemical analysis of the proliferative index. In addition, the qualitative analysis of myofibroblasts and periostin distribution in connective tissue was performed by immunofluorescence. Statistically significant differences were observed in the healing time between the experimental groups (means: 15.5 days for control mice and 13.5 days for Per2-KO; p = 0.001). The accelerated healing observed in the Per2-KO group (p < 0.05) was accompanied by statistical differences in wound diameter and length of the migrating epithelial tongue (p = 0.01) compared to the control group. Regarding BrdU immunoreactivity, higher expression was observed in the intact epithelium of Per2-KO animals (p = 0.01), and this difference compared to control was also present, to a lesser extent, at the wound site (p = 0.03). Immunofluorescence in the connective tissue underlying the wound showed a higher angiogenic potential in the Per2-KO group in the intact tissue area and the wound region (p < 0.01), where increased expression of myofibroblasts was also observed. Qualitative analysis revealed the distribution of periostin protein and collagen fibers in the connective tissue underlying the wound, with greater organization and maturation during the analyzed period. Our research showed that the absence of the Per2 gene positively impacts the healing time of the skin in vivo. This acceleration depends on the increase of epithelial proliferative and angiogenic capacity of cells carrying the Per2 deletion.

Sleep Deprivation Interferes with JAK/STAT Signaling Pathway and Myogenesis in the Masseter Muscle of Rats.

OBJECTIVES: The aim of the study was to study the Janus kinase/tyrosine kinase-activated transduction factor (JAK/STAT) signaling pathway and myogenesis on the masseter muscle after sleep deprivation and to investigate the role of stress in this scenario. SUBJECTS AND METHODS: A total of 18 male Wistar rats were divided into the following groups: control (n = 6): animals were not submitted to any procedures, and paradoxical sleep deprivation and vehicle (PSD + V; n = 6): animals were subjected to PSD for 96 h and (PSD + MET; n = 6): animals were subjected to PSD for 96 h with administration of metyrapone. Paradoxical sleep deprivation was performed by the modified multiple platforms method. Histopathological analysis, histomorphometry, and immunohistochemistry were performed. RESULTS: The results showed the presence of inflammatory infiltrate in the PSD + V and PSD + MET groups and atrophy. Histomorphometry showed that the cellular profile area decreased, while cellular density increased in both experimental groups. Expression of p-STAT 3, MyoD, and MyoG increased in the PSD + V group, while the PSD + MET group showed increased expression of IL-6 and p-STAT 3. CONCLUSION: Our results suggest that sleep deprivation induces an inflammatory response and atrophy in the masseter muscle of rats.

Paradoxical sleep deprivation induces differential biological response in rat masticatory muscles: Inflammation, autophagy and myogenesis.

BACKGROUND: The aim of this study was to evaluate whether sleep deprivation (SD) induces inflammation, autophagy and myogenesis in the following masticatory muscles: masseter and temporal. METHODS: In this study, 18 animals were randomly distributed into three groups: control group (CTL, n = 6), SD for 96 hours (SD96, n = 6), and SD for 96 hours and more 96 hours of sleep recovery (SD96 + R, n = 6). RESULTS: In the histopathological analysis, SD 96 was able to induce inflammation in masseter and temporal. Nevertheless, the lack of inflammatory process was evidenced to the masseter in the group SD96 + R. Upregulation of TNF-alpha production was detected in the SD96 group, while SD96 + R decreased TNF immunoexpression for both skeletal muscles evaluated. MyoD and myogenin increased in rats submitted to SD96. By contrast, the levels of MyoD decreased in the group SD96 + R. Myogenin pointed out high immunoexpression in SD96 + R groups. In temporal, pAkt decreased in animals submitted to SD96, but it increased in the group SD96 + R. The levels of LC3 protein increased in both skeletal muscles studied, and masseter decreased LC3 protein expression in the SD96 + R. CONCLUSION: In summary, our results demonstrate that SD is able to induce inflammation, atrophy and myogenesis in rat masticatory muscles, being more intense in temporal when compared to masseter.

The Use of Single-Cell Comet Assay on Oral Cells: A Critical Review.

BACKGROUND/AIM: Genotoxicity is the capacity of an agent to induce damage to DNA. Given the close relationship between genotoxicity and carcinogenesis, several assays have been developed for detecting genetic damage. Among them, the single-cell gel (comet) assay plays an important role for evaluating DNA damage in mammalian cells, including those of the oral cavity. The purpose of this article was to provide a critical review of the application of single-cell gel comet assay to buccal cells. MATERIAL AND METHODS: A search of the scientific literature was conducted of published studies available on single-cell gel comet assay and oral cells. RESULTS: The results showed that the majority of studies were conducted on humans, whereas few were designed for use in rodents and in vitro. CONCLUSION: Further studies within the field are relevant for better understanding the underlying mechanisms of genotoxicity in oral cells, especially since the use of humans is quite complicated due to issues of ethics.

