Infection and disruption of placental multidrug resistance (MDR) transporters: Implications for fetal drug exposure.

P-glycoprotein (P-gp, encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP/ABCG2) are efflux multidrug resistance (MDR) transporters localized at the syncytiotrophoblast barrier of the placenta and protect the conceptus from drug and toxin exposure throughout pregnancy. Infection is an important modulator of MDR expression and function. This review comprehensively examines the effect of infection on the MDR transporters, P-gp and BCRP in the placenta. Infection PAMPs such as bacterial lipopolysaccharide (LPS) and viral polyinosinic-polycytidylic acid (poly I:C) and single-stranded (ss)RNA, as well as infection with Zika virus (ZIKV), Plasmodium berghei ANKA (modeling malaria in pregnancy - MiP) and polymicrobial infection of intrauterine tissues (chorioamnionitis) all modulate placental P-gp and BCRP at the levels of mRNA, protein and or function; with specific responses varying according to gestational age, trophoblast type and species (human vs. mice). Furthermore, we describe the expression and localization profile of Toll-like receptor (TLR) proteins of the innate immune system at the maternal-fetal interface, aiming to better understand how infective agents modulate placental MDR. We also highlight important gaps in the field and propose future research directions. We conclude that alterations in placental MDR expression and function induced by infective agents may not only alter the intrauterine biodistribution of important MDR substrates such as drugs, toxins, hormones, cytokines, chemokines and waste metabolites, but also impact normal placentation and adversely affect pregnancy outcome and maternal/neonatal health.

Effect of whitening products on sound enamel and on artificial caries lesions during a cariogenic challenge.

OBJECTIVE: To investigate the effect of fluoride-containing whitening products on sound enamel and on artificial caries lesions during a cariogenic challenge. MATERIALS AND METHODS: Bovine enamel specimens (n = 120) with three areas [non-treated sound enamel (NSE), treated sound enamel (TSE), and treated artificial caries lesion (TACL)] were randomly assigned to the four groups: whitening mouthrinse (WM: 2.5% hydrogen peroxide-100 ppm F-), placebo mouthrinse (PM: 0% hydrogen peroxide-100 ppm F-), whitening gel (WG: 10% carbamide peroxide-1130 ppm F-), and deionized water (negative control; NC). The treatments (2 min for WM, PM, and NC, and 2 h for WG) were carried out during a 28-day pH-cycling model (6 × 60 min demineralization/day). Relative surface reflection intensity (rSRI) and transversal microradiography (TMR) analyses were performed. Fluoride uptake (surface and subsurface) was measured in additional enamel specimens. RESULTS: For TSE, a higher value of rSRI was observed in WM (89.99% ± 6.94), and a greater decrease in rSRI was observed for WG and NC, and no sign of mineral loss was verified for all groups (p > 0.05). For TACL, rSRI significantly decreased after pH-cycling for all experimental groups with no difference between them (p < 0.05). Higher amounts of fluoride were found in WG. WG and WM exhibited intermediate values of mineral loss, similar to PM. CONCLUSIONS: The whitening products did not potentialize the enamel demineralization under a severe cariogenic challenge, and they did not exacerbate mineral loss of the artificial caries lesions. CLINICAL RELEVANCE: Low concentrated hydrogen peroxide whitening gel and mouthrinse containing fluoride do not intensify the progression of caries lesions.

Disinfectant activities of extracts and metabolites from Baccharis dracunculifolia DC.

