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At least 307 records · Page 17Linked to original sources
PubMed1998

Rate adaptation of QT intervals during and after exercise in children with congenital long QT syndrome.

OBJECTIVES: To improve the diagnostic criteria of the congenital long QT syndrome in borderline cases we examined rate adaptation of ventricular repolarization phases during exercise and subsequent recovery in children with the long QT syndrome and controls. METHODS: Nineteen children with definite long QT syndrome and 19 healthy controls underwent exercise testing. QT intervals were measured to the apex (early QT), to the end (total QT) and from apex to the end of the T wave (late QT) at heart rates from 90 by steps of 10 to 150 beats, min-1. RESULTS: In 11/19 long QT syndrome patients (61%) and 2/19 controls (12%) the total QT lengthened during the recovery phase compared with exercise (P = 0.005) at the lowest comparable heart rate. No difference was found between the groups during exercise. The sensitivity of rate adaptation of repolarization intervals was analysed by calculating linear regression slopes relating the QT intervals to the heart rates. During recovery, slopes relating the total QT to heart rate were steeper in long QT syndrome patients than those in controls (-2.50 +/- 0.82 vs -1.79 +/- 0.47, P = 0.003). Total QT/heart rate slopes differed between exercise and recovery phases in the long QT syndrome group only (-1.77 +/- 0.71 vs 2.50 +/- 0.82, P = 0.009). In long QT syndrome patients, the difference in total QT/heart rate slopes was mainly because the late QT/heart rate slopes indicating inhomogeneity of repolarization were steeper during recovery (-1.27 +/- 0.74) than during exercise (-0.46 +/- 0.29, P < 0.0001). CONCLUSIONS: After exercise in long QT syndrome children the QT interval lengthens abnormally and inhomogeneity of repolarization increases. Evaluation of the QT interval, and especially its late portion after exercise, may help in establishing the diagnosis of long QT syndrome.

Adaptation, Physiological↗
PubMed1997

Bisphosphonate modulates proliferation and differentiation of rat periodontal ligament cells during wound healing.

BACKGROUND: Periodontal ligament (PL) width is precisely maintained throughout the lifetime of adult mammals, but the biological mechanisms that regulate the spatial locations of the cell populations for bone, cementum, and PL are unknown. METHODS: As bisphosphonates induce ankylosis in mouse molar teeth, we used ethane-1-hydroxy-1, 1-bisphosphonate-(HEBP, Etidronate; Didronel) in combination with a periodontal window wound model to identify those cell populations involved in the regulation of PL width during the reformation of cellular domains after wounding. Four groups of Wistar rats were wounded by drilling through the alveolar bone and extirpation of the PL. Rats were administered HEBP for 1 week and then sacrificed or allowed to recover for an additional week prior to sacrifice. Control rats were sacrificed after 1 or 2 weeks. One hour prior to sacrifice, rats were injected with 3H-thymidine to label proliferating cells. Tissue sections were immunohistochemically stained for osteopontin (OPN) or bone sialoprotein (BSP) or were prepared for in situ hybridization (BSP) to identify extra- and intracellular expression of these non-collagenous bone proteins associated with periodontal healing. RESULTS: HEBP treatment for 1 week induced a twofold increase in the thickness of the alveolar bone matrix in which weak immuno-staining for OPN and BSP mRNA signal was seen. During the recovery phase the increased bone width was reduced but was still considerably thicker than in control (P < 0.001). OPN staining as well as the BSP mRNA signal were much more intense than at 1 week. HEBP induced a > 40% reduction of PL width which returned to normal dimensions following the recovery phase. HEBP also modulated PL cell proliferation and differentiation: PL cell counts and labelling indices were reduced fivefold after 1 week of HEBP but returned to control values after the recovery phase. In controls, PL cells did not express OPN and BSP, but after HEBP treatment, and particularly after the recovery phase, PL cells expressed both of these markers intensely. In contrast, gingival and pulp connective tissues that were contiguous with the PL were not stained for OPN and did not express BSP mRNA after HEBP treatment. CONCLUSIONS: While wounding induced transient increases of proliferation which were followed by repopulation of the extirpated tissue, the effects of HEBP on cell differentiation were independent of wounding. HEBP modulates the differentiation of PL cells and recruits cells that contribute to alveolar bone formation and loss of PL width homeostasis. Conceivably, bisphosphonates could be used therapeutically to selectively alter the differentiation of PL cells and promote the formation of alveolar bone and cementum.

