Volatile Profiles and DNA Barcodes of Myrtaceae Species with Occurrence in the Brazilian Amazon.

Myrtaceae family includes many species with taxonomic challenges, making it one of the most complex families to identify. This study used DNA barcoding to find molecular markers for species authentication based on the Myrtaceae family's chemical composition and genetic diversity. Essential oils and genetic material were extracted from the leaves of six different species: Eugenia uniflora, E. patrisii, Myrcia splendens, Psidium guajava, P. guineense, and Psidium sp. The samples were analyzed based on compound classes and grouped into two categories. Group I included samples with high amounts of oxygenated sesquiterpenes (3.69-76.05 %) and fatty acid derivatives (0.04-43.59 %), such as E. uniflora, Myrcia splendens, and E. patrisii. Group II included samples P. guajava, P. guineense, and Psidium sp., which had a significant content of monoterpene hydrocarbons (0.69-72.35 %), oxygenated sesquiterpenes (8.06-68.1 %), phenylpropanoids (0.45-22.59 %), and sesquiterpene hydrocarbons (0.27-21.84 %). The PsbA-trnH gene sequences had a high genetic variability, allowing the species to be distinguished. A phylogenetic analysis showed two main clusters with high Bootstrap values corresponding to the subtribes Eugeniineae, Myrciinae, and Pimentinae. The results suggest a weak correlation between genetic and chemical data in these Myrtaceae species.

Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine.

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder's cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

Can Whitening Strips interfere with the Bond Strength of Composite Resins?

AIM: The aim of this study was to investigate in vitro the bond strength of composite resins on enamel previously treated with whitening strips. MATERIALS AND METHODS: A total of 48 bovine incisors were allocated to four experimental groups (n = 12 each): G1 (WSC)- treated with 9.5% hydrogen peroxide whitening strips (3D White Whitestrips® Advanced Vivid/CREST); G2 (WSO)-treated with 10% hydrogen peroxide whitening strips (3D WhiteTM/Oral B); G3 (WG)-treated with 7.5% hydrogen peroxide gel with fluorine, calcium and potassium nitrate (White Class®/FGM); and G4 (C)-control not subjected to bleaching treatment. The specimens were subjected to bleaching over 2 weeks following the manufacturers' instructions. Following the elaboration of the composite resin test specimens, the samples were stored in artificial saliva and subsequently subjected to the micro-shear test using the universal testing machine (EMIC®). The bond strength values were analyzed by one-way ANOVA and Tukey's statistical test (5%). RESULTS: Significant differences were observed among the investigated groups (p < 0.05). The G3-WG exhibited greater values compared with the control group and the groups treated with strips, G1-WSC and G2-WSO. Analysis of the bond interface revealed that a large fraction of the failures occurred at the enamel-resin interface. CONCLUSION: The bond strength decreased following 14 days of treatment with bleaching strips, whereas the whitening gel with 7.5% hydrogen peroxide, calcium and fluorine increased the bond strength.

Brazilian quilombos: A repository of Amerindian alleles.

OBJECTIVES: As a consequence of colonization of the Americas and decimation of the native population, an important portion of autochthonous genetic variation has been lost. However, some alleles have been incorporated into the growing populations of admixed mestizos. In this study, we evaluated the potential of African-derived communities in Brazil to be repositories of Amerindian alleles and, by extension, a source of information on American prehistory. METHODS: In this study, we describe the genetic variation of 15 ancestry informative markers (AIMs) of autosomal origin in two quilombos, Brazilian populations mainly of African descent, Santo Antônio do Guaporé (SAG; N = 31), and Santiago do Iguape (STI; N = 37). We compared the AIMs from these populations to those of other African-Brazilian populations, and to the Distrito Federal (N = 168), an urban population representative of Brazilian genetic diversity. RESULTS: By admixture analysis, we found that the SAG and STI communities have a much higher proportion (over 40%) of Amerindian contribution to their gene pools than other admixed Brazilian populations, in addition to marked African contributions. CONCLUSIONS: These results identify two living African-Brazilian populations that carry unique and important genetic information regarding Amerindian history. These populations will be extremely valuable in future investigations into American pre-history and Native American evolutionary dynamics.

Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip syndrome.

BACKGROUND/AIMS: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism. METHODS: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles. RESULTS: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals presented high triglyceride levels, and 68.1% of patients showed high cholesterol levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPARγ2 gene was found in 86.3% of patients; the Ala/Ala variant was not observed in any patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ polymorphism of the adiponectin gene was found in 54.6% of patients. CONCLUSIONS: No association was found between lipid parameters and the relevant Pvull, Avall and Sstl polymorphisms. However, we did observe an association of the Pro12Ala and ADIPOQ polymorphisms with higher lipid levels, suggesting a close relationship between these factors.