The concern regarding the harm caused by biocides to human health has been increasing over the years, making the natural products an alternative to less toxic and more efficient biocides. Therefore, this paper reports the investigation of the disinfectant potential of extracts and isolated compounds from Baccharis dracunculifolia. For this purpose, extracts of aerial parts (BD-C), tricomial wash (BD-L) and roots (BD-R) of B. dracunculifolia were obtained by maceration. The extracts were submitted to different chromatographic techniques, including high-speedy countercurrent chromatography (HSCCC) furnishing nine isolated compounds. The extracts and isolated compounds were evaluated regarding their antimicrobial activity by the broth microdilution method, according to the Clinical and Laboratory Standards Institute, and regarding their sanitizing activity according to Standard Operating Procedure No. 65·3210·007 (INCQS, 2011), developed by the National Institute for Quality Control in Health (INCQS) - Oswaldo Cruz Foundation (FIOCRUZ). In the antimicrobial evaluation the BD-C extract showed minimum inhibitory concentration (MIC) values of 200 and 100 µg/ml against Staphylococcus aureus and Tricophyton mentagrophytes, respectively. BD-L extract showed MIC value of 200 µg/ml against S. aureus. The isolated compounds caffeic acid (MBC 2·22 µmol l-1 ), ferulic acid (MBC 2·06 µmol l-1 ) and baccharin (MBC 0·27 µmol l-1 ) showed significant inhibitory activity against S. aureus. All B. dracunculifolia isolated compounds were active with exception of aromadrendin-4´-O-methyl-ether for T. mentagrophytes. Additionally, isosakuranetin was active against Salmonella choleraesuis (MIC 1·4 µmol l-1 ). Regarding the sanitizing activity, the hydroalcoholic solution containing 0·2% of B. dracunculifolia extract in 40°GL ethanol was effective in eliminating the microbial contamination on all carrier cylinders and against all microorganisms evaluated in the recommended exposure time of 10 min. Therefore, B. dracunculifolia has potential for the development of sanitizing agents to be used in hospitals, food manufactures and homes.

MRI findings of the cervical spine in patients with mucopolysaccharidosis type VI: relationship with neurological physical examination.

AIM: To describe the magnetic resonance imaging (MRI) findings of the cervical spine of patients with mucopolysaccharidosis type VI (MPS VI) and correlate them with clinical manifestations. MATERIALS AND METHODS: This is a cross-sectional study involving 12 patients with MPS VI. A limited neurological examination was undertaken in each patient including Tinel's test, assessment of muscle tone, and the evaluation of deep tendon reflexes. Additionally, each patient underwent cervical spine MRI to evaluate platybasia, odontoid dysplasia, periodontoid soft-tissue thickening, spinal canal stenosis, myelopathy, basilar invagination, platyspondyly, and reduction of nasopharyngeal airway. RESULTS: Nine patients were male (75%). The average age was 12.5 (±3.5 years). Tinel's test was negative in all patients. No muscle tone abnormalities were observed. Approximately 48% of the tested reflexes were considered abnormal, 10 of which (8.3%) were pathological occurring in five different patients (41.6%). At MRI, all patients showed periodontoid soft-tissue thickening and cervical spinal stenosis; six showed spinal cord compression and two showed myelopathy. Odontoid hypoplasia and basilar invagination were observed in nine patients. All patients with cervical stenosis on MRI had abnormal reflexes; however, only two of the six patients with evidence of cord compression on MRI had abnormal reflexes on clinical examination. CONCLUSIONS: The present study of 12 patients with MPS VI demonstrated that a normal neurological examination cannot confidently exclude potential cord compression in patients with this condition. MRI may aid in the timely identification of cervical spine abnormalities, and potentially play a role in lessening morbidity and mortality in patients with MPS.

Accuracy of a smartphone application for triage of skin lesions based on machine learning algorithms.

BACKGROUND: Machine learning algorithms achieve expert-level accuracy in skin lesion classification based on clinical images. However, it is not yet shown whether these algorithms could have high accuracy when embedded in a smartphone app, where image quality is lower and there is high variability in image taking scenarios by users. In the past, these applications were criticized due to lack of accuracy. OBJECTIVE: In this study, we evaluate the accuracy of the newest version of a smartphone application (SA) for risk assessment of skin lesions. METHODS: This SA uses a machine learning algorithm to compute a risk rating. The algorithm is trained on 131 873 images taken by 31 449 users in multiple countries between January 2016 and August 2018 and rated for risk by dermatologists. To evaluate the sensitivity of the algorithm, we use 285 histopathologically validated skin cancer cases (including 138 malignant melanomas), from two previously published clinical studies (195 cases) and from the SA user database (90 cases). We calculate the specificity on a separate set from the SA user database containing 6000 clinically validated benign cases. RESULTS: The algorithm scored a 95.1% (95% CI, 91.9-97.3%) sensitivity in detecting (pre)malignant conditions (93% for malignant melanoma and 97% for keratinocyte carcinomas and precursors). This level of sensitivity was achieved with a 78.3% (95% CI, 77.2-79.3%) specificity. CONCLUSIONS: This SA provides a high sensitivity to detect skin cancer; however, there is still room for improvement in terms of specificity. Future studies are needed to assess the impact of this SA on the health systems and its users.

Analytical strategies for clinical studies on dental erosive wear.

