C-Peptide Effects on Renal Physiology and Diabetes

The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studies have shown that biochemical pathways involving cellular kinases and inflammatory pathways may also be important. The matter theory concerning the C-peptide effects is a metabolic one involving the effects of the C-peptide on lipidic metabolic status.This review concentrates on the most convincing data which indicate that the C-peptide is a biologically active hormone for renal physiology

C-peptide, Na+,K+-ATPase, and Diabetes

Na+,K+-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K+-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K+-ATPase activity was strongly related to blood C-peptide levels in non–insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene.Apolymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K+-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K+-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K+-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K+-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K+-ATPase activity. This impairment in Na+,K+-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetesinduced decrease in Na+,K+-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K+-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K+-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K+-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications

Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii

Background: Obesity is associated with increased health risk and has been associated with alterations in bacterial gut microbiota, with mainly a reduction in Bacteroidetes, but few data exist at the genus and species level. It has been reported that the Lactobacillus and Bifidobacterium genus representatives may have a critical role in weight regulation as an anti-obesity effect in experimental models and humans, or as a growth-promoter effect in agriculture depending on the strains. Objectives and methods: To confirm reported gut alterations and test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status, we analyzed the stools of 68 obese and 47 controls targeting Firmicutes, Bacteroidetes, Methanobrevibacter smithii, Lactococcus lactis, Bifidobacterium animalis and seven species of Lactobacillus by quantitative PCR (qPCR) and culture on a Lactobacillus-selective medium. Findings: In qPCR, B. animalis (odds ratio (OR) 0.63; 95% confidence interval (CI) 0.39-1.01; P = 0.056) and M. smithii (OR = 0.76; 95% CI 0.59-0.97; P = 0.03) were associated with normal weight whereas Lactobacillus reuteri (OR = 1.79; 95% CI 1.03-3.10; P = 0.04) was associated with obesity. Conclusion: The gut microbiota associated with human obesity is depleted in M. smithii. Some Bifidobacterium or Lactobacillus species were associated with normal weight (B. animalis) while others (L. reuteri) were associated with obesity. Therefore, gut microbiota composition at the species level is related to body weight and obesity, which might be of relevance for further studies and the management of obesity. These results must be considered cautiously because it is the first study to date that links specific species of Lactobacillus with obesity in humans. International Journal of Obesity (2012) 36, 817-825; doi:10.1038/ijo.2011.153; published online 9 August 201

Mitochondrial myopathy and comorbid major depressive disorder. effectiveness of dTMS on gait and mood symptoms

Background: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. Case report: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. Conclusions: dTMSmay be an alternative antidepressant strategy in patients withMMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation

Ferromagnetism and large negative magnetoresistance in Pb doped Bi-Sr-Co-O misfit-layer compound

Ferromagnetism and accompanying large negative magnetoresistance in Pb-substituted Bi-Sr-Co-O misfit-layer compound are investigated in detail. Recent structural analysis of (Bi,Pb)${}_2$Sr${}_{3}$Co${}_2$O${}_9$, which has been believed to be a Co analogue of Bi${}_2$Sr${}_2$CaCu${}_2$O${}_{8+\delta}$, revealed that it has a more complex structure including a CoO${}_2$ hexagonal layer [T. Yamamoto {\it et al.}, Jpn. J. Appl. Phys. {\bf 39} (2000) L747]. Pb substitution for Bi not only introduces holes into the conducting CoO${}_2$ layers but also creates a certain amount of localized spins. Ferromagnetic transition appears at $T$ = 3.2 K with small spontaneous magnetization along the $c$ axis, and around the transition temperature large and anisotropic negative magnetoresistance was observed. This compound is the first example which shows ferromagnetic long-range order in a two-dimensional metallic hexagnonal CoO${}_2$ layer.Comment: 8 pages including eps figures. To be published in J. Phys. Soc. Jp

Evidence for a Low-Spin to Intermediate-Spin State Transition in LaCoO3

We present measurements of the magnetic susceptibility and of the thermal expansion of a LaCoO$_3$ single crystal. Both quantities show a strongly anomalous temperature dependence. Our data are consistently described in terms of a spin-state transition of the Co$^{3+}$ ions with increasing temperature from a low-spin ground state to an intermediate-spin state without (100K - 500K) and with (>500K) orbital degeneracy. We attribute the lack of orbital degeneracy up to 500K to (probably local) Jahn-Teller distortions of the CoO$_6$ octahedra. A strong reduction or disappearance of the Jahn-Teller distortions seems to arise from the insulator-to-metal transition around 500 K.Comment: an error in the scaling factor of Eq.(4) and consequently 2 values of table I have been corrected. The conclusions of the paper remain unchanged. See also: C. Zobel et al. Phys. Rev. B 71, 019902 (2005) and J. Baier et al. Phys. Rev. B 71, 014443 (2005

