Differential association of insulin resistance with cognitive and somatic symptoms of depression.

AIM: To examine the associations of depressive symptoms with insulin resistance, evaluating somatic and cognitive depressive symptoms separately. METHODS: A total of 328 individuals (mean age 60 years) referred for exercise stress testing, taking part in the Mechanisms and Outcomes of Silent Myocardial Ischemia study, completed the Beck Depression Inventory II. A fasting venous blood sample was collected for assessments of insulin and glucose level; the HOMA-IR (homeostatic model assessment of insulin resistance) was calculated. In principal component analysis, Beck Depression Inventory II items were forced to load onto two components (somatic and cognitive depressive symptoms). Adjusting for age, sex, BMI, medication use, smoking, physical activity, diabetes and cardiovascular disease, general linear model analyses were conducted to examine the associations between the components and log HOMA-IR . RESULTS: Principal component analysis showed that nine items loaded onto a cognitive depressive symptoms component and 10 items loaded onto a somatic depressive symptoms component. When examined separately, both components were significantly associated with log HOMA-IR however, when including both components simultaneously in the model, only somatic depressive symptoms remained significantly associated with log HOMA-IR. Back-transformed, a one-unit change in somatic depressive symptoms was associated with a 1.07 (95% CI 1.002, 1.14) change in HOMA-IR and a one-unit change in cognitive depressive symptoms was associated with a 1.03 (95% CI 0.97, 1.14) change in HOMA-IR. CONCLUSION: Somatic depressive symptoms seem to be more strongly associated with insulin resistance than do cognitive depressive symptoms. Monitoring somatic depressive symptoms may be more appropriate than monitoring cognitive depressive symptoms among depressed individuals with high insulin resistance.

Large-scale vibrating coil magnetometer for the magnetic characterization of bulk superconductors.

This work presents the design and validation of a vibrating coil magnetometer for the characterization of the field dependence of the critical current density of centimeter-sized bulk superconductors as an alternative to the destructive methods typically used. The magnetometer is also shown to be capable of measuring the magnetic moment in an applied field of up to 5 T for diverse magnetic materials, such as soft and hard ferromagnets and high-temperature superconducting pellets. The vibrating coil magnetometer was first optimized using finite element simulations and calibrated using a commercial vibrating sample magnetometer. The vibrating coil magnetometer was benchmarked with hysteresis measurements of a Nd2Fe14B disk made with a commercial hysteresisgraph, showing good agreement between the different setups. The magnetic hysteresis of a YBa2Cu3O7-x superconducting pellet was measured at 77 K, showing a penetration field of 1 T and an irreversibility field of 4 T. The field dependent critical current density of the superconductor was then inferred from the magnetic hysteresis measurements and extrapolated at low fields. Finally, the resulting critical current density was used to successfully reproduce the measured magnetization curve of the pellet at 2 T with finite element simulations.

Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation.

While several clinical studies have shown that HIV-1 infection is associated with increased permeability of the intestinal tract, there is very little understanding of the mechanisms underlying HIV-induced impairment of mucosal barriers. Here we demonstrate that exposure to HIV-1 can directly breach the integrity of mucosal epithelial barrier, allowing translocation of virus and bacteria. Purified primary epithelial cells (EC) isolated from female genital tract and T84 intestinal cell line were grown to form polarized, confluent monolayers and exposed to HIV-1. HIV-1 X4 and R5 tropic laboratory strains and clinical isolates were seen to reduce transepithelial resistance (TER), a measure of monolayer integrity, by 30-60% following exposure for 24 hours, without affecting viability of cells. The decrease in TER correlated with disruption of tight junction proteins (claudin 1, 2, 4, occludin and ZO-1) and increased permeability. Treatment of ECs with HIV envelope protein gp120, but not HIV tat, also resulted in impairment of barrier function. Neutralization of gp120 significantly abrogated the effect of HIV. No changes to the barrier function were observed when ECs were exposed to Env defective mutant of HIV. Significant upregulation of inflammatory cytokines, including TNF-alpha, were seen in both intestinal and genital epithelial cells following exposure to HIV-1. Neutralization of TNF-alpha reversed the reduction in TERs. The disruption in barrier functions was associated with viral and bacterial translocation across the epithelial monolayers. Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals.

