Cardiorespiratory fitness as a mediator in the relationship between lung function and blood pressure in adults.

It is unclear whether physical activity and cardiorespiratory fitness (CRF) are pathways that link low pulmonary function (LPF) to increased blood pressure (BP). Therefore, we investigated the extent to which CRF and moderate-to-vigorous physical activity (MVPA) mediate the relationship between LPF and high BP in adults. We conducted a cross-sectional study with 1,362 participants that underwent cardiopulmonary exercise testing (CPET), spirometry, and wore an accelerometer to determine physical activity patterns. We performed mediation analyses using structural equations considering peak oxygen uptake (V̇O2) and MVPA as mediators, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) as independent variables, and systolic and diastolic blood pressure (SBP, DBP) as dependent variables. The probability of alpha error was set at 5%. We found a significant total effect of FVC on SBP and DBP considering V̇O2 as mediator (P<0.01). Indirect effects were also significant, with 42.6% of the total effect of FVC on SBP and 77% on DBP mediated by V̇O2 (P<0.01). We did not observe a direct effect of FVC on SBP and DBP. Considering FEV1 as an independent variable, the total effect on SBP was also significant, as were the indirect effects, mediated by V̇O2 at 14.8% for SBP and 7.6% for DBP (P<0.01). We did not find an indirect effect of FVC or FEV1 considering the MVPA as a mediator. CRF mediates the pathway that links LPF and elevated BP. Therefore, CRF is more sensitive to variations in FVC and FEV1 than MVPA.

Anti-Inflammatory and Antioxidant Effects of the Indole-Derived N-Salicyloyltryptamine on Peritonitis and Joint Disability Induced by Carrageenan in Rodents.

Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats. Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO2 -) and thiobarbituric acid reactive species (TBARS) levels were determined. Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis. Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms.

Pregnancy in pigs: the journey of an early life.

Embryo mortality is responsible for greater losses in litter size in pigs. It is well known that pregnancy establishment is a complex process, and important changes occur continuously in both the corpora lutea and the endometrium, which varies depending on the pre-natal development phase: embryonic, pre-implantation or fetal stages. The placenta is a key organ responsible for the exchange of nutrients, metabolites and respiratory gases between mother and fetuses. The porcine placenta is diffuse, epitheliochorial, and placentation begins with implantation, which involves specialized cell adhesion and cell migration, leading to the attachment of the trophectoderm to the uterine endometrial lumen epithelium. The efficiency with which the placenta provides adequate amounts of nutrients and oxygen to the fetus is crucial for proper fetal growth and development. In the last decades, emphasis on selection for sow prolificacy has resulted in a substantial increase in the number of piglets born per litter, which had a direct effect on piglet quality, compromising birth weight and litter uniformity. Placental insufficiency will lead to fetal intrauterine growth restriction. This review addresses the main events of early embryo development, including preimplantation and implantation periods. In addition, placentation and its role on fetal development are covered, as well as intrauterine growth restriction, as it is a natural condition in the pig, with long lasting detrimental effects to the production chain.

Cardiorespiratory fitness as a mediator in the relationship between lung function and blood pressure in adults

It is unclear whether physical activity and cardiorespiratory fitness (CRF) are pathways that link low pulmonary function (LPF) to increased blood pressure (BP). Therefore, we investigated the extent to which CRF and moderate-to-vigorous physical activity (MVPA) mediate the relationship between LPF and high BP in adults. We conducted a cross-sectional study with 1,362 participants that underwent cardiopulmonary exercise testing (CPET), spirometry, and wore an accelerometer to determine physical activity patterns. We performed mediation analyses using structural equations considering peak oxygen uptake (V̇O2) and MVPA as mediators, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) as independent variables, and systolic and diastolic blood pressure (SBP, DBP) as dependent variables. The probability of alpha error was set at 5%. We found a significant total effect of FVC on SBP and DBP considering V̇O2 as mediator (P<0.01). Indirect effects were also significant, with 42.6% of the total effect of FVC on SBP and 77% on DBP mediated by V̇O2 (P<0.01). We did not observe a direct effect of FVC on SBP and DBP. Considering FEV1 as an independent variable, the total effect on SBP was also significant, as were the indirect effects, mediated by V̇O2 at 14.8% for SBP and 7.6% for DBP (P<0.01). We did not find an indirect effect of FVC or FEV1 considering the MVPA as a mediator. CRF mediates the pathway that links LPF and elevated BP. Therefore, CRF is more sensitive to variations in FVC and FEV1 than MVPA.

