Autonomic paroxysms: their pathogenesis, diagnosis and treatment

In the article the rules about etiology and pathogenesis of vegetative paroxysms are stated based on careful analysis of the publications of researches as Russian, so foreign authors, and also own experimental and clinical supervision. During experimental and clinical researches the modern methods were used, enabling to estimate from positions of the system analysis different parts of pathogenesis of vegetative paroxysms, and also to offer ways of differential diagnostics of the various forms of disease. The application of some new preparations and direction of therapy of vegetative paroxysms are substantiated, and also the various circuits of treatment of the patients with distinguishing forms of given pathology are motivated.     

Direct determination of allergens in ambient aerosols: methodological aspects

In Switzerland the birch tree (Betula verrucosa) major allergen Bet v 1 and the grass (Phleum pratense) pollen major allergen Phl p 5 are of particular relevance for inducing pollinosis. In this study, the protein and major allergen contents of aerosols of different aerodynamic diameters were determined. The aerosols were sampled by Andersen-Impactors and submitted to protein assays and allergen assays (ELISA) specific for Bet v 1 and Phl p 5. The total protein, Bet v 1 and Phl p 5 concentrations were correlated with the corresponding pollen counts. The presence of Bet v 1 in smaller aerosol fractions was demonstrated before and after birch pollen was counted, especially in the lower particle size ranges.     

The Perception of Procedures Questionnaire: psychometric properties of a brief parent report measure of procedural distress

Reported the reliability and validity of the Perception of Procedures Questionnaire (PPQ), a 19-item parent-report measure developed to assess child and parent distress related to lumbar punctures and bone marrow aspirates in the diagnosis and treatment of childhood cancer. PPQ data from 140 mothers and 96 fathers of children and adolescents with leukemia in a first remission were analyzed separately. Factor analyses yielded five factors for mothers and fathers: Parent Satisfaction; Child Distress: During; Child Distress: Before; Parent Distress; and Parent Involvement. Internal consistency (Cronbach's alpha) was high for the total score and the five factor scores as were interrater reliabilities between mothers and fathers. Validity was determined using the Parenting Stress Index-Short Form, the Pediatric Oncology Quality of Life Scale, and parent and nurse ratings during procedures. Factors 2 and 3, assessing child distress, show strong associations with the validation measures and support the distinction between distress before and during procedures. This developing scale is recommended for use in the assessment and evaluation of child and parent procedure-related distress in pediatric oncology.     

Role of cholesterol in regulating apolipoprotein B secretion by the liver

The review examines the evidence that the supply of cholesterol available for incorporation into nascent lipoprotein particles exerts a regulatory influence on apolipoprotein (apo) B secretion by the liver. Support for this hypothesis comes both from in vitro experiments and from recent observations in normal subjects and patients with dyslipidemia associated with familial hypercholesterolemia, obesity, noninsulin dependent diabetes mellitus, growth hormone deficiency and cholesteryl ester storage disease. The findings do not negate a role for triglyceride synthesis in determining apoB secretion in very low density lipoprotein, but the inhibitory effects on the latter process of pharmacological blockade of cholesterol synthesis or esterification suggest that it is conditional upon an adequate supply of cholesteryl ester.     

Survival of Mycobacterium paratuberculosis and preservation of immunoglobulin G in bovine colostrum under experimental conditions simulating pasteurization

OBJECTIVE: To determine whether Mycobacterium paratuberculosis could survive in colostrum after pasteurization. Additionally, this study investigated the effect pasteurization had on IgG concentration in colostrum. ANIMALS: Colostrum samples were collected from cattle (beef and dairy) owned by the state of Ohio. PROCEDURE: Colostrum was divided into aliquots and inoculated with variable concentrations of M paratuberculosis (ATCC No. 19698: 10(4), 10(3), and 10(2) colony-forming units/ml). Half the samples at each concentration were subjected to pasteurization temperatures (63 C) for 30 minutes and the remainder were kept at approximately 20 to 23 C. All samples were incubated (Herrold's egg yolk medium with and without mycobactin J) and observed for growth during the next 16 weeks. Additionally, the IgG concentration of colostrum was determined by radioimmunoassay before and after pasteurization. Samples that coagulated at pasteurization temperatures were mechanically resuspended before measurement of IgG concentration. RESULTS: Growth of M paratuberculosis was retarded but not eliminated by pasteurization. Growth was observed in all unpasteurized samples incubated on Herrold's egg yolk medium with mycobactin J but in only 2 of 18 pasteurized samples similarly cultured. Growth from pasteurized samples appeared 5 to 9 weeks after growth was observed from nonpasteurized samples. Mean colostral IgG concentration was 44.4 g/L in nonpasteurized samples and 37.2 g/L in pasteurized samples, a decrease of 12.3%. High-quality colostrum (> 48 g of IgG/L) had a significantly greater loss of IgG concentration than did colostrum of lesser quality (P = 0.002). CONCLUSIONS: Pasteurization lessened, but did not eliminate, growth of M paratuberculosis from experimentally inoculated colostrum samples. Pasteurization resulted in a significant decrease in colostral IgG concentration but not to an unmanageable level that would preclude the colostrum's use for passive transfer of immunity. CLINICAL RELEVANCE: Colostrum is macrophage rich and may serve as a source of M paratuberculosis infection to calves. Pasteurization of colostrum may lessen the risk of infection, but will not totally eliminate M paratuberculosis.     

