Is hypothalamic GABA involved in immune function in relation to dietary protein during aging?

Hypothalamic GABAergic activity and immune response in spleen were not significantly changed with the increase of age from 3 to 6 months in adult male albino rats. Further increase of age from 6 to 9 months increase the GABAergic activity and decreased the cell viability in spleen without any change in its T-lymphocyte cytotoxicity. Consumption of low protein diet (LPD) for a short-term period (STP; 7 consecutive days) increased the hypothalamic GABAergic activity without changing the immune response in 3 months old rats. When supplemented for a long-term period (LTP; 30 consecutive days) to 3 months old rats, a reduction of hypothalamic GABAergic activity and the immune response was observed. Intake of high protein diet (HPD) for both STP and LTP increased the GABAergic activity and immune response, but the increase of GABAergic activity in hypothalamus under STP was greater than that observed under LTP. In 6 months old rats consumption of LPD for STP reduced the GABAergic activity without any alteration of its immune response. Long-term supplementation of this LPD to the same age group increased GABAergic activity and the mitotic activity of spleen cells without any alteration of the functional activity of the T-cells in spleen. Consumption of HPD for STP failed to produce any change in hypothalamic GABAergic activity and the immune response of 6 months old rats. Supplementation of HPD for LTP reduced the hypothalamic GABAergic activity and the immune response of the same age group. The reduction in hypothalamic GABAergic activity without any change in the immune response was observed following the supplementation of low protein diet to 9 months old rat for STP. Intake of the LPD for LTP also reduced the hypothalamic GABAergic activity and the mitotic activity of the spleen cells without any alteration of the functional activity of the T-cells in spleen of 9 months old rats. Supplementation of HPD for STP to this aged rat, on the other hand, failed to produced any change in hypothalamic GABAergic activity and the immune response. Intake of HPD for LTP by this aged rats increased the hypothalamic GABAergic activity along with the immune response. The results of this study, thus, suggest that hypothalamic GABAergic activity during aging is an index of immune response and it is modulated following the short- and long-term consumption of protein poor and protein rich diet.     

The fetoplacental pressor effects of low-dose acetylsalicylic acid and angiotensin II in the ex vivo cotyledon model

OBJECTIVE: Our purpose was to investigate perfusion pressure changes ex vivo induced by angiotensin II on fetoplacental vasculature pretreated with low-dose acetylsalicylic acid. STUDY DESIGN: Two cotyledons from each of 12 placentas were perfused. The intervillous space of one cotyledon was infused with acetylsalicylic acid (5 x 10(-5) mol/L) similar to the serum concentration of women receiving daily low-dose aspirin therapy (60 to 81 mg). The control cotyledon was infused with an equivalent amount of normal saline solution. Two doses of angiotensin II, 1 x 10(-11.5) and 1 x 10(-10) moles, were injected as boluses into the chorionic arteries of each cotyledon. A 3 x 10(-7) mole dose of angiotensin II was also injected into the intervillous space. Statistical analysis was performed with analysis of variance, and results are expressed as mean pressure change in millimeters of mercury +/- SEM. RESULTS: Perfusion pressure response did not vary between cotyledons pretreated with acetylsalicylic acid and control cotyledons when 3 x 10(-7) moles of angiotensin II was injected into the intervillous space (8.0 +/- 1.9 mm Hg vs 9.8 +/- 1.6 mm Hg, p = 0.59). There were no differences between cotyledons in pressure response to 1 x 10(-11.5) moles of angiotensin II injected into the fetal circuit (5.9 +/- 0.8 mm Hg vs 6.7 +/- 0.9 mm Hg, p = 0.51). However, in the cotyledons pretreated with acetylsalicylic acid there was a decrease in the pressor response to 1 x 10(-10) moles of angiotensin II (14.1 +/- 1.4 mm Hg vs 21.5 +/- 3.3 mm Hg, p = 0.05). CONCLUSIONS: Low-dose aspirin infused into the intervillous space decreases vasoconstriction elicited by angiotensin II in the fetoplacental compartment. This suggests that maternal low-dose aspirin therapy has effects in the fetoplacental circulation in addition to its effects in the maternal circulation.     

