Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Eustigmatophyte strains with potential interest in cancer prevention and treatment: partial chemical characterization and evaluation of cytotoxic and antioxidant activity.

The interest in bioactive compounds from microalgae is increasing since they have medicinal and nutritional areas. The present work aims to evaluate the potential pharmaceutical interest of extracts from three eustigmatophyte strains from the Coimbra Collection of Algae (ACOI): Chlorobotrys gloeothece, Chlorobotrys regularis and Characiopsis aquilonaris. Antioxidant and antiproliferative activities were determined as well as chlorophyll a, carotenoid and phenolic total contents. In addition, major pigments and sterols were identified and quantified. The three strains were grown until the stationary phase and then the biomass was extracted. Antioxidant activity was measured by TEAC, DPPH and FRAP assays and antiproliferative effect was assessed by the MTT method on MCF-7, PC-3 and NHDF cells. The pigment and phenolic total contents were determined by spectrophotometry. Of these strains, C. aquilonaris showed the highest antioxidant activity measured by TEAC and FRAP assays (23.98 ± 0.01 µmol TE eq g-1 DW and 42.57 ± 0.04 µmol TE eq g-1 DW, respectively), a selective effect in reduting MCF-7 cells proliferation and a larger amount of chlorophyll a, carotenoids and phenolic content (18.40 ± 0.00 µg chlorophyll a mg-1 DW, 2.27 ± 0.00 mg carotenoids g-1 DW and 6.23 ± 0.01 mg GAE g-1 DW, respectively). A positive correlation between chlorophyll a and TEAC assay was observed, as well as between carotenoids and TEAC and FRAP assays, suggesting these compounds as important contributors to significant antioxidant activity. Violaxanthin, cholesterol and stigmasterol were present in larger amount in C. aquilonaris while C. regularis showed a higher amount of ß-carotene. These results suggest that these three ACOI eustigmatophytes are promising for applications in the improvement of human health, particularly in cancer prevention and treatment.

Dose to the interventional radiologist in CTF-guided procedures.

The aim of this work was to assess the occupational dose received by an interventional radiologist (IR) during computed tomography fluoroscopy (CTF)-guided procedures; to identify the most exposed areas of the body including the hands and fingers; to suggest recommendations for individual monitoring; and to improve radiation safety of the practice. A total of 53 CTF-guided procedures were studied. Twelve whole-body dosimeters were worn by the IR in each procedure for the assessment of the personal dose equivalent, Hp(10), on the chest, waist, and back, both over and under the lead apron, as well as the personal dose equivalent, Hp(0.07), on both arms, knees, and feet. Special gloves with casings to fit extremity dosimeters were prepared to assess Hp(0.07) to the fingers. The measured chest dose values were higher than those on the waist and back; the dominant hand or the left side was the most exposed. In general, the ring, middle, and index fingers of the dominant hand were the most exposed (maximum in the 36-39 mSv range), while wrist dose was negligible compared to finger doses. Based on the results obtained the following recommendations are suggested: protective devices (lead aprons, thyroid shield, and goggles) should be worn; Hp(10) should be assessed at the chest level both above and below the lead apron; finger doses can be measured on the basis of each middle finger; the arm closer to the beam should be monitored; and finally, a wrist dosimeter will not provide useful information.

Resveratrol administration increases Transthyretin protein levels ameliorating AD features- importance of transthyretin tetrameric stability.

Previous in vivo work showed that resveratrol has beneficial effects in the AD pathology, resulting in increased expression of transthyretin (TTR). TTR binds Aß peptide avoiding its aggregation and toxicity, and is reduced in the CSF and plasma, in AD. Further, resveratrol binds TTR, stabilizing the native TTR tetrameric structure. To further explore the mechanism of neuroprotection conferred by TTR in AD, resveratrol was administrated, in the diet, to 5-8 months old AD transgenic female mice carrying just one copy of the mouse TTR gene, for two months. Effects in brain Aß burden were evaluated by immunohistochemistry, and in total brain Aß levels by ELISA, showing a striking decrease in both parameters in treated animals. In addition, total brain LRP1 protein levels were increased in treated animals, although its gene expression was unaltered. To further understand the mechanism(s) underlying such improvement in AD features, we measured TTR plasma levels showing that TTR increased in resveratrol-treated mice, whereas liver TTR gene transcription was not altered. These results strengthen the stability hypothesis, which postulates that TTR is unstable in AD leading to accelerated clearance and lower levels. Therefore, resveratrol which stabilizes the TTR tetramer results in TTR normalized clearance, thus increasing the protein plasma levels. In turn, stabilized TTR binds more strongly to Aß peptide, avoiding its aggregation. Our results represent a step forward to the understanding of the mechanism underlying TTR protection in AD and highlight the possibility of using TTR stabilization as a therapeutic target in AD.

