The age-dependent relationship between resting heart rate variability and functional brain connectivity.

Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ±â€¯4.2 years, 119 middle-aged: 46.3 ±â€¯6.2 years, 129 older: 66.9 ±â€¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.

Super spin-glass state and exchange bias in Fe/CoO hybrid nanostructures.

Fe/CoO heterostructures were realized by depositing Fe thin films on CoO nanoparticle arrays. Magnetization measurements revealed that 1 nm Fe exhibits a superparamagnetic behavior at 300 K and a super spin-glass state at temperatures below 80 K. The superparamagnetic as well as super spin-glass state vanishes for higher Fe film thicknesses once Fe starts to form a continuous layer across the CoO nanoparticle arrays. Furthermore, all samples exhibit an exchange bias effect at 6 K after field cooling, with a maximum exchange bias field of about 60 Oe for a Fe thickness of 2 nm. M-H loops of thicker Fe samples show a two-step magnetization reversal where Fe in the area in between CoO nanoparticles reverses at low fields, while, in proximity to the CoO nanoparticles, Fe switches at substantially higher fields. Both reversals are exchange biased.

Identification and characterization of a novel variant in the highly conserved catalytic center of Rab11a.

Small GTPases of the Rab family regulate vesicular traffic and distribution of proteins in different cell types. Rab11a is a member of this GTP hydrolyzing protein class and acts as a mediator of insulin stimulated translocation of the glucose transporter GLUT4 in peripheral tissues including heart and skeletal muscle. Here we report on Rab11a Q70R, a mutation in the catalytic center of Rab11a, observed in the cardiomyoblast cell line H9c2. Analysis of GTPase activity showed that Rab11a Q70L acts as a classical constitutive active mutant. Interestingly, the GTPase activity of Rab11a Q70R was not significantly different from the enzymatic activity of the Rab11a Q70 wild type protein. We therefore conclude that the glutamine residue of Rab11a at position 70 is not strictly essential for GTPase activity of this protein in contrast to Ras and other Rab proteins.

Serum adiponectin levels and enzyme markers of liver dysfunction in diabetic and non-diabetic Caribbean subjects.

Low adiponectin levels are associated with elevated plasma alanine aminotransferase, a marker of reduced hepatic insulin sensitivity and a risk factor for type 2 diabetes. This study aims to determine the relationship between serum adiponectin level and alanine aminotransferase in diabetic and non-diabetic subjects. Fifty-six type 2 diabetic patients and 33 non-diabetic subjects participate in the study. Baseline plasma concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glucose are measured on a chemistry analyser. Insulin and adiponectin are measured using enzyme-linked immunoassay techniques and insulin resistance is determined using the homeostatic model assessment method. Diabetic patients showed significantly lower levels of serum adiponectin than did the non-diabetic subjects, whereas levels of alanine aminotransferase and alkaline phosphatase were similar in both groups. While female non-diabetic subjects showed higher serum adiponectin levels than did female diabetic patients, alanine aminotransferase level did not differ (P>0.05). No significant relationship was seen between adiponectin and alanine aminotransferase in diabetic and non-diabetic subjects (P>0.05). Serum adiponectin levels were higher in non-diabetic subjects but there was no significant correlation between adiponectin and alanine aminotransferase in both groups of subjects. The data suggest that low serum adiponectin level may not be a suitable marker for impaired liver function in diabetic patients.

Inhibition of thyroid hormone uptake by calcium antagonists of the dihydropyridine class.

A series of substituted 4-phenyl-1,4-dihydropyridines 2a-m was tested for their inhibitory effects on L-triiodothyronine (L-T3) uptake by human HepG2 hepatoma cells. The most potent compounds were the nitro-substituted derivatives 2,6-dimethyl-4-(4'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (2m) and the well-known calcium antagonists nitrendipine (2k) and nifedipine (2j) with an uptake inhibition between 80.5 and 85.8% at an application dose of 10(-5) M. On the basis of a theoretical conformational analysis (ab initio MO theory, molecular mechanics, molecular dynamics) of the dihydropyridine derivatives, a unifying stereochemical concept was derived postulating an angular arrangement of the two rings where the phenyl ring of the calcium antagonists, which corresponds to the outer phenyl ring of the thyroid hormones, is bisecting the dihydropyridine ring as a prerequisite for inhibitory potency. This model includes also inhibitors of the N-phenylanthranilic acid type. The interaction of the calcium antagonists with transthyretin (TTR) is discussed in relation to thyroid hormones. The influence of hydrophobicity was estimated by the experimental determination of the 1-octanol/water partition coefficients.

3-Amino-5-phenoxythiophenes: syntheses and structure-function studies of a novel class of inhibitors of cellular L-triiodothyronine uptake.