Neural network model of short-term horizontal disparity vergence dynamics

We present a neural network model of short-term dynamics of the human horizontal vergence system (HVS) and compare its predictions qualitatively and quantitatively with a large variety of horizontal disparity vergence data. The model consists of seven functional stages, namely: (1) computation of instantaneous disparity; (2) generation of a disparity map; (3) conversion of the disparity into a velocity signal; (4) push-pull integration of velocity to generate a position signal; (5) conversion of the position signal to motoneuron/plant activity for each eye; (6) gating of velocity overdrive signal to motoneuron/plant system; and finally (7) discharge path for position cells. Closed-loop (normal binocular viewing) symmetric step and staircase disparity vergence data were collected from three subjects and model parameters were determined to quantitatively match each subject's data. The simulated closed-loop as well as open-loop (disparity clamped viewing) symmetric step, sinusoidal, pulse, staircase, square and ramp wave responses closely resemble experimental results either recorded in our laboratory or reported in the literature. Where possible, the firing pattern of the neurons in the model have been compared to actual cellular recordings reported in the literature. The model provides insights into neural correlates underlying the dynamics of vergence eye movements. It also makes novel predictions about the human vergence system.     

Renal function tests for windows--a model for the development and distribution of medical software on the Internet

In the present study, pharyngeal size was investigated on the lateral cephalometric head films of 90 subjects, 45 males and 45 females, having different ANB angles. All of the subjects were aged 13 to 15 years. The films were taken at natural head position, and all were divided into three groups according to the ANB angle: ANB angles smaller than 1 degree, between 1 degree and 5 degrees, and larger than 5 degrees. In addition, each group was also divided into two subgroups according to sex. The effects of the ANB angle and sex on the pharyngeal size were investigated by means of variance analysis. It has been observed that two measurements, hy-apw4 and oropharynx area measurements, were affected by the change of ANB angle, and two other measurements, t-ppw and hy-apw2 measurements, by the sex; and that hy-apw4 measurement and oropharynx area became smaller with the increase of ANB angle.     

Apoptosis of late-stage erythroblasts in megaloblastic anemia: association with DNA damage and macrocyte production

An in vitro model of folate-deficient erythropoiesis has been developed using proerythroblasts isolated from the spleens of Friend virus-infected mice fed an amino acid-based, folate-free diet. Control proerythroblasts were obtained from Friend virus-infected mice fed the same diet plus 2 mg folic acid/kg diet. Our previous studies showed that, after 20 to 32 hours of culture in folate-deficient medium with 4 U/mL of erythropoietin, the folate-deficient proerythroblasts underwent apoptosis, whereas control erythroblasts survived and differentiated into reticulocytes over a period of 48 hours. The addition of folic acid or thymidine to the folate-deficient medium prevented the apoptosis of the folate-deficient erythroblasts, thereby implicating decreased thymidylate synthesis as the main cause of apoptosis in the folate-deficient erythroblasts. In the study reported here, we examined intracellular folate levels, uracil misincorporation into DNA, p53 and p21 proteins, and reticulocyte formation in erythroblasts cultured in folate-deficient or control medium. In all experiments, the folate-deficient erythroblasts cultured in folate-deficient medium gave results that varied significantly from folate-deficient erythroblasts cultured in control medium or control erythroblasts cultured in either folate-deficient or control media. Folate-deficient erythroblasts cultured in folate-deficient medium had marked decreases in all coenzyme forms of folate that persisted throughout culture, increased uracil misincorporation into DNA, persistent accumulations of p53 and p21, and decreased reticulocyte production but increased size of individual reticulocytes. A model of folate-deficient erythropoiesis based on apoptosis of late stage erythroblasts is presented. This model provides explanations for the clinical findings in megaloblastic anemia.     

