New skeletal muscle model for the longitudinal study of alterations in microcirculation following contusion and cryotherapy

This preliminary report describes the use of a rat model developed to study in vivo the effect of anesthesia, contusion, and cryotherapy on skeletal muscle microcirculation by use of an implanted chamber. The diameters of arterioles and venules within the chamber were determined by photomicroscopy in the contusion study and by compound videomicroscopy in the anesthesia study; microvascular perfusion was determined by laser Doppler fluxmetry (LDF). Combined ketamine and xylazine anesthesia significantly reduced (P < 0.05) arteriolar and venular diameters by 32.4% and 37.8%, respectively, and average LDF measurements by 36.1%. Contusion significantly increased arteriolar diameters over baseline values (P < 0.05); cryotherapy did not alter arteriolar diameters but increased venular diameters (P < 0.05). It is hypothesized that this increase in venular diameter may, by increasing the surface area available for reabsorption, explain one mechanism by which cryotherapy decreases the edema of contusion. Use of this model should help to advance the understanding of microcirculatory dynamics following contusion and cryotherapy.     

Study of the recrystallization process of AlMgSi alloys containing transition elements

The addition of small amounts of the transition elements such as Zr, Mn and Cr, which have a low solubility in the α-aluminium solid solution and thus form dispersoids, to AlMgSi alloys showed that these elements inhibit recrystallization when the alloys are pre-heated prior to deformation. The formation of coarse particles during casting is mainly due to the presence of Fe. This type of particles found, even, in solution treated samples. The particles, with a diameter exceeding 3 μm, accelerate the recrystallization as they provide good sites for nucleation of recrystallization. Precipitate free zones (PFZ's) developed around the coarse particles favour nucleation of recrystallization by subgrain growth. The presence of dispersoid particles is found to shift the recrystallization energy peak towards higher temperatures. Intermediate annealing before deformation allowed to achieve a high rate of deformation by cold rolling due to the removal of the solute from the matrix by the formation of the hardening phases. Optical and transmission electron microscopy, hardness measurements and differential scanning calorimetry (DSC) were used to study the kinetics of precipitation and recrystallization of the AlMgSi alloys.     

Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: impact of gonadal steroid and GH secretory changes on metabolic outcomes

Gonadal steroids are known to alter GH secretion as well as tissue metabolism. The present study was designed to examine the effects of short term (2- to 3-week) alterations in gonadal steroids on basal pulsatile (nonstimulated) and exercise- and GH-releasing hormone-stimulated GH secretion, urinary nitrogen excretion, and basal and exercise-stimulated oxygen consumption. Two protocols were conducted, which reflect a total of 18 separate studies. In the first paradigm, 5 healthy young men were each studied in a double blind, randomized manner during 3 different gonadal hormone manipulations, in which serum testosterone was varied from hypogonadal (induced by leuprolide) to eugonadal (saline injections) to high levels (testosterone enanthate, 3 mg/kg.week, i.m.). There was a washout period of 8 weeks between treatments. In the second protocol, 3 of the original subjects were studied after 2 weeks of treatment with stanozolol (0.1 mg/kg.day). Two to 3 weeks after the desired changes in serum testosterone, each subject was admitted to the General Clinical Research Center for study. The hypogonadal state (serum testosterone, 33 ng/dL) increased urinary nitrogen loss (by 34%; P < 0.005) and decreased basal metabolic rate (by 12%; P < 0.02) compared with the eugonadal state (testosterone, 796 ng/dL). High dose testosterone (1609 ng/dL) further decreased urinary nitrogen loss over the eugonadal state (by 16%; P < 0.05). Stanozolol yielded the lowest urinary nitrogen excretion of all (P < 0.03). Like urinary nitrogen, the basal metabolic rate showed the greatest change between the hypogonadal and eugonadal states (12%; P < 0.02), with a lesser change during high dose testosterone treatment (4%). Analogously, end-exercise oxygen consumption rose by 11% between the hypogonadal and eugonadal states (P < 0.05). Between the hypogonadal and eugonadal states, no significant changes in pulsatile (nonstimulated), exercise-stimulated, or GRF-stimulated GH secretion or serum insulin-like growth factor I concentrations were observed. Raising testosterone to supraphysiological levels increased pulsatile GH secretion by 62% over that with leuprolide and by 22% over that with saline (P < 0.05). High dose testosterone treatment also increased serum insulin-like growth factor I concentrations by 21% and 34% over those during the eugonadal and hypogonadal states, respectively (P < 0.01). Testosterone did not affect either exercise- or GRF-stimulated GH secretion. In protocol 2, stanozolol did not affect any parameter of GH secretion. To examine the interaction between GH secretion and testosterone on urinary nitrogen excretion and basal metabolic rate, a one-way analysis of covariance was undertaken. Statistical examination of GH production as the covariate and testosterone (by tertile) as the interactive factor demonstrated significant relationships between serum testosterone levels and either urinary nitrogen (P < 0.02) or basal metabolic rate (P < 0.01), but not GH secretion (P = NS). In summary, these results demonstrate that short term modulation of the androgen milieu affects metabolic outcome without necessitating changes in GH secretion. These results have significance for both normal physiology and for the treatment of hypogonadal GH-deficient patients.     

