Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Influences of a Supplemental Blend of Essential Oils Plus 25-Hydroxy-Vit-D3 and Zilpaterol Hydrochloride (ß2 Agonist) on Growth Performance and Carcass Measures of Feedlot Lambs Finished under Conditions of High Ambient Temperature.

Forty-eight Pelibuey × Katahdin male intact lambs (25.12 ± 3.79 kg LW) were used in a 70-d growing-finishing trial. Dietary treatments consisted of total mixed corn-based diet supplemented with: (1) no feed additives (Control); (2) 150 mg of essential oils blend plus 0.10 mg of 25-hydroxy-Vit-D3/kg diet offered throughout the 70-d experimental period (EOD3); (3) Control diet fed during the first 35 days and zilpaterol hydrochloride (ZH) supplementation at 6 mg/kg diet offered during the final 35 days of the experiment (32 days with ZH with a withdrawal 3-d before harvest), and (4) basal diet supplemented with EOD3 during first 35 days finishing, and EOD3 in combination with ZH (EOD3 + ZH) during the subsequent 32-days with ZH withdrawal 3 days before harvest. The temperature-humidity index during the experiment averaged 80.4 ± 3.2. There were no treatment interactions (p > 0.20) on growth performance and carcass measures. Supplemental EOD3 did not affect (p = 0.43) dry matter intake (DMI), but increased (p < 0.01) carcass adjusted average daily gain (ADG, 9.2%), gain efficiency (GF, 6.7%), and observed vs. expected dietary net energy for maintenance (NEm, 4.8%) and for gain (NEg, 6.4%). Supplemental ZH did not affect dry matter intake (DMI, p = 0.50) but increased (p < 0.01) carcass adjusted ADG (14.5%), GF (13%) and observed vs. expected dietary NEm (9%) and NEg (11.7%). Compared to control lambs, the combination of both additives increased ADG (24.9%), GF (21.2%), and observed vs. expected dietary NEm and NEg (14.2% and 18.9%, respectively). There were no treatment interactions on carcass characteristics, visceral organ mass, or on gene expression of IGF1, IGF2 and mTOR in longissimus muscle (LM). Supplemental EOD3 increased hot carcass weight (HCW; 4.0%, p < 0.01) but did not affect other carcass measures. Supplemental EOD3 decreased (3%, p = 0.03) intestine mass weight (g intestine/kg empty body weight). Supplemental ZH increased HCW (6%, p < 0.01), dressing percentage (1.7%, p = 0.04), and LM area (9.7%, p < 0.01), and decreased kidney-pelvic-fat percentage (16.2%, p < 0.01), fat thickness (14.7%, p = 0.03), and visceral fat. Compared to controls, the combination of EOD3 with ZH increased HCW (10.2%). It is concluded that growth performance responses to supplemental EOD3 and ZH are additive. Both supplements can be fed in combination without detrimental effects on expected benefits when fed separately. In addition, ZH supplementation improves carcass traits.

Ethylene dimethanesulfonate effects on gene promoter activities related to the endocrine function of immortalized Leydig cell lines R2C and MA-10.

Ethylene dimethanesulfonate (EDS) is a molecule with known selective cytotoxicity on adult Leydig cells. A single intraperitoneal injection in rats but not mice, leads to male androgen deprivation and infertility. In vitro studies using rat and mouse immortalized Leydig cell lines, showed similar effects of cell death promoted by EDS in rat cells as seen in vivo, and suggest that EDS affects gene transcription, which could firstly compromise steroidogenesis before the apoptosis process. Using gene reporter assay, this study aimed to investigate EDS effects on the promoter activity of genes important for endocrine function (Star, Insl3) and response to toxic agents (Gsta3) in immortalized Leydig cell lines (rat R2C and mouse MA-10 cells), as well as identify possible EDS-responsive elements in the Star gene promoter. EDS exposure of R2C and MA-10 Leydig cells increased Gsta3 promoter activity after 4 h of treatment and decreased Insl3 promoter activity only in R2C cells after 24 h of treatment. EDS also decreased Star promoter activity in both Leydig cell lines. Using R2C cells, the EDS-responsive region in the Star promoter was located between -400 and -195 bp. This suggests that this region and the associated transcription factors, which include MEF2, might be targeted by EDS. Additional somatic gonadal cell lines expressing Star were used and EDS did not affect Star promoter activity in DC3 granulosa cells while Star promoter activity was increased in MSC-1 Sertoli cells after 24 h of treatment. This study contributes to the knowledge regarding the mechanism of EDS action in Leydig cells, and in other gonadal cell lineages, and brings new light regarding the rats and mice differential susceptibility to EDS effects, in addition to providing new avenues for experimental approaches to better understand Leydig cell function and dynamics in different rodent species.