Animals↗
PubMed1999

[Influence of IL-4 on the expression of TNF-alpha and IL-1 alpha mRNA by PBMCs from patients with subfulminant viral hepatitis before and after treatment].

OBJECTIVE: The aim of this study was to compare the influence of IL-4 on the expression of TNF-alpha and IL-1 alpha mRNA by PBMCs from patients with subfulminant viral hepatitis(SFH) before and after IL-4 treatment. METHODS: The expression levels of TNF-alpha and IL-1 alpha mRNA by PBMCs were assessed by semiquantitative RT-PCR. RESULTS: IL-4 suppressed the expression of both TNF-alpha and IL-1 alpha mRNA by PBMCs from SFH patients before and after treatment dose-dependently. However, their dose-response curves showed significant differences. The inhibitory effect could be observed at a concentration of 100 U/ml and was near to maximum at 1,000 U/ml in acute phase, whereas the same suppressive action of IL-4 was reached at 100 U/ml in recovery phase. When PBMCs were cultured in the presence of IL-4 at a concentration of 100 U/ml, IL-4 down-regulated the production of both TNF-alpha and IL-1 alpha mRNA by acute phase PBMCs only to 18.18-21.98% of control cells(in absence of IL-4), while the inhibitory rates were all near to 50% in recovery phases. Moreover, it was also found that the suppressive effect of IL-4 on the expression of PBMCs TNF-alpha and IL-1 alpha mRNA in the patients with endotoxinemia and HBeAg was significantly decreased in acute phase. CONCLUSIONS: The inhibitory effect of IL-4 on the expression of PBMCs TNF-alpha and IL-1 alpha mRNA is markedly decreased in acute phase as compared with that in recovery phase and this declined response may be related to endotoxinemia and viremia.

Adult↗
PubMed1993

Blood responses under chronic low daily dose gamma irradiation: II. Differential preclinical responses of irradiated female dogs in progression to either aplastic anemia or myeloproliferative disease.

Female beagle dogs were chronically exposed to low daily doses of 60Co gamma rays (7.5 cGy day-1) and responded in one of three distinct hemopathological patterns. These patterns, reflective of distinct subgroups, were characterized by (a) low radioresistance resulting in progressive hematopoietic suppression, terminal aplastic anemia (AA), and relatively short (< 400 days) survival (-S-AA subgroup); (b) high radioresistance, initially coupled with strong but aberrant regenerative hematopoiesis, and later with the development of myeloproliferative disease (MPD) ((+)-R-MPD subgroup); and (c) high radioresistance, coupled with an early phase of strong regenerative hematopoiesis, but later with no myeloproliferative disease (+R-nonMPD subgroup). In this study, the changes in circulating blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes and platelets) were sequentially assessed in time and fitted to a flexible, quadratic-linear-type response model previously developed. These analyses provided definition to (a) an initial suppressive, radiotoxic phase and (b) the subsequent recovery phase for each of these subgroups. The magnitude and severity of blood cell loss during the initial suppressive phase was generally greatest in the -S-AA subgroup and lowest in the +R-nonMPD subgroup, with the +R-MPD subgroup showing intermediate level responses. A notable exception included a very high net loss of blood granulocytes by the +R-nonMPD subgroup relative to the other two subgroups. By contrast, the magnitude of blood cell restoration, as well as blood cell maintenance levels during the secondary, recovery phase, was generally highest in the +R-MPD subgroup, of intermediate strength in the +R-nonMPD subgroup, and extremely weak or absent in the -S-AA subgroup. Notable exceptions were in the +R-nonMPD subgroup's high recovery rates of monocyte and lymphocyte blood levels, as well as the high maintenance levels of blood granulocytes during recovery. These results are consistent with our earlier observations of blood responses of chronically irradiated male dogs, in that subgroups of female dogs prone to specific radiogenic hematopathologies (i.e. AA and MPD) can be readily identified and staged in specific preclinical periods by a series of marked differential blood responses.

