X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene.

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.

Infants Receiving Very Early Antiretroviral Therapy Have High CD4 Counts in the First Year of Life.

We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. CLINICAL TRIALS REGISTRATION: NCT02140255.

Summating Potential as Marker of Intracochlear Position in Bipolar Electrocochleography.

OBJECTIVES: Cochlear implantation criteria include subjects with residual low-frequency hearing. To minimize implantation trauma and to avoid unwanted interactions of electric- and acoustic stimuli, it is often recommended to stop cochlear implantation before the cochlear implant (CI) reaches the cochlear partition with residual hearing, as determined by an audiogram. For this purpose, the implant can be used to record acoustically evoked signals during implantation, including cochlear compound action potentials (CAP), cochlear microphonics (CMs), and summating potentials (SPs). The former two have previously been used to monitor residual hearing in clinical settings. DESIGN: In the present study we investigated the use of intracochlear, bipolar SP recordings to determine the exact cochlear position of the contacts of implanted CIs in guinea pig cochleae (n = 13). Polarity reversals of SPs were used as a functional marker of intracochlear position. Micro computed tomography (µCT) imaging and a modified Greenwood function were used to determine the cochleotopic positions of the contacts in the cochlea. These anatomical reconstructions were used to validate the SP-based position estimates. RESULTS: The precision of the SP-based position estimation was on average within ± 0.37 octaves and was not impaired by moderate hearing loss caused by noise exposure after implantation. It is important to note that acute hearing impairment did not reduce the precision of the method. The cochleotopic position of CI accounted for ~70% of the variability of SP polarity reversals. Outliers in the dataset were associated with lateral CI positions. Last, we propose a simplified method to avoid implantation in functioning parts of the cochlea by approaching a predefined frequency region using bipolar SP recordings through a CI. CONCLUSIONS: Bipolar SP recordings provide reliable information on electrode position in the cochlea. The position estimate remains reliable after moderate hearing loss. The technique presented here could be applied during CI surgery to monitor the CI approach to a predefined frequency region.

Milk kefir alters fecal microbiota impacting gut and brain health in mice.

Kefir is a fermented beverage made of a symbiotic microbial community that stands out for health benefits. Although its microbial profile is still little explored, its effects on modulation of gut microbiota and production of short-chain fatty acids (SCFAs) seems to act by improving brain health. This work aimed to analyze the microbiota profile of milk kefir and its effect on metabolism, oxidative stress, and in the microbiota-gut-brain axis in a murine model. The experimental design was carried out using C57BL-6 mice (n = 20) subdivided into groups that received 0.1 mL water or 0.1 mL (10% w/v) kefir. The kefir proceeded to maturation for 48 h, and then it was orally administered, via gavage, to the animals for 4 weeks. Physicochemical, microbiological, antioxidant analyzes, and microbial profiling of milk kefir beverage were performed as well as growth parameters, food intake, serum markers, oxidative stress, antioxidant enzymes, SCFAs, and metabarcoding were analyzed in the mice. Milk kefir had 76.64 ± 0.42% of free radical scavenging and the microbiota composed primarily by the genus Comamonas. Moreover, kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (butyrate), and in the brain (butyrate and propionate). Kefir reduced triglycerides, uric acid, and affected the microbiome of animals increasing fecal butyrate-producing bacteria (Lachnospiraceae and Lachnoclostridium). Our results on the brain and fecal SCFAs and the antioxidant effect found were associated with the change in the gut microbiota caused by kefir, which indicates that kefir positively influences the gut-microbiota-brain axis and contributes to the preservation of gut and brain health. KEY POINTS: • Milk kefir modulates fecal microbiota and SCFA production in brain and colon. • Kefir treatment increases the abundance of SCFA-producing bacteria. • Milk kefir increases antioxidant enzymes and influences the metabolism of mice.

Effects of Fructose and Palmitic Acid on Gene Expression in Drosophila melanogaster Larvae: Implications for Neurodegenerative Diseases.

