Slow-release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial

Minicucci L, Haupt M, Casciaro R, De Alessandri A, Bagnasco F, Lucidi V, Notarnicola S, Lorini R, Bertasi S, Raia V, Cialdella P, Haupt R. Slow‐release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial. Background: Early stages of glucose metabolism impairment are a period at risk in the long‐term prognosis of cystic fibrosis (CF). Slow‐release synthetic insulin glargine can be a therapeutic tool in this metabolic condition. Methods: In this phase 3 multicenter, controlled, two‐arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints. Results: Thirty‐four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04). Conclusions: Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow‐up period.     

The loss of conceptual associations in mild Alzheimer's dementia

Changes in semantic memory are a controversial topic in research on cognitive decline in aging. In this study, we analyzed whether the semantic deficits in mild Alzheimer's disease (AD) reflect the information acquisition process, and whether the deficits are related to when the information was initially stored. We hypothesized that in the earlier stages of dementia, the ability to access semantic associative relations reflects the use of these associations during different developmental stages. Specifically, we asserted that Alzheimer's patients might be able to access the relations that are learned earlier in life for the longest amount of time compared to those that are learned later. In this study, 254 subjects were divided into four groups (child, adult, senior, and Alzheimer's patients groups) and were evaluated with an experimental semantic association task that incorporated five semantic associative relations that were used to compare performance by age group. An analysis of variance (ANOVA) 4 × 5 test showed a significant main group effect, F(3, 250) = 97.1, p < .001, and an associative relations effect, F(4, 1000) = 23.1, p < .001, as well as an interaction of Group × Associative Relations, F(12, 1000) = 8.5, p < .001. The results demonstrated that the semantic associative relations that were acquired in later developmental stages were less preserved in persons with mild AD (i.e., superordinate relation, p < .0001). On the contrary, the semantic relations acquired earlier in childhood were better preserved in persons with mild AD. Our results suggest that semantic impairment begins with difficulties in using the associative relations that link concepts together in the semantic memory of patients with mild AD dementia (and possibly in individuals with mild cognitive impairment).     

Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth

OBJECTIVE: To investigate whether in the first half of pregnancy levels of leptin in amniotic fluid are sexually dimorphic, and are related to fetal growth. STUDY DESIGN: Samples of amniotic fluid were collected during amniocentesis from 211 pregnancies with a single fetus with a normal karyotype (107 from male fetuses). Fetal growth was evaluated at 16 and 32 weeks of gestation, by sonography, and in a subset of 137 women at delivery. RESULTS: Amniotic fluid leptin was significantly lower in male than female fetuses (7.91+/-0.36 ng/ml versus 10.45+/-0.38 ng/ml; p = 0.0001). In females, levels of leptin were inversely related to BPD measured at 16 weeks (r = -0.241; p = 0.013) to biparietal diameter (BPD) (r = -0.281; p = 0.0076) and abdominal circumference (r = 0.268; p = 0.0107) measured at 32 weeks of gestation and to neonatal weight (r = -0.236; p = 0.051), neonatal weight/height (r = -0.271; p = 0.026) or neonatal Kaup index (r = 0.255; p = 0.045). Leptin was not related to any fetal parameter in males. CONCLUSIONS: Levels of leptin in amniotic fluid at 16 weeks of gestation are sexually dimorphic and are inversely related to fetal growth, particularly of females.     

Salivary histatins in human deep posterior lingual glands (of von Ebner)

OBJECTIVE: Human saliva contains a family of low molecular weight histidine-rich proteins, named histatins, characterised by bactericidal and fungicidal activities in vitro against several microbial pathogens, such as Streptococcus mutans and Candida albicans. They represent a major component of an innate host non-immune defense system. In an earlier study we described the distribution of histatins in the glandular parenchyma of human major salivary glands, confirming that all human major salivary glands are involved in the secretion of histatins into saliva. In the present study we determined the expression and localisation of histatins in human posterior deep lingual glands (von Ebner's glands) by means of immunoelectron microscopy. DESIGN: Thin sections of normal human salivary glands, embedded in Epon resin, were incubated with rabbit polyclonal antibodies specific for human histatins and successively with a gold conjugated goat anti-rabbit IgG used as secondary antibody. Sections incubated with medium devoid of primary antibody or containing non-immune serum were used as controls. RESULTS: The serous secreting cells represented the main source of histatins in the glandular parenchyma of von Ebner's glands. At the electron microscopic level, labeling was associated with rough endoplasmic reticulum, Golgi complex and secretory granules that represented the main cytoplasmic site of histatin localisation. However, variability in the intensity of labeling was observed among adjacent cells. CONCLUSIONS: The present results show for the first time that human von Ebner's glands produce and represent a significant source of histatins, supporting the hypothesis of their important role in preventing microbial assaults on the tissues in the posterior region of the tongue and in the circumvallate papillae.     

Spontaneous recovery from anti-NMDAR encephalitis

Journal of Neurology -     

Immunohistochemical localization of receptor for advanced glycation end (RAGE) products in the R6/2 mouse model of Huntington's disease

The receptor for advanced glycation end (RAGE) products is a multi-ligand receptor that belongs to the immunoglobulin superfamily of cell surface receptors, whose ligands are known to be upregulated in neuropathological conditions. RAGE upregulation has been described in neurodegenerative diseases, such as Alzheimer's disease, Creutzfeldt-Jakob's disease and Huntington's disease (HD). To analyze in detail the implication of RAGE in HD, we studied the immunohistochemical distribution of RAGE in the striatum of the R6/2 mouse model of HD, with particular attention to the neuronal subpopulations and their relative vulnerability to HD neurodegeneration. We show that RAGE immunoreactivity is evenly distributed to the cytoplasm of neurons in the wild type mouse, while it is finely granular in the cytoplasm of striatal neurons of R6/2 mouse. RAGE is distributed in 98% of spiny projection neurons, both in the normal mouse and in the R6/2. RAGE co-localizes with all of the striatal interneuron subsets both in the wild-type and in the R6/2 mouse. However, the intensity of RAGE immunoreactivity is significantly higher in the spiny neurons and in the PARV neurons of R6/2 mouse, whereas it is comparable between R6/2 and wild-type in the cholinergic and somatostatinergic interneurons. These data support the concept that RAGE is upregulated in the neurodegenerative process of HD, and suggests that its activation is related to the individual vulnerability of the striatal neuronal subtype.     

Cortical Network Dynamics during Foot Movements

The present work intends to evaluate the dynamics of the cerebral networks during the preparation and the execution of the foot movement. In order to achieve this objective, we have used mathematical tools capable of estimating the cortical activity via high-resolution EEG techniques. Afterwards we estimated, the instantaneous relationships occurring among the time-series of sixteen regions of interest (ROIs) in the Alpha (7–12 Hz) and Beta (13–29 Hz) band through the adaptive multivariate autoregressive models. Eventually, we evaluated the weighted-topology of the cerebral networks by calculating some theoretical graph indexes. The results show that the main structural changes are encoded in the highest spectral contents (Beta band). In particular, during the execution of the foot movement the cingulate motor areas (CM) work as network “hubs” presenting a large amount of outgoing links to the other ROIs. Moreover, the connectivity pattern changes its structure according to the different temporal stages of the task. In particular, the communication between the ROIs reaches its highest level of efficiency during the preparation of the foot movement, as revealed by the “small-world” property of the network, which is characterized by the presence of abundant clustering connections combined with short average distances between the cortical areas.