Ferromagnetism and Superconductivity in the multi-orbital Hubbard Model: Hund's Rule Coupling versus Crystal-Field Splitting

The multi-orbital Hubbard model in one dimension is studied using the numerical diagonalization method. Due to the effect of the crystal-field splitting $\Delta$, the fully polarized ferromagnetism which is observed in the strong coupling regime becomes unstable against the partially polarized ferromagnetism when the Hund's rule coupling $J$ is smaller than a certain critical value of order of $\Delta$. In the vicinity of the partially polarized ferromagnetism, the orbital fluctuation develops due to the competition between the Hund's rule coupling and the crystal-field splitting. The superconducting phase with the Luttinger liquid parameter $K_{\rho}>1$ is observed for the singlet ground state in this region.Comment: 4 pages,5 figures,submitted to J.Phys.Soc.Jp

Synchronization of multi-phase oscillators: An Axelrod-inspired model

Inspired by Axelrod's model of culture dissemination, we introduce and analyze a model for a population of coupled oscillators where different levels of synchronization can be assimilated to different degrees of cultural organization. The state of each oscillator is represented by a set of phases, and the interaction --which occurs between homologous phases-- is weighted by a decreasing function of the distance between individual states. Both ordered arrays and random networks are considered. We find that the transition between synchronization and incoherent behaviour is mediated by a clustering regime with rich organizational structure, where some of the phases of a given oscillator can be synchronized to a certain cluster, while its other phases are synchronized to different clusters.Comment: 6 pages, 5 figure

Thermopower of the Correlated Narrow Gap Semiconductor FeSi and Comparison to RuSi

Iron based narrow gap semiconductors such as FeSi, FeSb2, or FeGa3 have received a lot of attention because they exhibit a large thermopower, as well as striking similarities to heavy fermion Kondo insulators. Many proposals have been advanced, however, lacking quantitative methodologies applied to this problem, a consensus remained elusive to date. Here, we employ realistic many-body calculations to elucidate the impact of electronic correlation effects on FeSi. Our methodology accounts for all substantial anomalies observed in FeSi: the metallization, the lack of conservation of spectral weight in optical spectroscopy, and the Curie susceptibility. In particular we find a very good agreement for the anomalous thermoelectric power. Validated by this congruence with experiment, we further discuss a new physical picture of the microscopic nature of the insulator-to-metal crossover. Indeed, we find the suppression of the Seebeck coefficient to be driven by correlation induced incoherence. Finally, we compare FeSi to its iso-structural and iso-electronic homologue RuSi, and predict that partially substituted Fe(1-x)Ru(x)Si will exhibit an increased thermopower at intermediate temperatures.Comment: 14 pages. Proceedings of the Hvar 2011 Workshop on 'New materials for thermoelectric applications: theory and experiment

Immersion Lithography Defectivity Analysis at DUV Inspection Wavelength

ABSTRACT Significant effort has been directed in recent years towards the realization of immersion lithography at 193nm wavelength. Immersion lithography is likely a key enabling technology for the production of critical layers for 45nm and 32nm design rule (DR) devices. In spite of the significant progress in immersion lithography technology, there remain several key technology issues, with a critical issue of immersion lithography process induced defects. The benefits of the optical resolution and depth of focus, made possible by immersion lithography, are well understood. Yet, these benefits cannot come at the expense of increased defect counts and decreased production yield. Understanding the impact of the immersion lithography process parameters on wafer defects formation and defect counts, together with the ability to monitor, control and minimize the defect counts down to acceptable levels is imperative for successful introduction of immersion lithography for production of advanced DR's. In this report, we present experimental results of immersion lithography defectivity analysis focused on topcoat layer thickness parameters and resist bake temperatures. Wafers were exposed on the 1150i-α-immersion scanner and 1200B Scanner (ASML), defect inspection was performed using a DUV inspection tool (UVision TM , Applied Materials). Defect material analysis was performed for different defects. Higher sensitivity was demonstrated at DUV through detection of small defects not detected at the visible wavelength, indicating on the potential high sensitivity benefits of DUV inspection for this layer. The analysis indicates that certain types of defects are associated with different immersion process parameters. This type of analysis at DUV wavelengths would enable the optimization of immersion lithography processes, thus enabling the qualification of immersion processes for volume production