Saúde de migrantes e refugiados / Migrants and refugees health

O livro aborda um dos temas mais urgentes da contemporaneidade: a situação de migrantes e refugiados no Brasil e em diversas partes do mundo e da mobilidade humana internacional. É fruto da produção híbrida de uma migrante boliviana e trabalhadora do Sistema Único de Saúde e de uma pesquisadora no campo da saúde global. Em cinco capítulos, as pesquisadoras abordam a situação atual da mobilidade humana no mundo e da imigração no Brasil, a saúde como um direito humano para as comunidades de migrantes e refugiados, além de resumos sobre as experiência realizadas na Secretaria de Saúde do município de São Paulo, que contemplou rodas de conversas e sensibilização entre gestores e trabalhadores da saúde em unidades com grande fluxo de migrantes internacionais

Genomic Instability in Buccal Mucosal Cells of Municipal Street Sweepers as Evaluated by Micronucleus Test.

BACKGROUND/AIM: Since street sweepers comprises a group of workers who are in daily contact with rubbish, dust and air pollution, the aim of this study was to evaluate potential cytotoxic and mutagenic effects in buccal mucosa cells of street sweepers. MATERIALS AND METHODS: A total of 20 male street sweepers aged from 22 to 56 years were included in the experimental group. A total of 20 men matched by age were used as the control group. Cytotoxicity and mutagenicity were analyzed by micronucleus test in buccal mucosal cells. RESULTS: Statistically significant differences (p<0.05) in the frequency of micronuclei was detected in the street sweepers when compared to the control group. No remarkable differences were found to other metanuclear alterations indicative for cytotoxicity such as pyknosis, karyolysis, and karryorhexis when compared to matched controls. CONCLUSION: Taken together, our results indicate that street sweepers comprise an at-risk group as a result of increased mutagenicity found to buccal mucosa cells.

Do Dental X-Rays Induce Genotoxicity and Cytotoxicity in Oral Mucosa Cells? A Critical Review.

Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals.

Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies.

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

Genotoxicity Induced by Dental Materials: A Comprehensive Review.

Genotoxicity is the capacity of an agent to produce damage in the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, evaluation of genotoxicity induced by dental materials is necessary for elucidating the true health risks to patients and professionals. The purpose of this article was to provide a comprehensive review of genotoxicity induced by dental materials. All published data showed some evidence of genotoxicity, especially related to dental bleaching, restorative materials and endodontic compounds. Certainly, such information will be added to that already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Putative mechanisms of genotoxicity induced by fluoride: a comprehensive review.

Genotoxicity is the ability of an agent to produce damage on the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, to elucidate the putative mechanisms of genotoxicity induced by fluoride are important to measure the degree of risk involved to human populations. The purpose of this article is to provide a comprehensive review on genotoxicity induced by fluoride on the basis of its mechanisms of action. In the last 10 years, all published data showed some evidence related to genotoxicity, which is due to mitochondrial disruption, oxidative stress, and cell cycle disturbances. However, this is an area that still requires a lot of investigation since the published data are not sufficient for clarifying the genotoxicity induced by fluoride. Certainly, the new information will be added to those already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Acute crack cocaine exposure induces genetic damage in multiple organs of rats.

Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats.

Genotoxicity and mutagenicity induced by acute crack cocaine exposure in mice.

CONTEXT: Crack cocaine is an illicit drug derived from cocaine, in which use and abuse have increased around the world, especially in developing countries. OBJECTIVES: The aim of this study was to evaluate genomic damage in multiple organs of mice following acute exposure to crack cocaine. For this purpose, single cell gel (comet) assay in peripheral blood, liver, kidney, and brain cells was performed and micronucleus test for bone narrow and liver cells was also made in this setting. MATERIAL AND METHODS: A total of 20 C57BL/10 male mice were distributed into four groups, as follows: 0, 4.5, 9, and 18 mg/kg b.w. of crack cocaine dissolved to 1% dimethyl sulfoxide by intraperitoneal (i.p.) route. All animals were sacrificed 24 h after i.p. injection. RESULTS: The results showed that crack cocaine induced DNA damage in peripheral blood, and brain cells for higher doses used as depicted by single cell gel (comet) assay data. Analysis of kidney cells showed no genetic damage for all groups tested. The number of micronucleated cells did not increase after crack cocaine exposure in bone narrow or liver cells. CONCLUSION: In summary, crack cocaine is a genotoxic agent in peripheral blood, liver, and brain cells but not mutagenic in multiple organs of mice.

Effect of an alcoholic diet on dental caries and on Streptococcus of the mutans group. Study in rats.