One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use Drosophila melanogaster to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of D. melanogaster were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.

High-intensity interval training attenuates the effects caused by arterial hypertension in the ventral prostate.

BACKGROUND: The prostatic effects induced by arterial hypertension is very controversial and its mechanism is unclear. High-intensity interval training (HIIT) is an exercise considered to be hypotensive. The objective of this work was to investigate the molecular, biochemical, and morphological effects of 8 weeks of HIIT in the prostatic tissue of spontaneously hypertensive rats (SHR). METHODS: Twenty male SHR rats, 51.4 weeks old, were used. The SHR animals were divided into two groups: spontaneously sedentary hypertensive and spontaneously hypertensive submitted to HIIT. We analyze androgens receptor and glucocorticoid receptors in the prostate. Still, we verify effects of the hypertension and HIIT on the physiopathology prostatic, for immunohistochemistry investigated BCL-2, BAX, IGF-1, FAS/CD95, data's inflammatory tumour necrosis factor α, nuclear factor kappa B and interleukin (IL)-6, anti-inflammatory IL-10. The echocardiographic evaluation was performed at the baseline and after the training period. RESULTS: Arterial hypertension promote high prostatic intraepithelial neoplasia incidence in the prostate, increases IGF-1, BCL-2 (p < 0.05), and inflammatory proteins (p < 0.05). Eight weeks of HIIT training reduced the arterial pressure and increase the concentration of tissue collagen and intracellular glycogen and showed a higher expression of BAX, FAS/CD95, and IL-10 proteins (p < 0.05), coinciding with a lower incidence of lesions and lower prostate weight (p < 0.05) and reduction of the BCL-2 and IGF-1. CONCLUSION: Our data suggested that arterial hypertension suppressed apoptosis and increased damage prostatic. On other hand, HIIT promotes morphology and function improves in the prostatic environment, inhibited inflammation, and increased apoptosis.

Different cell death mechanisms are involved in leprosy pathogenesis.

Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.

Unraveling the Cardiac Effects Induced by Carvacrol in Spontaneously Hypertensive Rats: Involvement of Transient Receptor Potential Melastatin Subfamily 4 and 7 Channels.

ABSTRACT: Accumulating evidence indicates that transient receptor potential (TRP) channels are involved in the pathophysiological process in the heart, and monoterpenes, such as carvacrol, are able to modulate these channels activity. In this article, our purpose was to evaluate the direct cardiac effect of carvacrol on the contractility of cardiomyocytes and isolated right atria from spontaneously hypertensive and Wistar Kyoto rats. In this way, in vitro experiments were used to evaluate the ventricular cardiomyocytes contractility and the Ca2+ transient measuring, in addition to heart rhythm in the right atria. The role of TRPM channels in carvacrol-mediated cardiac activities was also investigated. The results demonstrated that carvacrol induced a significant reduction in ventricular cell contractility, without changes in transient Ca2+. In addition, carvacrol promoted a significant negative chronotropic response in spontaneously hypertensive and Wistar Kyoto rats' atria. Selective blockage of TRPM channels suggests the involvement of TRP melastatin subfamily 2 (TRPM2), TRPM4, and TRPM7 in the carvacrol-mediated cardiac effects. In silico studies were conducted to further investigate the putative role of TRPM4 in carvacrol-mediated cardiac action. FTMap underscores a conserved pocket in both TRPM4 and TRPM7, revealing a potential carvacrol binding site, and morphological similarity analysis demonstrated that carvacrol shares a more than 85% similarity to 9-phenanthrol. Taken together, these results suggest that carvacrol has direct cardiac actions, leading to reduced cellular contractility and inducing a negative chronotropic effect, which may be related to TRPM7 and TRPM4 modulation.

Physical exercise regulates apoptosis and prostatic inflammatory effects induced by high-fat diet in PPAR-alpha deleted mice.

