Non-Markovianity through quantum coherence in an all-optical setup.

We propose an all-optical experiment to quantify non-Markovianity in an open quantum system through quantum coherence of a single quantum bit. We use an amplitude damping channel implemented by an optical setup with an intense laser beam simulating a single-photon polarization. The optimization over initial states required to quantify non-Markovianity is analytically evaluated. The experimental results are in very good agreement with the theoretical predictions.

Speckle patterns produced by an optical vortex and its application to surface roughness measurements.

In this work, we report on the analysis of speckle patterns produced by illuminating different rough surfaces with an optical vortex, a first-order (l=1) Laguerre-Gaussian beam. The generated speckle patterns were observed in the normal direction exploring four different planes: the diffraction plane, image plane, focal plane, and exact Fourier transform plane. The digital speckle patterns were analyzed using the Hurst exponent of digital images, an interesting tool used to study surface roughness. We show a proof of principle that the Hurst exponent of a digital speckle pattern is more sensitive with respect to the surface roughness when the speckle pattern is produced by an optical vortex and observed at a focal plane. We also show that Hurst exponents are not so sensitive with respect to the topological charge l. These results open news possibilities of investigation into speckle metrology once we have several techniques that use speckle patterns for different applications.

Differential effects of palmitoleic acid on human lymphocyte proliferation and function.

BACKGROUND: Palmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA). METHODS: Human lymphocytes were isolated from peripheral blood of health men and cultured in the presence of growing concentrations of PA or OA (5 to 200 µM), for 24 h. After that, cells were collected and cytotoxicity evaluated by flow cytometry. Then, we analyzed proliferative capacity in lymphocytes treated with non toxic concentrations of PA and OA (25 and 50 µM, respectively), in the presence or absence of concanavalin A (ConA). The Th1/Th2/Th17 cytokine production was determined by the Cytometric Bead Array. CD28 and CD95 surface expression and T regulatory cell percentage were determined by flow cytometry. RESULTS: We observed that PA is toxic to lymphocytes above 50 µM. PA promoted a decrease of lymphocyte proliferation stimulated by ConA in both concentrations. PA also decreased CD28 externalization and increased CD95. On the other hand, OA did not alter these parameters. In the same way, PA reduced IL6, IFN-gamma, TNF-alpha and IL17A production in both concentration and IL2 only at 50 µM (in the presence of ConA). OA promoted IFN-gamma reduction in both concentrations and an increase of IL-2, IL4 and IL10 at 25 µM. Both fatty acids decreased the percentage of T regulatory cells. CONCLUSION: In conclusion, PA promoted a suppressive effect on lymphocyte proliferation characterized by a decrease of Th1 and Th17 response, and co-stimulatory molecule (CD28). However, OA increased lymphocyte proliferation through IL2 production and Th2 response. These results also show a more suppressive effect of PA on lymphocytes in comparison to OA.

Regulation of insulin sensitivity by adiponectin and its receptors in response to physical exercise.

Adiponectin is an adipocyte-derived abundant plasma protein, also called Acrp30 (adipocyte complement-related protein), adipoQ, ApM1 (AdiPose Most abundant Gene transcript 1), or GBP28 (gelatin-binding protein-28). Insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-α pathways, respectively. In the same sense chronic exercise has been showed to induce numerous metabolic factors that can improve insulin resistance. It has been reported that physical exercise training increases adiponectin receptors, which may mediate the improvement of insulin resistance in response to exercise, which is the focus of the present review.

Resveratrol prevents hyperleptinemia and central leptin resistance in adult rats programmed by early weaning.