BACKGROUND: There is a need for analytical techniques for measuring Erosive Tooth Wear (ETW) on natural surfaces in clinical studies. The purpose was to investigate the use of two instruments aimed to assess initial to more advanced stages of ETW. METHODS: Human premolar enamel samples (2x3mm) (n = 24), were polished flat and mounted in resin cylinders (4 cylinders, 6 samples in each). Part 1: Baseline analyses by White Light Interferometer (WLI), Surface Reflection Intensity (SRI: TableTop and OptiPen) and Surface Hardness (SH). Erosion (1% citric acid (pH 3.6) for 1, 2, 4, 6, 8, 10 min. SRI and SH analyses after every erosion episode and by WLI after 10 min. New indentations were made and enamel loss; was measured by change in indentation depths from toothbrush abrasion (200 g, 60 strokes, 30 s). Another series of 2 × 5 min erosion (totally15 min and 20 min) was analysed with SH and SRI after each erosion, and by WLI (on samples and impressions of samples) after 20 min. Part 2 investigated WLI performance in the interface where initial erosion increases in severity and substance loss occurs. The samples were repolished. Baseline analyses by WLI, SRI (TableTop and OptiPen) and SH. Four cylinders were etched for 1, 2, 4, 8 min respectively and analysed by SRI, SH on samples, and WLI on samples and impressions). RESULTS: Part1: SRI decreased from baseline to ~ 6 min etch and increased slightly after abrasion, the two devices correlated well (ICC 0.98 p < 0.001, Spearmans rs 0.91 p < 0.001). SH decreased nearly linearly to 10 min etch, but increased distinctly after abrasion. Mean enamel loss from abrasion alone was 0.2 µm (change in indentation depths). After 10 min etch, it was 0.27 µm (WLI) and after 20 min etch, it was 2.2 µm measured on samples vs 2.4 µm on impressions of samples (7% higher). Part 2: From baseline to 8 min etch; SRI and SH decreased whereas WLI presented increasing etch depths. CONCLUSIONS: With some adjustments, the use of SRI and WLI in combination seems to be a promising strategy for monitoring ETW in clinical studies.

Keratoacanthoma-like nodules as first manifestation of metastatic epithelioid trophoblastic tumor.

Cutaneous metastases are rarely the initial manifestation of a previously undiagnosed malignancy and keratoacanthoma-like lesions are a notoriously unusual presentation pattern of cutaneous dissemination of a primary tumor. Herein, we report a 40-year-old woman presenting to our dermatology department with multiple keratoacanthoma-like scalp nodules. Subsequent investigation determined it to be the first manifestation of a disseminated endometrial epithelioid trophoblastic tumor, eventually causing the patient's death. Epithelioid trophoblastic tumor, a rare form of gestational trophoblastic disease, is a recently described neoplasm whose cutaneous metastasis has not been previously reported in the literature.

Anti-Leishmania activity of essential oil of Myracrodruon urundeuva (Engl.) Fr. All.: Composition, cytotoxity and possible mechanisms of action.

Myracrodruon urundeuva (Engl.) Fr. All., commonly known as "aroeira-do-sertão", is a medicinal plant from Anacardiaceae family. In this study, the chemical composition of M. urundeuva essential oil (MuEO) was evaluated by gas chromatography-mass spectrometry (GC-MS), as well as its anti-Leishmania potential, cytotoxicity, and macrophage activation capability as possible antiprotozoal mechanism of action were assessed. Fourteen compounds were identified, which constituted 94.87% of total oil composition. The most abundant components were monoterpenes (80.35%), with ß-myrcene (42.46%), α-myrcene (37.23%), and caryophyllene (4.28%) as the major constituents. The MuEO inhibited the growth of promastigotes (IC50 205 ± 13.4 µg mL-1), axenic amastigotes (IC50 104.5 ± 11.82 µg mL-1) and decreased percentage of macrophage infection and number of amastigotes per macrophage (IC50 of 44.5 ± 4.37 µg⋅mL-1), suggesting significant anti-Leishmania activity. The cytotoxicity of MuEO was assessed by MTT test in Balb/c murine macrophages and by human erythrocytes lysis assay and low cytotoxicity for these cells was observed. The CC50 value against macrophages were 550 ± 29.21 µg mL-1, while cytotoxicity for erythrocytes was around 20% at the highest concentration assessed, with HC50 > 800 µg mL-1. While MuEO-induced anti-Leishmania activity is not mediated by increases in both lysosomal activity and nitric oxide production in macrophages, the results suggest the antiamastigote activity is associated with an immunomodulatory activity of macrophages due to an increase of phagocytic capability induced by MuEO. Thus, MuEO presented significant activity against Leishmania amazonensis, probably modulating the activation of macrophages, with low cytotoxicity to murine macrophages and human erythrocytes.

