Identification of obesity in children and teenagers.

BACKGROUND: Obesity is a condition that increases the risk of developing several health problems, resulting in high health care costs worldwide. Therefore, it is important to investigate several avenues for the control of this condition. This study aimed to identify a dermatoglyphical condition that distinguishes obesity individuals from those of appropriate weight. METHODS: The sample comprised 2172 children and teenagers between the ages of 10 and 19 years, female and male, from public and private schools of the municipality of Joaçaba, Santa Catarina, Brazil. RESULTS: In a comparison of qualitative variables, i.e., patterns, significant differences were observed between groups, including a higher frequency of ulnar loops (LU) on the index and middle fingers (MET2 and MET3) in the appropriate weight group. In the obesity group, a greater frequency of whorls (W) on fingers MET2 and MET3 was observed in males. In females, there were statistically significant correlations between the presence of radial loops (LR) on MET3 in the appropriate weight group and arches (A) in the obesity group. CONCLUSIONS: The study uncovered dermatoglyphical marks characteristic of obesity individuals.

Effects of low-intensity training on the brain and muscle in the congenital muscular dystrophy 1D model.

INTRODUCTION: Congenital Muscular Dystrophy type 1D (MDC1D) is characterized by a hypoglycosylation of α-dystroglycan protein (α-DG), and this may be strongly implicated in increased skeletal muscle tissue degeneration and abnormal brain development, leading to cognitive impairment. However, the pathophysiology of brain involvement is still unclear. Low-intensity exercise training (LIET) is known to contribute to decreased muscle degeneration in animal models of other forms of progressive muscular dystrophies. AIM: The objective of this study was to analyze the effects of LIET on cognitive involvement and oxidative stress in brain tissue and gastrocnemius muscle. METHODS: Male homozygous (Largemyd-/-), heterozygous (Largemyd+/-), and wild-type mice were used. To complete 28 days of life, they were subjected to a low-intensity exercise training (LIET) for 8 weeks. After the last day of training, 24 h were expected when the animals were submitted to inhibitory avoidance and open-field test. The striatum, prefrontal cortex, hippocampus, cortex, and gastrocnemius were collected for evaluation of protein carbonylation, lipid peroxidation, and catalase and superoxide dismutase activity. RESULTS: LIET was observed to reverse the alteration in aversive and habituation memory. Increased protein carbonylation in the striatum, prefrontal cortex, and hippocampus and lipid peroxidation in the prefrontal cortex and hippocampus were also reversed by LIET. In the evaluation of the antioxidant activity, LIET increased catalase activity in the hippocampus and cortex. In the gastrocnemius, LIET decreased the protein carbonylation and lipid peroxidation and increased catalase and superoxide dismutase activity. CONCLUSION: In conclusion, it can be inferred that LIET for 8 weeks was able to reverse the cognitive damage and oxidative stress in brain tissue and gastrocnemius muscle in MDC1D animals.

Swimming Improves Memory and Antioxidant Defense in an Animal Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disease associated with progressive skeletal muscle degeneration. In humans, DMD has an early onset, causes developmental delays, and is a devastating disease that drastically diminishes the quality of life of young individuals affected. The objective of this study was to evaluate the effects of a swimming protocol on memory and oxidative stress in an animal model of DMD. Male mdx and wild-type mice aged ≥ 28 days were used in this study. The animals were trained for a stepped swimming protocol for four consecutive weeks. The swimming protocol significantly reduced the levels of lipid peroxidation and protein carbonylation in the gastrocnemius, hippocampus, and striatum in the exercised animals. It also prevented lipid peroxidation in the diaphragm. Moreover, it increased the free thiol levels in the gastrocnemius, the diaphragm, and all central nervous system structures. The results showed that the protocol that applied swimming as a low-intensity aerobic exercise for 4 weeks prevented aversive memory and habituation in mdx mice.

Involvement of NLRP3 inflammasome in schizophrenia-like behaviour in young animals after maternal immune activation.

OBJECTIVE: To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA). METHODS: To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements. RESULTS: It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1ß levels on 7, 14 and 45 postnatal days. CONCLUSION: This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

Effect of Aerobic Physical Exercise in an Animal Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a condition caused by an amendment to the X chromosome, inherited as a recessive trait, and affects 1:3500 live births, especially males. Low-intensity exercise is known to decrease certain parameters associated with muscular degeneration in animal models of progressive muscular dystrophies. In the present study, 28-day-old male mdx and wild-type (wild) mice were used. The animals were subjected to a low-intensity physical exercise protocol for 8 weeks. It was found that this protocol was able to reduce oxidative stress in muscle tissue and in most of the CNS structures analyzed, with a significant increase in antioxidant activity in all analyzed structures. It is thus possible to infer that this exercise protocol was able to reduce oxidative stress and improve the energy metabolism in brain tissue and in the gastrocnemius muscle of animals with DMD.

