“Synapse-like” connections between adipocytes and stem cells: morphological and molecular features of human adipose tissue

Adult mesenchymal stem cells are a heterogeneous population of stem cell that is not completely defined. The importance of increasing knowledge of this cell population will allow us to understand how to use them in multiple treatments for various diseases. Adipose tissue is a rich source from which to easily obtain a great amount of stem cells. We explore and study adipose stem cells (AdSCs) from human abdominal tissue by immunohistochemical analysis, transmission (TEM) and scanning (SEM) electron microscopy. The focus of this study is on the cell population that surrounds each adipocyte. In these populations of cells are included the adipose tissue stem cells (AdSCs) with different potentiality. We observe that the putative AdSCs have an intimate relationship involving close contact with adipocytes which we define here as “synapse-like.” We show “synapse-like” connections between adipocytes and small cells to be mediated by connexin43 (Cx43). Our data suggest AdSCs constitute a heterogeneous population both in size and expression of different stem cell markers. We found that some of the AdSC attached to adipocytes are positive for Sox2, Pax6 and Nestin by immunostaining methods. TEM and SEM analysis demonstrate that small cells and adipocytes are surrounded by a compact mesh of collagen fibers that maintain physical adhesion between these cells. TEM also shows structural characteristics of putative stem cells and a presence of vesicles in synapse-like contact. SEM images moreover exhibited a large variation and quantity of cell sizes coexisting with adipocytes. Direct cell-to-cell communication could serve at least two purposes: a) as a survival strategy to maintain cells as stem cells, and b) as a source of signaling for differentiation into a new cell type

1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120–139 mg/dL, n = 710; 140–159 mg/dL, n = 912; 160–179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCgluc and AUCins progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCgluc decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion

Concentración salival de inmunoglobulina A secretoria según la ingesta de fitoquímicos dietarios

OBJETIVO: analizar la influencia de los fitoquímicos (Fq) dietarios sobre la concentración salival de inmunoglobulina A secretoria (IgAs) en personas sanas de diferentes edades.MÉTODOS: se incluyeron 49 personas que fueron agrupadas en: mujeres de 20-39 años (G1; n=12) y de 40-60 años (G2; n=11); hombres de 20-39 años (G3; n=14) y de 40-60 años (G4; n=12). Mediante una encuesta de frecuencia de consumo alimentario cuali-cuantitativo validada se determinó la ingesta habitual de alimentos fuente de Fq -vegetales, frutas frescas y secas, derivados del tomate, cereales y legumbres- y el consumo de los siguientes Fq: antocianos, daidzeína, flavanoles, flavanonas, flavonas, flavonoles, genisteína, isoflavonas, licopeno y polifenoles. La información fue procesada por el programa informático Interfood v.1.3. Se obtuvieron muestras de saliva mixta no estimulada y se determinaron los valores de IgAs por inmunodifusión radial simple. Se compararon las variables según los grupos (prueba de Kruskal Wallis) y se correlacionaron los valores de IgAs con las variables mencionadas (coeficiente de correlación de Spearman) (p<0,05).RESULTADOS: la ingesta total de alimentos fuente de Fq fue menor en G3 que en G1 (p=0,043) y el consumo de frutas frescas fue menor en G3 que en los demás grupos (p=0,002). La ingesta de antocianos fue menor en G3 (p=0,007) y la de flavanonas mayor en G1 (p=0,037), ambos con respecto a los otros grupos. El consumo de flavonas fue superior en G1 que en G3 (p=0,025), y el de polifenoles fue mayor en G1 y G3 con relación a G2 y G4 (p=0,0002). Se halló una correlación negativa entre la ingesta del total de alimentos fuente de Fq y la concentración salival de IgAs en G3 (-0,61; p=0,03), y correlaciones positivas entre el consumo de flavanonas (0,59; p=0,05) y polifenoles (0,62; p=0,04) y los valores de IgAs en G1.CONCLUSIÓN: según estos resultados, el consumo de flavanonas y polifenoles se relaciona con una mayor concentración salival de IgAs en mujeres sanas de 20 a 39 años, en tanto que en hombres de esa edad la ingesta de alimentos fuente de Fq se asocia a una disminución de IgAs salival.Fil: Costantino, Evangelina. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Anatomía B; Argentina.Fil: Costantino, Evangelina. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Escandriolo Nackauzi, Jorge Dario. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Anatomía B; Argentina.Fil: Escandriolo Nackauzi, Jorge Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Bertolotto, Patricia Isolina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Heinze, Verónica. Universidad Nacional de Córdoba; Argentina.Fil: Pistoresi, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Actis, Adriana Beatríz. Universidad Nacional de Córdoba. Facultad de Odontología. Secretaría de Ciencia y Técnica; Argentina.Fil: Actis, Adriana Beatriz. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Otras Ciencias de la Salu

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity : An Exploratory Sub-Analysis of the DALI Study

Altres ajuts: Netherlands Organization for Health Research and Development (ZonMw, 200310013); Polish Ministry of Science (2203/7, PR/2011/2); Odense University Free Research Fund; NIHR Clinical Research Network: Eastern; In Spain (CAIBER 1527-B-226); Spanish Diabetes Society (SED) XI Grant for clinical research projects in diabetes.Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24-28 and 35-37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24-28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24-28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35-37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24-28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24-28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24-28 and 35-37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Agouti signalling protein is an inverse agonist to the wildtype and agonist to the melanic variant of the melanocortin-1 receptor in the grey squirrel (Sciurus carolinensis)

The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation. Melanism in the grey squirrel is associated with an eight amino acid deletion in the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RΔ24) variant. We demonstrate that the MC1RΔ24 exhibits a higher basal activity than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RΔ24. We conclude that the deletion in the MC1RΔ24 leads to a receptor with a high basal activity which is further activated by ASIP. This is the first report of ASIP acting as an agonist to MC1R