Unraveling the metabolomic profile and acute toxicity of ethanolic extract from Mimosa tenuiflora (Willd.) Poir. root bark.

Mimosa tenuiflora (Fabaceae) is popularly known in Brazil as "Jurema preta". From the bark of its root, "jurema wine" is obtained, a psychedelic drink used in Indigenous religious rituals in Northeastern Brazil. This work aimed to investigate the chemical composition and acute oral toxicity of the ethanolic extract of the root bark from M. tenuiflora (EEMt). EEMt was analyzed by UPLC-QToF-MS/MS and DI-ESI-IT-MSn. Oral administration of EEMt was performed once at doses of 300 and 2000 mg/kg in female Swiss mice. Signs and symptoms of intoxication, as well as mortality were monitored for 14 days. Thirteen compounds were annotated in EEMt: eight type B proanthocyanidins, three alkaloids, a glycosylated flavonol, and a dihydrochalcone derivative. The acute administration of 300 and 2000 mg/kg of EEMt did not show mortality. It also did not change the food intake or body weight of the animals. However, the relative weights of the kidneys were significantly changed for both doses. Changes in hematological and biochemical parameters were found. In addition, histopathological changes were also observed in the heart, liver, and kidneys. Thus, based on our findings, EEMt presented an LD50 greater than 2000 mg/kg and was therefore classified in category 5 of the Globally Harmonized Classification System (GHS). EEMt showed acute oral toxicity by altering hematological, biochemical and histological parameters.

Advances in Antitumor Effects Using Liposomal Citrinin in Induced Breast Cancer Model.

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 µg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

Substance misuse subtypes among women convicted of homicide.

BACKGROUND: The proportion of women incarcerated is growing at a faster pace than that for men. The reasons for this important increase have been mainly attributed to drug-using lifestyle and drug-related offenses. About half of female inmates have history of substance misuse and one third demonstrate high impulsiveness levels. The objectives of this study were to (a) identify subtypes of alcohol and drug problems and impulsiveness among women convicted of homicide, and (b) examine the association between psychosocial and criminological features and the resulting clusters. METHODS: Data come from 158 female inmates serving a sentence for homicide in the Penitentiary of Sant'Ana in São Paulo State, Brazil. Latent class analysis was used to group participants into substance misuse and impulsiveness classes. RESULTS: Two classes were identified: nonproblematic (cluster 1: 54.53%, n = 86) and problematic (cluster 2: 45.57%, n = 72) ones. After controlling for several psychosocial and criminological variables, cluster 2 inmates showed an earlier beginning of criminal activities and a lower educational level than their counterparts. CONCLUSIONS: To recognize the necessities of specific groups of female offenders is crucial for the development of an adequate system of health politics and for the decrease of criminal recidivism among those offenders who have shown higher risk.

Effects of ω-3 PUFA-Rich Oil Supplementation on Cardiovascular Morphology and Aortic Vascular Reactivity of Adult Male Rats Submitted to an Hypercholesterolemic Diet.

Atherosclerosis is a cardiovascular disease associated with abnormalities of vascular functions. The consumption of mono- and polyunsaturated fatty acids can be considered a strategy to reduce clinical events related to atherosclerosis. In the present study, we investigated the effects of supplementation with 310 mg of ω-3 PUFAs (2:1 eicosapentaenoic/docosahexaenoic acids) for 56 days on rats with hypercholesterolemia induced by a diet containing cholesterol (0.1%), cholic acid (0.5%), and egg yolk. Serum biochemical parameters were determined by the enzymatic colorimetric method. Assessment of vascular effects was performed by analysis of histological sections of the heart and aortic arch stained with hematoxylin and eosin and vascular reactivity of the aorta artery. We observed that treatment with ω-3 PUFAs did not promote alterations in lipid profile. On the other hand, we documented a favorable reduction in liver biomarkers, as well as contributions to the preservation of heart and aortic arch morphologies. Interestingly, the vascular reactivity of rat thoracic aortic preparations was improved after treatment with ω-3 PUFAs, with a decrease in hyperreactivity to phenylephrine and increased vasorelaxation promoted by acetylcholine. Our findings suggest that the supplementation of hypercholesterolemic rats with ω-3 PUFAs promoted improvement in liver and vascular endothelial function as well as preserving heart and aortic tissue, reinforcing the early health benefits of ω-3 PUFAs in the development of atherosclerotic plaque and further related events.