Erosive effect of different dietary substances on deciduous and permanent teeth.

OBJECTIVES: We investigated the effect of different dietary substances on deciduous and permanent enamel. MATERIALS AND METHODS: Enamel specimens were prepared from human teeth (n = 108 deciduous molars and n = 108 permanent premolars). We measured the chemical parameters (pH, titratable acidity, viscosity, calcium, phosphate, fluoride concentration and degree of saturation) of nine dietary substances. The teeth were immersed in the respective substance (2 × 2 min; 30 °C; shaking), and we measured the baseline surface hardness (SH) in Vickers hardness numbers (VHN), and the changes in SH after 2 min (ΔSH2-0) and the 4 min (ΔSH4-0) immersion. We analysed the differences between deciduous and permanent teeth using the Wilcoxon test and correlated ΔSH to the different chemical parameters. RESULTS: Deciduous teeth were significantly softer (549.53 ± 59.41 VHN) than permanent teeth (590.15 ± 55.31 VHN; p < 0.001) at baseline, but they were not more vulnerable to erosive demineralization. Only orange juice, which presented milder erosive potential, caused significantly more demineralisation in deciduous teeth at ΔSH4-0. Practically all chemical parameters significantly correlated with ΔSH (p < 0.05). Substances with lower pH, higher titratable acidity, lower Ca, higher Pi and lower F concentrations, higher viscosity and more undersaturated solutions presented more erosive demineralisation. CONCLUSION: Different parameters in dietary substances affect erosive demineralisation in deciduous and permanent teeth, but we generally observed no differences in susceptibility to erosion between both types of teeth; only orange juice (less severe acid conditions) caused perceptible differences. CLINICAL RELEVANCE: We observe that permanent teeth are harder than deciduous teeth, but most substances cause no perceptible difference in erosive demineralisation in both types of teeth.

Age-related morphological, histological and functional changes in teeth.

Throughout lifetime, the teeth are continuously exposed to numerous chemical and physical impacts, which cause the wear of the dental hard tissues, gingival recession and other oral changes with sometimes subsequent problems. Age-related wear of tooth surfaces reduces the dental enamel thickness and exposes deeper layers of enamel, which have different physical and chemical properties than the surface enamel. Gingival recession is the main causal factor of root caries and dentine hypersensitivity. Age-related changes in dentine include the formation of secondary dentine and the reduction in tubular lumen diameter (dentine sclerosis), which lead to a reduction in the volume of the pulp chamber. In addition to the reduction in the volume of pulp chamber, changes to the dental pulp also include dental pulp calcifications. The age-related physiological changes to the teeth should be carefully distinguished from pathological changes, especially when they induce pain or a negative impact on the oral health-related quality of life (OHRQoL) of the older individuals. Therefore, regular oral examinations coupled with early preventive measures should aim at maintaining oral health until old age.

Nice to meet you: genetic, epigenetic and metabolic controls of plant perception of beneficial associative and endophytic diazotrophic bacteria in non-leguminous plants.

A wide range of rhizosphere diazotrophic bacteria are able to establish beneficial associations with plants, being able to associate to root surfaces or even endophytically colonize plant tissues. In common, both associative and endophytic types of colonization can result in beneficial outcomes to the plant leading to plant growth promotion, as well as increase in tolerance against biotic and abiotic stresses. An intriguing question in such associations is how plant cell surface perceives signals from other living organisms, thus sorting pathogens from beneficial ones, to transduce this information and activate proper responses that will finally culminate in plant adaptations to optimize their growth rates. This review focuses on the recent advances in the understanding of genetic and epigenetic controls of plant-bacteria signaling and recognition during beneficial associations with associative and endophytic diazotrophic bacteria. Finally, we propose that "soil-rhizosphere-rhizoplane-endophytes-plant" could be considered as a single coordinated unit with dynamic components that integrate the plant with the environment to generate adaptive responses in plants to improve growth. The homeostasis of the whole system should recruit different levels of regulation, and recognition between the parties in a given environment might be one of the crucial factors coordinating these adaptive plant responses.

Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality.

The mGluR5 positive allosteric modulator, CDPPB, ameliorates pathology and phenotypic signs of a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin protein (htt), leading to motor dysfunction, cognitive decline, psychiatric alterations, and death. The metabotropic glutamate receptor 5 (mGluR5) has been implicated in HD and we have recently demonstrated that mGluR5 positive allosteric modulators (PAMs) are neuroprotective in vitro. In the present study we demonstrate that the mGluR5 PAM, CDPPB, is a potent neuroprotective drug, in vitro and in vivo, capable of delaying HD-related symptoms. The HD mouse model, BACHD, exhibits many HD features, including neuronal cell loss, htt aggregates, motor incoordination and memory impairment. However, chronic treatment of BACHD mice with CDPPB 1.5 mg/kg s.c. for 18 weeks increased the activation of cell signaling pathways important for neuronal survival, including increased AKT and ERK1/2 phosphorylation and augmented the BDNF mRNA expression. CDPPB chronic treatment was also able to prevent the neuronal cell loss that takes place in the striatum of BACHD mice and decrease htt aggregate formation. Moreover, CDPPB chronic treatment was efficient to partially ameliorate motor incoordination and to rescue the memory deficit exhibited by BACHD mice. Importantly, no toxic effects or stereotypical behavior were observed upon CDPPB chronic treatment. Thus, CDPPB is a potential drug to treat HD, preventing neuronal cell loss and htt aggregate formation and delaying HD symptoms.

Consensus report of the European Federation of Conservative Dentistry: erosive tooth wear--diagnosis and management.

OBJECTIVE: Due to an increased focus on erosive tooth wear (ETW), the European Federation of Conservative Dentistry (EFCD) considered ETW as a relevant topic for generating this consensus report. MATERIALS AND METHODS: This report is based on a compilation of the scientific literature, an expert conference, and the approval by the General Assembly of EFCD. RESULTS: ETW is a chemical-mechanical process resulting in a cumulative loss of hard dental tissue not caused by bacteria, and it is characterized by loss of the natural surface morphology and contour of the teeth. A suitable index for classification of ETW is the basic erosive wear examination (BEWE). Regarding the etiology, patient-related factors include the pre-disposition to erosion, reflux, vomiting, drinking and eating habits, as well as medications and dietary supplements. Nutritional factors relate to the composition of foods and beverages, e.g., with low pH and high buffer capacity (major risk factors), and calcium concentration (major protective factor). Occupational factors are exposition of workers to acidic liquids or vapors. Preventive management of ETW aims at reducing or stopping the progression of the lesions. Restorative management aims at reducing symptoms of pain and dentine hypersensitivity, or to restore esthetic and function, but it should only be used in conjunction with preventive strategies. CONCLUSIONS: Effective management of ETW includes screening for early signs of ETW and evaluating all etiological factors. CLINICAL RELEVANCE: ETW is a clinical condition, which calls for the increased attention of the dental community and is a challenge for the cooperation with other medical specialities.

Oral Health Education Program on Dental Caries Incidence for School Children.

OBJECTIVE: This 3-year retrospective controlled clinical trial assessed the effect of a school-based oral health education program on caries incidence in children. STUDY DESIGN: A total of 240 students, aged 5 to 7 years, from two public schools in Monte Sião, Brazil, were included in this study. A school-based oral health education program was developed in one of the schools (experimental group), including 120 students, while the 120 students from the other school did not participate in the program (control group). All children were initially examined for dental caries (dmf-t), and after 3 years, 98 children from the experimental group and 96 from the control group were again examined and answered a questionnaire on oral health issues. The between-groups difference in caries incidence on permanent teeth was calculated using Poisson regression analyses. Logistic regression was used to observe the association between caries incidence and other variables. RESULTS: More students from the experimental group stated knowing what was dental caries and declared that they use dental floss daily, but no significant differences in caries incidence was observed between the experimental and control groups. CONCLUSION: The school-based oral health education program is not adequately efficient to decrease caries incidence after three years, but some issues about oral health knowledge could be slightly improved.

Nitrogen signalling in plant interactions with associative and endophytic diazotrophic bacteria.