Anemia, Aplastic↗
PubMed1999

Electromyographic timing analysis of forward and backward cycling.

PURPOSE: Backward walking to running progressions are becoming a popular, nontraditional component of functional knee rehabilitation programs. The purpose of this electromyographic (EMG) and motion analysis study was to compare the activation duration of the vastus medialis, vastus lateralis, rectus femoris, medial hamstrings, lateral hamstring, tibialis anterior, and gastrocnemius muscles during forward and backward cycling. We hypothesized that the hamstrings would demonstrate greater activation duration during backward cycling. METHODS: The right lower extremity of 12 healthy subjects (6 male and 6 female) was instrumented with surface EMG electrodes and retroreflective markers to confirm lower extremity kinematic consistency between conditions. RESULTS: Statistical analysis of hip, knee, and ankle kinematics (200 Hz sampling rate) and gender failed to reveal significant differences between conditions (P > 0.05). Quadrant analysis of muscle activation duration with Bonferroni corrections for multiple comparisons revealed that medial and lateral hamstring activation duration was greater during the early recovery phase (quadrant III) of backward cycling than forward cycling (P < 0.00156). Rectus femoris activation duration was greater in the early propulsive phase of backward cycling (quadrant 1) (P < 0.00156) and in the early recovery phase of forward cycling (quadrant III) (P < 0.00156). CONCLUSIONS: These findings lend support for the use of backward cycling during the early recovery phase (quadrant III) to achieve a selective hamstring muscle response of relatively decreased patellofemoral stress and anterior cruciate ligament strain.

Adult↗
PubMed2005

Response of the arterial blood pressure of quadriplegic patients to treadmill gait training.

Blood pressure pattern was analyzed in 12 complete quadriplegics with chronic lesions after three months of treadmill gait training. Before training, blood pressure values were obtained at rest, during treadmill walking and during the recovery phase. Gait training was performed for 20 min twice a week for three months. Treadmill gait was achieved using neuromuscular electrical stimulation, assisted by partial body weight relief (30-50%). After training, blood pressure was evaluated at rest, during gait and during recovery phase. Before and after training, mean systolic blood pressures and heart rates increased significantly during gait compared to rest (94.16 +/- 5.15 to 105 +/- 5.22 mmHg and 74.27 +/- 10.09 to 106.23 +/- 17.31 bpm, respectively), and blood pressure decreased significantly in the recovery phase (86.66 +/- 9.84 and 57.5 +/- 8.66 mmHg, respectively). After three months of training, systolic blood pressure became higher at rest (94.16 +/- 5.15 mmHg before training and 100 +/- 8.52 mmHg after training; P < 0.05) and during gait exercise (105 +/- 5.22 mmHg before and 110 +/- 7.38 mmHg after training; P < 0.05) when compared to the initial values, with no changes in heart rate. No changes occurred in blood pressure during the recovery phase, with the lower values being maintained. A drop in systolic pressure from 105 +/- 5.22 to 86.66 +/- 9.84 mmHg before training and from 110 +/- 7.38 to 90 +/- 7.38 mmHg after training was noticed immediately after exercise, thus resulting in hypotensive symptoms when chronic quadriplegics reach the sitting position from the upright position.