New tree-ring data from Canadian boreal and hemi-boreal forests provide insight for improving the climate sensitivity of terrestrial biosphere models.

Understanding boreal/hemi-boreal forest growth sensitivity to seasonal variations in temperature and water availability provides important basis for projecting the potential impacts of climate change on the productivity of these ecosystems. Our best available information currently comes from a limited number of field experiments and terrestrial biosphere model (TBM) simulations of varying predictive accuracy. Here, we assessed the sensitivity of annual boreal/hemi-boreal forest growth in Canada to yearly fluctuations in seasonal climate variables using a large tree-ring dataset and compared this to the climate sensitivity of annual net primary productivity (NPP) estimates obtained from fourteen TBMs. We found that boreal/hemi-boreal forest growth sensitivity to fluctuations in seasonal temperature and precipitation variables changed along a southwestern to northeastern gradient, with growth limited almost entirely by temperature in the northeast and west and by water availability in the southwest. We also found a lag in growth climate sensitivity, with growth largely determined by the climate during the summer prior to ring formation. Analyses of NPP sensitivity to the same climate variables produced a similar southwest to northeast gradient in growth climate sensitivity for NPP estimates from all but three TBMs. However, analyses of growth from tree-ring data and analyses of NPP from TBMs produced contrasting evidence concerning the key climate variables limiting growth. While analyses of NPP primarily indicated a positive relationship between growth and seasonal temperature, tree-ring analyses indicated negative growth relationships to temperature. Also, the positive effect of precipitation on NPP derived from most TBMs was weaker than the positive effect of precipitation on tree-ring based growth: temperature had a more important limiting effect on NPP than tree-ring data indicated. These mismatches regarding the key climate variables limiting growth suggested that characterization of tree growth in TBMs might need revision, particularly regarding the effects of stomatal conductance and carbohydrate reserve dynamics.

Visualization of early intramembranous ossification by electron microscopic and spectroscopic imaging.

We present electron microscopic and electron spectroscopic images of putative nucleation sites and early mineral deposits during intramembranous ossification of the murine perichondrial ring. Electron spectroscopic imaging (ESI) permits the quantitative determination and direct visualization of spatial distribution of atomic elements within specimens at high spatial resolution. In this study ESI was used to determine the elemental distributions of phosphorus, sulfur, and calcium. Nucleation and subsequent mineralization in the perichondrial ring occurred sequentially along the longitudinal axis. Proximal regions of the ring contained a matrix with only a few nucleation sites that are characterized in conventional electron micrographs as small loci of low-density material in which dense particles are located. Elemental maps of these sites that we obtained by ESI reveal a sulfur-containing matrix in which localized concentrations of phosphorus occur. With further maturation the loci became centers for the genesis of numerous dense rods or crystals. These mineral deposits contained increased concentrations of P, S, and Ca, compared with the surrounding matrix. The appearance of S at nucleation sites and its persistence in developing mineral deposits suggests that a sulfur-containing moiety may serve as a locus within the osteoid matrix to attain high local concentrations of Ca and P, which leads to the controlled local formation of calcium phosphates. Calcification of the perichondrial ring has been found to occur in the absence of matrix vesicles, which illustrates that these membrane-bounded organelles are not obligatory sites for nucleation in this matrix.

The assessment of back muscle capacity using intermittent static contractions. Part II: validity and reliability of biomechanical correlates of muscle fatigue.