The propeptide of the vitamin K-dependent carboxylase substrate accelerates formation of the gamma-glutamyl carbanion intermediate

Vitamin K-dependent carboxylase catalyzes the post-translational gamma-carboxylation of 9-12 glutamyl residues of several blood coagulation proteins. Carboxylase purified from Chinese hamster ovary (CHO) cells as a recombinant FLAG-carboxylase fusion protein [Sugiura, I., et al. (1996) J. Biol. Chem. 271, 17837-17844] was utilized with pentapeptide substrate FL[3H-R,S]EAL with high specific radioactivity to probe the timing of glutamyl Cgamma-3H cleavage relative to Cgamma-COO- bond formation by 14CO2 incorporation rates. Studies were conducted over a range of NaH14CO3 concentrations to assess uncoupling of gamma-glutamyl carbanion formation and over a range of concentrations of ProPT18, the 18-residue peptide corresponding to the -18 to -1 propeptide region of prothrombin known to affect the catalytic efficiency of carboxylase. At saturation, ProPT18 accelerates Cgamma-3H cleavage 11-13-fold and Cgamma-14CO2- formation 6-7-fold, converting a Cgamma-3H cleavage/Cgamma-14CO2- formation ratio of 1.2-1.4 in the absence of ProPT18 to 2.3-2.8 in its presence, a relative increase in and uncoupling of Cgamma-3H cleavage from C-C bond formation. When the HCO3- concentration was varied, the V/K3H+/V/K14CO2 ratios rose as HCO3- fractional saturation dropped to a ratio of 9.3-10.8/l at low bicarbonate, indicating an uncoupling of nine out of ten gamma-glutamyl carbanion formations from carboxylative capture, consistent with prior reports on microsomal enzyme [Larson, A. E., et al. (1981) J. Biol. Chem. 256, 11032-11035]. These results with pentapeptide substrate FLEAL validate reversible gamma-glutamyl carbanion formation by pure carboxylase and indicate the ProPT18 increase in catalytic efficiency is in selective lowering of an energy barrier preceding the gamma-glutamyl carbanion intermediate.     

Dysgraphia in children: lasting psychomotor deficiency or transient developmental delay?

A longitudinal design was applied to differentiate between normal variations of psychomotor development and lasting handwriting deficiency (dysgraphia). Sixteen primary school children were tested with writing tasks that were recorded on a computer-monitored'XY tablet. These tasks represented different modules of the handwriting model of Van Galen (1991). Dependent variables were spatial errors, movement time, movement dysfluencies, trajectory length, stroke curvature, and the degree of neuromotor noise in the movement velocity profiles. The latter variable was measured by means of Power Spectral Density Analysis of the movement velocity signal, which revealed that movements of poor writers were substantially more noisy than those of proficient writers, with a noise peak in the region of neuromotor tremor. At the same time, the poor writers were less accurate. It was concluded that control of spatial accuracy rather than allograph retrieval or size control is the discriminating feature in dysgraphic children. Moreover, poor writers do not catch up with their peers within the 1 year time span tested.     

Monoclonal and polyclonal antibodies to chicken immunoglobulin isotypes specifically detect turkey immunoglobulin isotypes

Turkey immunoglobulin (Ig) isotypes IgG and IgM were isolated from blood and IgA was isolated from bile. Isolation was accomplished by gel filtration of the ammonium sulphate cut on Sephacryl S-200. Using immunoelectrophoresis and indirect ELISA, the cross-reactivity between antibodies, of monoclonal and polyclonal origin, specific for the Ig isotypes of chicken, and the purified turkey Ig isotypes was evaluated. Commercially available polyclonal antibodies, anti-chicken/IgA (alpha-chain specific, affinity purified), anti-chicken/IgG (Fc-fragment specific) and anti-chicken/IgM (mu-chain specific) showed an interspecies cross-reactivity with the corresponding turkey Ig isotypes. The monoclonal antibody (MAb) AV-G3 specifically detected turkey IgG, whereas MAb M1 reacted exclusively with turkey IgM. This panel of anti-immunoglobulins represents a useful tool for examining the humoral immune responses of turkeys.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.