M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures

Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5-and X4-Tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-Treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission

Gluten deprivation: What nutritional changes are found during the first year in newly diagnosed coeliac children?

Aim: A gluten-free diet (GFD) can expose children to excessive calories and fat intake. The study is intended to verify whether and how food intake, laboratory parameters, and growth are modified by a year of GFD. Methods: In 79 CD (coeliac disease) children (mean age 7.9 \ub1 3.8 years, 52 females, 27 males) diagnosed over 24 months, 24-h food diaries, food-frequency patterns, anthropometric and laboratory parameters (mainly blood sugar, insulin, lipid profile, and homocysteine) were prospectively collected before and during the first year of GFD. Nutrient intakes were compared over time and with recommendations. They were also used as regressors to explain the levels and changes of metabolic and growth variables. p-values < 0.05 were considered statistically significant. Results: Average macronutrient intake did not change during the year. Caloric intake remained below 90% (p 64 0.0001) and protein intake above 200% (p 64 0.0001) of recommendations. Lipid intake was stable at 34% of overall energy intake. Unsaturated fats increased (less omega-6 and more omega-3 with a ratio improvement from 13.3 \ub1 5.5 to 8.8 \ub1 3.1) and so did fibers, while folate decreased. The children who experienced a containment in their caloric intake during the year, presented a slower catch-up growth. Some differences were found across gender and age groups. In particular, adolescents consumed less calories, and females more omega-3. Fiber and simple sugar intakes emerged as implicated in lipid profile shift: fibers negatively with triglycerides (TG) (p = 0.033), simple sugars negatively with high-density lipoprotein (HDL) (p = 0.056) and positively with TG (p = 0.004). Waist-to-height ratio was positively associated with homocysteine (p = 0.018) and Homeostasis Model Assessment (p = 0.001), negatively with fibers (p = 0.004). Conclusion: In the short run, GFD is nutritionally very similar to any diet with gluten, with some improvements in unsaturated fats and fiber intake. Along with simple sugars containment, this may offer CD patients the opportunity for a fresh start. Caloric intakes may shift and should be monitored, especially in adolescents

Sugar Intake: Are All Children Made of Sugar?

Introduction: A healthy diet is characterized by a variety of food and a balanced energy intake, which should accompany every human being since early childhood. Unfortunately, excessive consumption of protein, fat, and lately sugar are very common in developed countries. Sugar intakes are not easily quantifiable and comparable among subjects. Therefore, we decide to analyze dietary patterns in children of different ages and diets (with and without gluten) using a food and nutrient database and a new application called the “Zuccherometro”. Patients and methods: This is a descriptive observational study conducted among children that are recruited consecutively either during a pediatric evaluation or through a school survey. Sociodemographic, nutritional and anthropometric data, degree of physical activity, and presence of medical conditions are collected. Dietary intake data are obtained by a 24 h recall diet. Results: The study analyzes 400 children: 213 girls and 187 boys. The majority of children (70.7%) are in normal weight range with similar extreme values (6.5% obese and 6.7% underweight). Celiac disease is diagnosed in 186 children. Caloric intakes are in line with the recommendations in all age-distributed groups with the exception of adolescents (11–17 years old), whose caloric intake is lower than recommendations. Protein intakes, on the contrary, are always exceeding recommendations and are significantly elevated in preschool children, (more than three times the population reference intakes). As for sugar intakes, all the children except the 11–17 years adolescents exceed the recommended cut off of 15% of daily calories. The same trend is obtained using the “Zuccherometro” that shows different percentages of age-stratified children exceeding the reference values: 1–3 years, 59% of children; 4–6 years, 68%; 7–10 years, 39.8%; 11–14 years, 25.5%; 15–17 years, 24.5%. The sugar load consists of both natural or added sugars (fructose and lactose) in food or beverages. Sugar intakes are more generously consumed by all age-stratified controls than by celiac children with the exception of the youngest ones (1–3 years old) and male adolescents. Conclusion: Since high sugar intakes are constantly accompanying children during their growth, important dietary education and coordination between families and institutions are mandatory