Plane of nutrition during gestation affects reproductive performance and retention rate of hyperprolific sows under commercial conditions.

Defining a maternal plane of nutrition during gestation is pivotal for improving sow productivity and the cost-effectiveness of feeding. The benefits of increasing the amount of feed during late gestation have been controversial. The objective of this study was to investigate the effects of different planes of nutrition during gestation on reproductive performance of hyperprolific sows and pre-weaning litter performance. One hundred and thirty-five gestating sows were randomly assigned to one of three planes of nutrition throughout parities three and four (P4), as follows: Req - plane designed to meet requirements of prolific sows (2.3 kg per day from day 1 to 21; 1.8 kg per day from day 22 to 75; 2.3 kg per day from day 76 to farrowing); Bump - plane designed as the Req, with increased feed intake during late gestation (3.0 kg per day from day 91 to farrowing); and Maintenance - plane designed to closely meet maintenance requirements of sows (1.8 kg per day from day 1 to farrowing). All treatments were fed the same gestation diet (2.50MCal NE/kg; 0.67% SID Lysine; 15.17% CP). Sow biometrical parameters at farrowing and at weaning, and litter characteristics were recorded. Also, blood samples were collected for pre- and post-prandial serum glucose and plasma insulin, as well as triglycerides, calcium, and phosphorus analyses. Culling, stratified by cause, and retention rates were recorded in all treatments for each parity. Over two parities, Bump sows had higher weight gain and, at P4, had a higher number of piglets born alive (P < 0.05). Bump sows lost more weight between the end of gestation and weaning over two parities (P < 0.05). Maintenance sows showed reduced body condition score with a higher percentage of piglets removed throughout lactation (due to inappetence and inability to reach the udder) at P4 (P = 0.03). Pre- and post-prandial glucose levels were higher in Bump sows, as well as post-prandial insulin and phosphorus levels at P4 (P < 0.05). Bump sows also showed increased plasma triglycerides compared to the other treatments (P = 0.03). Retention rate was reduced in Maintenance compared to Bump and Req sows at parity 5 (P = 0.02). Taken together, our results indicate that higher feed intake allowance during late gestation may improve the sow's nutritional status triggering positive results on litter size of hyperprolific sows (e.g., more than 17 total born). However, body condition score must be carefully evaluated to prevent excessive weight gain during successive parities.

Correction to: α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

The published online version contains figure in poor quality.

Breast cancer resistance protein (Bcrp/Abcg2) is selectively modulated by lipopolysaccharide (LPS) in the mouse yolk sac.

