Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies ³0.1 IU/mL). One individual (0.5%) was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001) and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014). Full immunity against tetanus (antibodies ³0.1 IU/mL) was higher among individuals with up-to-date vaccination (93.1%) when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001). All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

Lipoprotein lipase PvuII polymorphism is associated with variations in serum lipid levels in non-diabetic pregnant women

The aim of the present study was to determine if there is an association between the single nucleotide polymorphisms (SNPs) of the lipoprotein lipase (LPL) and apolipoprotein E (apo E) genes and the serum lipid profile in pregnancy and puerperium. Non-diabetic women of European descent in the third semester of pregnancy (N = 120) were selected. Those with diseases or other condition that could modify their lipid profile were excluded from the study (N = 32). Serum lipids were measured by routine laboratory procedures and genomic DNA was extracted by a salting out method. LPL (PvuII and HindIII) and apo E (HhaI) SNPs were detected by the polymerase chain reaction and restriction fragment length polymorphism. Categorical and continuous variables were compared by the chi-square test and Student t-test or ANOVA, respectively. Women carrying the LPL P1P1 genotype had higher serum LDL cholesterol (N = 21; 155 ± 45 mg/dL) than women carrying the P1P2/P2P2 genotypes (N = 67; 133 ± 45 mg/dL; P = 0.032). During the puerperium period, serum levels of triglycerides and VLDL cholesterol were significantly reduced in women carrying the P1P1 (73%, P = 0.006) and P1P2 (51%, P = 0.002) genotypes but not in women carrying the P2P2 genotype (23%, P > 0.05). On the other hand, serum concentrations of lipids did not differ between the LPL HindIII and apo E genotypes during pregnancy and after delivery. We conclude that LPL PvuII SNP is associated with variations in serum lipids during pregnancy and the puerperal period in non-diabetic women.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients

The objective of the present study was to evaluate the production of cytokines, interferon-g (INF-g) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-g and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-g levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-g and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-g and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

Do early life factors influence body mass index in adolescents?

The association between early life factors and body mass index (BMI) in adulthood has been demonstrated in developed countries. The aim of the present study was to assess the influence of early life factors (birth weight, gestational age, maternal smoking, and social class) on BMI in young adulthood with adjustment for adult socioeconomic position. A cohort study was carried out in 1978/79 with 6827 mother-child pairs from Ribeirão Preto city, located in the most developed economic area of the country. Biological, economic and social variables and newborn anthropometric measurements were obtained shortly after delivery. In 1996, 1189 males from this cohort, 34.3% of the original male population, were submitted to anthropometric measurements and were asked about their current schooling on the occasion of army recruitment. A multiple linear regression model was applied to determine variables associated with BMI. Mean BMI was 22.7 (95%CI = 22.5-23.0). After adjustment, BMI was 1.22 kg/m² higher among infants born with high birth weight (³4000 g), 1.21 kg/m² higher among individuals of low social class at birth and 0.69 kg/m² higher among individuals whose mothers smoked during pregnancy (P < 0.05). The association between social class at birth and BMI remained statistically significant (P < 0.05) even after adjustment for adult schooling. These findings suggest that early life social influences on BMI were more important and were not reversed by late socioeconomic position. Therefore, prevention of overweight and obesity should focus not only on changes in adult life styles but also on factors such as high birth weight.

