Ruthenium red affects the contractile apparatus but not sarcoplasmic reticulum Ca2+ release of skinned papillary muscle

Ruthenium red has been shown to have a positive inotropic effect on isolated perfused hearts. The cellular mechanism of this action is not clear. Ruthenium red is able to block the Ca²⁺ release channel in isolated sarcoplasmic reticulum (SR) vesicle and reconstituted channel preparations. However, the effect of ruthenium red on SR Ca²⁺ release has not been studied in skinned cardiac muscle preparations. In the present study we investigated the actions of ruthenium red on both the characteristics of force generation by the contractile apparatus and Ca²⁺ release from the SR in chemically skinned rat papillary muscle. Ruthenium red (2 and 10 M) significantly increased the Ca²⁺ sensitivity of the contractile apparatus (decreasing Ca²⁺ required for the half-maximal response from 1.56±0.04 M to 1.46±0.05 M) but had no effect on the maximal Ca²⁺-activated force in triton X-100 treated fibers. This result may suggest one explanation for the positive inotropic effect of ruthenium red on the heart. On the other hand, ruthenium red had no significant effect on either caffeine-induced Ca²⁺ release or Ca²⁺-induced Ca²⁺ release from the SR in saponin-skinned muscle fibers. Lack of a blocking effect on SR Ca²⁺ release by ruthenium red in skinned fibers suggests that the SR Ca²⁺ channels in intact preparations have characteristics that are different from those of either vesicular or reconstituted channel preparations.     

Topographical study of the neurons containing hpGRF immunoreactivity in monkey hypothalamus

Hypothalamic neurons producing growth hormone-releasing factor (GRF) have been characterized by immunohistochemistry in monkey hypothalamus, using an antiserum raised against hpGRF1-40, a peptide with GRF activity isolated from a human pancreatic tumor. Cell bodies with hpGRF immunoreactivity were found in arcuate and ventromedial nuclei. From these neurons, bundles of fibers innervate median eminence and appear to terminate in contact with portal vessels. In addition to median eminence, hpGRF immunoreactive fibers were found mostly in the anterior hypothalamus and the arcuate and ventromedial nuclei where they give perineuronal endings. These results correlate with earlier physiological data on hypothalamic control of growth hormone secretion and suggest that GRF is also involved in interneuronal relationships related or unrelated to neurohumoral control of pituitary secretions.     

Development and testing of a simple algorithm for a glucose clamp

The glucose clamp technique is widely used in clinical research studies to maintain a constant blood glucose (BG) level during metabolic perturbation. An algorithm is used to set the rate of an intravenous glucose infusion according to measured BG concentrations. Currently used clamp algorithms are unnecessarily complex. This paper describes the development and use of a new algorithm which is simpler to implement. The algorithm employs proportional and differential feedback control. Discrete BG sampling with a sampling period of 5 min is used. Computer simulation with a two-compartment model of glucose dynamics was used to refine the algorithm. A Monte Carlo approach was adopted to examine the effects of random variations in measured BG concentrations and the elapsed time between blood sampling and adjustment of the glucose infusion rate. A coefficient of variation in BG concentration of less than 4 per cent was predicted for a euglycemic clamp. This was confirmed when the algorithm was applied in clinical research studies. This degree of BG control compares well with other published algorithms.     

A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.     

Reduced responsiveness of locus coeruleus neurons to cutaneous thermal stimuli in capsaicin-treated rats

Recent electrophysiological experiments have shown that brain norepinephrine (NE) neurons in the locus coeruleus (LC) are activated by cutaneous thermal stimuli of both non-noxious and noxious character. In the present study the LC neuronal response to thermal stimuli was used to evaluate cutaneous thermal sensitivity in capsaicin-treated rats, a treatment that is described to cause impaired thermoregulation. Capsaicin treatment, of neonates as well as of adult rats, caused a reduced responsiveness of brain LC neurons to thermal stimuli. The results suggest that a reduction in peripheral thermal afferent transmission may be one mechanism underlying the capsaicin-induced thermoregulatory dysfunction.     

Insulin Minimal Model Indexes and Secretion: Proper Handling of Uncertainty by a Bayesian Approach

The identification of the insulin minimal model (MM) for the estimation of insulin secretion rate (ISR) and physiological indexes (e.g. beta-cell sensitivity) requires the knowledge of C-peptide (CP) kinetics. The four parameters of the two-compartment model of CP kinetics in a given individual can be derived either from an additional bolus experiment or, more frequently, from a population model. However, in both situations, the CP kinetics is uncertain and, in MM identification, it should be treated as such. This paper shows how to handle CP kinetics uncertainty by using a Bayesian methodology. In seven subjects, MM indexes and ISR were estimated together with their confidence intervals, using either the bolus data or the population model to assess CP kinetics. The two main results that arise from the application of the new methodology are: (i) the use of the population model in place of the bolus data to determine CP kinetics does not affect, on average, the point estimates of ISR profile and MM parameters but only the confidence intervals which becomes wider (less than 50%); (ii) in both the bolus and population situation neglecting the uncertainty of CP kinetics, as done in MM literature so far, introduces no bias, on average, on point estimates of MM indexes but only an underestimation of confidence intervals.     

