Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring.

Autism is characterized by social deficits, repetitive behaviors, and cognitive inflexibility. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces autistic-like behaviors. To understand the causes of autistic-like behaviors, we evaluated maternal serum metal concentrations, which are involved in intrauterine development and infection/inflammation. We identified reduced maternal levels of zinc, magnesium, selenium and manganese after LPS exposure. Because LPS induced maternal hypozincemia, we treated dams with zinc in an attempt to prevent or ease the impairments in the offspring. We evaluated the social and cognitive autistic-like behaviors and brain tissues of the offspring to identify the central mechanism that triggers the development of autism. Prenatal LPS exposure impaired play behaviors and T-maze spontaneous alternations, i.e., it induced autistic-like behaviors. Prenatal LPS also decreased tyrosine hydroxylase levels and increased the levels of mammalian target of rapamycin (mTOR) in the striatum. Thus, striatal dopaminergic impairments may be related to autism. Moreover, excessive signaling through the mTOR pathway has been considered a biomarker of autism, corroborating our rat model of autism. Prenatal zinc treatment prevented these autistic-like behaviors and striatal dopaminergic and mTOR disturbances in the offspring induced by LPS exposure. The present findings revealed a possible relation between maternal hypozincemia during gestation and the onset of autism. Furthermore, prenatal zinc administration appears to have a beneficial effect on the prevention of autism

Sagittal abdominal diameter: Comparison with waist circumference and its prediction of metabolic syndrome

Background: For an "in the field" estimate of visceral adiposity, simple, inexpensive, non-invasive and highly repetitive methods are needed. The anthropometric measurement most commonly used as an indicator for visceral fat deposits is waist circumference (W). Nevertheless, there are some doubts with regard to the anatomic landmark points where the evaluation needs to be carried out. Sagittal abdominal diameter (SAD) is another anthropometric measurement that has been proposed for the estimation of visceral fat. Objective: The aims of the study are to evaluate intra- and inter-operator variability of the estimation of the SAD compared to W; correlate SAD to other anthropometric parameters and to factors involved in the metabolic syndrome (MS); and identify the values for the estimation of the SAD able to classify different risk levels with respect to the MS. Methods: Ninety-five subjects at the Metabolic and Nutritional Rehabilitation Unit "Villa delle Querce" in Nemi were selected. Anthropometric and biochemical parameters were collected. The presence of a MS was detected. Intra- and inter-operator variability in the measurement of W and SAD and the predictive capacity of SAD in the estimation of the risk for MS were calculated. Results: The main results achieved were reduced intra- and inter-operator variability in the measurement of SAD compared to W; confirmation of the correlations between SAD and the anthropometric parameters as indicators of a higher fat mass; and good predictive capacity of SAD towards MS (cut-off points: 22.2 cm for men and 19.5 cm for women). © 2009 Springer-Verlag Italia

Predicting the outcome of artificial nutrition by clinical and functional indices

Objective: Artificial nutrition (AN) is now considered medical therapy and has progressively become one of the mainstays of the different therapeutic options available for home or hospitalized patients, including surgical, medical, and critically ill patients. The clinical relevance of any therapy is based on its efficacy and effectiveness and thus on the improvement of its cost efficiency, i.e., the ability to provide benefits to the patients with minimal wasting of human and financial resources. The aim of the present study was to identify those indices, clinical, functional, or nutritional, that may reliably predict, before the start of AN, those patients who are likely not to benefit from nutritional support. Methods: Three hundred twelve clinical charts of patients receiving AN between January 1999 and September 2006 were retrospectively examined. Data registered before starting AN were collected and analyzed: general data (age, sex), clinical conditions (comorbidity, quality of life, frailty), anthropometric and biochemical indices, type of AN treatment (total enteral nutrition, total parenteral nutrition, mixed AN), and outcome of treatment. Results: The percentage of negative outcomes (death or interruption of AN due to worsening clinical conditions within 10 d after starting AN) was meaningfully higher in subjects >80 y of age and with reduced social functions, higher comorbidity and/or frailty, reduced level of albumin, prealbumin, lymphocyte count, and cholinesterase and a higher level of C-reactive protein. The multivariate analysis showed that prealbumin and comorbidity were the best predictors of AN outcome. The logistic regression model with these variables showed a predictive value equal to 84.2%. Conclusion: Proper prognostic instruments are necessary to perform optimal evaluations. The present study showed that a patient's general status (i.e., comorbidity, social quality of life, frailty) and nutritional and inflammatory statuses (i.e., lymphocyte count, albumin, prealbumin, C-reactive protein) have good predictive value on the effectiveness of AN. © 2009 Elsevier Inc. All rights reserved

Maternal metal concentrations.