Adult↗
PubMed1976

Altered elimination of antipyrine in patients with acute viral hepatitis.

The plasma half-life and clearance of antipyrine was investigated in patients during the acute phase and again during the recovery phase of viral hepatitis. Each patient served as his own control, thereby eliminating genetic factors and minimising environmental factors that cause large interindividual variations in antipyrine elimination rates. Liver function tests, antipyrine, half-life, plasma clearance, and the apparent volume of distribution were determined in the acute and recovery period. It was found that the appaarent volume of distribution of antipyrine did not change in five of six patients as they recovered. Five of the six patients showed prolonged plasma half-lives and decreased plasma clearance of the drug at the time of acute illness and these parameters reached normal values during recovery. The plasma half-life and clearance of the drug did not correlate with biochemical indices of liver function in the recovery phase. This demonstration supports the concept that drug metabolism is frequently impaired in liver disease.

Adult↗
PubMed1993

Increased hepatic arterial blood flow in acute viral hepatitis: assessment by color Doppler sonography.

To evaluate the effect of acute viral hepatitis on hepatic arterial blood flow, we performed color Doppler sonography with point-spectral analysis in 15 patients with acute viral hepatitis and compared the results with those in 15 normal volunteers. During the acute phase of hepatitis, the peak-systolic and end-diastolic velocity of the hepatic artery were significantly larger than those in normal arteries (p < 0.01). During the recovery phase, these indexes of the hepatic artery decreased significantly to the control levels (p < 0.01). The resistive indexes related to vascular resistance in the hepatic artery during the acute phase were significantly less than those in normal arteries (p < 0.01), and they increased significantly to the control levels during the recovery phase (p < 0.01). No significant correlation was found between these indexes of the hepatic artery and conventional liver function parameters. However, the interval between the acute phase and the recovery phase did correlate negatively with the peak-systolic velocity of the hepatic artery in the acute phase (r = -0.630, p < 0.05) and with the end-diastolic velocity (r = -0.514, p < 0.05). We conclude that color Doppler sonography is useful for imaging increased hepatic arterial blood flow in patients with acute viral hepatitis. We believe that increased hepatic arterial blood flow during the acute phase may provide a marker for earlier recovery from hepatitis-induced damage.

Acute Disease↗
PubMed2005

Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration.

BACKGROUND: Ethylnitrosourea (ENU), a monofunctional alkylating agent, induces apoptosis and cell cycle arrest in neuroepithelial cells, neural stem cells in the fetal central nervous system (CNS). These effects occur immediately after the administration of ENU to pregnant animals resulting in fetal brain anomalies and long-term effects include brain tumors in the offspring. METHODS: Changes in gene expression were investigated in the fetal CNS after ENU administration to pregnant rats using microarray to identify the genes involved in the injury and recovery of the fetal CNS. RESULTS: The up-regulation of 21 genes in injury and 15 genes in recovery phases and down-regulation of 5 genes in injury and 3 genes in recovery phases were identified. The genes up-regulated in the injury phase contained p53-target genes that mediate apoptosis and cell cycle arrest, and those in the recovery phase contained cell proliferation-promoting genes. The genes down-regulated in the injury phase contained cholesterol biosynthesis-related genes. In addition, there were some genes that have not been identified to be involved in the CNS injury and recovery. CONCLUSIONS: The present study will provide a better understanding of the mechanisms of development, regeneration and carcinogenesis of the CNS as well as the mechanisms of ENU-induced fetal CNS injury and recovery.

Alkylating Agents↗
PubMed2006

Guidelines for clinical treatment of early course schizophrenia.

