Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake rat

Intensive insulin treatment during diabetic pregnancy is complicated by maternal hypoglycemia. To investigate whether pregnancy may contribute as an independent hypoglycemia risk factor, awake pregnant rats that were near term underwent stepped insulin hypoglycemic (3.4 and 2.3 mM) clamp studies in the fasted and nonfasted states. In the fasted state, the glucagon response to hypoglycemia was completely suppressed in the pregnant rats (P < 0.01). Epinephrine, but not norepinephrine, was also diminished by approximately 70-75% at both hypoglycemic steps, and more exogenous glucose was needed to maintain hypoglycemia during pregnancy. To avoid the potential confounding effect of increased ketone levels (beta-hydroxybutyrate was approximately 170% higher in the pregnant rats), experiments were repeated in the nonfasting state when ketosis was eliminated in both groups. The nonfasted pregnant rats continued to show near complete suppression of the glucagon response, even at glucose levels of 2.3 mM. In contrast, a brisk response occurred in nonpregnant controls when glucose fell to 3.4 mM. Although epinephrine levels in the pregnant rats were also markedly suppressed during the milder hypoglycemic stimulus, they approached values seen in nonpregnant controls when glucose was lowered further to 2.3 mM. We concluded that in the rat, pregnancy markedly suppresses glucagon responses to hypoglycemia. The release of epinephrine, but not norepinephrine, is also blunted, especially during mild hypoglycemia. These findings suggest that pregnancy may impair glucose counterregulation by inhibiting glucagon and epinephrine release during hypoglycemia.     

Widespread expression of an autoantigen-GAD65 transgene does not tolerize non-obese diabetic mice and can exacerbate disease

Glutamic acid decarboxylase (GAD)65 is a pancreatic beta cell autoantigen implicated as a target of T cells that initiate and sustain insulin-dependent diabetes mellitus (IDDM) in humans and in non-obese diabetic (NOD) mice. In an attempt to establish immunological tolerance toward GAD65 in NOD mice, and thereby to test the importance of GAD in IDDM, we generated three lines transgenic for murine GAD65 driven by a major histocompatibility complex class I promoter. However, despite widespread transgene expression in both newborn and adult mice, T cell tolerance was not induced. Mononuclear cell infiltration of the islets (insulitis) and diabetes were at least as bad in transgenic mice as in nontransgenic NOD mice, and in mice with the highest level of GAD65 expression, disease was exacerbated. In contrast, the same transgene introduced into mouse strain, FvB, induced neither insulitis nor diabetes, and T cells were tolerant to GAD. Thus, the failure of NOD mice to develop tolerance toward GAD65 reflects at minimum a basic defect in central tolerance, not seen in animals not predisposed to IDDM. Hence, it may not be possible experimentally to induce full tolerance toward GAD65 in prediabetic individuals. Additionally, the fact that autoimmune infiltration in GAD65 transgenic NOD mice remained largely restricted to the pancreas, indicates that the organ-specificity of autoimmune disease is dictated by tissue-specific factors in addition to those directing autoantigen expression.     

Local field potential spectral tuning in motor cortex during reaching.

In this paper, intracortical local field potentials (LFPs) and single units were recorded from the motor cortices of monkeys (Macaca fascicularis) while they preformed a standard three-dimensional (3-D) center-out reaching task. During the center-out task, the subjects held their hands at the location of a central target and then reached to one of eight peripheral targets forming the corners of a virtual cube. The spectral amplitudes of the recorded LFPs were calculated, with the high-frequency LFP (HF-LFP) defined as the average spectral amplitude change from baseline from 60 to 200 Hz. A 3-D linear regression across the eight center-out targets revealed that approximately 6% of the beta LFPs (18-26 Hz) and 18% of the HF-LFPs were tuned for velocity (p-value < 0.05), while 10% of the beta LFPs and 15% of the HF-LFPs were tuned for position. These results suggest that a multidegree-of-freedom brain-machine interface is possible using high-frequency LFP recordings in motor cortex.     

Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults

The actions of recombinant human insulin-like growth factor-I (rhIGF-I) and insulin were compared in 21 healthy young (24 +/- 1 yr) and 14 healthy middle-aged (48 +/- 2 yr) subjects during 3-h paired euglycemic clamp studies using one of three doses (rhIGF-I 0.2, 0.4, and 0.8 micrograms/kg.min and insulin 0.2, 0.4, and 0.8 mU/kg.min, doses chosen to produce equivalent increases in glucose uptake). In younger subjects, rhIGF-I infusions suppressed insulin by 19-33%, C-peptide by 47-59% and glucagon by 33-47% (all, P < 0.02). The suppression of C-peptide was less pronounced with insulin than with rhIGF-I (P < 0.007). The metabolic responses to rhIGF-I and insulin were remarkably similar: not only did both hormones increase glucose uptake and oxidation in a nearly identical fashion, but they also produced similar suppression of glucose production, free fatty acid levels, and fat oxidation rates. In contrast, rhIGF-I had a more pronounced amino acid-lowering effect than did insulin (P < 0.004). In middle-aged subjects, basal IGF-I levels were 44% lower (P < 0.0001) whereas basal insulin and C-peptide were 20-25% higher than in younger subjects. Age did not alter the response to rhIGF-I. However, insulin-induced stimulation of glucose uptake was blunted in older subjects (P = 0.05). Our data suggest that absolute IGF-I and relative insulin deficiency contribute to adverse metabolic changes seen in middle age.     

Periodic Breathing in Infants: A Model Study

A model has been adapted to explain periodic breathing in infants during sleep. Using parameter values determined in various studies by others, it is shown that the respiratory control system of certain infants is marginally stable so that a small change in one or more of the parameters can cause periodic breathing with a period of about 14 s.     

Investigation on the Wear Properties of Primary Si Modified Al–20Si Alloy

In the present study, Al?C20Si alloy has been modified by Cu?C13P master alloy to obtain Al?C20Si?C0.1P alloy. The wear properties of Al?C20Si?C0.1P alloy have been investigated and compared with that of Al?C20Si alloy. The microstructure of Al?C20Si?C0.1P alloy consisted of primary and eutectic silicon distributed in the Al matrix. The size of primary Si is much smaller than that observed in Al?C20Si alloy. Wear tests have been conducted over a wide range of loads and sliding velocities. It has been observed that the wear rates of Al?C20Si?C0.1P alloy are lower than that of Al?C20Si alloy. The coefficient of friction is more or less constant in both the alloys but is low in Al?C20Si?C0.1P alloy. The better wear resistance of Al?C20Si?C0.1P alloy is discussed in the light of its modified microstructure evolved during solidification.     

Analysing the pattern of pulse waves in arterial networks: a time-domain study

The mechanisms underlying the shape of pulse waves in the systemic arterial network are studied using the time-domain, one-dimensional (1-D) equations of blood flow in compliant vessels. The pulse waveform at an arbitrary location in the network is initially separated into a peripheral component that depends on the cardiac output, total compliance and total peripheral resistance of the network, and a conduit component governed by reflections at the junctions of the large conduit arteries and at the aortic valve. The dynamics of the conduit component are then analysed using a new algorithm that describes all the waves generated in the linear 1-D model network by a single wavefront starting at the root. This algorithm allows one to systematically follow all the waves arriving at the measuring site and identify all the reflection sites that these waves have visited. Application of this method to the pulse waves simulated using a 1-D model of the largest 55 systemic arteries in the human demonstrates that peripheral components make a larger contribution to aortic pressure waveforms than do the conduit components. Conduit components are closely related to the outflow from the left ventricle in early systole. Later in the cardiac cycle, they are the result of reflections at the arterial junctions and aortic valve. The number of reflected waves increases approximately as 3 ^m , with m being the number of reflection sites encountered. The pressure changes associated with these waves can be positive or negative but their absolute values tend to decrease exponentially. As a result, wave activity is minimal during late diastole, when the peripheral components of pressure and the flow are dominant, and aortic pressures tend to a space-independent value determined by the cardiac output, total compliance and total peripheral resistance. The results also suggest that pulse-wave propagation is the mechanism by which the arterial system reaches the mean pressure dictated by the cardiac output and total resistance that is required to perfuse the microcirculation. The total compliance determines the rate at which this pressure is restored when the system has departed from its equilibrium state of steady oscillation. This study provides valuable information on identifying and measuring the parameters and pathways of the arterial network that have the largest effect on the simulated pulse waveforms.