Influence of the postpolymerization type and time on the flexural strength and dimensional stability of 3D printed interim resins.

STATEMENT OF PROBLEM: The mechanical strength of 3-dimensionally (3D) printed interim resins is unclear but influenced by printing parameters. Evidence regarding standardization of the postpolymerization type and time for 3D printed interim resins is sparse. PURPOSE: The purpose of this in vitro study was to evaluate the influence of postpolymerization type and time on flexural strength and dimensional stability of 3D printed resins for interim restorations. MATERIAL AND METHODS: A total of 288 bars were 3D printed (Form 2; Formlabs, stereolithography-SLA, 50 µm, 30 degrees), (25×2×2 mm; International Organization for Standardization-ISO 4049:2019) abraded and randomly divided into 9 groups (n=30) according to postpolymerization (Ultraviolet device-UV; Microwave with water-MWA; Microwave without water-MW) and time (15, 20, and 30 minutes for UV; and 5, 8, and 10 minutes for MW and MWA). Each bar was then measured with digital calipers at 11 points for length, thickness, and width before and after postpolymerization to analyze dimensional stability. The flexural strength was then measured (σ; 980.6 N, 1 mm/minute) and the fractured surfaces were analyzed with scanning electron microscopy. The σ (MPa) data were evaluated by using a 2-way analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) pairwise comparisons test (α=.05). Dimensional stability data (mm) were analyzed by using the Kruskal-Wallis test and Dwass-Steel-Critchlow-Fligner multiple comparisons. The Weibull analysis was performed with σ data. RESULTS: The 2-way ANOVA revealed that all factors and their interaction were significant for σ (P<.001). The UV groups presented the highest σ values, being statistically higher than all MW and MWA groups. The Weibull analysis revealed that postpolymerization UV groups found the highest values regarding the characteristic strength, although the MW 8-minute group (13.71) found the highest value for the Weibull modulus. Furthermore, the Kruskal-Wallis test revealed that only the postpolymerization factor was significant for dimensional stability (P<.001). The postpolymerization microwave groups found greater expansion variations at all times, with the MW 8-minute group (0.78 ±0.54) presenting the greatest variation in dimensional stability. CONCLUSIONS: UV was determined to be the most suitable type of postpolymerization for interim printed resin among the postpolymerization methods, regardless of the application time. The postpolymerization MW groups found greater variations in dimensional stability.

Essential Oils Combined with Vitamin D3 or with Probiotic as an Alternative to the Ionophore Monensin Supplemented in High-Energy Diets for Lambs Long-Term Finished under Subtropical Climate.