Some beneficial plant-interacting bacteria can biologically fix N2 to plant-available ammonium. Biological nitrogen fixation (BNF) is an important source of nitrogen (N) input in agriculture and represents a promising substitute for chemical N fertilizers. Diazotrophic bacteria have the ability to develop different types of root associations with different plant species. Among the highest rates of BNF are those measured in legumes nodulated by endosymbionts, an already very well documented model of plant-diazotrophic bacterial association. However, it has also been shown that economically important crops, especially monocots, can obtain a substantial part of their N needs from BNF by interacting with associative and endophytic diazotrophic bacteria, that either live near the root surface or endophytically colonize intercellular spaces and vascular tissues of host plants. One of the best reported outcomes of this association is the promotion of plant growth by direct and indirect mechanisms. Besides fixing N, these bacteria can also produce plant growth hormones, and some species are reported to improve nutrient uptake and increase plant tolerance against biotic and abiotic stresses. Thus, this particular type of plant-bacteria association consists of a natural beneficial system to be explored; however, the regulatory mechanisms involved are still not clear. Plant N status might act as a key signal, regulating and integrating various metabolic processes that occur during association with diazotrophic bacteria. This review will focus on the recent progress in understanding plant association with associative and endophytic diazotrophic bacteria, particularly on the knowledge of the N networks involved in BNF and in the promotion of plant growth.

Altered cardiovascular reactivity to mental stress in patients with multiple sclerosis.

Cold pressure test (CPT) and mental stress test (MST) are distinct tests usually leading to blood pressure (BP) and heart rate (HR) increase. Their patterns in multiple sclerosis (MS) are still unknown. This study assessed cardiovascular reactivity to MST and CPT in patients with MS and controls. MST was performed with Stroop test card. CPT was performed with cold stimulus. The BP and HR were digitally recorded at rest and test phases. The delta (Δ) and the variance of BP and HR were compared between patients and controls. Patients with MS had lower Δ of diastolic BP and HR induced by MST than controls. There were no differences between patients and controls with CPT. The reduced autonomic reactivity to MST but not with CPT suggests that specific central nervous system pathways involved in MST may be responsible for autonomic findings in MS.

Epithelial urinary bladder tumors from cows with enzootic hematuria: structural and cell cycle-related protein expression.

Thirty-nine epithelial bladder tumor samples from 37 animals affected with bovine enzootic hematuria (BEH) were selected for immunohistochemical studies. The expression of structural proteins such as uroplakin III (UPIII) and cytokeratin 7 (CK7) and the cell cycle-related proteins cyclin D1 and p53 were evaluated in urothelial papillomas and carcinomas. Loss of UPIII and CK7 expression was seen in both high-grade and high-stage urothelial carcinomas (P < .001 and P < .02). Cyclin D1 expression showed no statistically significant association with grade or stage. In contrast, p53 immunoreactivity was positive in high-grade and high-stage carcinomas (P < .05 and P < .01), confirming its association with the highest malignant behavior of the bladder tumors in BEH.

Cytotoxicity of lapachol metabolites produced by probiotics.

UNLABELLED: Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9ß-hexahydroindeno[1,2-ß]pyran-9ß-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 µmol l(-1) ) than lapachol (IC50 = 72.3 µmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 µmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess the effects of bacterial metabolism on drug performance and toxicity.

Efficacy of fish embryo vitrification protocols in terms of embryo morphology - a systematic review.

BACKGROUND: Embryo cryopreservation has been used for the creation of genetic banks with diploid resources, and among different techniques, vitrification is considered as the most promising method. OBJECTIVE: The goal is to evaluate the major aspects of the existing vitrification techniques and to evaluate their efficacy in terms of embryo morphology. METHODS: Electronic searches in the PubMed and ScienceDirect databases were performed with the keyword combination: fish, embryo and vitrification. Pubmed retrieved 26 articles and Science Direct resulted in 464 articles. For this review, only studies that developed and tested vitrification protocols in fish embryos were included. Research regarding cryoprotectant toxicity and permeability were excluded. There were no restrictions on publication date or language. With these criteria, a total of ten articles were evaluated. RESULTS: In these articles, the major aspects to be considered for the development of new vitrification protocols are: the cryoprotectants' toxicity, the embryos' development stage, the exposure to and the permeability of the cryoprotectants, vitrification devices and vitrification-warning cycle. CONCLUSION: The survival were limited, however, the preservation of embryonic morphology after thawing indicates the possibility of preserving fish embryos via the vitrification technique.