Effects of doxorubicin, 4'-epirubicin, and antioxidant enzymes on the contractility of isolated cardiomyocytes

The purpose of this study was to determine the acute effects of doxorubicin and its less cardiotoxic epimer, 4'-epirubicin, on the contractile response of isolated myocytes, and to assess similarities or differences with respect to active oxygen-derived mechanisms. Calcium-tolerant myocytes from rat ventricle were field stimulated at 1.0 Hz, and the maximum extent of cell shortening, peak shortening velocity, and peak relaxation velocity of single twitches were measured by video edge detection. The contractile responses of the myocytes to the two anthracyclines were approximately equal. Exposure of the cells to 10 microM of either anthracycline for 20 min decreased all indices of contractility by 28% (p < 0.05). The active oxygen scavengers, superoxide dismutase and catalase, distinguished the extent to which active oxygen was involved in modifying cellular contractility. Paradoxically, superoxide dismutase alone (10 U/mL) decreased contractility by 21%. Nevertheless, superoxide dismutase (10 U/mL) prevented the decreases in contractility produced by doxorubicin. In contrast, superoxide dismutase only mildly (32%) protected against 4'-epirubicin. Catalase (10 U/mL), however, provided substantial (82-93%) protection against both anthracyclines. Hydrogen peroxide therefore, and presumably hydroxyl radicals, were involved in mediating the decreases in contractility from both doxorubicin and 4'-epirubicin. These results show that an acute exposure to clinically relevant concentrations of these anthracyclines significantly depresses myocyte contractility and that, in this respect, 4'-epirubicin is as potentially cardiotoxic as doxorubicin. The results with antioxidant enzymes also strongly support a free radical mechanism for the toxicity of doxorubicin and 4'-epirubicin to cardiomyocytes.     

Differential c-fos expression in the nucleus of the solitary tract and spinal cord following noxious gastric distention in the rat

c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric distension/80) was produced by repetitive inflation of a chronically implanted gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of the solitary tract, with the densest labeling observed within 300 microns of the rostral pole of the area postrema. This area was analysed quantitatively following several manipulations. Gastric distension/80 induced a mean of 724 c-Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was reduced to 293 per section, while spinal transection at T2 plus distention (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200 nuclei per section. Repetitive bolus injections of norepinephrine produced transient pressor responses mimicking the pressor response produced by gastric distension/80. This manipulation induced minimal c-Fos in the nucleus of the solitary tract and none in the spinal cord. It is concluded that noxious visceral input via parasympathetic vagal afferents, and to a lesser extent sympathetic afferents and the spinosolitary tract, contribute to gastric distention-induced c-Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective-emotional component of visceral pain.     

Inhibition of TEM-2 beta-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionization mass spectrometry

Clavulanic acid, the therapeutically important inhibitor of beta-lactamases containing a nucleophilic serine residue at their active sites, inhibits Escherichia coli TEM-2 beta-lactamase via a complex mechanism. Electrospray ionization mass spectrometry (ESIMS) studies revealed that a minimum of four different modified proteins are formed upon incubation of clavulanate with the TEM-2 enzyme. These exhibit mass increments relative to the unmodified TEM-2 beta-lactamase of 52, 70, 88, and 155 Da. Time course studies implied that no long-lived forms of clavulanate-inhibited TEM-2 beta-lactamase retain the carbons of the oxazolidine ring of clavulanate. The absence of a 199 Da increment to unmodified TEM-2 suggests rapid decarboxylation of clavulanate upon binding to the enzyme. Proteolytic digestions of purified forms of clavulanate inhibited TEM-2 beta-lactamase followed by analyses using high-performance liquid chromatography coupled to ESIMS (HPLC-ESIMS) and chemical sequencing were used to provide positional information on the modifications to the enzyme. Increments of 70 and 80 Da increments were shown to be located in a peptide containing Ser-70. A further 70 Da mass increment, assigned as a beta-linked acrylate, was localized to a peptide containing Ser-130. A mechanistic scheme for the reaction of clavulanate with TEM-2 beta-lactamase is proposed in which acylation at Ser-70 and subsequent decarboxylation is followed either by cross-linking with Ser-130 to form a vinyl ether or by reformation of unmodified enzyme via a Ser-70 linked (hydrated) aldehyde. Purified cross-linked vinyl ether was observed to slowly convert under acidic conditions to a Ser-70 linked (hydrated) aldehyde with concomitant conversion of Ser-130 to a dehydroalanyl residue.     

Infarct limitation of the second window of protection in a conscious rabbit model

Comparative cell transfer experiments have revealed that, despite their equal immune deficiency, C3H/SCID mice were markedly inferior compared with C.B-17/SCID mice in their ability to accept allogeneic and xenogeneic grafts. Allogeneic C.B-17/SCID bone marrow cells were engrafted poorly compared with syngeneic C3H/SCID when transplanted into C3H/SCID recipients, whereas cells of both strains were equally well engrafted into C.B-17/SCID mice. C.B-17/SCID mice were much more permissive for outgrowth of human Burkitt lymphoma (Raji), as well as for Epstein-Barr virus lymphoma development after transplantation of human peripheral blood lymphocytes. Human skin grafts were accepted by the C.B-17/SCID mice but were promptly rejected by the C3H/SCID mice. The resistance to human RaJi cells could be adoptively transferred by infusion of C3H/SCID splenocytes into C.B-17/SCID mice. Because the C.B-17/SCID and C3H/SCID mice equally lack both T and B lymphocytes, the latter may provide a relevant model for studies of non-T mechanisms of allograft or xenograft rejection.