Nephropathy of type II diabetes: evidence for hereditary factors?

Family studies point to an important genetic element in the genesis of diabetic nephropathy, but it is not known whether renal abnormalities are present prior to the onset of diabetes. To address this issue we examined all consecutive patients suffering from type II diabetes with a duration of more than 10 years who attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307 did not. All offspring who were phenotypically normal (no hypertension, normal oral glucose tolerance, non-smoking) and agreed to participate were examined, 26 from nephropathic and 30 from non-nephropathic diabetic parents. They were compared with 30 offspring matched for age, gender and BMI from non-diabetic parents as controls. We measured urinary albumin excretion under baseline conditions and at several time points after ingestion of 300 g cooked beef and submaximal treadmill exercise, respectively. In addition, casual blood pressure, ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were measured. Primary renal disease was excluded by clinical examination. Under baseline conditions, median urinary albumin excretion rate (AER; microgram/min) was significantly (P < 0.005) higher in offspring of nephropathic type II diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non-nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4; 0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional increase of AER in offspring of nephropathic type II diabetics (median 16-fold) than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls (4.8-fold). In offspring of nephropathic diabetic patients casual and particularly ambulatory systolic blood pressures were significantly higher, but AER was not correlated with blood pressure. In summary, higher values, albeit within the normal range, for baseline and postexercise albuminuria were noted in phenotypically normal offspring of parents with type II diabetes and nephropathy. The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.     

Estimation of sampling error variance in the meta-analysis of correlations: Use of average correlation in the homogeneous case.

The estimate of the population correlation used in the formula for sampling error variance of a correlation is typically the observed correlation, but in meta-analysis the average of the observed correlations can be used. For the case in which there is no variation in the study population correlations or sample sizes and the number of studies is very large, the authors found that use of the average correlation estimator is more accurate than use of the traditional, individual correlation estimator, except in those rare cases in which the uncorrected population correlation is greater than .60. For typical sample sizes, when the uncorrected population correlation is between -.40 and .40, there is virtually no error in the meta-analysis credibility interval based on the average correlation estimator. On the other hand, the amount of the error in the individual correlation estimator is qualitatively important if the sample is 25 or less and the population correlation is less than .40. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P

BACKGROUND: An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. METHODS: Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. RESULTS: Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist NG-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). NG-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.1) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). CONCLUSIONS: Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.     

Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine

BACKGROUND: Desflurane anesthesia can produce cerebral metabolic depression and increase cerebral blood flow. We evaluated the effect of desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during neurosurgery. METHODS: Following a craniotomy, the dura was opened and a Paratrend 7 sensor, which measures PO2, PCO2, pH and temperature, was inserted into brain tissue. In 6 control patients in group 1, anesthesia was maintained constant with 3% end-tidal desflurane over 60 min, including a 30-min stabilization period. In group 2, 9 patients were ventilated with 3% desflurane under baseline conditions. After a 30-min stabilization period, baseline tissue gases and pH were measured and end-tidal desflurane was increased to 6% and then 9% for 15-min intervals. Mean arterial pressure (MAP) was maintained with intravenous phenylephrine. RESULTS: Under baseline conditions, cardiovascular and brain tissue measures were similar between the 2 groups. Increasing end-tidal desflurane from 3% to 9% produced burst-suppression EEG in all patients and significantly increased tissue PO2 and pH and decreased PCO2. No parameters changed significantly in the control group during steady-state anesthesia. CONCLUSION: These results show that 9% desflurane can improve brain tissue metabolic status before temporary brain artery occlusion if cerebral perfusion pressure is maintained. This may be particularly important in patients with symptoms of ischemia before surgery.     

Wide-band symmetrical analog multiplier IC for coherentoptical-fiber receivers operating up to 10 Gb/s

A versatile analog four-quadrant multiplier IC with large bandwidth (DC to 6 GHz and 10 Gb/s) and large dynamic range is presented. It was mainly developed for differential-phase-shift-keying (DPSK) phase demodulator and polarization diversity receivers in coherent optical-fiber transmission systems. The circuit consumes 450 mW and only needs a single power supply of -5 V. The circuit principle used allows exact symmetry with respect to both linear inputs, which reduced multiplication errors. In the intended application, especially, the time jitter and the offset voltage of the output pulse patterns are reduced to negligible values. The IC was realized in a 1.25-μm double-polysilicon bipolar technology     

Homogenization of hardness distribution and distortion in high pressure gas quenching

Quenching with gases rather than oil or other liquid media has the advantages of reducing the risks concerning health and environment, while simultaneously homogenizing the quenching results and minimizing distortion due to a wide range of possible process parameter variations and the pure convective heat transfer. In this contribution, a coupled solution for increasing homogenization of quenching results within high pressure gas quenching will be presented. In the first stage, an experimental test facility was set up for flow investigations and in the second stage a numerical simulation model was generated. The numerical and experimental results of the flow through the chamber were compared for several boundary conditions. Finally, after complete verification of the simulation, the model may be used to assist in parameter variation for optimization of homogeneous high pressure gas quenching.     