Effects of chronic treatment with gold nanoparticles on inflammatory responses and oxidative stress in Mdx mice.

Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary myopathy characterised by progressive muscle degeneration in male children. As a consequence of DMD, increased inflammation and oxidative stress occur in muscle tissue along with morphological changes. Several studies have reported anti-inflammatory and antioxidant effects of gold nanoparticles (GNP) in muscle injury models. The objective of this study was to evaluate these effects along with the impacts of the disease on histopathological changes following chronic administration of GNP to Mdx mice. Two-month-old Mdx mice were separated into five groups of eight individuals each, as follows: wild-type (WT), Mdx-modified without treatment, Mdx + 2.5 mg/kg GNP, Mdx + 7.0 mg/kg GNP and Mdx + 21 mg/kg GNP. GNP with a mean diameter of 20 nm were injected subcutaneously at concentrations of 2.5, 7.0 and 21 mg/kg. Treatments continued for 30 d with injections administered at 48-h intervals. Twenty-four hours after the last injection, the animals were killed and the central region of the gastrocnemius muscle was surgically removed. Chronic administration of GNP reduced inflammation in the gastrocnemius muscle of Mdx mice and reduced morphological alterations due to inflammatory responses to muscular dystrophy. In addition, GNP also demonstrated antioxidant potential by reducing the production of reactive oxygen and nitrogen species, reducing oxidative damage and improving antioxidant activity.

Neonatal Immune Activation May Provoke Long-term Depressive Attributes.

BACKGROUND: Studies have shown the relationship between neuroinflammation and depressive- like parameters. However, research still has not been carried out to evaluate neuroinflammation in the neonatal period and psychiatric disorders in adulthood. OBJECTIVE: To verify the association between neonatal immune activation and depressive-like parameters in adulthood using an animal model. METHODS: Two days old C57BL/6 animals were exposed to lipopolysaccharides (LPS) or phosphate- buffered saline (PBS). When the animals were 46 days old, they received PBS or Imipramine at 14 days. At 60 days, the consumption of sucrose; immobility time; adrenal gland and the hippocampus weight; levels of plasma corticosterone and hippocampal Brain-derived neurotrophic factor (BDNF) were evaluated. RESULTS: It was observed that the animals exposed to LPS in the neonatal period and evaluated in adulthood decreased the consumption of sucrose and had reducted hippocampus weight. Also, the exposed animals presented an increase of immobility time, adrenal gland weight and plasma levels of corticosteroids. The use of imipramine did not only modify the decreased hippocampal weight. On the other hand, there were no alterations in the BDNF levels in the hippocampus with or without the use of imipramine. CONCLUSION: These results suggest that neonatal immune activation may be associated with depressive- like parameters in adulthood. It is believed that endotoxemia may trigger physiological and behavioral alterations, increasing vulnerability for the development of depression in adulthood.

Late Brain Involvement after Neonatal Immune Activation.

The neonatal immune system is still immature, which makes it more susceptible to the infectious agents. Neonatal immune activation is associated with increased permeability of the blood-brain barrier, causing an inflammatory cascade in the CNS and altering behavioral and neurochemical parameters. One of the hypotheses that has been studied is that neuroinflammation may be involved in neurodegenerative processes, such as Alzheimer's disease (AD). We evaluate visuospatial memory, cytokines levels, and the expression of tau and GSK-3ß proteins in hippocampus and cortex of animals exposed to neonatal endotoxemia. C57BL/6 mice aging two days received a single injection of subcutaneous lipopolysaccharide (LPS). At 60,120, and 180 days of age, visual-spatial memory was evaluated and the hippocampus and cortex were dissected to evaluate the cytokines levels and expression of tau and GSK-3ß proteins. The animals exposed to LPS in the neonatal period present with visuospatial memory impairment at 120 and 180 days of age. Here there was an increase of TNF-α and IL-1ß levels in the hippocampus and cortex only at 60 days of age. Here there was an increase in the expression of GSK-3ß in hippocampus of the animals at 60, 120, and 180 days of age. In the cortex, this increase occurred in the 120 and 180 days of age. Tau protein expression was high in hippocampus and cortex at 120 days of age and in hippocampus at 180 days of age. The data observed show that neonatal immune activation may be associated with visuospatial memory impairment, neuroinflammation, and increased expression of GSK-3ß and Tau proteins in the long term.