Antiproliferative and Genotoxic Action of an Underexploited Organoteluran Derivative on Sarcoma 180 Cells.

BACKGROUND: The search for novel metallic chemical compounds with toxicogenic effects has been of great importance for more efficient cancer treatment. OBJECTIVE: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the S-180 cell line. METHODS: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5µM. RESULTS: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5µM, which is thought to avoid an aggressive immune response of the organism. CONCLUSION: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.

Amateur ballet practicing, body image and eating behaviors: a comparative study of classical ballet dancers, gym users and sedentary women.

BACKGROUND: Ballet dancers are a risk group for body image (BI) distortion, dissatisfaction and eating disorders (ED), but few studies have investigated these aspects in amateur adult practitioners. This study aimed to evaluate if amateur female adult classical ballet dancers presented different BI and behaviors for ED than gym users and sedentary women. METHODS: This is a cross-sectional study where classical ballet dancers (n = 19) were compared to gym users (n = 19) and sedentary women (n = 19). Body mass index (BMI) was assessed, and a figure rating scale was applied to assess BI distortion/dissatisfaction. The body shape questionnaire (BSQ) was used to measure BI concern. The eating attitudes test (EAT-26) and the bulimic investigatory test, Edinburgh (BITE) were used for behaviors toward anorexia and bulimia. RESULTS: BMI was significantly lower in ballet dancers than gym users and sedentary women (F, p = .04). BI distortion did not differ among the studied groups. BI dissatisfaction was lower (X2, p = .041) in ballet dancers (75.0%) and gym users (70.6%) compared to sedentary women (100%). Correspondence analysis showed ballet dancers were mostly not concerned with BI, which was not observed among the other groups. The EAT-26 did not differ between the studied groups. The BITE score was lower (Tukey's post hoc test, p = .005) in the ballet dancers [mean 5.3 (5.6)] compared to the sedentary women [mean 10.9 (4.8)]. CONCLUSIONS: Data suggest that amateur classical ballet practicing is associated to better BI and fewer behaviors for ED in the studied population. The lower BMI in ballet dancers might explain these findings, and further studies should explore these associations.

Chemotherapeutic and Safety Profile of a Fraction from Mimosa caesalpiniifolia Stem Bark.

Mimosa caesalpiniifolia (Fabaceae) is used by Brazilian people to treat hypertension, bronchitis, and skin infections. Herein, we evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile. Initially, the cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage. DFMC and betulinic acid revealed similar in vitro antiproliferative action on S180 cells and induced a reduction in viable cells, induced a reduction in viable cells and caused the emergence of bridges, buds, and morphological features of apoptosis and necrosis. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels. Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules.

preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?

Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6 mg/kg.

Toxicological evaluation of the biflavonoid, agathisflavone in albino Swiss mice.

Agathisflavone (AGF) is a biflavonoid with a number of important biological and pharmacological activities, such as antioxidant, antimicrobial, and neuroprotective effects. However, its toxicological effects have not been fully investigated. Accordingly, the aim of this study was to investigate the toxicological effects of AGF in mice. For this purpose, the median lethal dose 50% (LD50) was determined along with the anatomic and histopathological parameters (weight, alimentation, excretion, biochemical, and hematological) in fertile untouched female Swiss mice. Results suggest that during the treatment, no deaths were reported at 300 and 2000 mg/kg (n = 03/group, p.o.). Moreover, AGF did not cause significant change in the above mentioned parameters in test animals when compared with the control group (0.05% Tween 80 dissolved in 0.9% saline). Taken all together, this non-clinical toxicological study revealed that AGF has an LD50 larger than 2000 mg/kg and did not change significantly the hematological, biochemical, histopathological, behavioral, as well as physiological parameters in the female mice.

Lactational exposure to inorganic mercury: evidence of neurotoxic effects.