The modulatory cholinergic system in goldfish tectum may be necessary for retinotopic sharpening

The cholinergic circuit within the tectum and the cholinergic input from the nucleus isthmi mediate a presynaptic augmentation of retinotectal transmitter release via nicotinic receptors. In this study, the cholinergic systems were either eliminated using the cholinergic neurotoxin AF64A or blocked using nicotinic antagonists to test for effects on the activity-driven sharpening of the regenerating retinotectal projection. The effectiveness of the AF64A was verified by recording field potentials elicited by optic tract stimulation and by immunohistochemical staining for choline acetyltransferase (ChAT). At 1 week after intracranial (IC) injection of AF64A (12 to 144 nmoles) into the fluid above the tectum, field potentials showed a selective dose-dependent decrement of the cholinergic polysynaptic component with no effect on the amplitude of the glutamatergic monosynaptic component. The decrement was only partially recovered in recordings at 2 and 6 weeks. In normal fish, the ChAT antibody stains a population of periventricular neurons, their apical dendrites, and a dense plexus within the optic terminal lamina that consists of their local axons and fine dendrites and of input fibers from the nucleus isthmi. One week after IC AF64A injection (48-72 nmoles), most immunostaining in superficial tectum was lost but most neuronal somas in the deep tectum could still be seen, and staining in the tegmentum below the tectum was completely intact. At 2 weeks and later, the staining of neuronal somata largely recovered, but staining of the superficial plexus did not. AF64A treatment at 18 days after nerve crush, when regenerating retinal fibers are beginning to form synapses, prevented retinotopic sharpening of the projection. Recordings showed a rough retinotopic map on the tectum but the multiunit receptive fields (MURFs) at each tectal point averaged 34 deg vs. 11 deg in vehicle-injected control regenerates. AF64A treatment before nerve crush also blocked sharpening, ruling out a direct effect on retinal growth cones or retinal fibers, as AF64A rapidly decomposes, whereas its effect on the cholinergic fibers is long-lasting. IC injection or minipump infusion of the nicotine antagonists alpha-bungarotoxin (alpha BTX), neuronal bungarotoxin (nBTX), and pancuronium during regeneration also prevented sharpening (MURFs averaging 29.4 deg, 33.0 deg, and 31.4 deg, respectively). Control Ringer's solution infusions or injections over the same period (19-37 days postcrush) had no effect on regenerated MURF size (11.7 deg). The results show that the cholinergic innervation, which modulates transmitter release, is required for activity-driven retinotopic sharpening, thought to be triggered by NMDA receptor activation.     

One-step synthesis of functional Co nanoparticles for surface-initiated polymerization

Much effort is conducted to construct artificial objects that are capable of converting chemical or electromagnetic energy into a specific, predetermined motion on the nanoscale. We present results on the synthesis of core–shell nanoparticles capable to be set in rotation by the application of electromagnetic fields. The nanorotors implied in the study are based on the cobalt nanospheres decorated with a stabilizing brush shell composed of poly(?-caprolactone) that is attached by surface-initiated polymerization. The functional cores used as macroinitiators can be fabricated alternatively by a two-step or a one-step process.     

Laboratory simulated slipstream testing of novel sulfur removal processes for gasification application

The Wabash River Integrated Methanol and Power Production from Clean Coal Technologies (IMPPCCT) project is investigating an Early Entrance Coproduction Plant (EECP) concept to evaluate integrated electrical power generation and methanol production from coal and other carbonaceous feedstocks. Research, development and testing (RD&T) that is currently being conducted under the project is evaluating cost effective process systems for removing contaminants, particularly sulfur species, from the generated gas which contains mainly synthesis gas (syngas), CO₂ and steam at concentrations acceptable for the methanol synthesis catalyst. The RD&T includes laboratory testing followed by bench-scale and field testing at the SG Solutions Gasification Plant located in West Terre Haute, Indiana. Actual synthesis gas produced by the plant was utilized at system pressure and temperature for bench-scale field testing.     

Effects of combined nimodipine and metrifonate on rat cognition and cortical EEG

The present study investigated if short-term treatment with an L-type Ca2+-channel inhibitor, nimodipine, can stimulate cognitive functioning and cortical electroencephalograph (EEG) arousal, and potentiate the effect of a cholinesterase inhibitor, metrifonate. Pretraining administration of nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on water maze and passive avoidance behavior of young neurologically intact controls, or water maze and passive avoidance performance failure induced by scopolamine pretreatment (i.p.; 0.4 mg/kg during the water maze and 2.0 mg/kg during the passive avoidance study), medial septal lesioning, or aging. Furthermore, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on the improvement by metrifonate (10 mg/kg, p.o.) of the water maze and passive avoidance failure induced by scopolamine pretreatment or medial septal lesioning, nor did it affect the potential of metrifonate (30 mg/kg. p.o.) to improve the water maze or passive avoidance behavior of aged rats. Finally, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on spontaneously occurring thalamically generated neocortical high-voltage spindles or spectral EEG activity of young controls, nor did it alleviate the spectral EEG abnormality induced by scopolamine (0.2 mg/kg, i.p.) administration. Also, the combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10 mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced spectral EEG activity abnormalities. According to the present results, short-term treatment with nimodipine does not stimulate cognitive functions or increase cortical EEG arousal, and does not block or potentiate the propensity of metrifonate to improve cognitive performance of rats.