Neurocognitive Impairment in mdx Mice.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that affects muscles and also the brain, resulting in memory and behavioral problems. In the pathogenesis of DMD, inflammation is an important factor during the degenerative process. However, the involvement of the brain is still unclear. Therefore, the objective of this study is to evaluate the cognitive involvement, BDNF levels, cytokine levels through the levels of TNF-α and IL-1ß, the myeloperoxidase (MPO) activity, and the expression of proteins postsynaptic density (PSD)-95 and synaptophysin in the brain of mdx mice. To this aim, we used adult mdx mice. It was observed that mdx mice presented deficits on the habituation, aversive, and object recognition memory. These animals also had a depression-like behavior and an anxiety-like behavior, a decrease of BDNF levels, an increase in the levels of TNF-α and IL-1ß, an increase of MPO activity, and an overexpression of synaptophysin and PSD-95 in brain tissue. In conclusion, these data show that mdx mice possibly present a neuroinflammatory component and the involvement of synaptic proteins associated to memory storage and restoring process impairment as well as a depressive- and anxiety-like behavior.

Dextran Sulphate of Sodium-induced colitis in mice: antihyperalgesic effects of ethanolic extract of Citrus reticulata and potential damage to the central nervous system.

Citrus species are widely related to antihyperalgesic and anti-inflammatory effects. The aim of this study was to investigate if treatment with ethanolic extract from peels of mature Citrus reticulata Blanco causes antihyperalgesic effects on the referred mechanical hyperalgesia in a model of dextran sulphate of sodium (DSS)-induced colitis in mice, as well as the possible oxidative damage in different regions of the brain induced by its inflammatory reaction. Antihyperalgesia (30 to 300 mg/kg) was investigated by behavioral response (frequency of response to von Frey filament stimulation) in Swiss mice, while damage to central nervous system was investigated through techniques that evaluated oxidative stress using male black C57 BL6 mice (n=8). Treatment of the animals with the extract (100 mg/kg) from days 3 to 5 after colitis induction reduced referred the mechanical hyperalgesia (32.6 ± 5.1) in relation to the control group (57.4 ± 2.0). Levels of lipid peroxidation or carbonyl proteins were augmented in colitis-induced animals in relation to the disease group. These results indicated an antihyperalgesic effect of the studied extract and a potential impairment of the central nervous system functioning caused by inflammation during colitis, which could be related to mental disorders observed in patients suffering of this pathology.

Early fragmentation of polyester urethane sheet neither causes persistent oxidative stress nor alters the outcome of normal tissue healing in rat skin.

Silicone breast implant is associated with complications inherent to the surgical procedure. Prosthesis coating with polyurethane, however, commonly reduces the incidence of such complications. In this paper, the authors evaluated the inflammatory histomorphometric profile and oxidative damage associated to the implant of polyester urethane sheets. Forty-eight Wistar rats were divided into Sham or polyester urethane groups (n = 8/group) and underwent a polyester urethane implant in the dorsal skinfold. Tissue samples were collected on days seven, 30, and 90 after surgery and subjected to histomorphometric analysis and biochemical tests. Results were analyzed by one-way ANOVA (p ≤ 0.05). Peri-implant tissue samples exhibited characteristic inflammatory response associated with the biomaterial, with increased vascularization on day seven and augmented levels of IL1-b and TNF-a after 30 days. Peri-implant fibrocystic population was small on day seven, but increased considerably after 90 days. A rise in the carbonyl group levels of skin samples in the polyester urethane group was observed on day seven. Findings suggest that polyester urethane sheets undergo biodegradation at an early stage after implantation, followed by increased vascularity and microencapsulation of biomaterial fragments, without persistent oxidative damage. Fiber arrangement inside the collagen matrix results in a fibrotic scar because of polyester urethane degradation.

Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis.

Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment.

Congenital Muscular Dystrophy type 1D (CMD1D) is characterized by an abnormal glycosylation of α-DG (α-dystroglycan) and is associated to the central nervous system (CNS) abnormalities such as cognitive impairment. The purpose of the research was to evaluate the blood-brain barrier permeability (BBB) permeability and matrix metalloproteinases (MMP) -2 and -9 in adult Largemyd-/- mice in order to understand the physiopathology of brain involvement during the CMD1D process. To this aim, we used adult homozygous Largemyd-/- (mutation in Large), heterozygous Largemyd+/- as well as wild-type (C57BL/6) mice. The animals were submitted to the evaluation of BBB permeability and MMP-2 and MMP-9 in striatum, hippocampus and cerebral cortex. There was an increase in BBB permeability in the hippocampus and striatum associated with an increase in the protein levels of MMP-2 in the cerebral cortex and striatum and MMP-9 in the hippocampus in adult Largemyd-/- mice. Our results suggest that the pathophysiologic processes can be associated to the action of MMPs and BBB disruption and that the BBB breakdown is relevant to the perpetuation of brain inflammation and can be related to brain dysfunction observed in CMD1D patients.