Gluten-free diet and lipid profile in children with celiac disease: Comparison with general population standards

Objectives: A gluten-free diet (GFD) may carry high energy and fat load. We verified lipid profile and dietary indicators cross-sectionally and prospectively in patients with celiac disease (CD). Methods: In any consecutive child receiving a GFD (group 1) or newly diagnosed as having CD (group 2), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, blood pressure (BP), anthropometric data, physical activity, and a 24-hour food diary were collected during follow-up visits (yearly in group 1 and during the first year of GFD in group 2). Results: In group 1 (132 girls, 73 boys, 10.7\ub14.2 years), TC (P=0.006), TG (P=0.014), and HDL (P=0.019) were significantly higher in girls than in boys. Compared with the general pediatric population, group 1 girls had higher TC, TG, HDL, and low-density lipoprotein; group 1 boys had lower TC, TG, and low-density lipoprotein and higher HDL. TC was significantly and positively affected by age, sex, and time receiving GFD, whereas HDL was significantly and positively affected by body mass index, diastolic BP, and sex; TG was negatively affected by diastolic BP. Compared with recommendations, group 1 children introduced less calories, iron, and calcium; one-third more sodium; similar amounts of fiber; and twice as many proteins. In group 2 (20 girls, 10 boys, 8.6\ub13.55 years), TC did not change over time and TG diminished, whereas HDL, blood glucose, and body mass index increased; saturated fats and caloric intake were below recommendations, whereas proteins were excessively introduced. Fibers were optimal. HDL was inversely correlated to calories and saturated fat (R2=80, P=0.011). Conclusions: Lipid profiles of children with CD differ across sexes and from reference population. GFD, being unexpectedly appropriate in fibers and fat proportion, may be a contributor

Gluten Deprivation: What Nutritional Changes Are Found During the First Year in Newly Diagnosed Coeliac Children?

Aim: A gluten-free diet (GFD) can expose children to excessive calories and fat intake. The study is intended to verify whether and how food intake, laboratory parameters, and growth are modified by a year of GFD. Methods: In 79 CD (coeliac disease) children (mean age 7.9 ± 3.8 years, 52 females, 27 males) diagnosed over 24 months, 24-h food diaries, food-frequency patterns, anthropometric and laboratory parameters (mainly blood sugar, insulin, lipid profile, and homocysteine) were prospectively collected before and during the first year of GFD. Nutrient intakes were compared over time and with recommendations. They were also used as regressors to explain the levels and changes of metabolic and growth variables. p-values < 0.05 were considered statistically significant. Results: Average macronutrient intake did not change during the year. Caloric intake remained below 90% (p ≤ 0.0001) and protein intake above 200% (p ≤ 0.0001) of recommendations. Lipid intake was stable at 34% of overall energy intake. Unsaturated fats increased (less omega-6 and more omega-3 with a ratio improvement from 13.3 ± 5.5 to 8.8 ± 3.1) and so did fibers, while folate decreased. The children who experienced a containment in their caloric intake during the year, presented a slower catch-up growth. Some differences were found across gender and age groups. In particular, adolescents consumed less calories, and females more omega-3. Fiber and simple sugar intakes emerged as implicated in lipid profile shift: fibers negatively with triglycerides (TG) (p = 0.033), simple sugars negatively with high-density lipoprotein (HDL) (p = 0.056) and positively with TG (p = 0.004). Waist-to-height ratio was positively associated with homocysteine (p = 0.018) and Homeostasis Model Assessment (p = 0.001), negatively with fibers (p = 0.004). Conclusion: In the short run, GFD is nutritionally very similar to any diet with gluten, with some improvements in unsaturated fats and fiber intake. Along with simple sugars containment, this may offer CD patients the opportunity for a fresh start. Caloric intakes may shift and should be monitored, especially in adolescents