Citrus aurantium L. and synephrine improve brown adipose tissue function in adolescent mice programmed by early postnatal overfeeding.

Introduction and aims: Obesity is a multifactorial condition with high health risk, associated with important chronic disorders such as diabetes, dyslipidemia, and cardiovascular dysfunction. Citrus aurantium L. (C. aurantium) is a medicinal plant, and its active component, synephrine, a ß-3 adrenergic agonist, can be used for weight loss. We investigated the effects of C. aurantium and synephrine in obese adolescent mice programmed by early postnatal overfeeding. Methods: Three days after birth, male Swiss mice were divided into a small litter (SL) group (3 pups) and a normal litter (NL) group (9 pups). At 30 days old, SL and NL mice were treated with C. aurantium standardized to 6% synephrine, C. aurantium with 30% synephrine, isolated synephrine, or vehicle for 19 days. Results: The SL group had a higher body weight than the NL group. Heart rate and blood pressure were not elevated. The SL group had hyperleptinemia and central obesity that were normalized by C. aurantium and synephrine. In brown adipose tissue, the SL group showed a higher lipid droplet sectional area, less nuclei, a reduction in thermogenesis markers related to thermogenesis (UCP-1, PRDM16, PGC-1α and PPARg), and mitochondrial disfunction. C. aurantium and synephrine treatment normalized these parameters. Conclusion: Our data indicates that the treatment with C. aurantium and synephrine could be a promising alternative for the control of some obesity dysfunction, such as improvement of brown adipose tissue dysfunction and leptinemia.

Humanization of care for adult ICU patients: a scoping review protocol.

OBJECTIVE: The objective of this review is to review and map data from studies on the humanization of care in intensive care units based on a conceptual framework. INTRODUCTION: The critical context of adult patients in intensive care units directs the focus on clinical medical interventions, drawing attention away from the humanization of care. Rethinking intensive care is imperative and the humanization of care is an absolute priority. Literature on this topic is scattered under umbrella terms such as "patient-centered care" or specific terms referring to target interventions. A scoping review based on a conceptual framework will map the literature on humanization in intensive care units. INCLUSION CRITERIA: The review will consider studies on the humanization of care, or on one of the seven components of the conceptual framework (communication, visiting hours, patients' and health care professionals' well-being, family involvement and satisfaction, post-intensive care unit syndrome, and physical environment) focusing on adult patients in intensive care units. Studies on co-existing states or end-of-life care will be excluded. METHODS: A search of Embase, PubMed, and CINAHL will be conducted to identify relevant studies in English or French on the humanization of care, holistic care, or person-centered care in an adult intensive-care environment. The time period covered will be January 1, 2010 to the present. An iterative team approach will be used to screen and select studies and extract data. Data will be charted according to study design, distribution in time, cultural context, concepts, use of theoretical models, and intervention. The results will be summarized and reported, identifying the implications for policy, practice, and research.

Anti-Inflammatory Potential of the Oleoresin from the Amazonian Tree Copaifera reticulata with an Unusual Chemical Composition in Rats.

Copaifera reticulata Ducke is a popularly known species known as copaíba that is widely spread throughout the Amazon region. The tree yields an oleoresin which is extensively used in local traditional medicine mainly as an anti-inflammatory and antinociceptive agent. The aim of the present study was to assess the anti-inflammatory potential of this oleoresin obtained from a national forest in the central Amazon which presented an unusual chemical composition. The chemical composition of volatile compounds of oleoresin was analyzed by gas chromatography-mass spectrometry. The acute toxicity assay was performed with a single dose of 2000 mg/kg. The anti-inflammatory potential was evaluated by carrageenan-induced paw edema and air pouch assays using four different C. reticulata oleoresin concentrations (10, 100, and 400 mg/kg). The exudate was evaluated for nitrite concentration through the colorimetric method and for TNF-α, IL-1ß, and PGE2 by ELISA. C. reticulata oleoresin collected in the Amazonian summer contained six major sesquiterpene compounds (ß-bisabolene, cis-eudesma-6,11-diene, trans-α-bergamotene, ß-selinene, α-selinene, and ß-elemene) and was nontoxic at a dose of 2000 mg/kg, showing low acute toxicity. Different from oleoresin obtained from other sites of the Brazilian Amazon, the major volatile compound found was ß-Bisabolene with 25.15%. This ß-Bisabolene-rich oleoresin reduced the formation of paw edema induced by carrageenan and reduced the global number of cells in the air pouch assay, as well as exudate volume and nitrite, TNF-α, IL-1ß, and prostaglandin E2 levels (p < 0.05). C. reticulata oleoresin with a high ß-Bisabolene concentration showed anti-inflammatory activity, reducing vascular permeability and consequently edema formation, and thus reducing cell migration and the production of inflammatory cytokine, confirming its traditional use by local Amazonian communities.