A series of substituted 3-amino-5-phenoxythiophenes was synthesized starting from malodinitrile and carbon disulfide. The resulting dicyanoketenedithiolate reacts via Thorpe-Dieckmann cyclization with halogen methanes bearing electron-withdrawing groups to give thiophene-2-thiolates, which can be transformed into 3-amino-5-(methylsulfonyl)thiophene-4-carbonitriles. Replacement of the methylsulfonyl groups by substituted phenolates provides the substituted 3-amino-5-phenoxythiophenes. Some of the derivatives show a considerable inhibitory potency for the L-T3 uptake in inhibition studies on human HepG2 hepatoma cells with maximum values of about 60% at a dose of 10(-5) M for the most potent 2-benzoyl derivatives. The structure of the phenoxythiophenes fits well into a general concept derived for other classes of L-T3 uptake inhibitors, which postulates an angular and perpendicular orientation of the ring systems in these compounds as a prerequisite for an inhibitory potency. Docking studies for the phenoxythiophenes with transthyretin as a receptor model show their preferred attack at the L-T4/L-T3 binding channel.

[Histochemical and biochemical investigations of the hippocampus and neocortex of the Wistar rat. I. Carboxylic ester hydrolases, transmitter enzymes and transmitters of the normal animal (author's transl)]. / Histochemische und biochemische Untersuchungen am Hippocampus und Neocortex der Wistarratte. I. Carboxylsäureesterasen, Transmitterenzyme und Transmitter im Normaltier.

Some enzymatic parameters of neuronal transmission as well as the occurrence and the properties or carboxylic ester hydrolases in the hippocampal region of the wistar rat are investigated by histochemical and comparable biochemical methods. The acetylcholinesterase-, the monoamine oxidase- and the GABA-transaminase reaction are found at fibre structures, the course of which is seen more or less clearly. The histochemical picture of these enzymes is very different in each hippocampal layer and mainly limited by the corresponding number of reacting fibres. The origin and attribution of the fibres to the afferent and efferent systems are discussed. The occurrence of the acetylcholinesterase, the monoamine oxidase and the GABA-transferase as well as of the biogenic amines and the GABA are hints for the existence of cholinergic as well as aminergic and GABA-ergic processes of transmission in the hippocampal region. In the hippocampal region, the cingular and the optic cortex carboxylic ester hydrolases acetylcholinesterase, unspecific cholinesterase and the A-, B- and C-esterase could be demonstrated. The acetylcholinesterase of the hippocampal region is for the most part firmly membrane-bound and exists at least in two multiple, formalin-sensitive forms which are histochemically located in fibre structures. The unspecific cholinesterase, localized in the hippocampal region within vessel and capillary walls, exists in an electrophoretic mobile, formalin-sensitive form. Nearly half of the enzymes is soluble. A preferred binding to definite cell organelles was not demonstrable. In the hippocampal region the 3 multiple forms of the A-esterase are formalin-instable lyoenzymes. Good solubility and high formalin-sensitivity are the reason, why A-esterases are not demonstrable with usually histochemical methods. In the hippo ampal region the B-esterase is tightly bound to n electrophoretic mobile formalin-sensitive form in the microsomal fraction. In the cytoplasm of the neurones the desmoenzyme appears more or less granular. The 3 multiple forms of the C-esterase are formalin-sensitive to a different degree. Good solubility and low formalin-sensitivity, compared to the A-esterases are responsible for the fact, that the C-esterases can be shown histochemically only after en-bloc-fixation. The reaction products are granular. The similar behaviour of C-esterase and acid phosphatase, stated by many tests, suggests the C-esterases of the B- and C-type results in the same reactivity of pyramidal and granular cells of the hippocampal region. Some small, very strongly reacting cells belong to other cell types (probably basket cells or polymorphic cells).

[Histochemical and biochemical study of the hippocampus and neocortex of the wistar rat. II. The activity of carboxylic acid esterases and transmitter enzymes after a learning experiment]. / Histochemische und biochemische Untersuchungen am Hippocampus und Neocortex der Wistarratte.

In the present paper the behaviour of the enzymes monoaminoxidase, GABA-transaminase, acetylcholinesterase, nonspecific cholinesterase, A-, B-, C-esterase and acid phosphatase was investigated by histochemical and biochemical methods for 1 min, 1, 4 and 24 h after a "brightness-discrimination" of male wistar rats in a Y-chamber. Learning induced significant changes of activity of the B-esterase in the hippocampus region 4 h (increase of 30%) and 24 h (decrease of 25%) and of the acetylcholinesterase in the cingular cortex 4 h after training (increase of 38%) are to be observed and regarded and discussed as hints for a changed protein synthesis (B-esterase) or altered synaptic activity (acetylcholinesterase). On the strength of these results and various findings in the literature it may be reputed as sure, that the protein synthesis of the cells of hippocampus in evident. Certain proteins show increased rates of synthesis by the influence of a learning experiment. These proteins are at least partially enzymes, serving as extension of the protein synthesis apparatus of the neurons and may be regarded as part mechanism of the intracellular regulation of the synaptic connectivity.