Effect of Ginkgo biloba on the reproductive outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats

The aim of the present study was to evaluate the effect of Ginkgo biloba treatment (EGb 761, 200 mg kg-1 day-1) administered from day 0 to 20 of pregnancy on maternal reproductive performance and on the maternal and fetal liver antioxidant systems of streptozotocin-induced diabetic Wistar rats. On day 21 of pregnancy, the adult rats (weighing approximately 250 ± 50 g, minimum number = 13/group) were anesthetized to obtain maternal and fetal liver samples for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total glutathione (GSH-t) determinations. The uterus was weighed with its contents. The diabetic (G3) and treated diabetic (G4) groups of rats presented significant maternal hyperglycemia, reduced term pregnancy rate, impaired maternal reproductive outcome and fetal-placental development, decreased GSH-Px (G3 = G4 = 0.6 ± 0.2) and SOD (G3 = 223.0 ± 84.7; G4 = 146.1 ± 40.8), and decreased fetal CAT activity (G3 = 22.4 ± 10.6; G4 = 34.4 ± 14.1) and GSH-t (G3 = G4 = 0.3 ± 0.2), compared to the non-diabetic groups (G1, untreated control; G2, treated). For G1, maternal GSH-Px = 0.9 ± 0.2 and SOD = 274.1 ± 80.3; fetal CAT = 92.6 ± 82.7 and GSH-t = 0.6 ± 0.5. For G2, G. biloba treatment caused no toxicity and did not modify maternal or fetal-placental data. EGb 761 at the nontoxic dose used (200 mg kg-1 day-1), failed to modify the diabetes-associated increase in maternal glycemia, decrease in pregnancy rate, decrease in antioxidant enzymes, and impaired fetal development when the rats were treated throughout pregnancy (21 days).

A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

Gross proteinuria is a strong risk predictor for cardiovascular mortality in Brazilian type 2 diabetic patients

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7%) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.

Influence of gender on psychomotor vigilance task performance by adolescents

During adolescence, the sleep phase delay associated with early school times increases daytime sleepiness and reduces psychomotor performance. Some studies have shown an effect of gender on psychomotor performance in adults and children. Males present faster reaction times (RT) compared with females. The aim of the present study was to evaluate the influence of gender on Palm psychomotor vigilance task (PVT) performance in adolescents. Thirty-four adolescents (19 girls, 13 to 16 years old) attending morning school classes of a public school in Curitiba, PR, Brazil, participated in the study. Sleep patterns were measured using actigraphy and sleepiness data were accessed with the Karolinska Sleepiness Scale (KSS). KSS and PVT measurements were collected at two times in the morning (8:00 and 11:00 h). The data were compared using one-way ANOVA, considering gender as a factor. ANOVA indicated that gender did not affect sleep patterns and subjective somnolence; however, a statistically significant effect of gender was detected for PVT performance. Boys presented faster RT (RT-PVT1: 345.51 ms, F = 6.08, P < 0.05; RT-PVT2: 343.30 ms, F = 6.35, P < 0.05) and fewer lapses (lapses-PVT1: 8.71, F = 4.45, P < 0.05; lapses-PVT2: 7.82, F = 7.06, P < 0.05) compared with girls (RT-PVT1: 402.96; RT-PVT2: 415.70; lapses-PVT1: 16.33; lapses-PVT2: 17.80). These results showed that this effect of gender, already reported in adults and children, is also observed in adolescents. The influence of gender should be taken into account in studies that use Palm PVT to evaluate psychomotor performance in this age range.

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-β1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg-1·day-1 (D0.01, N = 14), 1 mg·kg-1·day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-β1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ≤ 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-β1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95%CI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95%CI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95%CI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100% to the odds for diabetic retinopathy (OR = 2.01, 95%CI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

The prevalence of chronic diabetic complications and metabolic syndrome is not associated with maternal type 2 diabetes