Reduced graphene oxide, but not carbon nanotubes, slows murine melanoma after thermal ablation using LED light in B16F10 lineage cells.

Photodynamic therapy is a minimally invasive health technology used to treat cancer and other non-malignant diseases, as well as inactivation of viruses, bacteria and fungi. In this work, we sought to combine the phototherapy technique using low intensity LED (660 nm) to induce ablation in melanoma tumor in mice treated with nanoparticles. In vitro and in vivo studies were conducted, and our results demonstrated that multi-walled carbon nanotubes (MWCNTs) do not destroy tumor cells in vivo, but stimulate the inflammatory process and angiogenesis. Reduced graphene oxide (rGO), has been shown to play a protective role associated with the LED ablation, inducing necrosis, stimulation of immune response by lymphoproliferation, and decreased tumor mass in vivo. We consider that LED alone can be very effective in controlling the growth of melanoma tumors and its association with rGO is potentiated.

Maternal coconut oil intake on lactation programs for endocannabinoid system dysfunction in adult offspring.

Maternal exposure to coconut oil metabolically programs adult offspring for overweight, hyperphagia and hyperleptinemia. We studied the neuroendocrine mechanisms by which coconut oil supplementation during breastfeeding as well as continued exposure of this oil throughout life affect the feeding behavior of the progeny. At birth, pups were divided into two groups: Soybean oil (SO) and Coconut oil (CO). Dams received these oils by gavage (0.5 g/kg body mass/day) during lactation. Half of the CO group continued to receive CO in chow throughout life (CO + C). Adult CO and CO + C groups had overweight; the CO group had hyperphagia, higher visceral adiposity, and hyperleptinemia, while the CO + C group had hypophagia only. The CO group showed higher DAGLα (endocannabinoid synthesis) but no alteration of FAAH (endocannabinoid degradation) or CB1R. Leptin signaling and GLP1R were unchanged in the CO group, which did not explain its phenotype. Hyperphagia in these animals can be due to higher DAGLα, increasing the production of 2-AG, an orexigenic mediator. The CO + C group had higher preference for fat and lower hypothalamic GLP1R content. Continuous exposure to coconut oil prevented an increase in DAGLα. The CO + C group, although hypophagic, showed greater voracity when exposed to a hyperlipidemic diet, maybe due to lower GLP1R, since GLP1 inhibits short-term food intake.

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet.

PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

In vitro and in vivo antimalarial potential of oleoresin obtained from Copaifera reticulata Ducke (Fabaceae) in the Brazilian Amazon rainforest.

BACKGROUND: In view of the wide variety of the flora of the Amazon region, many plants have been studied in the search for new antimalarial agents. Copaifera reticulata is a tree distributed throughout the Amazon region which contains an oleoresin rich in sesquiterpenes and diterpenes with ß-caryophyllene as the major compound. The oleoresin has demonstrated antiparasitic activity against Leishmania amazonensis. Because of this previously reported activity, this oleoresin would be expected to also have antimalarial activity. PURPOSE: In this study we evaluated the in vitro and in vivo antimalarial potential of C. reticulata oleoresin. METHODS: In vitro assays were done using P. falciparum W2 and 3D7 strains and the human fibroblast cell line 26VA Wi-4. For in vivo analysis, BALB/c mice were infected with approximately 106 erythrocytes parasitized by P. berghei and their parasitemia levels were observed over 7 days of treatment with C. reticulata; hematological and biochemical parameters were analyzed at the end of experiment. RESULTS: The oleoresin of C. reticulata containing the sesquiterpenes ß-caryophyllene (41.7%) and ß-bisabolene (18.6%) was active against the P. falciparum W2 and 3D7 strains (IC50 = 1.66 and 2.54 µg/ml, respectively) and showed low cytotoxicity against the 26VA Wi-4 cell line (IC50 > 100 µg/ml). The C. reticulata oleoresin reduced the parasitemia levels of infected animals and doses of 200 and 100 mg/kg/day reached a rate of parasitemia elimination resembling that obtained with artemisinin 100 mg/kg/day. In addition, treatment with oleoresin improved the hypoglycemic, hematologic, hepatic and renal parameters of the infected animals. CONCLUSION: The oleoresin of C. reticulata has antimalarial properties and future investigations are necessary to elucidate its mechanism of action.

Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood.

Previously, we demonstrated that maternal prolactin inhibition at the end of lactation, using bromocriptine (BRO), leads to an increase in leptin transfer via milk and induces the adult progeny to present hypothyroidism, leptin resistance and metabolic syndrome (obesity, hyperglycemia, hypertriglyceridemia, lower HDL). To test if these alterations are due to direct BRO action on the pups, in the present study we evaluated the long-term effects of direct injection of BRO (0.1µg/once daily) in male Wistar rats from postnatal (PN) day 1 to 10 (early treatment) or from PN11 to 20 (late treatment) on: food intake, body mass, cardiovascular parameters, hormone profile, hypothalamic leptin signaling, glucose homeostasis and thyroid hormone-dependent proteins. The respective controls were injected with methanol-saline. Offspring were killed at adulthood (PN180). Adult PN1-10 BRO-treated animals had lower food intake, hypoprolactinemia, lower leptin action (lower OBR-b, STAT-3 and SOCS-3 mRNA levels in the arcuate nucleus), lower TRH-TSH-thyroid axis as well as lower thyroid hormone markers. On the other hand, adult animals that were BRO-treated during the PN11-20 period showed hyperphagia, higher blood pressure, higher prolactinemia and OBR-b, higher TRH and plasma T3, hypercorticosteronemia as well as higher Dio2 and UCP1 mRNA expression in the brown adipose tissue. Glucose homeostasis was not changed treatment in either period. Our data show that early and late dopamine overexposure during lactation induces diverse metabolic disturbances later in life, increasing the risk of thyroid dysfunction and, consequently, changes in prolactinemia.

Role of vitamin D in adipose tissue in obese rats programmed by early weaning and post diet calcium.

SCOPE: Early weaning (EW) is associated with an impairment of offspring development and leads to overweight and higher 25-hydroxyvitamin D (25(OH)D) levels in adulthood, which can be corrected by calcium supplementation, potentially via vitamin D regulation of adipogenesis. METHODS AND RESULTS: We examined vitamin D status in adipose tissue in EW obese rats, treated with calcium. Dams were separated into: EW- dams were wrapped with a bandage to interrupt lactation (last 3 days), and C- pups with free access to milk. At PN120, EW pups were divided in: EW- standard diet, and EWCa- calcium supplementation (10 g of calcium carbonate/kg of chow). On PN21, EW group has hypocalcemia. On PN180, EW group showed lower intestinal calbidin, higher adiposity, and 25(OH)D. In adipose tissue, Cyp27b1/1alpha-Hydroxylase, C/EBPB, PPAR-γ, IL6, TNF-A, and MCP1 were increased, while VDR and IL10 were decreased. Calcium increased calbidin, VDR and prevented adipose tissue dysfunction. EW group has a long-term effect of vitamin D on adipocyte, contributing to pro-inflammatory status and obesity. CONCLUSION: We propose that in obese rat adipocytes, 1,25(OH)2 D down-regulates VDR, resulting in vitamin D resistance, characterized by higher Cyp27b1/1α-Hydroxylase and adipogenesis. Calcium therapy appears to be an outstanding strategy for weight loss and improving endocrine metabolic disorders that are obesity associated.

Postnatal overnutrition programs the thyroid hormone metabolism and function in adulthood.