The high-fat diet (HFD) promotes obesity and develops inflammation, causing dysregulation of energy metabolism and prostatic neoplastic tissue changes. PPARɑ deletion leads to loss of homeostasis between the pro and anti-inflammatory response, and dysregulation of lipid metabolism, causing changes in different physiological processes and damage to the prostate. On the other hand, aerobic physical exercise has been suggested as a non-pharmacological tool to improve energy metabolism and cellular metabolism in the prostate, however, the underlying molecular mechanism remains unclear. the current study aimed to evaluate PPARα as a possible regulator of the protective effects of aerobic physical exercise in the prostate by examining prostatic alterations in wild-type and PPARα deletion mice fed a standard diet or an HFD. Wild-type and PPARα-null mice were fed a standard or HFD diet for 12 weeks, and submitted to aerobic physical exercise for 8 weeks. The HFD promoted the increase of inflammatory markers IL-6, TNF-α, NF-kB, and an increase of inflammatory foci in animals in both genotypes. Although the PPARα deletion animals submitted to the aerobic physical exercise were not able to regulate response pro-inflammatory, but promoted an increase in IL-10 in the prostate. In animals WT, the aerobic physical exercise, reduced all inflammatory markers, improve the inflammatory response, and showed a higher expression of BAX and IL-10 proteins was protective against prostatic tissue lesions. Suggested that PPARα deletion associated with HFD suppressed apoptosis and increased damage prostate. On other hand, aerobic physical exercise improves prostatic tissue by increasing the response to anti-inflammatory and apoptosis protein.

Strength training protects against prostate injury in alcoholic rats.

Alcoholic injury can alter the hormonal signaling pathway and lead to glucose and lipid metabolism disorders. In this study, we investigated whether the strength training could exert protective effects against the alterations caused by ethanol consumption on prostatic metabolism. A UChB, ethanol-preferring rats were used in this study. Strength training was conducted for 3 days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a strength training protocol. The reduced alcohol consumption by strength training was accompanied by increased glucose, serum lipid profile, total protein levels, and reduced hormonal levels. The results of protein expression of prostatic tissues in the ethanol- and strength training-treated groups indicated that "steroidal hormone receptors," "fatty acid translocation," and "cell regulation" were significantly different between ethanol- and strength training-treated groups. Taken together, these findings show that strength training effectively ameliorated prostatic injuries in alcoholic rats at least partially by acting on lipids receptors and steroidal hormone receptors pathway, suggesting the strength training as a potential novel therapeutic strategy for treating prostate injuries caused by ethanol.

Lactobacillus paracasei DTA81, a cholesterol-lowering strain having immunomodulatory activity, reveals gut microbiota regulation capability in BALB/c mice receiving high-fat diet.

AIMS: In-vitro/In-vivo evaluation of cholesterol-lowering probiotic strain Lactobacillus paracasei DTA81 and the possible connection with the gut microbiota modulation. METHODS AND RESULTS: In the present study, strain DTA81 has been evaluated for the possible influence on blood lipid and glucose concentrations, modulation of the immune system, gastrointestinal survivability and modulation of gut microbiota in BALB/c mice receiving a high-fat diet. After 6 weeks of treatment, a significant reduction of total cholesterol and fasting blood sugar (FBS) among animals treated with L. paracasei DTA81 has been recorded. Comparison of colon tissue levels of different cytokines revealed a significant reduction of the inflammatory cytokine interleukin-6. The comparison of gut microbiota using the 16S rRNA approach indicated that the treatment with L. paracasei DTA81 significantly increased the taxa Bacteroidetes and Coprococcus. Moreover, the genome of DTA81 was sequenced for the in-silico assessment, and the analysis indicated the presence of cholesterol assimilation-related genes as well as the absence of negative traits such as transmissible antibiotic resistance genes, plasmids and prophage regions. CONCLUSION: The outcome of this study revealed the in-vitro and in-vivo properties of L. paracasei DTA81 and the possible mechanism between consumption of this strain, the abundance of Bacteriodetes/Coprococcus taxa, immunomodulatory activity and the subsequent reduction of cholesterol/FBS in BALB/c mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus paracasei DTA81 as a non-pharmacological potential probiotic supplement can influence metabolic homeostasis in individuals, particularly those adopting high-fat diets, and it can contribute to reduce coronary heart disease.