<p>*<i>p</i> < 0.05 compared with the SAL group (Student’s t-test).</p><p>The effects of LPS (100 μg/kg) exposure at gestational day 9.5 in rats on maternal serum metal concentrations (μg.kg^-1) measured 24 h after treatment. SAL, prenatal saline injection (n = 8); LPS, prenatal LPS injection (n = 9). Data are expressed as the mean ± SEM.</p

Acute Effect on Satiety, Resting Energy Expenditure, Respiratory Quotient, Glucagon-Like Peptide-1, Free Fatty Acids, and Glycerol Following Consumption of a Combination of Bioactive Food Ingredients in Overweight Subjects

Objective: A combination of bioactive food ingredients (capsaicinoids, epigallocatechin gallate, piperin, and L-carnitine, CBFI) may promote satiety and thermogenesis. The study was conducted in order to assess whether there is any effect on satiety, resting energy expenditure (REE), respiratory quotient, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol release, following a standardized mixed meal with or without single consumption of a CBFI. Design: An 8-week randomized double-blind placebo-controlled trial. Setting: Dietetic and Metabolic Unit, Azienda di Servizi alla Persona, University of Pavia and "Villa delle Querce" Clinical Rehabilitation Institute, Rome, Italy. Participants: Thirty-seven overweight adults (body mass index [BMI]: 25-35). Intervention: Nineteen overweight subjects were included in the supplemented group (14 women, 5 men; age 46.4 +/- 6.4; BMI: 30.5 +/- 3.3) and 18 in the placebo group (13 women, 5 men; age 40.8 +/- 11.5; BMI: 30.1 +/- 2.6). Satiety was assessed using 100-mm visual analogue scales (VAS) and the area under the curve was calculated. Results: All measured parameters increased significantly in comparison with baseline in response to meal, both with CBFI and with placebo. However, throughout the study day, the supplemented group experienced a significantly greater increase than the placebo group in their sensation of satiety following acute administration of the supplement. Conclusion: CBFI may therefore be of great value in the treatment of overweight patients by increasing satiety and stimulating thermogenesis

Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects

This randomized, double blind, placebo-controlled, 8 week trial assessed the efficacy on metabolic changes produced by a consumption of a combination of bioactive food ingredients (epigallocatechin gallate, capsaicins, piperine and l-carnitine) versus a placebo, as part of a therapeutic 'lifestyle change' diet, in 86 overweight subjects. Forty-one patients (2/14 F/M; age 43.7 ± 8.5; BMI 30.3 ± 3.5 kg/m2) were randomized to the supplemented group and 45 (29/16; age 40.7 ± 10.2; BMI 30.0 ± 2.7) to the control group. We observed that consumption of the dietary supplement was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment (p &lt; 0.001), leptin/adiponectin ratio (p &lt; 0.04), respiratory quotient (p &lt; 0.008). LDL-cholesterol levels (p &lt; 0.01). Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels (p &lt; 0.001). Leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group (p &lt; 0.05, 0.03, 0.02 and 0,02 respectively), but not in the placebo group; adiponectin decreased significantly in the placebo group (0.001) but not in the supplemented group, although no statistical significance between the groups was elicited. BMI, fat mass (assessed by DXA) and vascular endothelial growth factor significantly decreased, whilst the resting energy expenditure/free fat mass significantly increased in both groups. In general, a greater change was recorded in the supplemented group compared to the placebo, although no statistically significant difference between the two groups was recorded. These results suggest that the combination of bioactive food ingredients studied might be useful for the treatment of obesity-related inflammatory metabolic dysfunctions. © 2012 The Author(s)

TH and mTOR expression in the offspring.

<p>The effects of prenatal LPS (100 μg/kg) and zinc (ZnSO₄; 2 mg/kg) exposure at gestational day 9.5 on the TH and mTOR levels in the striatum and substantia nigra (normalized optical density/Beta-actin ratio, western blotting) in young male rat offspring (PND 30). (A) striatal TH levels; (B) substantia nigra TH levels; (C) striatal mTOR levels; (D) substantia nigra mTOR levels. SAL+SAL, prenatal saline injection and another saline injection 1 h later; LPS+SAL, prenatal LPS injection and a saline injection 1 h later; LPS+Zn, prenatal LPS injection and a zinc injection 1 h later (<i>n</i> = 6–7 rats/group). *<i>p</i> < 0.05 and **<i>p</i> < 0.01 compared with the SAL+SAL group; ^###<i>p</i> < 0.0001 compared with the LPS+Zn group (one-way ANOVA followed by the Bonferroni test). The data are expressed as the mean ± SEM.</p

Maternal metal concentrations.

<p>*<i>p</i> < 0.05 compared with the SAL group (Student’s t-test).</p><p>The effects of LPS (100 μg/kg) exposure at gestational day 9.5 in rats on maternal serum metal concentrations (μg.kg^-1) measured 24 h after treatment. SAL, prenatal saline injection (n = 8); LPS, prenatal LPS injection (n = 9). Data are expressed as the mean ± SEM.</p

Play behaviors in the offspring.

<p>The effects of prenatal LPS (100 μg/kg) and zinc (ZnSO₄; 2 mg/kg) exposure at gestational day 9.5 on play behaviors in young male rat offspring (PND 30). SAL+SAL, prenatal saline injection and another saline injection 1 h later; LPS+SAL, prenatal LPS injection and a saline injection 1 h later; LPS+Zn, prenatal LPS injection and a zinc injection 1 h later (<i>n</i> = 10 rats/group). **<i>p</i> < 0.01 and ***<i>p</i> < 0.0001 compared with the SAL+SAL group; ^#<i>p</i> < 0.01 and ^###<i>p</i> < 0.0001 compared with the LPS+Zn group (one-way ANOVA followed by the Bonferroni test). The data are expressed as the mean ± SEM.</p