Early overnutrition (EO) during lactation leads to obesity, leptin resistance and lower thyroid hormone (TH) levels during adulthood. To better understand the biological significance of this thyroid hypofunction, we studied the long-term effects of postnatal EO on both the function of hypothalamic-pituitary-thyroid (HPT) axis and the metabolism and action of TH. To induce EO, the litter size was reduced to three pups per litter (small litter (SL) group) on the third day of lactation. In the controls (normal litter group), litter size was adjusted to 10 pups per litter. Rats were killed at PN180. TRH content and in vitro TSH were evaluated. Iodothyronine deiodinase (D1 and D2) activities were measured in different tissues. Mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD), uncoupling protein 1 (UCP1) and TH receptor (TRß1) were evaluated to assess TH action. The SL group presented lower TRH, intra-pituitary and released TSH levels, despite unchanged plasma TSH. They presented lower D1 activity in thyroid, muscle and white adipose tissue (WAT) and higher D2 activity in the hypothalamus, pituitary, brown adipose tissue (BAT) and WAT, which confirmed the hypothyroidism. UCP1 in BAT and TRß1 in WAT were decreased, which can contribute to a lower catabolic status. Despite the lower TH, the D2 activity in the thyroid, heart and testes was unchanged. Hepatic D1, mGPD and TRß1 were also unchanged in SL rats, suggesting that the TH conversion and action were preserved in the liver, even with lower TH. Thus, this model indicates that postnatal EO changes thyroid function in adult life in a tissue-specific way, which can help in the understanding of obesogenesis.

Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and astrogliosis in the hypothalamus of the adult rat offspring.

The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82% in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model.

Anti-obesogenic effects of calcium prevent changes in the GLP-1 profile in adult rats primed by early weaning.

SCOPE: Gut peptides regulate appetite and adipogenesis. Early weaning (EW) leads to later development of obesity that can be prevented by calcium supplementation. We evaluated gut peptides that may have a role in the establishment of this dysfunction. METHODS AND RESULTS: At birth, lactating Wistar rats were separated in: EW, lactating rats involved with a bandage interrupting the lactation during the last 4 days of standard lactation, and C (control) dams whose pups had free access to milk during throughout lactation. At 120 days old, half of EW group received calcium supplementation (EWCa); EW and C received standard diet. At 21 days old, EW presented higher glucagon-like peptide 1 (GLP-1) in plasma and glucagon-like peptide 1 receptor (GLP1-R) in adipose tissue and hypothalamus, but lower GLP-1 and GLP1-R in the gut. At 180 days old, GLP-1 response to food intake was blunted in EW and restored by calcium. GLP-1 in the gut was lower in EW and its receptor was lower in adipose tissue, and GLP1-R was higher in the gut of calcium EW group. CONCLUSION: Thus, EW had short- and long-term effects upon GLP-1 profile, which may have contributed to obesity development, hyperphagia, and insulin resistance due to its adipogenic and appetite control roles. Calcium supplementation was able to prevent most of the changes in GLP-1 caused by EW.

Effects of Ilex paraguariensis (yerba mate) treatment on leptin resistance and inflammatory parameters in obese rats primed by early weaning.

AIMS: We evaluated the effects of yerba mate treatment over 30 days on body weight, food intake, hypothalamic leptin action and inflammatory profile in adult rats that were weaned early. MAIN METHODS: To induce early weaning, the teats of lactating rats were blocked with a bandage to interrupt milk access for the last 3 days of lactation (EW group). Control offspring had free access to milk throughout lactation. On postnatal day (PN) 150, EW offspring were subdivided into: EW and M groups were treated with water and mate aqueous solution (1g/kg BW/day, gavage), respectively, for 30 days. Control offspring received water by gavage. On PN180, offspring were killed. KEY FINDINGS: EW group presented hyperphagia; higher adiposity; higher NPY and TNF-α expression in the ARC nucleus; higher TNF-α and IL-1ß levels in the adipose tissue; and lower IL-10 levels in the adipose tissue. These characteristics were normal in M group. As expected, the leptin injection in control offspring caused lower food intake. However, EW group exhibited no change in food intake after the leptin injection, indicating leptin resistance. In contrast, M group had a normal response to the leptin injection. SIGNIFICANCE: Thirty days of mate treatment prevented the development of hyperphagia, overweight, visceral obesity and central leptin resistance. This beneficial effect on the satiety of M offspring most likely occurred after the improvement of inflammatory markers in the hypothalamus and adipocytes, which suggests that Ilex paraguariensis plays an important role in the management of obesity by acting on the inflammatory profile.

Flaxseed oil during lactation changes milk and body composition in male and female suckling pups rats.

We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation.

Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning.

PURPOSE: We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content. METHODS: To induce early weaning, lactating rats' teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed. RESULTS: EW+ mate group presented lower body weight (-10 %), adipose mass (retroperitoneal:-40 % and epididymal:-44 %), total body fat (-43 %), subcutaneous fat (-46 %), visceral adipocyte area (-21 %), triglyceridemia (-31 %) and hypothalamic NPY content (-37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored. CONCLUSION: Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model.

Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny.

Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had p<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fiber density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.

Use of the Gait Deviation Index and spatiotemporal variables for the assessment of dual task interference paradigm.

Three-dimensional gait analysis (3DGA) is an important element in the quantitative evaluation of gait in subjects with Parkinson's disease (PD). Indexes, such as the Gait Deviation Index (GDI), have recently been proposed as a summary measure of gait. The aim of the present study was to investigate the effectiveness of the GDI and spatiotemporal variables in the quantification of changes in gait during a dual-task (DT) exercise. Fourteen patients with idiopathic PD and nine healthy subjects (CG) participated in the study. All subjects walked under two conditions: free walking and DT walking. The GDI was computed from the 3DGA data. The results show gait impairment during DT, a significant difference between groups regarding GDI and an interaction effect involving the group, side and task factors. The CG and PDG were different independent of interference and side, but interference was only different for the PDG group. The results also demonstrate that the GDI should be an appropriate outcome measure for the evaluation of the effects of DT on patients with Parkinson's disease.

Early weaning is associated with higher neuropeptide Y (NPY) and lower cocaine- and amphetamine-regulated transcript (CART) expressions in the paraventricular nucleus (PVN) in adulthood.

The interruption of lactation for a short period, without the use of pharmacological substances or maternal separation, causes offspring malnutrition and hypoleptinaemia and programmes for metabolic disorders such as higher body weight and adiposity, hyperphagia, hyperleptinaemia and central leptin resistance in adulthood. Here, in order to clarify the mechanisms underlying the phenotype observed in adult early-weaned (EW) rats, we studied the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in different hypothalamic nuclei by immunohistochemistry and Western blot. In the EW group, the teats of lactating rats were blocked with a bandage to interrupt lactation during the last 3 d, while control pups had free access to milk throughout the entire lactation period. At age 180 d, EW offspring showed higher NPY staining in the paraventricular nucleus (PVN), as well as NPY protein content (+68 %) in total hypothalamus than control ones. AgRP showed no changes in staining or Western blot. POMC content was not affected; however, its distribution pattern was altered. CART-positive cells of EW offspring had lower immunoreactivity associated with reduced cell number in the PVN and lower protein content ( - 38 %) in total hypothalamus. The present data indicate that precocious weaning can imprint the neuronal circuitry, especially in the PVN, and cause a long-term effect on the expression of specific orexigenic and anorexigenic neuropeptides, such as NPY and CART, that can be caused by leptin resistance and are coherent with the hyperphagia observed in these animals.

Adipocyte morphology and leptin signaling in rat offspring from mothers supplemented with flaxseed during lactation.

OBJECTIVE: We have recently shown that maternal flaxseed supplementation during lactation induces insulin resistance in adult offspring. Here, we studied the effects of maternal dietary flaxseed during lactation on adipocyte morphology and leptin signaling in the hypothalamic-pituitary-thyroid axis as well as on behavioral traits in the adult progeny. METHODS: Lactating rats were fed a control (C) diet or a diet with 25% flaxseed (F). After weaning, pups received a standard diet until postnatal day (PN) 180. Male offspring were killed at PN21 and 180. Data were considered significant at P < 0.05. RESULTS: Weaned F rats presented a lower total and subcutaneous fat mass and higher subcutaneous adipocyte area (+48%), but at adulthood they presented higher subcutaneous and visceral adipocyte areas (+40% and 1.9-fold increase, respectively), with no change in body fat mass. At PN21, F pups had hyperleptinemia (+69%), lower T(3) (-33%), higher TSH (2.1-fold increase), higher pituitary leptin receptor (Ob-R, +11%), signal transducer and activator of transcription 3 (STAT3, +21%), and phosphorylated-STAT3 (p-STAT3, +77%) protein content. Adult F offspring only showed lower T(4) (-28%) and higher thyroid Ob-R (+52%) expression. Maternal flaxseed intake during lactation did not result in behavioral changes in the adult offspring. CONCLUSIONS: Maternal flaxseed supplementation decreases offspring adiposity and increases pituitary leptin signaling at weaning, but it induces hypertrophic adipocytes and higher thyroid leptin receptor in adulthood. The present data suggest that extensive use of flaxseed during lactation is undesirable.

Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning.

It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D3 (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.