The objective of this study was to evaluate the effects of an alcohol diet on Streptococcus of the mutans group and on dental caries in the oral cavity of rats. Forty animals were divided into 3 groups according to the following liquid diets: 20% ethanol solution (Alcohol Group, AG), 27% sucrose solution (Isocaloric Group, IG), and water (Control Group, CG). After 56 days, samples were collected and plated on Mitis Salivarius Bacitracin agar to assess the number of colony forming units (CFU/mL) of Streptococcus of the mutans group. The animals were sacrificed and the jaws were removed in order to assess the occurrence of dental caries on the smooth and occlusal surfaces using stereomicroscopy. The data were submitted to ANOVA and Tukey test. The average numbers of CFU/mL (10(3)) were: 8.17 (AG), 9.78 (IG), and 5.63 (CG). There was no significant difference among the groups for the occurrence of occlusal caries. Regarding smooth surface caries, in the upper jaw, the caries number in the IG (1.58) was similar to that in the AG (2.06) and in the CG (1.14), and the number of caries in the AG was higher than in the CG; in the lower jaw there was significant difference among the 3 groups: AG (1.14), IG (2.00) and CG (0.43). The diets with the alcohol and sucrose solutions presented a tendency of increasing the colonization by Streptococcus of the mutans group and of increasing the occurrence of smooth surface dental caries in rat molars when compared to the control diet.

Effect of an alcoholic diet on dental caries and on Streptococcus of the mutans group: study in rats

The objective of this study was to evaluate the effects of an alcohol diet on Streptococcus of the mutans group and on dental caries in the oral cavity of rats. Forty animals were divided into 3 groups according to the following liquid diets: 20 percent ethanol solution (Alcohol Group, AG), 27 percent sucrose solution (Isocaloric Group, IG), and water (Control Group, CG). After 56 days, samples were collected and plated on Mitis Salivarius Bacitracin agar to assess the number of colony forming units (CFU/mL) of Streptococcus of the mutans group. The animals were sacrificed and the jaws were removed in order to assess the occurrence of dental caries on the smooth and occlusal surfaces using stereomicroscopy. The data were submitted to ANOVA and Tukey test. The average numbers of CFU/mL (10³) were: 8.17 (AG), 9.78 (IG), and 5.63 (CG). There was no significant difference among the groups for the occurrence of occlusal caries. Regarding smooth surface caries, in the upper jaw, the caries number in the IG (1.58) was similar to that in the AG (2.06) and in the CG (1.14), and the number of caries in the AG was higher than in the CG; in the lower jaw there was significant difference among the 3 groups: AG (1.14), IG (2.00) and CG (0.43). The diets with the alcohol and sucrose solutions presented a tendency of increasing the colonization by Streptococcus of the mutans group and of increasing the occurrence of smooth surface dental caries in rat molars when compared to the control diet.

O presente estudo avaliou o efeito de uma dieta alcoólica sobre estreptococos do grupo mutans e sobre cárie dentária na cavidade bucal de ratos. Quarenta animais foram divididos em 3 grupos conforme a dieta líquida administrada: solução de etanol a 20 por cento (Grupo álcool, GA), solução de sacarose a 27 por cento (Grupo isocalórico, GI) e água (Grupo controle, GC). Após 56 dias, amostras bucais foram coletadas e semeadas em ágar Mitis Salivarius Bacitracina para contagem de unidades formadoras de colônias (UFC/mL) de estreptococos do grupo mutans. Os animais foram sacrificados, maxila e mandíbula foram removidas para analisar a ocorrência de cárie nas faces livres e oclusais usando lupa estereoscópica. Os dados foram submetidos à ANOVA e ao teste de Tukey. As médias dos números de UFC/mL (10³) foram: 8,17 (GA), 9,78 (GI), e 5,63 (GC). Não houve diferença significativa entre os grupos para a ocorrência de cárie oclusal. Em relação ao número de cáries em face livre, na maxila este número no GI (1,58) foi similar ao encontrado no GA (2,06) e no GC (1,14), e o número de cáries no GA foi maior do que no GC; na mandíbula houve diferença significante entre os três grupos: GA (1,14), GI (2,00) e GC (0,43). A dieta com soluções de álcool e sacarose apresentou tendência de aumento na colonização de estreptococos do grupo mutans e aumentou a incidência de lesões de cárie de faces livres nos molares de ratos quando comparada à dieta controle.

The role of metronidazole on the establishment and persistence of oral candidosis

The aim of this study was to study the effects of metronidazole on the establishment of oral candidosis and Candida albicans colonization in the oral cavity of rats. Forty-eight male rats, negative for yeasts in the oral cavity, were used in the study. The rats were inoculated with a suspension of Candida albicans and treated with metronidazole or plain water (control group). The rats of the candidosis experimental group were sacrificed 7, 15, or 30 days after inoculation and their tongues were analyzed by light microscopy. Colonization by Candida albicans was evaluated 1, 2, 5 and 7 days after inoculation and progressively at 15-day intervals, with a total of 18 collections. The results demonstrated the development of candidosis on the tongue dorsum was similar between the Control and Metronidazole groups for each sacrifice period. However, the colonization results showed that yeasts were recovered in the Metronidazole group in greater numbers than in the Control group after the 37th day of the experiment (6th collection). According this, the long term metronidazole therapy favored the colonization of C. albicans in the oral cavity of rats.