Bacterial infection alters placental ABC transporters expression. These transporters provide fetal protection against circulating xenobiotics and environmental toxins present in maternal blood. We hypothesized that lipopolysaccharide (LPS-bacterial mimic) alters the yolk sac morphology and expression of key ABC transporters in a gestational-age dependent manner. Yolk sac samples from C57BL/6 mice were obtained at gestational ages (GD) 15.5 and GD18.5, 4 or 24 h after LPS exposure (150ug/kg; n = 8/group). Samples underwent morphometrical, qPCR and immunohistochemistry analysis. The volumetric proportions of the histological components of the yolk sac did not change in response to LPS. LPS increased Abcg2 expression at GD15.5, after 4 h of treatment (p < 0.05). No changes in Abca1, Abcb1a/b, Abcg1, Glut1, Snat1, Il-1ß, Ccl2 and Mif were observed. Il-6 and Cxcl1 were undetectable in the yolk sac throughout pregnancy. Abca1, breast cancer resistance protein (Bcrp, encoded by Abcg2) and P-glycoprotein (P-gp/ Abcb1a/b) were localized in the endodermal (uterine-facing) epithelium and to a lesser extent in the mesothelium (amnion-facing), whereas Abca1 was also localized to the endothelium of the yolk sac blood vessels. LPS increased the labeling area and intensity of Bcrp in the yolk sac's mesothelial cells at GD15.5 (4 h), whereas at GD18.5, the area of Bcrp labeling in the mesothelium (4 and 24 h) was decreased (p < 0.05). Bacterial infection has the potential to change yolk sac barrier function by affecting Bcrp and Abcg2 expression in a gestational-age dependent-manner. These changes may alter fetal exposure to xenobiotics and toxic substances present in the maternal circulation and in the uterine cavity.

α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1ß were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1ß. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.

Spermatogonial asynchrony in Tex14 mutant mice lacking intercellular bridges.

The existence of cytoplasmic passages between germ cells and their potential function in the control of the spermatogenic process has long been an intriguing question. Evidence of the important role of such structures, known as intercellular bridges (ICB), in spermatogenesis has been implicated by the failure of spermatogenesis in testis-expressed gene 14 (Tex14) mutant mice, which lack the ICBs, to progress past the pachytene spermatocyte stage. Using these Tex14 mutants, the present study evaluated, for the first time, the behavior and synchrony of the spermatogonial lineage in the absence of ICBs. Our data suggest that the absence of these cytoplasmic connections between cells affects the expansion of the undifferentiated type A (Aundiff) spermatogonia compartment and their transition to A1, resulting in a significant numerical reduction of differentiating A1 spermatogonia, but did not interfere with cell amplification during subsequent mitotic steps of differentiating spermatogonia from A1 through intermediate (In). However, beginning at the type B spermatogonia, the synchrony of differentiation was impaired as some cells showed delayed differentiation compared to their behavior in a normal seminiferous epithelium cycle. Thus although spermatogonial development is able to proceed, in the absence of ICBs in Tex14-/- mutants, the yield of cells, specific steps of differentiation, the synchrony of the cell kinetics, and the subsequent progression in meiosis are quantitatively lower than normal.

A subpopulation of human Adark spermatogonia behaves as the reserve stem cell.

Human spermatogonial stem cells (SSCs) are an essential source to maintain spermatogenesis as an efficient process for daily sperm production with high self-renewal capacity along adulthood. However, the phenotype and the subpopulation that represent the real reserve SSC for the human testis remain unknown. Moreover, although SSC markers have been described for undifferentiated spermatogonia (Adark and Apale), the existence of a specific subtype that could be identified as the actual/true SSC has not yet been fully determined. Herein we evaluated spermatogonial morphology, kinetics, positioning regarding blood vasculature in relation to protein expression (UTF1, GFRA1, and KIT) as well as proliferative activity (MCM7) and identified a small subpopulation of Adark with nuclear rarefaction zone (AdVac) that behaves as the human reserve SSC. We show that AdVac is the smallest human spermatogonial population (10%), staying quiescent (89%) and positioned close to blood vessels throughout most of the stages of the seminiferous epithelium cycle (SEC) and divides only at stages I and II. Within this AdVac population, we found a smaller pool (2% of A undifferentiated spermatogonia) of entirely quiescent cells exhibiting a high expression of UTF1 and lacking GFRA1. This finding suggests them as the real human reserve SSC (AdVac UTF1+/GFRA1-/MCM7-). Additionally, Adark without nuclear vacuole (AdNoVac) and Apale have similar kinetic and high proliferative capacity throughout the SEC (47%), indicating that they are actively dividing undifferentiated spermatogonia. Identification of human stem cells with evident reserve SSC functionality may help further studies intending to sort SSCs to treat male diseases and infertility.