Supplementation with natural additives such as essential oils (EO) or probiotics has resulted in comparable growth performance to that of supplemental monensin in fattening lambs in hot environments. Supra-supplementation levels of vitamin D3 improved the carcass weight and dressing percentage of steers fattened under tropical conditions. We hypothesized that certain combinations of these natural additives could be complementary. For this reason, a feeding trial was carried out using 48 Pelibuey × Katahdin non-castrated male lambs (107 ± 14 d age; 17.9 ± 2.51 kg LW). Lambs were fed an 88:12 concentrate to forage ratio basal diet supplemented (dry matter basis, DMI) with: (1) no additive (CON); (2) 28 mg monensin/kg diet (MON); (3) 150 mg of essential oils containing a combination of thymol, eugenol, vanillin, guaiac, and limonene plus 0.12 mg vitamin D3 (EO + D3)/kg diet; and (4) 300 mg of essential oils containing a combination of carvacrol and cynamaldehyde plus 2 g probiotic (2.2 × 108 CFU of bacillus subtilis/kg diet, EO + BS). Lambs were grouped by initial weight and assigned within six weight groupings to 24 pens (2 lambs/pen, 6 replicas per treatment) in a randomized complete block design. The experiment lasted 121 days. Daily maximal THI exceeded the 80 "danger or "emergency" range for 119 days of the 121 days of the trial. Lambs supplemented with MON had similar DMI, growth performance, and dietary energetics to those of CON lambs. Lambs supplemented with EO + BS had a greater (9.2%, p ≤ 0.05) average daily gain (ADG) than the CON and MON groups due to enhanced (10.2%, p ≤ 0.05) dry matter intake. Thus, gain efficiency (GF) and estimated dietary energy were similar for CON, MON, and EO + BS. Lambs receiving EO + D3 had similar (0.254 vs. 0.262 kg/d) ADG but a lower DMI (8%, p < 0.05) compared with EO + BS lambs. Consequently, GF and estimated dietary net energy were greater (4.9 and 3.7%, respectively; p ≤ 0.05) for EO + D3 lambs. Even when ambient heat load was elevated, the efficiency of utilization of dietary energy (observed-to-expected dietary net energy) was close to 1.00 (0.992) expected for EO + D3 lambs. In contrast, efficiency of energy utilization was depressed by -4.4% for lambs on the other treatments. Compared with the other treatments, lambs receiving EO + D3 had greater longissimus muscle area (5.6%, p < 0.05) and lower kidney pelvic fat (21.8%, p ≤ 0.05). There were no treatment effects on shoulder tissue composition or whole cuts (expressed as % of cold carcass weight). Compared to CON, lambs that were fed with natural additives showed 3.5% lower (p ≤ 0.05) intestine mass. All supplemental additives decreased visceral fat mass, which was minimal with EO + D3 treatment. Combinations of essential oils with vitamins or probiotics were superior to antibiotic monensin in finishing diets for feedlot lambs. Combining EO with probiotics promoted DM intake and gain but not gain efficiency, while combining EO with vitamin D3 supra-supplementation increased dietary energy efficiency and improved some carcass characteristics in lambs fattening under high ambient heat loads.

Effect of Combining the Ionophore Monensin with Natural Antimicrobials Supplemented in the Last Phase of Finishing of Lambs: Growth Performance, Dietary Energetics, and Carcass Characteristics.

With the aim of evaluating the effect of combining an antibiotic ionophore with plant extracts and probiotics on the productive efficiency (performance and carcass) during the last phase of lamb fattening, 24 Pelibuey × Katahdin male lambs (38.47 ± 3.92 kg, initial weight) were fed with a high-energy diet during for 56 days, and assigned, under a complete randomized block design experiment to one of the following supplement treatments: (1) 28 mg of monensin/kg diet DM supplemented alone (MON), (2) combination of MON plus 2 g/kg diet of a product contained Bacillus subtilis 2.2 × 108 CFU kg diet DM (MON + BS), (3) combination of MON + BS plus 300 mg essential oils/kg diet DM (MON + BS + EO), and (4) BS alone. At the end of the feeding trial (56-d), lambs were slaughtered and carcass variables were measured. Compared to the rest of the treatments, combining MON with BS improved dietary NE by 3.4% and the efficiency of utilization of dietary energy consumed. Inclusion of EO in the MON + BS combination resulted in a similar average daily weight gain (ADG) and feed efficiency (GF) when compared with MON + BS, but showed a lower dietary net energy (NE), hot carcass weight, and dressing percentage. Lambs receiving BS alone showed greater average ADG and dry matter intake (DMI) than lambs receiving MON + BS + EO, but similar feed GF and dietary NE. There were no treatment effects on tissue composition, whole cut, or visceral organ mass. It was concluded that combining probiotics with the ionophore monensin can improve the efficiency of dietary energy utilization in the last phase of finishing. Probiotics supplemented alone result in greater ADG without a difference in dietary energy efficiency when compared with MON alone. Inclusion of EO in the MON + BS combination did not show advantages; on the contrary, it reduced carcass weight and dressing percentage. It is necessary to further research the potential complementary effects of combining diverse sources of natural additives with synthetic antibiotics.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Peripheral isolation and demographic stability are reflected in the genetic diversity of the populations of the Helmeted Manakin: a bird endemic to the gallery forests.