INTRODUCTION: In a previous paper, standard surface electromyographic (EMG) indices of muscle fatigue, which are based on the lowering of the median or mean frequencies of the EMG power spectrum in time, were applied during an intermittent absolute endurance test and were evaluated relative to criterion validity and test-retest reliability. The aims of this study were to assess mechanical and alternative EMG correlates of muscle fatigue. METHODS: Healthy subjects (44 males and 29 females; age: 20-55 yrs) performed three maximal voluntary contractions (MVC) and an endurance test while standing in a static dynamometer. Surface EMG signals were collected from four pairs of back muscles (multifidus at the L5 level, iliocostalis lumborum at L3, and longissimus at L1 and T10). The test, assessing absolute endurance (90 Nm torque), consisted of performing an intermittent extension task to exhaustion. Strength was defined as the peak MVC whereas our endurance criterion was defined as the time to reach exhaustion (Tend) during the endurance test. Mechanical indices quantifying physiological tremor and steadiness were computed from the dynamometer signals (L5/S1 extension moments) along with EMG indices presumably sensitive to variable load sharing between back muscle synergists during the endurance test. RESULTS: Mechanical indices were significantly correlated to Tend (r range: -0.47 to -0.53) but showed deceiving reliability results. Conversely, the EMG indices were correlated to Tend (r range: -0.43 to -0.63) with some of them particularly correlated to Strength (r=-0.72 to -0.81). In addition, their reliability results were acceptable (intra-class correlation coefficient >0.75; standard error of measurement <10% of the mean) in many cases. Finally, several analyses substantiated their physiological relevance. These findings imply that these new EMG indices could be used to predict absolute endurance as well as strength with the use of a single intermittent and time-limited (5-10min) absolute endurance test, a practical way to assess the back capacity of chronic low back pain subjects.

The assessment of back muscle capacity using intermittent static contractions. Part I - Validity and reliability of electromyographic indices of fatigue.

INTRODUCTION: Back muscle capacity is impaired in chronic low back pain patients but no motivation-free test exists to measure it. The aims of this study were to assess the reliability and criterion validity of electromyographic indices of muscle fatigue during an intermittent absolute endurance test. METHODS: Healthy subjects (44 males and 29 females; age: 20-55 yrs) performed three maximal voluntary contractions (MVC) and a fatigue test while standing in a static dynamometer. Surface EMG signals were collected from four pairs of back muscles (multifidus at the L5 level, iliocostalis lumborum at L3, and longissimus at L1 and T10). The fatigue test, assessing absolute endurance (90-Nm torque), consisted in performing an intermittent extension task to exhaustion. Strength was defined as the peak MVC whereas our endurance criterion was defined as the time to reach exhaustion (Tend) during the fatigue test. From the first five min (females) or ten min (males) of EMG data, frequency and time-frequency domain analyses were applied to compute various spectral indices of muscle fatigue. RESULTS: The EMG indices were more reliable when computed from the time-frequency domain than when computed from the frequency domain, but showed comparable correlation results (criterion validity) with Tend and Strength. Some EMG indices reached moderate to good correlation (range: 0.64-0.69) with Tend, lower correlations (range: 0.39-0.55) with Strength, and good to excellent between-day test-retest reliability results (intra-class correlation range: 0.75-0.83). The quantification of the spectral content more locally in different frequency bands of the power spectrum was less valid and reliable than the indices computed from the entire power spectrum. Differences observed among muscles were interpreted in light of specific neuromuscular activation levels that were observed during the endurance test. These findings supported the use of an intermittent and time-limited (5-10min) absolute endurance test, that is a practical way to assess the back capacity of chronic low back pain subjects, to assess absolute endurance as well as strength with the use of electromyographic indices of muscle fatigue.

The comparison of wavelet- and Fourier-based electromyographic indices of back muscle fatigue during dynamic contractions: validity and reliability results.

The purpose of this study was to compare the electromyographic (EMG) fatigue indices computed from short-time Fourier transform (STFT) and wavelet transform (WAV), by analyzing their criterion validity and test-retest reliability. The effect of averaging spectral estimates within and between repeated contractions (cycles) on EMG fatigue indices was also demonstrated. Thirty-one healthy subjects performed trunk flexion-extension cycles until exhaustion on a Biodex dynamometer. The load was determined theoretically as twice the L5-S1 moment produced by the trunk mass. To assess reliability, 10 subjects performed the same experimental protocol after a two-week interval. EMG signals were recorded bilaterally with 12 pairs of electrodes placed on the back muscles (at L4, L3, L1 and T10 levels), as well as on the gluteus maximus and biceps femoris. The endurance time and perceived muscle fatigue (Borg CR-10 scale) were used as fatigue criteria. EMG signals were processed using STFT and WAV to extract global (e.g, median frequency and instantaneous median frequency, respectively) or local (e.g., intensity contained in 8 frequency bands) information from the power spectrum. The slope values of these variables over time, obtained from regression analyses, were retained as EMG fatigue indices. EMG fatigue indices (STFT vs. WAV) were not significantly different within each muscle, had a variable association (Pearson's r range.: 0.06 to 0.68) with our fatigue criteria, and showed comparable reliability (Intra-class correlation range: 0.00 to 0.88), although they varied between muscles. The effect of averaging, within and between cycles, contributed to the strong association between EMG fatigue indices computed from STFT and WAV. As for EMG spectral indices of muscle fatigue, the conclusion is that both transforms carry essentially the same information.

Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

BACKGROUND: The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. AIMS AND METHODS: Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. RESULTS: Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. CONCLUSIONS: The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

The role of ischaemia and pain in the blood pressure response to exercise stress testing in patients with coronary heart disease.

Silent myocardial ischaemia is a common phenomenon in patients with coronary heart disease. However, very little is known about the underlying mechanisms of silent ischaemia. One potential pathway that may contribute to this absence of pain is increased blood pressure. The main aim of the current study was to assess the associations among blood pressure, pain and ischaemia in patients undergoing a standard exercise stress test. We hypothesized that patients who experienced chest pain during exercise would have lower baseline and peak blood pressures compared to those who did not experience chest pain. A total of 1,355 patients (418 women) who underwent a single-photon emission computed tomography treadmill exercise stress test and had not experienced a cardiac event in the past 2 weeks participated in the current study. Myocardial perfusion defects were assessed at rest and during the stress challenge. Systolic blood pressure (SBP), diastolic blood pressure, heart rate (HR) and rate pressure product (RPP) were assessed during rest and at peak exercise. There were no main effects of either pain or ischaemia on the baseline cardiovascular variables. Peak exercise data revealed main effects of pain on SBP, RPP and HR, and main effects of ischaemia on SBP and RPP, controlling for age, sex, baseline level, medication status and cardiac history. These findings suggest that acute rather than chronic increases in blood pressure may be one mechanism to explain the phenomena of silent myocardial ischaemia in cardiac patients, and may potentially provide a target for future treatment strategies.

Detection of exercise-induced myocardial ischemia from symptomatology experienced during testing in men and women.

BACKGROUND AND OBJECTIVES: To examine the capacity of angina and related symptoms experienced during exercise-stress testing to detect the presence of ischemia, controlling for other clinical factors. METHOD: The authors undertook a prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. One hundred forty-six women and 127 men reported chest pain, and of these, 25% of women and 66% of men had myocardial perfusion imaging evidence of ischemia during testing. The present article focuses on patients with chest pain during testing. MAIN OUTCOME MEASURES: Outcome measures included chest pain localization, extension, intensity and quality, as well as the presence of various nonpain-related symptoms. Backward logistical regression analyses were performed separately on men and women who had experienced chest pain during testing. RESULTS: Men who described their chest pain as 'heavy' were 4.6 times more likely to experience ischemia during testing (P=0.039) compared with other men, but this pain descriptor only slightly improved accuracy of prediction beyond that provided by control variables. In women, several symptoms added to the sensitivity of the prediction, such as a numb feeling in the face or neck region (OR 4.5; P=0.048), a numb feeling in the chest area (OR 14.6; P=0.003), muscle tension (OR 5.2; P=0.013), and chest pain that was described as hot or burning (OR 4.3; P=0.014). CONCLUSIONS: A more refined evaluation of symptoms experienced during testing was particularly helpful in improving detection of ischemia in women, but not in men. Attention to these symptoms may favour timely diagnosis of myocardial perfusion defects in women.

Gender influence on fatigability of back muscles during intermittent isometric contractions: a study of neuromuscular activation patterns.