The effects of immunization against gonadotropin-releasing hormone on growth performance, reproductive activity and carcass traits of heavy weight gilts.

Heavy weight gilts commonly show signs of oestrus during the late finishing phase, which results in a period of reduced feed intake and growth rate. Immunization against gonadotropin-releasing hormone (GnRH) (IM, immunocastration) was developed for finishing boars and recently extrapolated to females. Immunocastration acts by suppressing reproductive activity and improving the growth potential. The objective of this study was to evaluate the effects of IM on growth performance, reproductive activity and carcass characteristics of late finishing gilts. Seventy-two gilts (63.49 ± 0.39 kg) were either injected with saline (Intact) or immunized against GnRH (Immunized). The study consisted of three experimental periods: between the first to second immunization (V1 to V2, 15 to 19 weeks of age), from the second immunization to the beginning of daily boar exposure (DBE) (V2 to DBE, 19 to 21 weeks of age) and from the beginning of DBE to slaughter (S) (DBE to S, 21 to 25 weeks of age). Immunized gilts showed an overall increase (from 15 to 25 weeks) of 3.90 kg (P 0.05). Immunized gilts showed 4.4% increased cold carcass weight (P 0.05). Immunocastration reduced ovarian and uterine weights by 82% (P < 0.001) and 93% (P < 0.001), respectively, and suppressed oestrus manifestation in all gilts in the immunized group (P < 0.001). These results indicate that immunization against GnRH is a promising tool for stimulating growth performance with no detrimental effects on carcass quality of heavy weight finishing gilts, by means of oestrus suppression.

Spermatogonial behavior in marmoset: a new generation, their kinetics and niche.

STUDY QUESTION: Could a more detailed evaluation of marmoset spermatogonial morphology, kinetics and niches using high-resolution light microscopy (HRLM) lead to new findings? SUMMARY ANSWER: Three subtypes of marmoset undifferentiated spermatogonia, which were not evenly distributed in terms of number and position along the basal membrane, and an extra premeiotic cell division not present in humans were identified using HRLM. WHAT IS KNOWN ALREADY: The seminiferous epithelium cycle (SEC) of marmosets is divided into nine stages when based on the acrosome system, and several spermatogenic stages can usually be recognized within the same tubular cross-section. Three spermatogonial generations have been previously described in marmosets: types Adark, Apale and B spermatogonia. STUDY DESIGN, SIZE, DURATION: Testes from five adult Callithrix penicillata were fixed by glutaraldehyde perfusion via the cardiac route and embedded in Araldite plastic resin for HRLM evaluation. Semi-thin sections (1 µm) were analyzed morphologically and morphometrically to evaluate spermatogonial morphology and kinetics (number, mitosis and apoptosis), spermatogenesis efficiency and the spermatogonial niche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Shape and nuclear diameter, the presence and distribution of heterochromatin, the granularity of the euchromatin, as well as the number, morphology and degree of nucleolar compaction were observed for morphological characterization. Kinetics analyses were performed for all spermatogonial subtypes and preleptotene spermatocytes, and their mitosis and apoptosis indexes determined across all SEC stages. Spermatogenesis parameters (mitotic, meiotic, Sertoli cell workload and general spermatogenesis efficiency) were determined through the counting of Adark and Apale spermatogonia, preleptotene and pachytene primary spermatocytes, round spermatids, and Sertoli cells at stage IV of the SEC. MAIN RESULTS AND THE ROLE OF CHANCE: This is the first time that a study in marmosets demonstrates: the existence of a new spermatogonial generation (B2); the presence of two subtypes of Adark spermatogonia with (AdVac) and without (AdNoVac) nuclear rarefaction zones; the peculiar behavior of AdVac spermatogonia across the stages of the SEC, suggesting that they are quiescent stem spermatogonia; and that AdVac spermatogonia are located close to areas in which blood vessels, Leydig cells and macrophages are concentrated, suggesting a niche area for these cells. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The C. penicillata spermatogonial kinetics evaluated here consider spermatogonial number across the SEC and their mitotic and apoptotic figures identified in HRLM sections. Therefore, caution is required when comparing absolute values between species. Although morphometric evaluation has suggested that AdVac spermatogonia are stem cells, a functional proof of this is still missing. It is known that parameters of the spermatogenic process in C. penicillata have similarities with those of the common marmoset C. jacchus, however, a detailed study of spermatogonial morphology, kinetics and niche has not yet been performed in C. jacchus, and a full comparison of the two species is not possible. WIDER IMPLICATIONS OF THE FINDINGS: Our findings in C. penicillata contribute to a better understanding of the spermatogonial behavior and spermatogenesis efficiency in non-human primates. Given the phylogenetic closeness of the marmoset to the human species, similar processes might occur in humans. Therefore, marmosets may be an excellent model for studies regarding human testicular biology, fertility and related disorders. STUDY FUNDING/COMPETING INTEREST(S): Experiments were partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq). The authors declare that there are no conflicts of interest.

