Cardiovascular Variability Analysis and Baroreflex Estimation in Patients with Type 2 Diabetes in Absence of Any Manifest Neuropathy

Introduction

Indexes derived from spontaneous heart period (HP) and systolic arterial pressure (SAP) fluctuations can detect autonomic dysfunction in individuals with type 2 diabetes mellitus (DM) associated to cardiovascular autonomic neuropathy (CAN) or other neuropathies. It is unknown whether HP and SAP variability indexes are sensitive enough to detect the autonomic dysfunction in DM patients without CAN and other neuropathies.

Methods

We evaluated 68 males aged between 40 and 65 years. The group was composed by DM type 2 DM with no manifest neuropathy (n = 34) and healthy (H) subjects (n = 34). The protocol consisted of 15 minutes of recording of HP and SAP variabilities at rest in supine position (REST) and after active standing (STAND). The HP power in the high frequency band (HF, from 0.15 to 0.5 Hz), the SAP power in the low frequency band (LF, from 0.04 to 0.15 Hz) and BRS estimated via spectral approach and sequence method were computed.

Results

The HF power of HP was lower in DM patients than in H subjects, while the two groups exhibited comparable HF power of HP during STAND. The LF power of SAP was similar in DM and H groups at REST and increased during STAND in both groups. BRSs estimated in the HF band and via baroreflex sequence method were lower in DM than in H and they decreased further during STAND in both populations.

Conclusion

Results suggest that vagal control of heart rate and cardiac baroreflex control was impaired in type 2 DM, while sympathetic control directed to vessels, sympathetic and baroreflex response to STAND were preserved. Cardiovascular variability indexes are sensitive enough to typify the early, peculiar signs of autonomic dysfunction in type-2 DM patients well before CAN becomes manifest.     

Enhanced susceptibility to seizures modulated by high interleukin‐1β levels during early life malnutrition

Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin‐1β (IL‐1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL‐1β, IL‐1R1, PSD‐95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL‐1β and IL‐1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL‐1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL‐1β and IL‐1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD‐95 and synapsin expression in the hippocampus. We suggest that malnutrition‐induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150–1159, 2016     

Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice

The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic.     

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer,Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis

Background

There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms.

Methods

The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03.

Results

Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele.

Conclusion

ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations.     

A Three-Dimensional Stereotaxic MRI Brain Atlas of the Cichlid Fish Oreochromis mossambicus

The African cichlid Oreochromis mossambicus (Mozambique tilapia) has been used as a model system in a wide range of behavioural and neurobiological studies. The increasing number of genetic tools available for this species, together with the emerging interest in its use for neurobiological studies, increased the need for an accurate hodological mapping of the tilapia brain to supplement the available histological data. The goal of our study was to elaborate a three-dimensional, high-resolution digital atlas using magnetic resonance imaging, supported by Nissl staining. Resulting images were viewed and analysed in all orientations (transverse, sagittal, and horizontal) and manually labelled to reveal structures in the olfactory bulb, telencephalon, diencephalon, optic tectum, and cerebellum. This high resolution tilapia brain atlas is expected to become a very useful tool for neuroscientists using this fish model and will certainly expand their use in future studies regarding the central nervous system.     

Structure-Based Peptide Design to Modulate Amyloid Beta Aggregation and Reduce Cytotoxicity

The deposition of Aβ peptide in the brain is the key event in Alzheimer disease progression. Therefore, the prevention of Aβ self assembly into disease-associated oligomers is a logical strategy for treatment. π stacking is known to provide structural stability to many amyloids; two phenylalanine residues within the Aβ 14–23 self recognition element are in such an arrangement in many solved structures. Therefore, we targeted this structural stacking by substituting these two phenylalanine residues with their D-enantiomers. The resulting peptides were able to modulate Aβ aggregation in vitro and reduce Aβ cytotoxicity in primary neuronal cultures. Using kinetic analysis of fibril formation, electron microscopy and dynamic light scattering characterization of oligomer size distributions, we demonstrate that, in addition to altering fibril structural characteristics, these peptides can induce the formation of larger amorphous aggregates which are protective against toxic oligomers, possibly because they are able to sequester the toxic oligomers during co-incubation. Alternatively, they may alter the surface structure of the oligomers such that they can no longer interact with cells to induce toxic pathways.