Indigenous microbiota and Leishmaniasis.

Animals are colonized by their indigenous microbiota from the early days of life. The estimated number of associated bacterial cells in humans is around of 10(14) per individual, most of them in the gut. Several studies have investigated the microbiota-host relationship, and the use of germfree animals has been an important tool in these studies. These animals, when infected with a pathogen, have shown to be sometimes more resistant and other times more susceptible than conventional animals. Leishmaniasis is a worldwide public health problem and presents a spectrum of clinical manifestations. However, very few studies have addressed the role of the indigenous microbiota on the outcome of this disease. In this review, we will highlight and discuss the data available on the ways by which the microbiota can influence the outcome of the disease in murine experimental models of cutaneous infection with Leishmania.

Self-declared ethnicity and genomic ancestry in prostate cancer patients from Brazil.

Some studies of polymorphisms in prostate cancer (PCa) analyze individuals in a uniform manner, regardless of genetic ancestry. However, PCa aggressiveness differs between subjects of African descent and those of European extraction. Thus, genetic ancestry analysis may be used to detect population stratification in case-control association studies. We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 PCa patients. We compared this data with self-reported ancestry and the stratification of cases by PCa aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European contribution (61%) among controls. Self-declaration data revealed that 74% of PCa patients considered themselves non-white (black and brown), and 41.3% of controls viewed themselves as white. Our data showed a higher degree of European ancestry among fast-growing cancer cases than those of intermediate and slow development. This differs from many previous studies, in which the prevalence of African ancestry has been reported for all grades. Differences were observed between degrees of PCa aggressiveness in terms of genetic ancestry. In particular, the greater European contribution among patients with high-grade PCa indicates that a population's genetic structure can influence case-control studies. This investigation contributes to our understanding of the genetic basis of tumor aggressiveness among groups of different genetic ancestries, especially admixed populations, and has significant implications for the assessment of inter-population heterogeneity in drug treatment effects.

Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice.

Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.

Activity of glutamate dehydrogenase and protein content in the breast of broilers fed diets containing different sources and levels of glycerine.

According to scientific literature, glycerol in the diet can spare glucogenic amino acids by inhibiting the activity of enzymes, such as glutamate dehydrogenase, thereby promoting protein deposition in muscle tissues. Therefore, the objective of this study was to evaluate the effect of three sources of glycerine (crude glycerine from soybean oil--CGSO, mixed crude glycerine from frying oil and lard--MCG and a semipurified glycerine from soybean oil--SPGSO) in four concentrations in the diet (17.5, 35.0, 52.5 and 70.0 g of each type of glycerine/kg of feed) on the activity of hepatic glutamate dehydrogenase, performance and protein content in the breast of broilers, during 22-35 days of age (experiment I) and 33-43 days of age (experiment II). In both experiments, an increase in MCG induced a linear decline in glutamate dehydrogenase activity (p < 0.05). In contrast, increasing the concentration of SPGSO in the diet caused a linear increase in enzyme activity (p < 0.05). There was no (p > 0.05) isolated effect of glycerine on the enzyme activity in either evaluated phase; however, during 33-42 days of age, MCG inhibited (p < 0.05) the glutamate dehydrogenase activity by up to 34.43%. During 22-35 days of age, the diet containing SPGSO induced a higher protein content (p < 0.05) in the breast, and regardless of the source utilized, the maximum protein deposition was estimated (p < 0.05) when broilers were fed with 55.08 g glycerine/kg of diet. There was no (p > 0.05) interaction or isolated effects of the sources and levels of glycerine on the protein content in the breast of broilers at 33-42 days of age, and moreover, all diets containing glycerine promoted a similar protein deposition in the breast compared with birds that received the diet without glycerine. The bird age also showed to influence the feed intake and weight gain of broilers fed diet containing glycerine. It is concluded that for both rearing phases, an increase in glycerine in the diet did not necessarily reduce the glutamate dehydrogenase activity, and the protein deposition in the breast of broilers may not be strictly correlated with the activity of this enzyme.

[First- and second-line hospital management of ophthalmologic emergencies: Clinical pathway study of 1360 patients]. / Prise en charge des urgences ophtalmologiques en premier et second recours hospitaliers : analyse du parcours de 1360 patients.