BACKGROUND: Gender difference in the fatigability of muscles can be attributed to muscle mass (or strength) and associated level of vascular occlusion, substrate utilization, muscle composition, and neuromuscular activation patterns. The purpose of this study was to assess the role of neuromuscular activation patterns to explain gender differences in back muscle fatigability during intermittent isometric tasks. METHODS: Sixteen males and 15 females performed maximal voluntary contractions (Strength) and a fatigue test to exhaustion (fatigue criterion=time to exhaustion), while standing in a static dynamometer measuring L5/S1 extension moment. The fatigue test consisted of repetitions of an 8-s cycle (1.5 s ramp to reach 40% of maximal voluntary contraction +5s plateau at 40% of maximal voluntary contraction +1.5s rest). Surface electromyography signals were collected bilaterally from 4 back muscles (multifidus at the L5 level, iliocostalis lumborum at L3, and longissimus at L1 and T10). FINDINGS: Males were stronger (P<0.05) than females (316, SD 82>196, SD 25 Nm) but showed significantly shorter time-to-exhaustion values (7.1, SD 5.2<13.0, SD 6.1 min.), the latter result being corroborated by electromyographic indices of fatigue. However, the gender effect on time to exhaustion disappeared when accounting for Strength, thus supporting the muscle mass hypothesis. Among the various electromyographic indices computed to assess neuromuscular activation patterns, the amount of alternating activity between homolateral and between contralateral muscles showed a gender effect (females>males). INTERPRETATION: These results support the muscle mass hypothesis as well as the neuromuscular activation hypothesis to explain gender differences in back muscle fatigability.

Altered plasma membrane ultrastructure in multidrug-resistant cells.

Multidrug resistance is mediated by P-glycoprotein, an integral plasma membrane component which is thought to function as a drug export pump. This model can explain drug resistance, but fails to account for the broader pleiotropy of the multidrug resistance phenotype. We report here a freeze-fracture study revealing increases in the densities of protoplasmic face intramembrane particles in multidrug-resistant Chinese hamster ovary (CHO) and human leukemic cells. The intramembrane particle density in a CHO cell revertant which had lost the characteristics of the multidrug resistance phenotype was indistinguishable from that of the drug-sensitive parental cell line. This demonstration of a global multidrug resistance-linked change in plasma membrane architecture may have significant implications for understanding the variety of concurrent membrane-related changes which are not easily explained by the current model for multidrug resistance.

Technetium-99m sestamibi tomography in patients with spontaneous chest pain: correlations with clinical, electrocardiographic and angiographic findings.

The sensitivity and specificity of technetium-99m hexakis-2-methoxy-2-isobutyl-isonitrile (sestamibi) single-photon emission computed tomographic (SPECT) imaging for the diagnosis of coronary artery disease were studied in 45 patients admitted to the hospital for clinical suspicion of unstable angina. Only patients without prior myocardial infarction were included and all patients had technetium-99m sestamibi injection and a 12-lead electrocardiogram (ECG) during and less than or equal to 4 h after an episode of chest pain. Coronary angiography performed in all patients during hospitalization showed significant coronary artery disease (greater than or equal to 50% luminal diameter reduction) in 26 of the 45 patients. The SPECT studies obtained after injection of technetium-99m sestamibi during an episode of spontaneous chest pain showed a sensitivity of 96% for the detection of coronary artery disease; the 12-lead ECG obtained at the time of the injection had a sensitivity of 35%. With the patient in the pain-free state, respective sensitivity values were 65% and 38%. Specificity for the radionuclide study was 79% during pain and 84% in the pain-free state; for the ECG, it was 74% both during and between episodes of pain. The site of the perfusion defect corresponded to the most severe coronary artery lesion in 88% of patients. The severity of the perfusion defect correlated with the extent of coronary artery disease: the defect score was 5.3 +/- 3.3 with one-vessel disease, 4.9 +/- 2.8 with two-vessel disease and 10.5 +/- 5.0 with three-vessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the paraspinal muscles of subjects presenting an idiopathic scoliosis: an EMG pilot study.