We have previously shown that early weaning in rats increases the risk of obesity and insulin resistance at adulthood, and leptin resistance can be a prime factor leading to these changes. Resveratrol is reported to decrease oxidative stress, insulin resistance, and cardiovascular risk. However, there is no report about its effect on leptin resistance. Thus, in this study we have evaluated resveratrol-preventing effect on the development of visceral obesity, insulin, and leptin resistance in rats programmed by early weaning. To induce early weaning, lactating dams were separated into 2 groups: early weaning (EW)--dams were wrapped with a bandage to interrupt lactation in the last 3 days of lactation and control (C)--dams whose pups had free access to milk during throughout lactation period (21 days). At 150 days-old, EW offspring were subdivided into 2 groups: EW+res--treated with resveratrol solution (30 mg/kg BW/day) or EW--receiving equal volume of vehicle solution, both given by gavage during 30 days. Control group received vehicle solution. Resveratrol prevented the higher body weight, hyperphagia, visceral obesity, hyperleptinemia, hyperglycemia, insulin resistance, and hypoadiponectinemia at adulthood in animals that were early weaned. Leptin resistance, associated with lower JAK2 and pSTAT3 and higher NPY in hypothalamus of EW rats were also normalized by resveratrol. The present results suggest that resveratrol is useful as therapeutic tool in treating obesity, mainly because it prevents the development of central leptin resistance.

Intense intermittent exercise provides weak stimulus for vascular endothelial growth factor secretion and capillary growth in skeletal muscle.

The effect of acute intense intermittent exercise compared with moderate-intensity exercise on angiogenic factors and the effect of 4 weeks of intense intermittent training on capillary growth were examined in nine healthy young men, preconditioned by moderate-intensity endurance training. The intense training consisted of 24 bouts of 1 min cycling at an initial work rate of 316 ± 19 W (~117% of pretraining maximal oxygen uptake), performed three times per week. Skeletal muscle biopsies and muscle microdialysates were obtained from the vastus lateralis before, during and after acute exercise performed at either moderate or high intensity. Comparison of the response in angiogenic factors to acute moderate- versus high-intensity exercise, performed prior to the intense training intervention, revealed that intense exercise resulted in a markedly lower (~60%; P < 0.05) increase in interstitial vascular endothelial growth factor than did moderate-intensity exercise. Muscle interstitial fluid obtained during moderate-intensity exercise increased endothelial cell proliferation in vitro more than interstitial fluid obtained during intense exercise (sixfold versus 2.5-fold, respectively; P < 0.05). The 4 weeks of high-intensity training did not lead to an increased capillarization in the muscle but abolished the exercise-induced increase in mRNA for several angiogenic factors, increased the protein levels of endothelial nitric oxide synthase, lowered the protein levels of thrombospondin-1 in muscle but increased the interstitial protein levels of thrombospondin-1. We conclude that intense intermittent exercise provides a weak stimulus for vascular endothelial growth factor secretion and endothelial cell proliferation and that intense intermittent training does not induce a sufficient angiogenic stimulus to induce capillary growth in muscle previously conditioned by moderate-intensity exercise.

Effects of growth differentiation factor-9 and FSH on in vitro development, viability and mRNA expression in bovine preantral follicles.

The present study investigated the role of growth differentiation factor (GDF)-9 and FSH, alone or in combination, on the growth, viability and mRNA expression of FSH receptor, proliferating cell nuclear antigen (PCNA) and proteoglycan-related factors (i.e., hyaluronan synthase (HAS) 1, HAS2, versican, perlecan) in bovine secondary follicles before and after in vitro culture. After 12 days culture, sequential FSH (100 ng mL⁻¹) from Days 0 to 6 and 500 ng mL⁻¹ from Days 7 to 12) increased follicular diameter and resulted in increased antrum formation (P<0.05). Alone, 200 ng mL⁻¹ GDF-9 significantly reduced HAS1 mRNA levels, but increased versican and perlecan mRNA levels in whole follicles, which included the oocyte, theca and granulosa cells. Together, FSH and GDF-9 increased HAS2 and versican (VCAN) mRNA levels, but decreased PCNA mRNA expression, compared with levels in follicles cultured in α-minimum essential medium supplemented with 3.0 mg mL⁻¹ bovine serum albumin, 10 µg mL⁻¹ insulin, 5.5 µg mL⁻¹ transferrin, 5 ng mL⁻¹ selenium, 2 mM glutamine, 2mM hypoxanthine and 50 µg mL⁻¹ ascorbic acid (α-MEM⁺). Comparisons of uncultured (0.2 mm) and α-MEM⁺ cultured follicles revealed that HAS1 mRNA expression was higher, whereas VCAN expression was lower, in cultured follicles (P<0.05). Expression of HAS1, VCAN and perlecan (HSPG2) was higher in cultured than in vivo-grown (0.3 mm) follicles. In conclusion, FSH and/or GDF-9 promote follicular growth and antrum formation. Moreover, GDF-9 stimulates expression of versican and perlecan and interacts positively with FSH to increase HAS2 expression.

