Endocrine and immune responses to resistance training in prostate cancer patients.

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

[Aortic root enlargement in elderly patients].

From January 2003 to June 2005, 12 elderly patients with severe aortic stenosis underwent aortic root enlargement (ARE) by Nicks procedure. Their ages ranged from 74 to 87 with a mean of 79.3. Stented bioprosthesis were used in 11 cases. There was no death. Cardiothoracic ratio on chest X-ray decreased from 59.4 to 53.6% and New York Heart Association (NYHA) functional class improved from 3.4 to 1.3. Echocardiography also showed remarkable improvement, in peak pressure gradient (PG) from 98.3 to 20.7 mmHg, in left ventricular mass index (LVMI) 181 to 137 g/m2. LVM and LVMI regression rates were 25.3 and 22.3%, respectively. Comparative study of those with ARE alone and those with combined operation showed much hazardous effect in the latter, but no significant difference in echocardiographic findings postoperatively. ARE by Nicks procedure, if it could be performed without concomitant procedure, is a safe and effective option also in elderly patients with small aortic annulus.

Characterization of the mutational specificity of DNA cross-linking mutagens by the Lac+ reversion assay with Escherichia coli.

The mutational specificities of DNA cross-linking compounds such as cisplatin, transplatin, carboplatin, mitomycin C, psoralen, and 8-methoxypsoralen were investigated in lacZ reversion assay systems of Escherichia coli. Tester strains were constructed by introducing the six kinds of F' plasmids (lacI-, lacZ461, and proAB+), each of which carries a different base-substitution mutation within the lacZ gene. Each of the six possible base-substitution mutations was assayed by Lac+ reversion. Cisplatin induced G.C-->A.T transitions and G.C-->T.A transversions, with the former predominating. Transplatin induced A.T-->G.C transitions in addition to G.C-->A.T transitions and G.C-->T.A. Carboplatin weakly induced G.C-->A.T transitions. On the other hand, mitomycin C induced only G.C-->T.A transversions, while psoralen and 8-methoxypsoralen reactivated with near-UV irradiation induced A.T-->G.C transitions preferentially. The Lac(+) reversion system was very convenient for rapidly determining mutational spectra.

Immediate contact hypersensitivity induced by repeated hapten challenge in mice.

An immediate reaction was investigated during repeated challenge testing for contact hypersensitivity to dinitrofluorobenzene (DNFB) in BALB/c mice. The mice were sensitized to DNFB on back skin and repeatedly challenged with the same hapten on the left ear at 1 week intervals. The ear after the 5th challenge showed biphasic responses which consisted of an immediate and a delayed-type reaction. The reactions were hapten specific. Mast cell-deficient WBB6F1 W/WV mice did not show any immediate reaction, while congenic normal mice showed both immediate and delayed-type reactions. Histologically, numerous dermal mast cells were found in the left ear of repeatedly challenged BALB/c and WBB6F1 normal mice, while there were few mast cells in the ear of WBB6F1 W/WV mice. Anti-DNP IgE antibodies were detected in BALB/c, WBB6F1 normal and W/WV mice after repeated challenge with DNFB. Intradermal injection of anti-IgE antibodies in the repeatedly DNFB-challenged ear elicited an immediate reaction. These results suggest that immediate contact hypersensitivity develops through the production of anti-DNP IgE antibodies and an increase in dermal mast cells after repeated challenge with DNFB.

Evaluation for roles of nitric oxide generated in the anteroventral third ventricular region in controlling vasopressin secretion and cardiovascular system of conscious rats.