Habitual versus affective motivations in obsessive-compulsive disorder and alcohol use disorder.

OBJECTIVE: To (1) confirm whether the Habit, Reward, and Fear Scale is able to generate a 3-factor solution in a population of obsessive-compulsive disorder and alcohol use disorder (AUD) patients; (2) compare these clinical groups in their habit, reward, and fear motivations; and (3) investigate whether homogenous subgroups can be identified to resolve heterogeneity within and across disorders based on the motivations driving ritualistic and drinking behaviors. METHODS: One hundred and thirty-four obsessive-compulsive disorder (n = 76) or AUD (n = 58) patients were assessed with a battery of scales including the Habit, Reward, and Fear Scale, the Yale-Brown Obsessive-Compulsive Scale, the Alcohol Dependence Scale, the Behavioral Inhibition/Activation System Scale, and the Urgency, (lack of ) Premeditation, (lack of ) Perseverance, Sensation Seeking, and Positive Urgency Impulsive Behavior Scale. RESULTS: A 3-factor solution reflecting habit, reward, and fear subscores explained 56.6% of the total variance of the Habit, Reward, and Fear Scale. Although the habit and fear subscores were significantly higher in obsessive-compulsive disorder (OCD) and the reward subscores were significantly greater in AUD patients, a cluster analysis identified that the 3 clusters were each characterized by differing proportions of OCD and AUD patients. CONCLUSIONS: While affective (reward- and fear-driven) and nonaffective (habitual) motivations for repetitive behaviors seem dissociable from each other, it is possible to identify subgroups in a transdiagnostic manner based on motivations that do not match perfectly motivations that usually described in OCD and AUD patients.

Efficacy of Three Antiretroviral Regimens Initiated during Pregnancy: Clinical Experience in Rio de Janeiro.

Few studies have compared the clinical efficacy and adverse events of combined antiretroviral therapy (cART) regimens in pregnant women seeking obstetrical care. The objective of this study was to compare the efficacy (virus load response), adverse events, and obstetrical and neonatal outcomes of three different regimens of cART in HIV-infected pregnant women initiating treatment in Rio de Janeiro, Brazil. This was a retrospective cohort study of cART-naive pregnant women who initiated either ritonavir-boosted protease inhibitors (atazanavir or lopinavir), efavirenz, or raltegravir plus a backbone regimen. From 2014 to 2018, 390 pregnant women were followed over time. At baseline, the median viral load (VL) for HIV was 4.1 log copies/ml. Among participants who received cART for 2 to 7 weeks, the VL decline was greater for raltegravir (2.24 log copies/ml) than for efavirenz or protease inhibitors (P < 0.001). Virologic suppression was achieved in 87% of women on raltegravir near delivery versus 73% on efavirenz and 70% on protease inhibitors (P = 0.011). Patients on raltegravir achieved virologic suppression faster than those on other regimens (P = 0.019). Overall, the HIV perinatal infection rate was 1.5%. This clinical study compared three potent and well-tolerated cART regimens and demonstrated that a higher proportion of participants on raltegravir achieved an undetectable HIV VL near delivery (P = 0.011) compared to the other arms. These findings suggest that raltegravir-containing regimens are optimal regimens for women with HIV initiating treatment late in pregnancy.

Genotoxicity assessment of four novel quinazoline-derived trypanocidal agents in the Drosophila wing somatic mutation and recombination test.