Relationship between adiponectin and metabolic variables in Caribbean offspring of patients with type 2 diabetes mellitus.

AIM: To examine the relationship between adiponectin and metabolic variables in the offspring of patients with type 2 diabetes mellitus. METHODS: Fasting blood samples and anthropometric indices were taken from 34 subjects, offspring of patients with type 2 diabetes, and 24 healthy control subjects without any immediate family history of diabetes. Plasma glucose and serum adiponectin, insulin, triglycerides, total cholesterol, HDL and LDL cholesterol levels were measured, and insulin resistance (IR) was calculated based on the homeostasis model assessment (HOMA) method. RESULTS: Offspring and control subjects were sex-matched, but the offspring were older and had higher body mass index and waist circumference than the control subjects (p < 0.05). The offspring had significantly higher mean fasting plasma glucose concentrations; however, their mean serum insulin, adiponectin, triglyceride, total cholesterol, HDL and LDL cholesterol and HOMA-derived IR levels did not significantly differ from those of the control subjects (p > 0.05). While the negative correlation between serum adiponectin and HDL cholesterol levels in the offspring remained statistically significant after adjusting for the effect of age, sex and BMI (r = -0.37, p < 0.05), the negative correlation between adiponectin and serum triglyceride, LDL cholesterol or IR levels became non-significant after controlling for the above variables (p > 0.05 in all cases). CONCLUSION: The correlation between adiponectin and some known biochemical risk factors for developing diabetes and cardiovascular disease in the offspring of patients with diabetes warrants further study to evaluate its potential in assessing the risk of developing these disorders.

Serum adiponectin levels and enzyme markers of liver dysfunction in diabetic and non-diabetic Caribbean subjects

Low adiponectin levels are associated with elevated plasma alanine aminotransferase, a marker of reduced hepatic insulin sensitivity and a risk factor for type 2 diabetes. This study aims to determine the relationship between serum adiponectin level and alanine aminotransferase in diabetic and non-diabetic subjects. Fifty-six type 2 diabetic patients and 33 non-diabetic subjects participate in the study. Baseline plasma concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glucose are measured on a chemistry analyser. Insulin and adiponectin are measured using enzyme-linked immunoassay techniques and insulin resistance is determined using the homeostatic model assessment method. Diabetic patients showed significantly lower levels of serum adiponectin than did the non-diabetic subjects, whereas levels of alanine aminotransferase and alkaline phosphatase were similar in both groups. While female non-diabetic subjects showed higher serum adiponectin levels than did female diabetic patients, alanine aminotransferase level did not differ (P>0.05). No significant relationship was seen between adiponectin and alanine aminotransferase in diabetic and non-diabetic subjects (P>0.05). Serum adiponectin levels were higher in non-diabetic subjects but there was no significant correlation between adiponectin and alanine aminotransferase in both groups of subjects. The data suggest that low serum adiponectin level may not be a suitable marker for impaired liver function in diabetic patients.

Relationship between adiponectin and metabolic variables in Caribbean offspring of patients with type 2 diabetes mellitus.

AIM: To examine the relationship between adiponectin and metabolic variables in the offspring of patients with type 2 diabetes mellitus. METHODS: Fasting blood samples and anthropometric indices were taken from 34 subjects, offspring of patients with type 2 diabetes, and 24 healthy control subjects without any immediate family history of diabetes. Plasma glucose and serum adiponectin, insulin, triglycerides, total cholesterol, HDL and LDL cholesterol levels were measured, and insulin resistance (IR) was calculated based on the homeostasis model assessment (HOMA) method. RESULTS: Offspring and control subjects were sex-matched, but the offspring were older and had higher body mass index and waist circumference than the control subjects (p < 0.05). The offspring had significantly higher mean fasting plasma glucose concentrations; however, their mean serum insulin, adiponectin, triglyceride, total cholesterol, HDL and LDL cholesterol and HOMA-derived IR levels did not significantly differ from those of the control subjects (p > 0.05). While the negative correlation between serum adiponectin and HDL cholesterol levels in the offspring remained statistically significant after adjusting for the effect of age, sex and BMI (r = - 0.37, p < 0.05), the negative correlation between adiponectin and serum triglyceride, LDL cholesterol or IR levels became non-significant after controlling for the above variables (p > 0.05 in all cases). CONCLUSION: The correlation between adiponectin and some known biochemical risk factors for developing diabetes and cardiovascular disease in the offspring of patients with diabetes warrants further study to evaluate its potential in assessing the risk of developing these disorders.