Time of physical exercise practice after injury in cervical spinal cord-injured men is related to the increase in insulin sensitivity.

OBJECTIVES: Physical exercise has an important role in reducing body fat, risk of chronic disease and systemic inflammation. The aim of this study was to determine serum leptin and insulin concentrations and their relationship to the time of physical exercise after injury in men with cervical spinal cord injury (c-SCI). METHODS: c-SCI subjects with lesion level in C5-C7 (n=25) were divided into two groups: physically active (PA, n=13; those who practiced physical exercise for at least 3 months, three times per week or more, for a total minimum of 150 min of physical activity per week) and non-physically active (N-PA, n=9). Body composition was assessed by dual energy X-ray absorptiometry. Blood samples were obtained 12 h after an overnight fast to measure insulin and leptin in serum, and glucose and C-reactive protein (CRP) in plasma, by validated methods. RESULTS: Comparing the PA and N-PA group, the first presented lower: total body mass (-13%), body mass index (-16%), fat mass (kg -39%, FM% -30%), CRP (-23%), serum insulin (-61%), homeostasis model assessment (HOMA, -35%) and serum leptin (-62%; P<0.05). Both serum insulin (r=-0.561; P<0.05) and HOMA (r=-0.591; P<005) were inversely proportional to the time of practice of physical activity after injury. CONCLUSION: Our results suggest that exercise was able to reduce fat mass and increase insulin sensitivity, decreasing plasma levels of risk factors in c-SCI subjects.

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats.

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 µg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.

Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.

Postnatal low protein diet programs leptin signaling in the hypothalamic-pituitary-thyroid axis and pituitary TSH response to leptin in adult male rats.

Maternal protein restriction (PR) during lactation programs a lower body weight, hyperthyroidism, leptin resistance, and over-expression of leptin receptor in the pituitary gland at adulthood. Because leptin regulates energy homeo-stasis and the hypothalamus-pituitary-thyroid (HPT) axis, we evaluated adipocyte morphology, the leptin signaling pathway in the HPT axis and the in vitro thyrotropin (TSH) response to leptin in adult progeny in this model. At birth, dams were separated in control diet with 23% protein or PR diet with 8% protein. After weaning, offspring received a normal diet. Adult PR offspring showed lower adipocytes area, higher leptin:visceral fat ratio, lower hypothalamic signal transducer and activator of transcription 3 (STAT3), higher pituitary leptin receptor (Ob-R) and lower thyroid janus tyrosine kinase 2 (JAK2) contents. Regarding the in vitro study, 10(-7) M leptin stimulated TSH secretion in C offspring at 30 min, but had no effect in PR offspring. At 120 min, 10(-7) M leptin decreased TSH secretion in C offspring and increased in PR offspring. Maternal nutritional status during lactation programs for adipocyte atrophy, higher relative leptin secretion and changes in the downstream leptin signaling in the HPT axis and the TSH response to leptin, suggesting a role for leptin in the development of the HPT axis and helping to explain thyroid dysfunction and leptin resistance in this programming model. Because leptin stimulates thyroid function, it is unlikely that these alterations were responsible for the increased in serum T4 and T3. Therefore, neonatal PR programs a hyperthyroidism, lower adipogenesis, and impairment of leptin action.

Levels of mRNA for bone morphogenetic proteins, their receptors and SMADs in goat ovarian follicles grown in vivo and in vitro.