OBJECTIVE: To examine local actions of nitric oxide (NO) on the neural mechanisms controlling the release of vasopressin (AVP) and the cardiovascular system in the anteroventral third ventricular region (AV3V), a pivotal area for autonomic functions, and to pursue the problem of whether it may have any role in the AVP and cardiovascular responses evoked by plasma hypertonicity or by increased prostaglandin E(2) (PGE(2)) in the AV3V - one possible factor implicated in osmotic responses. METHODS: We infused NO-related agents into the AV3V, its adjacent area, the nucleus of the vertical limb of the diagonal band (VDB), or into the lateral cerebral ventricle of conscious rats, monitoring effects on plasma AVP, osmolality, sodium, potassium and chloride, arterial pressure and heart rate in the presence or absence of an osmotic or PGE(2) stimulus. The infusion sites were determined histologically. RESULTS: Infusion of L-arginine, the substrate of NO synthase (NOS), into the AV3V structures such as the median preoptic nucleus and periventricular nucleus produced dose-related increases in plasma AVP, arterial pressure and heart rate 5 or 15 min later, whereas infusion of D-arginine (which is not a substrate for NO synthesis) was without significant effect on these variables. Plasma osmolality or electrolytes were not changed by these treatments. The AV3V infusion of sodium nitroprusside (SNP), a spontaneous releaser of NO, also induced dose-dependent augmentations of plasma AVP, without evoking remarkable alteration in the cardiovascular parameters. The infusion of L- or D-arginine into the VDB affected none of the variables significantly. When applied intracerebroventricularly, L-arginine caused only increases in plasma AVP, whereas SNP caused only reductions in arterial pressure, leaving other variables at stable values. The effects of AV3V L-arginine on plasma AVP and the cardiovascular variables were abolished by N(G)-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of NOS, applied 15 min before. In contrast, infusion of L-NAME to the AV3V did not exert a significant effect on the responses of plasma AVP or cardiovascular variables to AV3V application of PGE(2) or i.v. infusion of hypertonic NaCl. The infusion of L-NAME alone did not affect plasma variables including AVP, although it tended to increase basal arterial pressure and heart rate. CONCLUSION: These results suggest that NO generated in or near the AV3V may act to enhance AVP release, arterial pressure and heart rate, but it may not play an essential role in eliciting the responses of these variables to osmotic or PGE(2) stimuli.

Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans.

To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1beta) and interferon gamma (IFN-gamma) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-alpha and tumour necrosis factor alpha (TNF-alpha) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-beta) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.

Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

The usefulness of [131I]-metaiodobenzylguanidine ([131I]-MIBG) scintigraphy performed one week after administration in diagnosing pheochromocytoma.

BACKGROUND: Imaging performed 36-48 h after metaiodobenzylguanidine (MIBG) injection is being widely used in the diagnosis of pheochromocytoma. However, there are some difficult cases to diagnose due to a high concentration of MIBG remaining in the background. We studied the significance of scans on the 7th day after MIBG injection when the concentration of MIBG in the background has declined. METHODS: Imaging was carried out on 11 cases before operation, five cases (eight times) after operation and 12 cases which had been strongly suspected of being pheochromocytoma, but later proved to be non-pheochromocytoma. RESULTS: In all the cases of pheochromocytoma, except one, the tumor imaging was clear 24-72 h after MIBG injection. As for the images after operation and those of the 12 non-pheochromocytoma cases, the scintigram made on the 7th day proved the negative pheochromocytoma. CONCLUSION: This approach was very effective not only for finding early small pheochromocytomas and the remnants of tumors after resection, but also in diagnosing non-pheochromocytoma.

Pyruvate augments mechanical function via activation of the pyruvate dehydrogenase complex in reperfused ischemic immature rabbit hearts.

BACKGROUND: Reperfusion of ischemic adult hearts is associated with increased fatty acid oxidation, reduced pyruvate oxidation, and reduced pyruvate dehydrogenase (PDH) activity, leading to a decrease in cardiac efficiency. These effects may be amplified in newborn hearts because of the immaturity of their PDH pathway. We hypothesize that pyruvate can augment mechanical function in the immature heart by activating the PDH complex (PDC) during reperfusion in severely ischemic hearts. MATERIALS AND METHODS: Seven-day old isolated working rabbit hearts (n = 12) were perfused with modified Krebs solution containing 0.4 mM palmitate. Pyruvate (5 mM) was added for a 10-min period either before or after a 30-min period of normothermic global ischemia. Cardiac functional indices before global ischemia and during reperfusion were correlated with active and total PDC activity measured in 28 additional hearts frozen at the various time points throughout the perfusion protocol. RESULTS: Addition of pyruvate before ischemia increased the proportion of active PDC but did not affect any measured functional indices. During early reperfusion, aortic flow, cardiac output, and cardiac work were all significantly depressed compared to preischemic values. Addition of pyruvate significantly increased the proportion of active PDC and was also associated with a significant increase in aortic flow, cardiac work, and developed pressure. Removal of pyruvate from the perfusate resulted in a subsequent significant decrease in PDC activity and these functional parameters. CONCLUSION: During reperfusion of neonatal rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC.

[A case report: successful treatment of acute type B aortic dissection with renal and leg ischemia].

A 56-year-old patient of acute type B aortic dissection with renal and leg ischemia successfully underwent emergency replacement of the descending thoracic aorta. Prior to this operation, we reperfused the ischemic legs in a controlled manner using a cardiopulmonary bypass circuit. This controlled limb reperfusion method could reduce reperfusion injury. Postoperatively, the patient also suffered from renovascular hypertension due to stenosis of the right renal artery. Renal stent angioplasty, performed 10 days after the operation, stabilized his blood pressure. Controlled limb reperfusion and renal stent angioplasty may be useful for managing branch complications associated with aortic dissection.

Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise.

To investigate the cause of disagreement within the large body of literature concerning the effect of exercise on the capacity of circulating neutrophils to produce reactive oxygen species (ROS), 10 male endurance-trained athletes underwent maximal exercise. The generation of superoxide radical (O2-.) by neutrophils was first detected on a cell-by-cell basis by using histochemical nitro blue tetrazolium tests performed directly on fresh unseparated blood, which showed that responsive neutrophils under several stimulatory conditions relatively decreased after exercise. Similarly, O2-. detected with bis-N-methylacridinium nitrate (lucigenin)-dependent chemiluminescence (CL) of a fixed number of purified neutrophils on stimulation with opsonized zymosan was decreased slightly after exercise. In contrast, the 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-dependent CL response of the neutrophils indicative of the myeloperoxidase (MPO)-mediated formation of highly reactive oxidants was significantly enhanced after exercise. It therefore suggests that the pathway of neutrophil ROS metabolism might be forwarded from the precursor O2-. production to the stages of more reactive oxidant formation due to the facilitation of MPO degranulation. In addition, these phenomena were closely associated with the exercise-induced mobilization of neutrophils from the marginated pool into the circulation, which was mediated by the overshooting of catecholamines during exercise. These findings indicate that the use of different techniques for detecting ROS or the different stages of neutrophil ROS metabolism could explain some of the disparate findings of the previous studies.

[Estimation of catecholamine release based on dialyzer clearance rate during hemodialysis].

To estimate catecholamine (CA) release during hemodialysis (HD), plasma-free and conjugated CAs and their dialyzer clearance rates were measured in 10 HD patients (age; 49.8 +/- 15.2 years, duration of HD; 5.8 +/- 5.0 years). Although free dopamine (f-DA) and all conjugated CAs decreased to about one half of the pre-HD levels at the end of HD, no significant change was seen in free norepinephrine (f-NE) and epinephrine (f-E) during HD. For every CA, the clearance rate was the highest in the sulfate and the lowest in the glucuronide form, and NE was the highest in every form. In the comparison between the measured CA and calculated CA using the clearance rate and the pre-HD level, the measured values of f-NE and f-E were significantly higher than the calculated values, unlike the results for f-DA and conjugated CAs. The difference in f-NE between the measured and the calculated values correlated negatively with the change in mean blood pressure (delta MBP), and delta MBP was also correlated with the ultrafiltration volume. From these data, it was suggested that f-NE was released by the decrease of MBP due to the increase of ultra-filtration volume during HD.

[Effects of oral alpha 2 adrenergic agonists, clonidine and tizanidine, on tetracaine spinal anesthesia].

This study was conducted to evaluate the effects of oral clonidine and tizanidine, alpha 2 adrenergic agonists, as premedication for tetracaine spinal anesthesia in 63 gynecological patients. The patients were randomly allocated to one of six groups. Group 1 (n = 7), group 2 (n = 8) and group 3 (n = 7) received 13 mg of tetracaine intrathecally in 10 % glucose solution 2.6 ml. Group 4 (n = 13), group 5 (n = 14) and group 6 (n = 13) received 13 mg of tetracaine intrathecally in a volume of 2.6 ml of 10 % glucose solution which contained 0.65 mg of phenylephrine. As premedication, group 1 and 4 received 0.25 mg of oral triazolam; group 2 and 5 received 3 mg of oral tizanidine; group 3 and 6 received 0.15 mg of oral clonidine. Group 2 and 3, or group 5 and 6 (clonidine or tizanidine group, respectively) needed significant longer time for regression of Th10 sensory blockade than group 1 or 4 (triazolam). The time for appearance of postoperative pain and the time to require postoperative analgesics were longer in the groups which had received either clonidine or tizanidine than in the groups which had received triazolam. Heart rate and systolic blood pressure in group 6 (clonidine-tetracaine-phenylephrine group) showed significant decreases (P < 0.05) after the spinal anesthesia. We concluded that oral premedication of clonidine and tizanidine prolonged tetracaine spinal anesthesia. From the view point of the prolongation of spinal anesthesia and the hemodynamic stability, oral premedication with tizanidine seems to be useful.

Blood coagulation and fibrinolytic activity during femoral neck prosthetic replacement using bone cement.