The Cerrado encompasses a complex network of hydrographic basins, which is responsible for the formation and maintenance of the riparian and gallery forests. Alterations in the vegetation resulting from the paleoclimatic changes that occurred during the Pleistocene influenced the current distribution of these humid forests. To understand of the evolutionary dynamics of this landscape on the population structure of the associated organisms, we studied the population genetics of the Antilophia galeata (Pipridae), a bird endemic to the gallery forests of the Cerrado. For this, we evaluated the variability of the mitochondrial control region of 71 A. galeata specimens from 18 localities distributed throughout the Cerrado. The results indicated the existence of significant substructure among the populations located in the peripheral areas of the Cerrado, in comparison with the populations found in the central portion, reflecting historical changes in the environment. We also found high levels of diversity in all the populations, while the analysis of the demographic history revealed a scenario of stability. Overall, then, these findings indicate that the historical modifications of the gallery forest distribution may have been most accentuated in the peripheral zones, with a greater stability and connectivity persisting in the central portion of the biome.

New Isoquinoline Alkaloids from Paraphaeosphaeria sporulosa F03, a Fungal Endophyte Isolated from Paepalanthus planifolius.

As part of our continuing efforts to discover new bioactive compounds from endophytic fungal sources, we have investigated the extract of the Paraphaeosphaeria sporulosa F03 strain. The study led to the isolation of four new 3-methyl-isoquinoline alkaloids (1:  - 4: ) and four known polyketides (5:  - 8: ). The structures of compounds 1:  - 4: were elucidated by 1D and 2D NMR experiments and HRMS analysis. The absolute configuration of 4: was determined by comparison of its experimental electronic circular dichroism spectrum with calculated data. Compounds 1:  - 4: exhibited antifungal activity with minimal inhibitory concentration values ranging from 6.25 - 50 µg/mL against six Candida species but they did not present any cytotoxic activity against the human tumor cell lines A549 (lung), MCF-7 (breast), and HepG2 (hepatocellular). In addition, compound 4: exhibited antiplasmodial activity in the low micromolar range (IC50 = 4 µM).

Sensitivity of Colletotrichum acutatum Isolates from Citrus to Carbendazim, Difenoconazole, Tebuconazole, and Trifloxystrobin.

Postbloom fruit drop (PFD) of citrus is caused by the Colletotrichum acutatum and C. gloeosporioides species complexes. The disease is important when frequent rainfall occurs during the flowering period of citrus trees. In Brazil, until 2012, PFD was mainly controlled by preventive applications of the methyl-benzimidazole carbamate (MBC) carbendazim and demethylation-inhibitor (DMI) fungicides such as difenoconazole. Since then, mixtures containing the DMI tebuconazole and the quinone-outside inhibitor (QoI) trifloxystrobin have been commonly used. Fungicides are often applied preventively, sometimes even when conditions are not conducive for PFD development. Excessive fungicide applications may favor the selection of resistant populations of Colletotrichum spp. In this study, we assessed the fungicide sensitivity of C. acutatum isolates collected during the two distinct periods of PFD management in Brazil: before and after the trifloxystrobin and tebuconazole mixture became widely employed. The sensitivity of 254 C. acutatum isolates to carbendazim and difenoconazole and of 164 isolates to tebuconazole and trifloxystrobin was assessed. Mycelial growth inhibition of these isolates was evaluated for all the fungicides using either serial dilution of fungicide rates or the spiral gradient dilution method. In addition, inhibition of conidial germination was also assessed for trifloxystrobin. Analysis of partial ß-tub, cytb, and cyp51b gene sequences did not reveal any mutations related to resistance to MBCs, QoIs, and DMIs, respectively. In mycelial growth assays, mean EC50 values were 0.14, 0.11, and 0.21 µg/ml for difenoconazole, tebuconazole, and trifloxystrobin, respectively. The conidial germination inhibition by trifloxystrobin was similar among the tested isolates, and the mean EC50 value was 0.002 µg/ml. All isolates had similar mean mycelial growth inhibition for carbendazim, regardless of the fungicide concentrations. Therefore, based on similar EC50 values and molecular analyses, no shift in the sensitivity of isolates has been observed to the fungicides commonly used in different citrus-producing areas in Brazil.

GLS2 is protumorigenic in breast cancers.

Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2'-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.

Depressant effect of geraniol on the central nervous system of rats: Behavior and ECoG power spectra.

Geraniol is a monoterpene alcohol that is derived from the essential oils of aromatic plants, with anti-inflammatory, antimicrobial, antioxidant and neuroprotective properties. This study characterized the effect of geraniol on behavior and brainwave patterns in rats. Male rats were submitted to administration of geraniol (25, 50 and 100 mg/kg). The hole board (HB) and open field (OF) tests were performed to evaluate anxiety and motor behavior, respectively. In addition, barbiturate-induced sleeping time (BIST) was used to analyze sedative effect. Finally, electrocorticogram (ECoG) recordings were used to characterize brain-wave patterns. The results showed that geraniol treatment in rats decreased the distance traveled, rearing numbers and lead to increase in immobility time in HB and OF tests. In BIST test, geraniol treatment increased sleep duration but not sleep latency in the animals. Furthermore, geraniol-treated animals demonstrated an increase in the percentage of delta waves in the total spectrum power. Taken together, our results suggested that geraniol exerted a depressant effect on the central nervous system of rats.

The main spoilage-related psychrotrophic bacteria in refrigerated raw milk.

Refrigerated raw milk may contain psychrotrophic microorganisms that produce thermoresistant exoproteases and lipases, which may compromise the quality of processed fluid milk and dairy products during storage. The aim of this work was to quantify and identify the deteriorating psychrotrophic microbiota in Brazilian refrigerated raw milk using genetic diversity analysis. The mean psychrotrophic count was 1.1 × 104 cfu/mL. Of the total isolates, 47.8 and 29.8% showed deteriorating activity at 35°C within 48 h and 7°C within 10 d, respectively. Among the proteolytic species, more isolated by this study were Lactococcus lactis (27.3%), Enterobacter kobei (14.8%), Serratia ureilytica (8%), Aerococcus urinaeequi (6.8%), and Bacillus licheniformis (6.8%). Observed among lipolytics were E. kobei (17.7%), L. lactis (15.6%), A. urinaeequi (12.5%), and Acinetobacter lwoffii (9.4%). The isolates S. ureilytica, E. kobei, Pseudomonas spp., and Yersinia enterocolitica potentially produced alkaline metalloprotease (aprX). Despite the low counts, a considerable portion of the psychrotrophic microbiota presented spoilage potential, which reaffirms the need for rigor in the control of contamination and the importance of rapid processing as factors that maintain the quality of milk and dairy products.

18F-Fluoride PET/CT and 99mTc-MDP SPECT/CT can detect bone cancer at early stage in rodents

Noninvasive imaging using positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT) are considered revolutionized approaches to detect bone cancer. Both PET/CT and SPECT/CT technologies have advanced to permit miniaturization, which has provided the advantage of including animals as their own controls in longitudinal studies. The present study was designed to evaluate the potential of PET/CT and SPECT/CT as research tools to detect bone cancer in rats. We used a rat model of bone cancer induced by injecting Walker 256 tumor cells into the femoral cavity. Computed tomography demonstrated that rats presented a solid tumor at 15 days post injection (dpi). However, CT was not an effective method for identifying tumors at an earlier time point (8 dpi), when mechanical hyperalgesia (the most common symptom during bone cancer progression) had already initiated. At this early stage, PET/CT and SPECT/CT analysis detected higher uptake in the injected femur of the tracers F-18-Fluoride and Tc-99m-Methyl diphosphonate (Tc-99m-MDP), respectively. These findings demonstrated for the first time that both F-18-Fluoride PET/CT and Tc-99m-MDP SPECT/CT can detect cancer at early stages in rats and advocates for the PET/SPECT/CT as research tools to evaluate bone cancer in further longitudinal studies involving small animals.

Reproductive disorders in female rats after prenatal exposure to betamethasone.

Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation and decreasing mortality. Previous studies in rats reported male programming and alteration in sperm parameters and sexual behavior following intrauterine betamethasone exposure. The impact on the female reproductive development is not known. In this study, rat female offspring was assessed for sexual development, morphophysiology of the reproductive tract and fertility after maternal exposure to 0.1 mg kg-1 of betamethasone or vehicle on gestational days 12, 13, 18 and 19. The treatment promoted reduction of litter weight on postnatal day 1, morphological masculinization in females, delay in the age of puberty onset, reduction in estrus number, increase in estrous cycle length and increase in luteinizing hormone serum levels and uterus weight. The females from the betamethasone group showed an increase of myometrial uterine area and decrease in endometrial uterine area. These animals also performed less lordosis during the sexual behavior test and showed impaired reproductive performance. The uterus showed higher contraction in the treated group as shown by a pharmacological assay. In conclusion, prenatal betamethasone exposure in rats promoted female masculinization, altered sexual development and reproductive parameters. Copyright © 2017 John Wiley & Sons, Ltd.

Neuroprotección por ácido valproico y cambios en la expresión de Bcl-2 y caspasa-3 activada en ratas sometidas a isquemia/reperfusión / Neuroprotective action of valproic acid accompanied of the modification on the expression of Bcl-2 and activated caspase-3 in the brain of rats submitted to ischemia/reperfusion

El ácido valproico, que además de ser un conocido antiepiléptico, una serie de trabajos en los últimos años lo proponen como un agente neuroprotector. En éste trabajo se investigó primeramente, si el ácido valproico protege a las neuronas del daño producido por el estrés oxidativo inducido por la isquemia-reperfusión en el cerebro de ratas sanas sometidas a la oclusión transitoria de la arteria cerebral media derecha; en segundo lugar, se indagó si este fármaco induce cambios en la expresión de Bcl-2 y caspasa 3-activada como un posible mecanismo de acción sobre la muerte celular del tipo apoptótico. La evaluación neurológica de los animales que fueron sometidos a isquemia/reperfusión y recibieron ácido valproico fue mejor que los que no lo recibieron. Por otro lado, los niveles de malondialdehído en el hemisferio cerebral derecho en las ratas tratadas con ácido valproico fueron inferiores a los del mismo hemisferio del grupo control, mientras la cantidad de proteínas carboniladas se redujeron un 67% en comparación al grupo control. Además, se encontró por western blot, que en homogeneizados de tejido cerebral de los animales sometidos a isquemia/reperfusión y que recibieron ácido valproico, hubo un aumento significativo de la densidad de las bandas correspondientes a Bcl-2 y una disminución de caspasa 3-activada en comparación a los que no fueron tratados con este fármaco. Se concluye que el tratamiento con ácido valproico previno el déficit neurológico en ratas sanas sometidas a isquemia-reperfusión, bloqueando el efecto de los radicales libres sobre lípidos y proteínas de la corteza cerebral afectada y se sugiere que posiblemente este fármaco interviene en la muerte por apoptosis inducida durante este tipo de lesión, pudiendo ser una alternativa terapéutica en el tratamiento de la isquemia cerebral.

Valproic acid, apart from being known as an anti-epileptic drug, has been proposed in the past few years, as a neuroprotective agent. The purpose of this study was to investigate firstly, if valproic acid protects the neurons from the damage produced by oxidative stress induced by ischemia-reperfusion in the brain of healthy rats, under the transitory occlusion of the right middle cerebral artery. Secondly it was studied if this antiepileptic drug induces changes on the expression of Bcl-2 and activated caspase-3 as a possible mechanism of action on apoptosis. The neurological evaluation of the animals that were subject to ischemia-reperfusion and received valproic acid was better than the ones who didn’t receive it. On another subject, the levels of malondialdehyde on the right cerebral hemisphere in the rats treated with valproic acid were below the levels of the control group in the same hemisphere, whereas the amount of carbonylated proteins was reduced by 67% compared to the control group. Besides, it was found by western blot, that in homogenized brain tissue of the animals under ischemia-reperfusion which received valproic acid, there was a rise on the density of the bands corresponding to Bcl-2, and a reduction of activated 3-capase in comparison to the ones who were not treated with the antiepileptic drug. It’s concluded that the treatment with valproic acid prevented the neurological deficit in healthy rats under Ischemia-reperfusion, blocking the effect of free radicals on lipids and proteins of the affected brain cortex, and it is suggested that the same drug intervenes on apoptosis induced during this type of damage, being able to be a therapeutic alternative in the treatment of cerebral ischemia.