Revisiting the human seminiferous epithelium cycle.

STUDY QUESTION: Can all types of testicular germ cells be accurately identified by microscopy techniques and unambiguously distributed in stages of the human seminiferous epithelium cycle (SEC)? SUMMARY ANSWER: By using a high-resolution light microscopy (HRLM) method, which enables an improved visualization of germ cell morphological features, we identified all testicular germ cells in the seminiferous epithelium and precisely grouped them in six well-delimitated SEC stages, thus providing a reliable reference source for staging in man. WHAT IS ALREADY KNOWN: Morphological characterization of germ cells in human has been done decades ago with the use of conventional histological methods (formaldehyde-based fixative -Zenker-formal- and paraffin embedding). These early studies proposed a classification of the SEC in six stages. However, the use of stages as baseline for morphofunctional evaluations of testicular parenchyma has been difficult because of incomplete morphological identification of germ cells and their random distribution in the human SEC. STUDY DESIGN, SIZE, DURATION: Testicular tissue from adult and elderly donors with normal spermatogenesis according to Levin's, Johnsen's and Bergmann's scores were used to evaluate germ cell morphology and validate their distribution and frequency in stages throughout human spermatogenesis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular tissue from patients diagnosed with congenital bilateral agenesis of vas deferens (n = 3 adults) or prostate cancer (n = 3 elderly) were fixed in glutaraldehyde and embedded in araldite epoxy resin. Morphological analyses were performed by both light and transmission electron microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: HRLM method enabled a reliable morphological identification of all germ cells (spermatogonia, spermatocytes and spermatids) based on high-resolution aspects of euchromatin, heterochromatin and nucleolus. Moreover, acrosomal development of spermatids was clearly revealed. Altogether, our data redefined the limits of each stage leading to a more reliable determination of the SEC in man. LIMITATIONS, REASONS FOR CAUTION: Occasionally, germ cells can be absent in some tubular sections. In this situation, it has to be taken into account the germ cell association proposed in the present study to classify the stages. WIDER IMPLICATIONS OF THE FINDINGS: Our findings bring a new focus on the morphology and development of germ cells during the SEC in human. Application of HRLM may be a valuable tool for research studies and clinical andrology helping to understand some testicular diseases and infertility conditions which remain unsolved. STUDY FUNDING/COMPETING INTEREST: Experiments were partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors declare that there are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Effects of birthweight on reproductive system development and onset of puberty in gilts.