Aberrant T-cell function in vitro and impaired T-cell dependent antibody response in vivo in vitamin A-deficient rats

We have previously reported that vitamin A deficiency resulted in a reduced IgA antibody response to cholera toxin (CT) after per-oral immunization. In the present investigation we have studied the in vivo and in vitro immune response in vitamin A-deficient rats to two parenterally applied antigens, beta-lactoglobulin (beta-LG) and picrylsulphonic acid (TNP)-Ficoll. The serum IgG and IgM antibody responses to the T-cell dependent antigen beta-LG were significantly lower in the vitamin A-deficient rats than in the pair-fed control rats. No such differences were seen with the IgG and IgM responses to the T-cell independent antigen TNP-Ficoll. However, the biliary IgA and the serum IgE antibodies against both antigens were decreased in the vitamin A-deficient rats. In vitro lymphocyte stimulation with concanavalin A (Con A) or beta-LG gave higher T-cell proliferation rates in the vitamin A-deficient than in the control rats. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) levels in supernatants from Con A-stimulated mesenteric lymph node cells were also higher in the vitamin A-deficient rats, while IL-6 levels were decreased, which is consistent with an up-regulated Th1 activity. Proliferation studies on purified accessory cells and T cells from the deficient and the control rats, mixed in different combinations, showed that the T cells, but not the accessory cells, were disturbed in the vitamin A-deficient rats. Despite the increased T-cell activity in vitro the vitamin A-deficient rats had a lower delayed-type hypersensitivity (DTH) reaction than the pair-fed control rats. In conclusion, the increased IL-2 and IFN-gamma levels may reflect an up-regulation of Th1 cell function, while the decreased IgA, IgE and IL-6 levels indicate a suppression of Th2 cells. The disturbed T-lymphocyte function is manifested in vivo as a decreased DTH reaction and suppressed antibody production, the latter possibly due to a lack of B-cell switching and proliferation factors in vitamin A-deficient rats.     

A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction

We have identified the site of molecular interaction between nitric oxide (NO) and p21(ras) responsible for initiation of signal transduction. We found that p21(ras) was singly S-nitrosylated and localized this modification to a fragment of p21(ras) containing Cys118. A mutant form of p21(ras), in which Cys118 was changed to a serine residue and termed p21(ras)C118S, was not S-nitrosylated. NO-related species stimulated guanine nucleotide exchange on wild-type p21(ras), resulting in an active form, but not on p21(ras)C118S. Furthermore, in contrast to parental Jurkat T cells, NO-related species did not stimulate mitogen-activated protein kinase activity in cells transfected with p21(ras)C118S. These data indicate that Cys118 is a critical site of redox regulation of p21(ras), and S-nitrosylation of this residue triggers guanine nucleotide exchange and downstream signaling.     

Dot Enumeration Perceptual Organization Task (DEPOT): evidence for a short-term visual memory deficit in schizophrenia

The Dot Enumeration Perceptual Organization Task (DEPOT) evaluates the validity of 2 specific competing cognitive models of early input dysfunction in schizophrenic individuals: a primary Stage 1, sensory store, perceptual organization deficit vs. a Stage 2, short-term visual memory (STVM) deficit. DEPOT was also designed to assess the hypothesis that schizophrenic individuals tend to perform poorly on all cognitive tasks. In DEPOT both number and form judgments are made about the same dot patterns. A response delay manipulation assesses the persistence and operation of STVM. The study included 41 psychotic inpatients (8 with acute and 16 with chronic schizophrenia and 7 with bipolar and 10 with nonbipolar affective disorder) and 38 controls (22 college students and 16 hospital personnel). Although the pattern of results was consistent with neither the Stage 1 deficit nor the general deficit hypotheses, a Stage 2, STVM deficit hypothesis could account parsimoniously for the data.