Tamoxifen Improves Final Height Prediction in Girls with McCune-Albright Syndrome: A Long Follow-Up.

BACKGROUND: McCune-Albright syndrome (MAS) is a genetic disorder characterized by the triad of fibrous dysplasia, skin hyperpigmentation, and autonomous hyperfunction of various endocrine organs. MAS frequently presents in females as precocious puberty (PP). Although many treatments have been proposed, the preservation of final height (FH) in these patients remains a challenge. OBJECTIVES: To evaluate the efficacy of tamoxifen in improving the FH prediction (FHP) in patients with MAS. METHOD: We retrospectively analyzed 8 female patients with MAS who presented with café-au-lait spots and gonadotropin-independent PP. The patients were followed for a mean period of 8.3 years (range: 3-16). RESULTS: All patients were treated with tamoxifen (10-20 mg/day) for 3-8 years (mean ± SD: 5.75 ± 2.05), which resulted in the cessation of vaginal bleeding and the stabilization of bone age maturation. There was a significant difference between the FHP at the beginning of treatment and at the end of treatment (145.1 ± 8.6 cm; Z score -2.84 ± 1.44 cm) and at the last evaluation (157.0 ± 9.2 cm; Z score -0.85 ± 0.54 cm; p < 0.001). CONCLUSION: Our results support a role for tamoxifen in improving the FHP in patients with MAS.

Neuroprotective action of valproic acid accompanied of the modification on the expression of Bcl-2 and activated caspase-3 in the brain of rats submitted to ischemia/reperfusion. / Neuroprotección por ácido valproico y cambios en la expresión de Bcl-2 y caspasa-3 activada en ratas sometidas a isquemia/reperfusión

Valproic acid, apart from being known as an anti-epileptic drug, has been proposed in the past few years, as a neuroprotective agent. The purpose of this study was to investigate firstly, if valproic acid protects the neurons from the damage produced by oxidative stress induced by ischemia-reperfusion in the brain of healthy rats, under the transitory occlusion of the right middle cerebral artery. Secondly it was studied if this antiepileptic drug induces changes on the expression of Bcl-2 and activated caspase-3 as a possible mechanism of action on apoptosis. The neurological evaluation of the animals that were subject to ischemia-reperfusion and received valproic acid was better than the ones who didn't receive it. On another subject, the levels of malondialdehyde on the right cerebral hemisphere in the rats treated with valproic acid were below the levels of the control group in the same hemisphere, whereas the amount of carbonylated proteins was reduced by 67% compared to the control group. Besides, it was found by western blot, that in homogenized brain tissue of the animals under ischemia-reperfusion which received valproic acid, there was a rise on the density of the bands corresponding to Bcl-2, and a reduction of activated 3-capase in comparison to the ones who were not treated with the antiepileptic drug. It's concluded that the treatment with valproic acid prevented the neurological deficit in healthy rats under Ischemia-reperfusion, blocking the effect of free radicals on lipids and proteins of the affected brain cortex, and it is suggested that the same drug intervenes on apoptosis induced during this type of damage, being able to be a therapeutic alternative in the treatment of cerebral ischemia.

Performance and morphometry of the intestinal mucosa of laying hens fed diets containing xylanase

The objective of this study was to evaluate the effect of dietary energy level reduction and xylanase inclusion on the performance and on intestinal mucosa morphometry of two- to six-week-old laying hens. In total, 400 Hy-line W36 laying hens were distributed according to a completely randomized design in 2 x 2 factorial arrangement (energy level x inclusion of xylanase), totaling four treatments with 10 replicates of 10 birds per experimental unit. The following treatments were evaluated: positive control (balanced diet); positive control + xylanase; negative control (diet with of 100 kcal ME reduction /kg); negative control + xylanase. Body weight, weight gain, feed conversion ratio, uniformity and livability were not influenced by diets with metabolizable energy reduction and xylanase inclusion; however, the addition of xylanase to the diets resulted in shallower crypts depth and greater villus:crypt ratio in the ileum. The energy reduction of the diet associated with the supplementation of xylanase did not influence performance, but increased the feed intake of 2- to 6-week-old laying hens and increased villus height in the ileum of 6-wk-old hens. Xylanase reduces crypt depth in the ileum of 6-week-old hens.(AU)