This study examined the effects of inorganic mercury (mercuric chloride - HgCl2) exposure exclusively through maternal milk on biochemical parameters related to oxidative stress (glutathione and thiobarbituric acid reactive substances levels, glutathione peroxidase and glutathione reductase activities) in the cerebellum of weanling mice. These parameters were also evaluated in the cerebellum of mothers, which were subjected to intraperitoneal injections of HgCl2 (0, 0.5 and 1.5 mg/kg, once a day) during the lactational period. Considering the relationship between cerebellar function and motor activity, the presence of motor impairment was also evaluated in the offspring exposed to HgCl2 during lactation. After treatments (at weaning), pups lactationally exposed to inorganic mercury showed high levels of mercury in the cerebellar tissue, as well as significant impairment in motor performance in the rotarod task and decreased locomotor activity in the open field. Offspring and dams did not show changes in cerebellar glutathione levels or glutathione peroxidase activity. In pups, lactational exposure to inorganic mercury significantly increased cerebellar lipoperoxidation, as well as the activity of cerebellar glutathione reductase. However, these phenomena were not observed in dams. These results indicate that inorganic mercury exposure through maternal milk is capable of inducing biochemical changes in the cerebellum of weanling mice, as well as motor deficit and these phenomena appear to be related to the pro-oxidative properties of inorganic mercury.

Evaluation of the effectiveness of arnica montana 6ch in the control of postoperative myalgia by isometric effort in dentistry

Arnica montana 6CH is a medicine indicated for inflammatory and painful conditions, especially in muscle structures. The RDC / TMD Axis II questionnaire is a validated tool for the diagnosis of Temporomandibular Muscle Dysfunction. Objective: This multicenter, randomized and controlled study, approved by Human or Animal Research Ethics Committee UniFOA -CAAE: 48680015.3.0000.5237 aimed to verify the clinical performance of Arnica montana 6CH in contractures and muscle pain triggered by isometric stress. Materials and Methods: 70 patients underwent prolongeddental treatment sessions, and they were selected after clinical examination and positive responses to the RDC / TMD questionnaire to confirm signs and symptoms of Temporomandibular Muscle Dysfunction at the first consultation. Randomly, Arnica montana 6CH was prescribed for 35 patients called group I, and placebo for 35 patients called group II, at a dose of 5 globules, 03 times a day, for 1 week. In the second endodontic consultation, after 15 days, a new clinical examination was performed at the beginning and end of the prolonged dental consultation with crossing of data from the RDC questionnaire, to monitor the prevalence of TMD muscle signs and symptoms. The data were tabulated and analyzed. Statistical analysis: The test t de Student was used for paired samples, significant at the level ≤ 0.05%. Results:Anamnetic data from the RDC questionnaire, 86% of the individuals in the GI had lower pain and muscle contracture rates in the second consultation, compared with 22% in the GII. Conclusion:The drug Arnica montana 6CH proved to be effective in preventing muscle changes and clinical symptoms resulting from isometric efforts with a statistically significant difference (p ≤ 0.05).

Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic preconditioning in the pregnant.

PURPOSE:: To evaluate the effect of remote ischemic preconditioning (r-IPC) administered to pregnant rats, in the ileum of newborn rats subjected to hypoxia and reoxygenation. METHODS:: We used three pregnant rats and their newborn rats distributed in three groups: 1) Control (C) - Newborn rats born from a pregnant rat which did not undergo any intervention; 2) Hypoxia-Reoxygenation (H/R) - Newborn rats born from a pregnant rat which did not undergo any intervention, and were subjected to hypoxia-reoxygenation; 3) Remote Ischemic Preconditioning (r-IPC) - newborn rats born from a pregnant rat which was subjected to remote ischemic preconditioning twenty-four hours before giving birth and the newborn rats were subjected to hypoxia-reoxygenation. Segments of ileum were prepared for histological analysis by HE and immunohistochemistry by the Ki67 to evaluate cell proliferation, crypt depth and villus height and evaluation of apoptosis by cleaved caspase-3. RESULTS:: The intensity of the lesions was lower in the r-IPC than in the H/R group, showing significant difference (p<0.01). The r-IPC group showed a higher proliferative activity compared to the H/R group (p<0.01), with deeper crypts (r-IPC > H/R - p < 0.05), and higher villi, showing significant difference (r-IPC > H/R - (p <0.01). The occurrence of apoptosis in the H/R group was lower in comparison to groups C and r-IPC, with significant difference (H/R < r-IPC; p<0.05). CONCLUSION:: The remote ischemic preconditioning applied to the pregnant rat protected the ileum of newborn rats subjected to hypoxia and reoxygenation, with decreased intensity of the lesions in the ileum mucosa and preservation of proliferative activity, keeping the villus height and crypt depth similar to group C.

Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients.