Chagas disease, caused by the protozoan Trypanosoma cruzi, has increased in the world due to migration, travelling and climate change; at present, the principal problem is that common trypanocidal agents have resulted in toxic or inconvenient side effects. We tested for genotoxicity in the standard (ST) and high bioactivation (HB) crosses of Drosophila wing somatic mutation and recombination test, four novel trypanocidal agents derived from 2, 4, 6-triaminquinazoline (TAQ): 2,4-diamino-6 nitro-1,3 diazonaftalene (S-1QN2-1), 2,4-diacetamino-6-amino 1,3 diazonaftalene (D-1), N6-(4,methoxybenzyl)quinazoline-2,4,6-triamine (GHPM) and N6-[4-(trifluoromethoxy)benzyl]quinazoline-2,4,6-triamine (GHPMF) at 1.9, 3.9, 7.9 and 15 µM, respectively. Also, high-pressure liquid chromatography (HPLC) analysis was run to determine the remanence of either drug in flare, and Oregon R(R)-flare flies emerged from treated larvae. S-1QN2-1 showed genotoxicity only in the ST cross, increasing the small, large and total spot frequencies at all concentrations and twin spots only at 1.9 µM; D-1 and GHPM showed significant increments of large spots only at 15 µM in the ST cross; GHPMF was not genotoxic at any concentration or either cross. In the mwh clones accumulated distribution frequencies analysis, associated with disrupted cell division, S-1QN2-1 caused alterations in the ST cross at all concentrations but only at 15 µM in the HB cross; D-1 caused alterations at 3.9, 7.9 and 15 µM in the ST cross and at 1.9 and 15 µM in the HB cross; GHPM caused alterations at 7.9 and 15 µM in the ST cross and also at 1.9, 3.9 and 7.9 µM in the HB cross; GHPMF caused those alterations at all concentrations in the ST cross and at 1.9, 3.9 and 7.9 µM in the HB cross. The HPLC results indicated no traces of either agent in the flare and Oregon R(R)-flare flies. We conclude that S-1QN2-1 is clearly genotoxic, D-1 and GHPM have an unclear genotoxicity and GHPMF was not genotoxic; all quinazoline derivatives disrupted cell division. GHPMF is a good candidate to be tested in other genotoxicity and cytotoxic bioassays. The differences in the genotoxic activity of these trypanocidal agents are correlated with differences in their chemical structure.

Synbiotic VSL#3 and yacon-based product modulate the intestinal microbiota and prevent the development of pre-neoplastic lesions in a colorectal carcinogenesis model.

Colorectal cancer is a public health problem, with dysbiosis being one of the risk factors due to its role in intestinal inflammation. Probiotics and synbiotics have been used in order to restore the microbiota balance and to prevent colorectal carcinogenesis. We aimed to investigate the effects of the probiotic VSL#3® alone or in combination with a yacon-based prebiotic concentrate on the microbiota modulation and its influence on colorectal carcinogenesis in an animal model. C57BL/6J mice were divided into three groups: control (control diet), probiotic (control diet + VSL#3®), and synbiotic (yacon diet + VSL#3®). The diets were provided for 13 weeks and, from the third one, all animals were subjected to induction of colorectal cancer precursor lesions. Stool samples were collected to evaluate organic acids, feces pH, ß-glucuronidase activity, and microbiota composition. The colon was used to count pre-neoplastic lesions and to determine the cytokines. The microbiota composition was influenced by the use of probiotic and synbiotic. Modifications were also observed in the abundance of bacterial genera with respect to the control group, which confirms the interference of carcinogenesis in the microbiota. Pre-neoplastic lesions were reduced by the use of the synbiotic, but not with the probiotic. The protection provided by the synbiotic can be attributed to the modulation of the intestinal inflammatory response, to the inhibition of a pro-carcinogenic enzyme, and to the production of organic acids. The modulation of the composition and activity of the microbiota contributed to beneficial changes in the intestinal microenvironment, which led to a reduction in carcinogenesis. KEY POINTS: • Synbiotic reduces the incidence of colorectal cancer precursor lesions. • Synbiotic modulates the composition and activity of intestinal microbiota. • Synbiotic increases the abundance of butyrate-producing bacteria.