The general practitioner (GP) might offer a good alternative for the management of certain ophthalmologic emergencies in his or her practice, given the increasing demand for ophthalmological care and difficulties with access to ophthalmologists. The main objective of the study was to describe ophthalmological complaints and their management in general emergency departments compared to ophthalmological emergency departments in order to assess which pathologies can be treated by the GP. This was a single-center retrospective study at the University Hospital of Reims, based on consultation data from the general and ophthalmological emergency departments for all adult patients presenting for an ophthalmological problem in September 2019 and September 2020. Consultations where patients were brought back following a first emergency consultation and consultations for another non-ophthalmological reason were excluded. Out of 1360 consultations recorded, 16% of patients had initially consulted their GP. The 4 most frequent diagnoses were: "ocular trauma," "conjunctivitis," "eye pain" and "visual impairment." A prescription for medication was issued in 77% of cases, 37% of which were for antibiotics. Only 29% of consultations carried out in general emergency departments led to a request for a complementary ophthalmology consultation. The GP might therefore be able to manage certain ophthalmological emergencies in his or her practice as a first line and refer certain ophthalmologic emergencies. However, the training of GPs in this specialty must be reinforced in collaboration with ophthalmologists.

(±)-2,2-Dimethyl-5-oxotetrahydrofuran-3-carboxylic acid (terebic acid): a racemic layered structure.

A racemic crystalline form of terebic acid, C(7)H(10)O(4), which is an important industrial chemical compound, is reported for the first time. The crystal structure is stabilized by O-H···O and C-H···O hydrogen bonds which form racemic double layers parallel to (001).

Study on the dose profile in CT-fluoroscopy.

This work aims to contribute to the description of the dose profile in Computed Tomography Fluoroscopy (CTF). Our approach uses a function model to fit the single slice dose profiles (SSDP) for any point inside the gantry of the CT unit, with special attention to points off the rotation axis. The function model was successfully tested with measurements performed using GafChromic film. The parameters of the SSDP at the rotation axis (isocenter) and at 8 cm and 16 cm off the isocenter were determined. The model allows an estimation of the slice thickness at the isocenter and for points at 8 cm and 16 cm off the isocenter. The differences between the slice thicknesses results in overestimation of the Computed Tomography Dose Index, CTDI, by values as high as 20% if the nominal slice thickness instead of the model estimated value is used. The results obtained in this work provided a good description of the dose profiles, which can be used in further studies such as comparisons with measurements performed with phantoms and patients.

Lactobacillus delbrueckii UFV-H2b20 increases IFN-γ production and CD39+CD73+ Treg cell numbers in lungs, and protects mice against experimental allergic asthma.

Asthma is a disorder characterized by airflow obstruction, inflammation, declining airway function, bronchial hyperresponsiveness and tissue remodelling. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". The use of probiotics is becoming increasingly studied and recent evidence has suggested that it may provide therapeutic benefits in asthma and other diseases. Lactobacillus delbrueckii UFV-H2b20 fulfils all the requirements to be classified as probiotic. Previous studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the immune system. Our objective was to evaluate the protective effects of L. delbrueckii UFV-H2b20 in experimental allergic asthma. We used a murine model of ovalbumin-induced allergic airway inflammation to mimic allergic asthma. Oral treatment with L. delbrueckii UFV-H2b20 improves respiratory parameters and inhibits the inflammatory response in the lungs by decreasing the numbers of inflammatory monocytes, eosinophils and alveolar macrophages, as well as IgE levels. Treatment increased the IFN-γ/IL-4 cytokine ratio. Levels of IL-10 in the lungs were also increased in treated animals. Our results also showed that the probiotic administration increases the number of CD39+CD73+ T regulatory lymphocytes in the lung, suggesting a role for purinergic signals in the regulation of inflammation promoted by the treatment. Understanding the mechanisms of modulation of the immune system by probiotics could allow the development of probiotic preparations that are safe and have a direct action. Our results suggest that oral administration of L. delbrueckii UFV-H2b20 could be helpful to treat chronic inflammatory airway diseases, such as asthma.

Depression and anxiety disorders in patients with multiple sclerosis: association with neurodegeneration and neurofilaments.

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.

Anti-Candida activity of the water-soluble lectin from Moringa oleifera seeds (WSMoL).

This work reports the effects of the water-soluble lectin from Moringa oleifera seeds (WSMoL) on growth and survival of Candida species. In addition, cellular alterations linked to the antifungal effect were investigated. The minimal inhibitory (MIC) and fungicidal (MFC) concentrations were determined and 24-h growth curves in absence and presence of lectin were established. Flow cytometry was used to evaluate the induction of apoptosis/necrosis, alterations in mitochondrial membrane potential (ΔΨm), and occurrence of lysosomal damage. WSMoL inhibited the growth of C. albicans, C. glabrata, C. krusei and C. parapsilosis with MIC of 20µg/mL. The lowest MFC (20µg/mL) was detected for C. glabrata and the highest (80µg/mL) for C. albicans and C. parapsilosis. The inhibitory effect started from the ninth to nineteenth hour of incubation depending on the fungal species. Incubation with the lectin at the MIC for 24h increased the number of cells undergoing apoptosis and necrosis. Hyperpolarization of the mitochondrial membrane was detected after 12-h treatment, followed by reduction of ΔΨm or depolarization after 24h. No lysosomal damage was detected in treated cells. In conclusion, WSMoL is a fungistatic and fungicide agent against Candida with differential effects depending on the species.