The aim of the present study was to investigate the effects of birthweight on bodyweight development, development of the genital tract, onset of puberty and their associations with insulin-like growth factor (IGF) 1 and leptin concentrations. Pairs of littermate gilts from 51 litters were selected: one piglet with the highest birthweight (HW; 1.5±0.2kg) and the other with the lowest birthweight (LW; 1.0±0.2kg). Gilt pairs were killed at either fixed ages (80.8±1.2 days; AG; 16 pairs), fixed bodyweight (35.2±1.4kg; WG; 16 pairs) or after first oestrus (EG; 19 pairs). In the AG group, HW gilts were 5.6kg heavier at the time of death than LW gilts. In the WG group, LW gilts were 5.9 days older at the time of death (P<0.05). There were no significant differences in the number or size of total antral follicles or in the follicle population among birthweight classes. Age at puberty was similar between the HW and LW gilts, but bodyweight at time of death was greater for HW gilts (P<0.05). Birthweight did not affect the development of the genital tract, ovulation rate or hormone plasma concentrations. These results suggest that birthweight does not affect the development of the genital tract before puberty and puberty onset.

Testicular parameters and spermatogenesis in different birthweight boars.

The present study investigated the effect of birthweight on testicular development and spermatogenesis in boars. Twenty-four pairs of littermate boars were selected: one piglet with the highest birthweight (HW) and the other with the lowest birthweight (LW) within the litter. Two subsets of 12 pairs of male littermates from each birthweight group were obtained after selection: one subset was orchiectomised at 8 days and the other at 8 months of age. HW boars had higher body and testicular weights at both ages (P<0.05). Testosterone concentrations and the relative expression of 17α-hydroxylase in the testis were similar between birthweight groups. Birthweight affected somatic and germ cell numbers in the neonatal testis, which were higher in HW boars (P<0.05). Moreover, a significant reduction in the number of pachytene spermatocytes and round spermatids was observed in LW boars (P<0.05) at 8 months of age, which caused a decrease in the total number of elongated spermatids and daily sperm production (P<0.05). Hence, HW boars have the potential to produce more spermatozoa and consequently more semen doses per ejaculate, and would be very valuable to an industry that relies on AI.

Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.

Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

Migração espermática em suínos após inseminação artificial intrauterina profunda / Sperm migration in pigs after deep intrauterine artificial insemination

A inseminação artificial intrauterina profunda (IIP) é de grande importância para a indústria suinícola, em função do maior número de doses produzidas por reprodutores de alto mérito genético e da possibilidade da utilização de biotecnologias, como sêmen sexado e/ou congelado. Entretanto, necessita-se compreender com maior propriedade os mecanismos pelos quais os espermatozoides colonizam as tubas uterinas. Assim sendo, pretende-se com o presente experimento avaliar a existência ou não de migração intraperitoneal de espermatozoides inseminados profundamente em um dos cornos uterinos, mediante a obtenção de oócitos fertilizados no corno contralateral à inseminação e seccionado na base, na junção com o corpo do útero. Quatorze fêmeas pluríparas foram divididas em dois grupos experimentais, sendo que em um deles as fêmeas foram submetidas à secção da base de um dos cornos uterinos (Grupo Operado, n = 7), enquanto as do Grupo Controle (n = 7) não foram submetidas a nenhuma intervenção cirúrgica. Ambos os grupos foram submetidos à IIP, sendo as fêmeas abatidas 5±1,2 dias após a última inseminação. Os sistemas genitais das fêmeas foram coletados, dissecados e o número de corpos lúteos contados em ambos os ovários. A recuperação dos embriões foi feita por meio de lavagem das tubas e cornos uterinos com solução de PBS (Phosphate Buffered Saline), após o que se avaliou os fluidos coletados em lupa para a identificação de embriões. Em ambos os grupos experimentais, foram encontrados embriões nos segmentos do sistema genital de ambos os lados. Apenas uma fêmea apresentou embriões nos segmentos em somente um dos lados no grupo operado. Diante dos resultados aqui observados, concluiu-se que a migração espermática no suíno pode ocorrer tanto por via retrógrada pelo útero quanto por migração intraperitoneal. Estes achados certamente contribuirão para aumentar a eficiência da técnica de IIP, sendo de grande valia para o aprimoramento da indústria suinícola...