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate.

BACKGROUND: Altered lipid metabolism is an important characteristic of neoplastic cells, with androgens and growth factors being major regulatory agents of the lipid metabolism process. We investigated the effect of physical resistance training on lipid metabolism and apoptosis in the adult Wistar rat prostate. METHODS: Two experimental groups represented sedentary and physical resistance training. Three days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a physical resistance exercise protocol. Two days after the last training session, rats were anesthetized and sacrificed for blood and prostate analysis. RESULTS: Physical exercise improved feeding efficiency, decreased weight gain, regulated the serum-lipid profile, and modulated insulin-like growth factor-1 (IGF-1) and free testosterone concentration. Furthermore, upregulation of cluster of differentiation 36 (CD36), sterol regulatory element binding protein-1 (SREBP-1), sterol regulatory element-binding protein cleavage-activating protein (SCAP), and reduced lysosome membrane protein (LIMPII) expression were also observed in the blood and prostates of trained rats. Consistent with these results, caspase-3 expression was upregulating and the BCL-2/Bax index ratio was decreased in trained rats relative to sedentary animals. CONCLUSIONS: In this work, physical resistance training can alter lipid metabolism and increase markers of apoptosis in the prostate, suggesting physical resistance training as a potential novel therapeutic strategy for treating prostate cancer.

Larvicide Activity on Aedes aegypti of Essential Oil Nanoemulsion from the Protium heptaphyllum Resin.

The aim of this work was to prepare a nanoemulsion containing the essential oil of Protium heptaphyllum resin and to evaluate the larvicidal activity and the residual larvicidal effect against Aedes aegypti. The essential oil was identified by gas chromatography coupled to a mass spectrometer, and the nanoemulsions were prepared using a low-energy method and characterized by photon correlation spectroscopy. The results indicated the major constituents as p-cimene (27.70%) and α-Pinene (22.31%). Nanoemulsions had kinetic stability and a monomodal distribution in a hydrophilic-lipophilic balance of 14 with particle diameters of 115.56 ± 1.68 nn and zeta potential of -29.63 ± 3.46 mV. The nanoemulsion showed larvicidal action with LC50 = 2.91 µg∙mL-1 and residual larvicidal effect for 72 h after application to A. aegypti larvae. Consequently, the nanobiotechnological product derived from the essential oil of P. heptaphyllum resin could be used against infectious disease vectors.

d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

Variable Ventilation Associated With Recruitment Maneuver Minimizes Tissue Damage and Pulmonary Inflammation in Anesthetized Lung-Healthy Rats.

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.

Mineral trioxide aggregate enriched with iron disulfide nanostructures: an evaluation of their physical and biological properties.

The purpose of this study was to characterize mineral trioxide aggregates (MTA) enriched with iron disulfide (FeS2 ) nanostructures at different concentrations, and to investigate their storage modulus, radiopacity, setting time, pH, cytotoxicity, and antimicrobial activity. Iron disulfide nanostructures [with particle size of 0.357 ± 0.156 µm (mean ± SD)] at weight ratios of 0.2, 0.4, 0.6, 0.8, and 1.0 wt% were added to white MTA (wMTA). The radiopacity, rheological properties, setting time, and pH, as well as the cytotoxicity (assessed using the MTT assay) and antibacterial activity (assessed using the broth microdilution test) were determined for MTA/FeS2 nanostructures. The nanostructures did not modify the radiopacity values of wMTA (~6 mm of aluminium); however, they reduced the setting time from 18.2 ± 3.20 min to 13.7 ± 1.8 min, and the storage modulus was indicative of a good stiffness. Whereas the wMTA/FeS2 nanostructures did not induce cytotoxicity when in contact with human pulp cells (HPCs) and human gingival fibroblasts (HGFs), they showed bacteriostatic activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. Adding FeS2 nanostructures to MTA might be an option for improving the root canal sealing and antibacterial effects of wMTA in endodontic treatments.