Genetic differences based on AFLP markers in the mosquito species Anopheles darlingi collected in versus near houses in the region of Porto Velho, RO, Brazil.

Anopheles darlingi is the most important malaria vector in Central and South America. After a dramatic reduction of malaria cases in the whole Brazilian territory, with the lowest abundance being attained by 1970, the disease resurged in the Amazon region, where it is now a great public health concern. Consequently, better knowledge about vector species became urgent. We examined the genetic diversity and population structure of A. darlingi, sampled in four localities in the State of Rondônia, Brazil, using 139 amplified fragment length polymorphism marker loci. In each locality, samples were collected in two environments: a peri-domicile one (in the balconies of houses) and an extra-domicile environment (about 15 m from the house). Estimates of expected heterozygosity, Shannon diversity index and percentage of polymorphic loci showed medium to high values, with the samples from the areas closer to Porto Velho exhibiting the smallest values. There was evidence of small population differences, evaluated by F(st), genetic distance and analysis of molecular variance. Comparison between peri- and extra-domicile samples showed greater values of F(st) and genetic distance than between pairs of localities, indicating influence of environmental conditions on the genetics of populations.

Toxocara canis infection may impair bovine herpesvirus type 5 immunization.

Helminths have developed complex mechanisms to suppress the host immune response. These mechanisms may impair the host vaccine response. This study aimed to evaluate the effect of Toxocara spp. infection on the vaccine immune response to bovine herpesvirus type 5 (BoHV-5). First, 30 heifers received two doses of an experimental BoHV-5 vaccine. At 42nd days after the primo vaccination the vaccine efficacy was evaluated, and the presence of anti-Toxocara antibodies. Second, 20 Balb/c mice were divided into two groups, one infected with T. canis and the other without infection. After infection, both groups received two doses of vaccine. The vaccine immune response was assessed by BoHV-5 serum neutralization and splenic cytokines transcription by qPCR. All heifers positive for Toxocara spp. (40%) showed BoHV-5 SN titer ≤1:32, whereas heifers negative for Toxocara spp. (60%) had BoHV-5 SN titer ≥1: 128. Infected T. canis mice showed BoHV-5 SN titer ≤1:2, whereas mice not infected with T. canis BoHV-5 SN titer ≥1:8. Splenocytes from control mice stimulated with BoHV-5 had a significant (p < .05) mRNA transcription for the cytokines IL-12, IL-17, and IL-23, whereas the same cytokines were down-regulated in T. canis infected mice. These results suggest that Toxocara spp. infection may impair BoHV-5 immunization and should be considered for efficient herd immunization.

Overcoming recalcitrance in Porphyridium aerugineum Geitler employing encapsulation-dehydration cryopreservation methods.

Cultures of the recalcitrant microalga Porphyridium aerugineum were cryopreserved. A two-step, uncontrolled rapid freezing protocol, using methanol as cryoprotectant resulted in 23.8 percent viable cells. Cultures in the exponential growth phase, grown under low light intensity to prevent vacuole formation in cells, cryopreserved using a passive freezer, showed 22.4 percent viability. This value was enhanced to 31.5 percent when a controlled-rate freezer was employed. Optimized cultures in the exponential growth phase, cultivated in medium supplemented or not with vitamin B12, were then tested for freezing using the encapsulation-dehydration protocol. High cell loss was observed early during the sorbitol dehydration steps, but 63.6 percent of the remaining encapsulated cells were viable after thawing. This study confirmed the potential of encapsulation-dehydration as a method allowing to improve the low viability obtained with two-step freezing protocols. It also showed the importance of monitoring the response of algal cells to bead osmotic and evaporative dehydration pretreatments before freezing.

TYPE TESTING OF LiF:Mg,Cu,P (TLD-100H) WHOLE-BODY DOSEMETERS FOR THE ASSESSMENT OF Hp(10) AND Hp(0.07).

In this work, the initial results of the type testing of the LiF:Mg,Cu,P (TLD-100H) whole-body personal dosemeters are presented. An assessment of reproducibility, linearity of the response, the residual signal as a function of the dose, energy and angular dependence of the response was performed. In general, the dosemeters show good reproducibility for different dose values and a linear behaviour for a range between 0.1 and 300 mSv. The detection limits obtained are lower than 50 µSv. The system presents a good energy and angular response for different radiation qualities.