BACKGROUND: It is known that the back muscles of scoliotic subjects present abnormalities in their fiber type composition. Some researchers have hypothesized that abnormal fiber composition can lead to paraspinal muscle dysfunction such as poor neuromuscular efficiency and muscle fatigue. EMG parameters were used to evaluate these impairments. The purpose of the present study was to examine the clinical potential of different EMG parameters such as amplitude (RMS) and median frequency (MF) of the power spectrum in order to assess the back muscles of patients presenting idiopathic scoliosis in terms of their neuromuscular efficiency and their muscular fatigue. METHODS: L5/S1 moments during isometric efforts in extension were measured in six subjects with idiopathic scoliosis and ten healthy controls. The subjects performed three 7 s ramp contractions ranging from 0 to 100% maximum voluntary contraction (MVC) and one 30 s sustained contraction at 75% MVC. Surface EMG activity was recorded bilaterally from the paraspinal muscles at L5, L3, L1 and T10. The slope of the EMG RMS/force (neuromuscular efficiency) and MF/force (muscle composition) relationships were computed during the ramp contractions while the slope of the EMG RMS/time and MF/time relationships (muscle fatigue) were computed during the sustained contraction. Comparisons were performed between the two groups and between the left and right sides for the EMG parameters. RESULTS: No significant group or side differences between the slopes of the different measures used were found at the level of the apex (around T10) of the major curve of the spine. However, a significant side difference was seen at a lower level (L3, p = 0.01) for the MF/time parameter. CONCLUSION: The EMG parameters used in this study could not discriminate between the back muscles of scoliotic subjects and those of control subject regarding fiber type composition, neuromuscular efficiency and muscle fatigue at the level of the apex. The results of this pilot study indicate that compensatory strategies are potentially seen at lower level of the spine with these EMG parameters.

Effect of reperfusion on 111In-antimyosin monoclonal antibody uptake by salvaged and necrotic myocardium in the dog.

OBJECTIVE: The aim was to investigate the ability of 111In-antimyosin monoclonal antibody (111In-AMA) to differentiate between salvaged and necrotic myocardium following reperfusion. METHODS: Dogs submitted to a 24 h left anterior descending coronary artery occlusion (group 1, n = 10) or to a 90 min occlusion followed by a 22.5 h reperfusion (group 2, n = 11, group 3, n = 5) were given radiolabelled microspheres and 111In-AMA after 75 min of ischaemia (groups 1 and 2), or after 19.5 h of reperfusion (group 3). After delimiting the area at risk and the infarct by dye perfusion and triphenyltetrazolium chloride, the heart slices were imaged by scintigraphy and dissected into necrotic, viable ischaemic, and normal myocardium. Myocardial blood flow was estimated by microspheres and 111In-AMA uptake was expressed as the ratio of the corresponding non-ischaemic tissue samples taken from opposite ventricular wall. RESULTS: 111In-AMA ratios in necrotic and salvaged myocardium were respectively 5.4(SEM 1.9) and 3.2(0.5) times the normal value, giving a 1.7 to 1 factor between the two areas in dogs with permanent occlusion (group 1). Similar results were obtained in group 3 with ratios of 6.1(1.1) and 3.0(0.3) times normal values. In contrast, ratios of 43.6(5.6) and 5.6(0.9) (p < 0.05) in necrotic and salvaged myocardium, respectively, were found in reperfused group 2, giving a 7.8 to 1 factor between the two tissue areas of the risk territory. Clear delineation between salvaged and necrotic tissue territories could be made on scintigrams only in group 2, which otherwise presented smaller infarcts: 35.1(7.9)% of the risk area v 58.0(8.7)% in non-reperfused animals (p < 0.05). 111In-AMA uptake by necrotic myocardium did not correlate with collateral (group 1) or reperfusion blood flows (group 3), indicating that the greater uptake in reperfused myocardium is flow independent. CONCLUSIONS: 111In-AMA does not clearly identify necrotic from viable ischaemic myocardium within 24 h of injection in a coronary artery occlusion model. Thus it may not be a sensitive enough method to evaluate infarct size progression. However, reperfusion greatly increased 111In-AMA uptake by the infarct in a flow independent manner, this may prove to be useful for clinical assessment of infarct size and reperfusion injury.

Effects of sino-atrial ischaemia on the heart rate response to phasic burst stimulation of the right cervical vagus in the dog.

The effects of occluding sinus node arteries on the pacemaker responses to graded phasic burst stimulation of the right cervical vagus were studied in anaesthetised dogs. In six dogs (Group I), phase response curves (vagally affected atrial cycle plotted against the phase of the stimulus in the cycle) to 1, 3 and 5 pulse burst stimulations were determined at control and hourly for 3 h after the occlusion. In four dogs, the occlusion produced a slowing of the heart rate, a shift of pacemaker outside sinus node region and a displacement of the phase response curves upward and to the right. Identical stimulation bursts resulted in significantly longer atrial cycles than at control, and bursts introduced with a longer phase remained effective and resulted in significantly longer atrial cycles than the maximum one reached at control. However, when the vagal responses were corrected for occlusion-induced changes in spontaneous PP intervals, the occlusion was found not to significantly affect the vagal responses except to increase their variability. Time-related differences in the effects of the occlusion were not statistically significant. In six control dogs (Group II) submitted to the same protocol, occlusion excepted, the vagal response curves changed very little over the 3 h experiments, thus confirming the stability of the experimental preparation used and of the vagal responses obtained in the absence of ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular organization at the epiphyseal-metaphyseal junction of growing rats.