Deep intrauterine insemination (DUI) is of great importance for the swine industry as it can increase the efficiency in the use of boars of high genetic merit, and facilitate the use of biotechnologies such as frozen and sexed semen. However, a better understanding of the mechanisms by which the sperm colonize the uterine tubes is essential. The aim of the present study was to investigate the existence of intrauterine sperm migration after DUI in one uterine horn, through the fertilization of oocytes in the contra lateral uterine horn. Fourteen multiparous sows were divided into two experimental groups: Operated (n = 7), where females had a segment close to the base of the uterine horn surgically removed, and Control (n = 7), females with intact uterus. Both groups were inseminated through DUI and slaughtered 5±1.2 days after the last insemination. The reproductive tracts collected were dissected and the number of corpora lutea counted in both ovaries. Embryo recovery was performed though flushings of uterine tubes and horns with Phosphate Buffered Saline solution and further examination under a dissecting microscope. Embryos were found in the uterine horns of both sides of the reproductive tract in both experimental groups. In the operated group, just one female had embryos in only one side of the reproductive tract. The results presented herein suggest that sperm migration in pigs may occur both in a retrograde way through the uterus and by intraperitoneal migration. These findings will certainly contribute to increase the efficiency of the DUP technique, which is of great importance for the improvement of the swine industry...

Cardiovascular function alterations induced by acute paradoxical sleep deprivation in rats.

Sleep loss has been implicated in triggering the hypertension. The goal of the present study was investigated the possible mechanisms underlying cardiovascular alterations after acute paradoxical sleep deprivation (PSD). Male Wistar rats were assigned in two experimental groups: (1) control and (2) PSD for 24 h using the modified single platform method. Paradoxical sleep deprived rats exhibited higher blood pressure, heart rate (HR) and impaired baroreceptor sensitivity. After pharmacological autonomic double blockade (propranolol and methylatropine administration), intrinsic heart rate was decreased after PSD. The PSD rats showed a reduction in the vagal tone without affecting sympathetic tone. Isoproterenol administration (0.001, 0.01 and 1 µg/kg) induced an increase in ΔHR responses in PSD group. Electrocardiographic analysis in response to ß-adrenergic stimulation indicated that PSD contributed to ventricular cardiac arrhythmias. Our findings suggest that acute paradoxical sleep loss induce cardiovascular alterations, autonomic imbalance accompanied by impaired baroreflex sensitivity and increased arrhythmia susceptibility.

Fatty acid profile, oxidative stability of pork lipids and meat quality indicators are not affected by birth weight.

The aim of this study was to investigate whether fatty acid (FA) profile, oxidative stability of lipids and other meat quality traits differed between high (HW: 1.8 to 2.2 kg) and low (LW: 0.8 to 1.2 kg) birth weight piglets. Forty new-born male pigs (n=20 HW, n=20 LW) were reared in separate pens until the finishing period, when they were slaughtered at 150 days of age, and pH and temperature were measured in the carcass. Afterwards, the Longissimus dorsi muscle was excised from the carcass, and samples were collected for subsequent meat quality analyses (thaw loss, cooking loss, shear force, chemical analysis and sensory analysis for tenderness). Birth weight had minor impacts on meat quality traits, which were limited to higher shear force in the LW group (P<0.01). Chemical components (moisture, protein, fat, ash), cholesterol levels and lipid oxidation (thiobarbituric acid-reactive substances) were not affected by birth weight (P>0.05). FA profile and the amount of saturated, monounsaturated and polyunsaturated fatty acids were similar, but HW pigs had higher atherogenic index than their LW counterparts (P<0.01). Notwithstanding the higher shear force presented by the lower birth weight pigs, in the sensory test, the panelists did not detect any differences in the tenderness of pork from HW and LW animals. Therefore, our results suggest that low birth weight has minimal impact on meat quality.