This study investigated the stability of housekeeping genes (glyceraldehyde-3-phosphate dehydrogenase, ß-tubulin, ß-actin, phosphoglycerate kinase (PGK), 18S rRNA, ubiquitin and ribosomal protein 19) and the levels of mRNA for bone morphogenetic protein-2 (BMP-2), -4 (BMP-4), -6 (BMP-6), -7 (BMP-7) and -15 (BMP-15), their receptors (BMPR-IA, -IB and -II) and Similar to Mothers Against Decapentaplegic (SMADs) (-1, -5 and -8) in goat follicles of 0.2, 0.5 and 1.0mm, as well as in secondary follicles before and after culture for 18 days. ß-tubulin and PGK were the most stable housekeeping genes and the levels of mRNA for BMP-2 in follicles of 0.2mm were higher than in follicles of 0.5 and 1.0mm. For BMP-4, -6 and -7, the highest levels of mRNA were found in follicles of 1.0mm. The expression of BMPR-IB was higher in follicles of 0.2mm, whereas the levels of BMPR-II were higher in follicles of 0.5mm. The levels of mRNA for SMAD-5 were higher in follicles of 0.2mm, whereas SMAD-8 had higher levels in 0.5-mm follicles. After culture, follicles showed increased levels of mRNA for BMP-2 and reduced mRNA for BMP-4, BMP-7, BMPR-IA and SMAD-5. In conclusion, ß-tubulin and PGK are the most stable reference genes, and BMPs, their receptors and SMADs have variable levels of mRNA in the follicular size classes analysed.

Clinical and therapeutic aspects of vulvodynia: the importance of physical therapy.

Vulvodynia affects a large number of women worldwide. It is estimated that the prevalence rate of vulvodynia is 16% in women aged 18 to 64 years, resulting in constant demand for specialized medical care, although little therapeutic success is achieved. Furthermore, the cause of this disorder remains unknown and involves different symptoms that are implicated in important chronic vulvar pain with disastrous consequences for the afflicted women. In view of these data, the authors have proposed a bibliographic review of the pathophysiology and treatment of vulvodynia. The aim of this review was to assist in clinical diagnosis and elucidate the multidisciplinary treatment that appears to be associated with a higher success rate in these women. Physical therapy using diverse techniques has an important role in multidisciplinary care, obtaining satisfactory results in the treatment of pelvic floor muscle dysfunction and thus improving the symptoms and quality of life in women with vulvodynia.

Morphology, molecular phylogeny and biomass evaluation of Desmodesmus abundans (Scenedesmaceae-Chlorophyceae) from Brazil.

The biotechnological potential of microalgae has been the target of a range of research aimed at using its potential to produce macromolecules with high added value. Particular focus has been given to biofuels' production, such as biohydrogen, biodiesel, and bioethanol from lipids and carbohydrates extracted from microalgal biomass. Bioprospecting and accurate identification of microalgae from the environment are important in the search for strains with better performance. Methodologies that combine morphology and molecular techniques allow more precise knowledge of species. Thereby, this work aimed to identify the new strain LGMM0013 collected at Iraí Reservoir, located in Paraná state, Brazil, and to evaluate the production of biomass, carbohydrates, and lipids from this new microalgal strain. Based on morphology and phylogenetic tree from internal transcribed spacer (ITS), strain LGMM0013 was identified as Desmodesmus abundans. D. abundans accumulated 1500 mg L-1 of dried biomass after 22 days of cultivation in autotrophic conditions, 50% higher than Tetradesmus obliquus (LGMM0001) (Scenedesmaceae-Chlorophyceae), usually grown in photobioreactors located at NPDEAS at the Federal University of Paraná (UFPR) to produce biomass. Analysis of the D. abundans biomass from showed an accumulation of 673.39 mg L-1 of carbohydrates, 130% higher than T. obliquus (LGMM0001). Lipid production was 259.7 mg L-1, equivalent to that of T. obliquus. Nitrogen deprivation increased the production of biomass and carbohydrates in D. abundans LGMM0013, indicating this new strain greater biomass production capacity.

Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry.

BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of cancer are of great interest for early cancer detection. Urine is potentially a rich source of volatile organic metabolites (VOMs) that can be used as potential cancer biomarkers. Our aim was to develop a generally reliable, rapid, sensitive, and robust analytical method for screening large numbers of urine samples, resulting in a broad spectrum of native VOMs, as a tool to evaluate the potential of these metabolites in the early diagnosis of cancer. METHODS: To investigate urinary volatile metabolites as potential cancer biomarkers, urine samples from 33 cancer patients (oncological group: 14 leukaemia, 12 colorectal and 7 lymphoma) and 21 healthy (control group, cancer-free) individuals were qualitatively and quantitatively analysed. Dynamic solid-phase microextraction in headspace mode (dHS-SPME) using a carboxen-polydimethylsiloxane (CAR/PDMS) sorbent in combination with GC-qMS-based metabolomics was applied to isolate and identify the volatile metabolites. This method provides a potential non-invasive method for early cancer diagnosis as a first approach. To fulfil this objective, three important dHS-SPME experimental parameters that influence extraction efficiency (fibre coating, extraction time and temperature of sampling) were optimised using a univariate optimisation design. The highest extraction efficiency was obtained when sampling was performed at 50°C for 60 min using samples with high ionic strengths (17% sodium chloride, w v(-1)) and under agitation. RESULTS: A total of 82 volatile metabolites belonging to distinct chemical classes were identified in the control and oncological groups. Benzene derivatives, terpenoids and phenols were the most common classes for the oncological group, whereas ketones and sulphur compounds were the main classes that were isolated from the urine headspace of healthy subjects. The results demonstrate that compound concentrations were dramatically different between cancer patients and healthy volunteers. The positive rates of 16 patients among the 82 identified were found to be statistically different (P<0.05). A significant increase in the peak area of 2-methyl-3-phenyl-2-propenal, p-cymene, anisole, 4-methyl-phenol and 1,2-dihydro-1,1,6-trimethyl-naphthalene in cancer patients was observed. On average, statistically significant lower abundances of dimethyl disulphide were found in cancer patients. CONCLUSIONS: Gas chromatographic peak areas were submitted to multivariate analysis (principal component analysis and supervised linear discriminant analysis) to visualise clusters within cases and to detect the volatile metabolites that are able to differentiate cancer patients from healthy individuals. Very good discrimination within cancer groups and between cancer and control groups was achieved.

Maternal prolactin inhibition during lactation is associated to renal dysfunction in their adult rat offspring.

The renal function of rats whose mothers had hypoprolactinemia at the end of lactation was evaluated during development. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg twice a day, s.c.) or saline on days 19, 20, and 21 of lactation, and their male offspring were followed from weaning until 180 days old. 1 rat from each of the 12 litters/group was evaluated at 2 time points (90 and 180 days). Body and kidney weights, sodium, potassium, and creatinine were measured. Values were considered significant when p<0.05. Adult BRO-treated offspring presented higher body weight (+10%), lower relative renal weight at 90 and 180 days (-9.2% and -15.7%, respectively), glomerulosclerosis, and peritubular fibrosis. At 90 and 180 days, creatinine clearance was lower (-32% and -30%, respectively), whereas serum potassium was higher (+19% and +29%, respectively), but there were no changes in serum sodium. At 180 days, higher proteinuria (+36%) and serum creatinine levels (+20%) were detected. Our data suggest that prolactin inhibition during late lactation programs renal function damage in adult offspring that develops gradually, first affecting the creatinine clearance and potassium serum levels with further development of hyperproteinuria and higher serum creatinine, without affecting sodium. Thus, precocious weaning programs some components of the metabolic syndrome, which can be a risk factor for further development of kidney disease.

Blocking leptin action one week after weaning reverts most of the programming caused by neonatal hyperleptinemia in the adult rat.

Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected or leptin-injected from postnatal day 1 to day 10. At 29 and 30 days old, animals were injected with anti-leptin antibody (LA and CA) or saline (LS and CS). In adult animals, higher visceral (+53%) and total fat mass (+33%), hyperleptinemia (+67%), hypertriglyceridemia (+47%), and hypoadiponectinemia (-44%) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin-treated animals, in addition to lower serum adiponectin (-77% vs. CS) and higher insulin resistance index (+37%). Liver sirtuin1 (SIRT1) was higher (+41%) only in LA group, suggesting a role for SIRT1 in the prevention of leptin programming. Hypothalamic OBR was lower and SOCS3 higher in LS group and these changes were normalized in LA group. In conclusion, blocking leptin action one week after weaning seems to revert most of the alterations observed in rats programmed by neonatal hyperleptinemia. Higher liver SIRT1 expression may be one of the mechanisms involved, leading to a better glucose and lipid metabolism. Our data suggest that the lack or the excess of leptin programs an adverse metabolic phenotype in adulthood.

Maternal flaxseed diet during lactation programs thyroid hormones metabolism and action in the male adult offspring in rats.

Flaxseed has several benefits for health such as improvement in lipid profile; and since thyroid hormones increases cholesterol biliary excretion, we decide to evaluate the programming effect of maternal flaxseed diet during lactation upon thyroid hormone metabolism and action in the adult offspring in rats. At birth, lactating rats were divided into: flaxseed dams (F) - diet with 25% of flaxseed - and controls dams (C). F and C pups received normal diet after weaning and male offspring were sacrificed at 21 and 180 days old. We evaluated serum T3, T4, and TSH; type 1 and 2 deiodinase activities (D1 and D2) in the liver, thyroid, brown adipose tissue (BAT), and pituitary; thyroid hormone receptor (TRß1) expression and mitochondrial glycerophosphate-dehydrogenase activity (GPDm) in the liver. F offspring showed lower T3 levels at weaning (-30%, p<0.05) probably caused by lower liver D1 activity (-32%, p<0.05) and higher TSH levels (+84.6%, p<0.05) characterizing a profile of hypothyroidism. At 180 days old, F offspring had lower T4 and thyroid D1 and D2 activities (-28.3%, -18.5%, and -44.2%, respectively, p<0.05) and higher BAT D2 activity (+34.5%, p<0.05). We suggest that adult F animals present an inappropriate TSH action on the thyroid, since thyroid deiodinase was lower. Serum T3 was normal probably due to a higher BAT D2 activity and may reflect the tissue T3 concentration because liver D1, TRß1, and GPDm were normal. Thus, maternal flaxseed diet during lactation may affect the thyroid hormones metabolism in a long-term.

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway.

Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (+78% and 2-fold increase, respectively; P < 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P < 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (-17%, P < 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (-22%, P < 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (-61% and -29%, respectively, P < 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (+2-fold, P < 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension.

Prolactin inhibition at mid-lactation influences adiposity and thyroid function in adult rats.

Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition model) on milk leptin transfer, leptinemia, body composition, and thyroid function. Lactating rats were treated with bromocryptine (BRO, 1 mg/twice daily) or saline on days 7, 8, and 9 of lactation. Offspring were sacrificed 10, 21, and 90 days after birth. After treatment, BRO-treated dams showed hypoprolactinemia and hyperleptinemia, and produced less milk with lower levels of lactose and higher milk triglycerides. Milk leptin levels were lower at weaning. Offspring of BRO-treated dams had lower body weight and length as well as less visceral fat during lactation and adulthood. Total fat was also lower at weaning and adult life, whereas total protein was higher at 90 days-old. BRO offspring presented lower serum T4 and TSH at 10 days-old and weaning, respectively. When adults, these rats exhibited hypoleptinemia, lower levels of thyroid hormones, and higher TSH. Early inhibition of PRL therefore leads to offspring malnutrition and affects subsequent growth. Also, inhibition of PRL during lactation predisposes offspring to hypothyroidism; however, when the inhibition occurs during late lactation, the hypothyroidism is secondary, whereas when it is restricted to mid-lactation, the thyroid hypofunction is primary. The programming effect of milk suppression thus depends on the developmental stage of offspring.