Bounds in the Sensitivity of BioMEMS Devices for Cell Detection

This paper presents an ongoing effort to characterize performance and reliability of micro electromechanical systems used for biomedical diagnostics (BioMEMS). In order to study the interactions of human osteosarcoma (HOS) cells with BioMEMS devices, cultures were performed on silicon (Si) surfaces as well as silicon surfaces coated with 50 nm of titanium (Ti). Cell spreading on the surfaces was observed over time for up to 2 hours. It was seen that titanium coated silicon surfaces have the potential to provide a better interface for BioMEMS devices, due to enhanced adherence and spreading of the cells on these surfaces. Atomic force microscope (AFM) cantilevers were used as cell detection sensors. These cantilevers were coated with 50nm of titanium metal to provide a cell friendly surface. Theoretical models were then developed for the prediction of the vibrational responses of the AFM cantilevers before and after cell attachment. The models were used to relate the experimentally observed changes in frequency to the number of cells that are attached on the cantilever. The bounds in the possible frequency changes were determined within a theoretical framework. From experimentally calculated values for the mass of cells, random number simulations were carried out to determine the probability of cell attachment as a function of the change in resonance frequency of the cantilever sensor. The implications of the results are then discussed for the future reliability modeling of the sensor.     

Assessment of Baroreceptor Reflex Function During Mental Stress and Relaxation

This paper describes a method of measuring baroreceptor cardiac reflex sensitivity noninvasively from spontaneous patterns of blood pressure and interbeat interval, and the application of this technique in psychophysiology. Baroreflex function was assessed in 24 female volunteers during relaxation and performance of the cold pressor test and a non-verbal mental arithmetic task. Blood pressure and interbeat interval were monitored continuously from the finger using the vascular unloading technique. Sequences of three or more cardiac cycles were identified over which systolic blood pressure increased progressively in conjunction with lengthening interbeat interval, or systolic blood pressure decreased as interbeat interval was reduced. The regression between systolic blood pressure and interbeat interval was computed as an index of baroreflex sensitivity. Relaxation was associated with a small prolongation of interbeat interval, whereas baroreflex sensitivity increased from 17.1 to 19.8 ms/mmHg. Baroreflex sensitivity was reduced significantly during mental arithmetic (mean 14.2 ms/mmHg) but not during the cold pressor test (mean 17.4 ms/mmHg). The difference between mental arithmetic and the cold pressor test may be related to the relative intensity of cardiac and vascular responses in the two situations. The implications of these results for the understanding of behavioural influences on haemodynamic function are discussed and the advantages of noninvasive methods are considered.     

152株解脲支原体对9种抗生素药物敏感性检测

目的了解深圳地区解脲支原体（UU）对常用9种抗生素的药物敏感情况，指导临床合理用药。方法采用UU培养和药敏试剂盒检测UU的体外抗菌活性。结果152株UU对9种抗生素的敏感性依次为原始霉素、多西环素、交沙霉素、克拉霉素、阿奇霉素、红霉素、四环素、氧氟沙星、环丙沙星，其总的耐药发生率为33．92％。结论对UU耐药性的检测，对指导临床合理用药具有重要意义。     

Sensitivity to mechanical stimuli and the role of general sensory and perceptual processes in heartbeat detection

Sensitivity to heartbeat sensations is commonly assessed using tasks that require individuals to judge the simultaneity of heartbeats and tones. In two experiments, we investigated the suitability of this paradigm for examining cardioception. In the first experiment, participants judged the simultaneity of near–threshold vibrations and suprathreshold tones. Precision in judging vibration–tone simultaneity was directly related to the detectability of the mechanical stimuli, thereby supporting use of the simultaneity paradigm to assess heartbeat detection. In the second experiment, we examined the influences of sensitivity to mechanical stimuli and the ability to make intermodality simultaneity judgments on the precision of heartbeat detection. We measured participants' vibrotactile thresholds, precision in judging light–tone simultaneity, and precision in judging heartbeat–tone simultaneity. The ability to judge the simultaneity of lights and tones accounted for 24.3% of the variance in precision of heartbeat detection, and mechanical sensitivity accounted for a further 8.5%.