To assess the blood coagulative and fibrinolytic responses during cemented femoral neck replacement, we measured these parameters in 9 patients, including anti-thrombin III (AT-III), prothrombin time (PT) and activated partial thromboplastin time (APTT) before surgery, just before packing bone cement and after the insertion of the prosthesis. We also measured thrombin-anti-thrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC), and D-dimer. A significant increase in APTT, and decrease in AT-III and PT were observed before the insertion of bone cement and prosthesis. The value of TAT and D-dimer increased significantly after the insertion of the prosthesis, but there were no significant changes in PIC. The data suggest that blood coagulation is activated after the insertion of bone cement and prosthesis into the femoral shaft, and in addition, the fibrinolysis is also accelerated secondary to the activation of the coagulation. Further investigations are needed to establish whether the activation of the coagulation induced by the cemented replacement exerts a great influence on the appearance of pulmonary thrombosis or circulatory depression.

Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on the osmotic release of vasopressin in conscious rats.

The aim of the present study was to evaluate a role in vasopressin secretion of the catecholaminergic neurons, including the tuberohypophysial dopaminergic neurons situated in the arcuate hypothalamic nucleus. A neurotoxin, 6-hydroxydopamine (6 g/l), was injected locally into the arcuate nucleus and its effects on catecholamine levels of the hypothalamic tissue and the neurointermediate lobe, and on the plasma vasopressin concentrations before and during i.v. infusion (0.1 ml kg-1 min-1) of isotonic (0.15 mol/l) or hypertonic saline (2.5 mol/l), were examined in conscious rats. The infusion of hypertonic saline produced increases of plasma vasopressin 15 and 30 min later, accompanied by elevations of plasma osmolality, sodium, chloride and arterial pressure. The vasopressin response was potentiated markedly by the 6-hydroxydopamine injection performed 8 days before, which hardly affected the responses of the other variables. Histological examination indicated that the injection sites of 6-hydroxydopamine in those rats had been located in the area ranging from rostral to medial arcuate nucleus. The i.v. infusion of isotonic saline did not change plasma vasopressin, osmolality, sodium, chloride or arterial pressure, regardless of the presence or absence of pretreatment with 6-hydroxydopamine. It was confirmed that when 6-hydroxydopamine was injected into the arcuate nucleus region 8 days before, noradrenaline and adrenaline concentrations of the hypothalamic tissue containing the injection site were decreased remarkably, although we could not detect any significant alteration in the dopamine concentration of the hypothalamic tissue or the neurointermediate lobe. On the basis of these results, we concluded that catecholaminergic neurons in the arcuate nucleus may act to inhibit osmotic vasopressin secretion.

The utility of MRI in acute stage of carbon monoxide poisoning.

Intracranial abnormalities by magnetic resonance imaging (MRI) in acute carbon monoxide (CO) poisoning have been described in two cases. Edematous bilateral lesions have been demonstrated in the globus pallidus. Findings correspond with the pathological changes described in literature. In our experience MIR is a more sensitive examination compared to serial computed tomography (CT) in acute CO poisoning.

[Continuous infusion of ketamine and midazolam for prolonged sedation in the intensive care unit].

The clinical effects and pharmacokinetics of ketamine and midazolam, administered continuously for prolonged sedation were studied in 7 critically ill patients under mechanical ventilation. Initially ketamine 1 mg.kg-1 and midazolam 0.1 mg.kg-1 were administered intravenously and these were followed by infusion at a rate of 1.0 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam. The infusion rate was changed every 30 minute with increments of 0.5 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam until the sedative score by Ramsy RAE reached rank 4 (i.e. slow response to loud verbal commands). The plasma concentrations of ketamine were analyzed using high performance liquid chromatography and those of midazolam using gas chromatography. The mean maintenance doses of ketamine and midazolam were 2.25 +/- 0.61 mg.kg-1.hr-1 and 0.11 +/- 0.05 mg.kg-1.hr-1 (mean +/- SD), respectively. There were no significant changes in blood pressure or heart rate before and after the injection of ketamine and midazolam in all the patients. The plasma concentrations of ketamine and midazolam were 2.98 +/- 0.20 micrograms.ml-1 and 494.1 +/- 66.7 ng.ml-1, respectively. The time to clear response to verbal commands after cessation of the continuous infusion was 168 +/- 109 min. The plasma concentrations of ketamine and midazolam decreased rapidly, and plasma half-life of ketamine was about 1 hour and for midazolam less than 2 hours. In conclusion, continuous infusion of ketamine and midazolam was very useful to sedate critically ill patients under mechanical ventilation, with minimal effect on the cardiovascular system and rapid recovery of consciousness.