The maternal history of type 2 diabetes mellitus (DM) has been reported more frequently in patients with type 2 DM than paternal history. The aim of the present study was to determine if there was an association between maternal history of DM and the presence of chronic complications or metabolic syndrome (MetS) in patients with type 2 DM. A cross-sectional study was conducted with 1455 patients with type 2 DM. All outpatients with type 2 diabetes attending the endocrine clinics who fulfilled the eligibility criteria were included. Familial history of DM was determined with a questionnaire. Diabetic complications were assessed using standard procedures. The definition of MetS used was that of the World Health Organization and the National Cholesterol Education Program's Adult Treatment Panel III report criteria. Maternal history of DM was present in 469 (32.3%), absent in 713 (49.1%) and unknown in 273 patients (18.7%). Paternal history of DM was positive in 255 (17.6%), negative in 927 (63.8%) and unknown in 235 patients (16.1%). The frequency of microvascular chronic complications in patients with and without a positive maternal history of DM was similar: diabetic nephropathy (51.5 vs 52.5%), diabetic retinopathy (46.0 vs 41.7%), and diabetic sensory neuropathy (31.0 vs 37.1%). The prevalence of macrovascular chronic complications and MetS was also similar. Patients with type 2 DM were more likely to have a maternal than a paternal history of DM, although maternal history of DM was not associated with an increased prevalence of chronic complications or MetS.

Can the fractal dimension be applied for the early diagnosis of non-proliferative diabetic retinopathy?

The fractal dimension has been employed as a useful parameter in the diagnosis of retinal disease. Avakian et al. (Curr Eye Res 2002; 24: 274-280), comparing the vascular pattern of normal patients with mild to moderate non-proliferative diabetic retinopathy (NPDR), found a significant difference between them only in the macular region. This significant difference in the box-counting fractal dimension of the macular region between normal and mild NPDR patients has been proposed as a method of precocious diagnosis of NPDR. The aim of the present study was to determine if fractal dimensions can really be used as a parameter for the early diagnosis of NPDR. Box-counting and information fractal dimensions were used to parameterize the vascular pattern of the human retina. The two methods were applied to the whole retina and to nine anatomical regions of the retina in 5 individuals with mild NPDR and in 28 diabetic but opthalmically normal individuals (controls), with age between 31 and 86 years. All images of retina were obtained from the Digital Retinal Images for Vessel Extraction (DRIVE) database. The results showed that the fractal dimension parameter was not sensitive enough to be of use for an early diagnosis of NPDR.

Stem cell factor protects against neuronal apoptosis by activating AKT/ERK in diabetic mice

Neuronal apoptosis occurs in the diabetic brain due to insulin deficiency or insulin resistance, both of which reduce the expression of stem cell factor (SCF). We investigated the possible involvement of the activation of the MAPK/ERK and/or AKT pathways in neuroprotection by SCF in diabetes. Male C57/B6 mice (20-25 g) were randomly divided into four groups of 10 animals each. The morphology of the diabetic brain in mice treated or not with insulin or SCF was evaluated by H&E staining and TUNEL. SCF, ERK1/2 and AKT were measured by Western blotting. In diabetic mice treated with insulin or SCF, there was fewer structural change and apoptosis in the cortex compared to untreated mice. The apoptosis rate of the normal group, the diabetic group receiving vehicle, the diabetic group treated with insulin, and the diabetic group treated with SCF was 0.54 ± 0.077%, 2.83 ± 0.156%, 1.86 ± 0.094%, and 1.78 ± 0.095% (mean ± SEM), respectively. SCF expression was lower in the diabetic cortex than in the normal cortex; however, insulin increased the expression of SCF in the diabetic cortex. Furthermore, expression of phosphorylated ERK1/2 and AKT was decreased in the diabetic cortex compared to the normal cortex. However, insulin or SCF could activate the phosphorylation of ERK1/2 and AKT in the diabetic cortex. The results suggest that SCF may protect the brain from apoptosis in diabetes and that the mechanism of this protection may, at least in part, involve activation of the ERK1/2 and AKT pathways. These results provide insight into the mechanisms by which SCF and insulin exert their neuroprotective effects in the diabetic brain.

Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.

Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

Interleukin-10 (IL-10) appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α). However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15) and Wistar rats with streptozotocin (STZ)-induced diabetes (N = 15). At term, the dams (100 days of life) were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL). The placental scores of immunostaining intensity did not differ between groups (P > 0.05). Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.