Experimental Neonatal Sepsis Causes Long-Term Cognitive Impairment.

Neonatal sepsis is a major cause of morbidity and mortality in neonatal intensive care units. Treatment with antibiotics reduces mortality and morbidity, but neonatal sepsis remains a serious life-threatening condition. The objective of this study was to evaluate cognitive impairment in adult mice submitted to sepsis in the neonatal period. To this aim, 2-day-old male C57BL/6 mice were submitted to sepsis by injection of 25 µg of LPS. Sixty days after, the learning and memory were evaluated. It was observed that the mice submitted to neonatal sepsis presented impairment of habituation, aversive, and object recognition memories, and had an increase of immobility time in forced swimming test in adulthood. In conclusion, this study shows that the neonatal sepsis causes long-term brain alterations. These alterations can persist to adulthood in an animal model due to a vulnerability of the developing brain.

Behavioral Responses in Animal Model of Congenital Muscular Dystrophy 1D.

Congenital muscular dystrophies 1D (CMD1D) present a mutation on the LARGE gene and are characterized by an abnormal glycosylation of α-dystroglycan (α-DG), strongly implicated as having a causative role in the development of central nervous system abnormalities such as cognitive impairment seen in patients. However, in the animal model of CMD1D, the brain involvement remains unclear. Therefore, the objective of this study is to evaluate the cognitive involvement in the Large(myd) mice. To this aim, we used adult homozygous, heterozygous, and wild-type mice. The mice underwent six behavioral tasks: habituation to an open field, step-down inhibitory avoidance, continuous multiple trials step-down inhibitory avoidance task, object recognition, elevated plus-maze, and forced swimming test. It was observed that Large(myd) individuals presented deficits on the habituation to the open field, step down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance, object recognition, and forced swimming. This study shows the first evidence that abnormal glycosylation of α-DG may be affecting memory storage and restoring process in an animal model of CMD1D.

Activity of Krebs cycle enzymes in mdx mice.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a degenerative disease of skeletal, respiratory, and cardiac muscles caused by defects in the dystrophin gene. More recently, brain involvement has been verified. Mitochondrial dysfunction and oxidative stress may underlie the pathophysiology of DMD. In this study we evaluate Krebs cycle enzymes activity in the cerebral cortex, diaphragm, and quadriceps muscles of mdx mice. METHODS: Cortex, diaphragm, and quadriceps tissues from male dystrophic mdx and control mice were used. RESULTS: We observed increased malate dehydrogenase activity in the cortex; increased malate dehydrogenase and succinate dehydrogenase activities in the diaphragm; and increased citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities in the quadriceps of mdx mice. CONCLUSION: This study showed increased activity of Krebs cycle enzymes in cortex, quadriceps, and diaphragm in mdx mice.

Interleukin-1ß Receptor Antagonism Prevents Cognitive Impairment Following Experimental Bacterial Meningitis.

Pneumococcal meningitis is characterized by high rates of mortality and long-term cognitive impairment. In this study, we evaluated the effects of interleukin (IL)-1ß receptor antagonist (IL-1Ra) on memory, cytokine, and brain-derived neurotrophic factor (BDNF) levels in hippocampus after experimental pneumococcal meningitis. In a first experiment the animals were divided into four groups: control/saline, control treated with IL-1Ra, meningitis/saline, and meningitis treated with IL-1Ra. In the meningitis/saline group IL-1ß and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels increased at 24 h post-infection; adjuvant treatment with IL-1Ra reversed the increased levels in the hippocampus. The levels of tumour necrosis factor-alpha (TNF-α), IL-4, IL-6, IL-10, and BDNF did not change in all groups at 24 h post-infection. In a second experiment, the animals were subjected to behavioural tasks (open field, step-down inhibitory avoidance task, and object recognition task), cytokine, and BDNF levels analysis 10 days after experimental meningitis induction. In the open-field task, the meningitis/saline group did not exhibit difference between the training and test sessions, in the motor and exploratory activity indicating memory injury. The meningitis/IL-1Ra group presented difference between training and test session indicating habituation memory. The meningitis/saline group showed impairment in long-term memory for novel object recognition and in aversive memory. The adjuvant treatment with IL-1Ra prevented memory impairment. After behavioural tasks the hippocampus was evaluated. The levels of IL-4, IL-6, IL-10, and BDNF were maintained elevated 10 days post-infection. CINC-1 levels were elevated only in meningitis/saline group and IL-1ß decreased in meningitis/IL-Ra group. The levels of TNF-α did not change at 10 days post-infection. These findings illustrate the anti-inflammatory activity of IL-1Ra inhibitor in the first hours after meningitis induction. Adjuvant treatment with IL-1ß receptor antagonist could be a new avenue as therapeutic target during bacterial meningitis.