The microarchitecture of the rat metaphyseal nutrient artery, the major blood supply to the calcifying epiphyseal growth plate, was studied by light microscopic serial sections, model reconstruction of serial sections, and scanning electron microscopy of plastic corrosion castings. These techniques illustrate how the metaphyseal artery undergoes extensive arborization and anastomosis upon route through the metaphysis. From this vascular network, closed capillary sprouts abut hypertrophic chondrocytes bordered by scaffolds of mineralized matrix.

Aluminum intoxication in vitamin D-deficient rats: studies of bone aluminum localization and histomorphometry before and after vitamin D repletion.

Aluminum accumulation by both dialysis patients and nonuremic patients, requiring chronic total parenteral nutrition, may be an etiological factor in the development of severe osteomalacia. To study the role of aluminum toxicity in bone, further experiments have been conducted in the nonuremic, vitamin D-deficient rat. Weanling rats were raised on vitamin D-deficient diets, and half received parenteral aluminum (5 mg/wk), for 30 days. In the first experiment low doses of 25-OH cholecalciferol (500 ng/week) were given subcutaneously for a further 30 days. Control rats were maintained on a similar protocol, but were supplemented with cholecalciferol (5 micrograms/week) from the outset until sacrifice at 60 days. In the second experiment a single bolus of cholecalciferol (5 micrograms) was given to study short-term changes in serum biochemistry and bone histology at 96 hr. Quantitative bone histomorphometric analyses of the proximal tibial metaphysis were made in all experimental groups. In the experimental vitamin D-deficient group, with the highest bone aluminum content (as assessed by extraction of whole bone aluminum), X-ray microanalysis was performed to determine the distribution of aluminum in bone tissue and bone cell organelles. The results showed that control rats treated with prolonged aluminum therapy (30 mg over 60 days) had evidence of both reduced osteoid matrix synthesis and mineralization. However, in vitamin D-deficient rats, there was no evidence that aluminum exacerbated the osteomalacic lesion, even though there was histochemical evidence of aluminum deposition at the bone-osteoid interface.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment of the primary structure of the major lipid-dependent Ca2+ binding proteins of chicken growth plate cartilage matrix vesicles: identity with anchorin CII (annexin V) and annexin II.

Electron microscopic studies of calcifying vertebrate tissues reveal the locus of de novo mineral formation within matrix vesicles (MV). The direct involvement of MV in the initiation of mineral formation is supported by the fact that MV isolated from avian growth plate cartilage rapidly accumulate large amounts of Ca2+ and P(i) and induce mineral formation. Exploration of the constituents of MV has revealed two major protein components, a 33 and a 36 kD protein, the former of which binds to cartilage-specific collagens. These annexin-like proteins bind to acidic phospholipids in the presence of submicromolar levels of Ca2+. Antibodies raised against both the purified 33 and the 36 kD MV annexin do not cross-react with the other, indicating that they are distinct proteins. Reported here are studies elucidating the primary structure of both MV proteins using both conventional protein and molecular biologic methods. These studies establish that the 33 kD protein is nearly identical to anchorin CII (annexin V) and that the 36 kD protein is identical to avian annexin II. Immunolocalization studies show that hypertrophic chondrocytes at the calcification front of avian growth plate contain the highest level of these annexins. Further, immunogold labeling indicates that the annexins are localized within MV isolated from the growth plate. Recent studies indicate that annexin V is a new type of ion-selective Ca2+ channel protein that possesses selective collagen binding properties. Since MV are tightly associated with the collagen- and proteoglycan-rich matrix, it is tempting to speculate that this MV protein may be a component of stretch-activated ion channels that enhance Ca2+ uptake during mechanical stress.