BACKGROUND: Data on psychological harm in multiple endocrine neoplasia type 2 (MEN2) are scarce. OBJECTIVES: The aim of this study was to assess anxiety, depression, quality of life, and coping in long-standing MEN2 patients. PATIENTS AND METHODS: Patients were 43 adults (age ≥18 years) with clinical and genetic diagnosis of MEN2 and long-term follow-up (10.6 ± 8.2 years; range 1-33 years). This was a cross-sectional study with qualitative and quantitative psychological assessment using semi-directed interviews and HADS, EORTC QLQ C30, and MINI-MAC scales. Adopting clinical criteria from 2015 ATA Guidelines on MEN2, biochemical cure (39%; 16/41), persistence/recurrence (61%; 25/41), and stable chronic disease (22/41) of medullary thyroid carcinoma (MTC) were scored. Pheochromocytoma affected 19 (44%) patients, with previous adrenalectomy in 17 of them. RESULTS: Overall, anxiety (42%; mean score 11 ± 2.9; range 8-18; anxiety is defined as a score ≥8) and depression (26%; mean score 11 ± 3.8; range 8-20; depression is defined as a score ≥8) symptoms were frequent. Patients who transmitted RET mutations to a child had higher scores for weakness-discouragement/anxious preoccupation and lower scores for cognitive, emotional, and physical functioning (p < 0.05). Feelings of guilt were present in 35% of patients with mutation-positive children. Lower mean score values for depression and anxiety and higher scores for role, cognitive, and emotional functioning were noticed in 33 patients who were well-informed about their disease (p < 0.05). Fighting spirit was more frequently found in patients with multiple surgical procedures (p = 0.019) and controlled chronic adrenal insufficiency (p = 0.024). Patients with MEN2-related stress-inducing factors had lower scores for fighting spirit and cognitive functioning and higher scores for insomnia and dyspnea (p < 0.05). Eleven patients required sustained psychotherapeutic treatment. Mean global health status was relatively good in MEN2 cases (68.1 ± 22.3), and the cured group had higher physical functioning (p = 0.021). CONCLUSIONS: Psychological distress is likely chronic in MEN2 patients. This study identified diverse MEN2-related factors (degree of information on disease, mutation-positive children, number of surgeries, comorbidities, stress-inducing factors, and cure) interfering positively or negatively with the results of the psychometrics scales. The active investigation of these factors and the applied psychological assessment protocol are useful to identify MEN2 patients requiring psychological assistance.

[Epidemiological aspects of American tegumentary leishmaniasis in Varzelândia, Minas Gerais, Brazil]. / Aspectos epidemiológicos da leishmaniose tegumentar americana em Varzelândia, Minas Gerais, Brasil.

To characterize an area of endemic leishmaniasis, aiming to test a candidate leishmania vaccine, a prospective epidemiological survey was implemented in 1999 in a rural area of Varzelândia, Minas Gerais, Brazil. From a total of 1,253 persons in 246 households, 1,170 were included, of whom 593 (50.6%) were males and 662 (56.5%) were under 21 years of age. A Montenegro intradermal test performed in 1,120 individuals and evaluated in 1,020 was reactive in 282 (27.6%). Serological testing through indirect immunofluorescence and ELISA was performed in 970 individuals (82.9%). Antibodies to Leishmania sp. were detected in 117 (13.1%) and 170 (17.5%), respectively, by the two tests. Cutaneous scars similar to those seen in American tegumentary leishmaniasis were found in 297 individuals (25.4%), 282 of whom were submitted to the intradermal test, while only 168 (59.6) were reactive. Initial leishmaniasis prevalence of 5.8% was recorded, and an annual leishmaniasis incidence rate of 4.6% was observed after one year of follow-up. The epidemiological characteristics observed in this location are suggestive of an endemic area with old colonization.

[Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]. / Rastreamento gênico da neoplasia endócrina múltipla tipo 2: experiência da Unidade de Endocrinologia Genética da USP.

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited tumor syndrome that includes medullary thyroid carcinoma (MTC), primary hyperparathyroidism, pheochromocytoma and other non-endocrine diseases. Since the first RET missense mutations in association with MEN-2 were identified, RET mutation analysis had a great impact in the clinical management of MEN-2, such as in early diagnosis and treatment of MTC. Presently, early total thyroidectomy provides real cure of MTC for cases in which molecular diagnosis has been performed at early ages. After RET mutation identification, family members should be screened for this mutation by using methods as DGGE, SSCP, restriction enzyme, genetic sequencing or mini-sequencing. In this paper, we briefly review our experience with the direct RET gene sequencing and DGGE approaches. In 50 typical MEN-2 patients analyzed using both methods, we found no false results suggesting that DGGE is a reliable screening method for RET proto-oncogene mutation analysis.