Several practice guidelines have been developed for the management of schizophrenia based on the current evidence base, but only a few have focused on the early course of this illness. In this article, we review the current literature on the approaches to management of early schizophrenia (ie, the prodromal, psychotic, and recovery phases of this illness). The efficacy of psychosocial and antipsychotic agents in the prodromal phase is an area of active research. Atypical antipsychotics are the mainstay of treatment for stabilization of the acute psychotic phase. Effective approaches in the recovery phase include combining medications with individual and family interventions, supported employment, assertive community treatment, cognitive remediation, and social skills training. Although evidence-based interventions have generated new optimism among those with the illness, more efforts are needed to increase access to care in community settings.

Antipsychotic Agents↗
PubMed2001

Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes: comparison with mexiletine and disopyramide.

The effects of bidisomide, an antiarrhythmic agent, on sodium current (I(Na)) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method. Bidisomide blocked I(Na) with a Ki of 214 microM at a holding potential of -140 mV. The blockade of I(Na) was enhanced at a less negative holding potential of -100 mV with a Ki of 21 microM. Bidisomide shifted the steady state inactivation curve to a negative potential direction by 20 mV without a significant change in the slope factor. Bidisomide slowed the time course of recovery of I(Na) at a holding potential of -140 mV with a slow recovery phase. The time constant of recovery phase for bidisomide, disopyramide and mexiletine were 2703, 1858 and 757 ms, respectively. The development of the block of I(Na) consisted of two phases in the presence of bidisomide. The fast and slow time constants were 11 and 648 ms. Bidisomide produced a use-dependent block of I(Na) when the depolarizing pulse was repeated at 1-3 Hz. Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide.

Animals↗
PubMed2002

Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion.

OBJECTIVES: To classify stroke patterns of manual wheelchair users and to determine if different patterns of propulsion lead to different biomechanics. DESIGN: Case series. SETTING: Biomechanics laboratory. PARTICIPANTS: Thirty-eight individuals with paraplegia who use manual wheelchairs for mobility. INTERVENTION: Subjects propelled their own wheelchair on a dynamometer at 2 different steady state speeds. Bilateral biomechanical data were obtained by using a force and moment sensing pushrim and a motion analysis system. MAIN OUTCOME MEASURES: The propulsive stroke of each participant for each speed and side was classified as following 1 of 4 patterns. These 4 patterns were then compared by using a mixed-model analysis of variance. The biomechanical variables that were compared were cadence, peak and rate of rise of the resultant force, mechanical effective force, push angle, and ratio of time spent pushing to time in recovery. RESULTS: The most common propulsive stroke involved the user lifting the hand over the pushrim during the recovery phase. The stroke pattern was independent of axle position and varied from side to side and between speeds. After controlling for subject characteristics, significant differences were observed between stroke patterns in cadence and ratio of time spent pushing to time in recovery. A stroke pattern that involves using a semicircular motion with the hand below the pushrim during the recovery phase of the propulsion stroke was associated with a lower cadence and more time spent in the push phase relative to the recovery phase. CONCLUSION: The semicircular motion of propulsion displayed characteristics consistent with reduced repetition and more efficient propulsion. Use of this propulsion style may reduce trauma to the upper extremities. Clinicians should consider training individuals in this propulsion style.

Adult↗
PubMed2005

[The characteristics during exercise test in long QT syndrome patients and the effects of left cardiac sympathetic denervation].

OBJECTIVE: To explore the mechanism of the left cardiac sympathetic denervation (LCSD) surgery to reduce the incidence of cardiac events for long QT syndrome (LQTS) patients. METHODS: 12 LQTS patients were selected to do exercise test (ET) to mimic sympathetic activation. The dynamic alterations on ECG during exercise and recovery phases (Rec) were observed and the exercise test characteristics for LQTS patients before and after surgery were summarized and compared. RESULTS: The QTc at resting was shortened from 0.54 s +/- 0.04 s to 0.50 s +/- 0.04 s, P = 0.026, while the maximum heart rate during exercise decreased from 141 beat/min +/- 18 beat/min to 124 beat/min +/- 14 beat/min, P = 0.003. QTc was shortened during exercise, however, it was prolonged during the early recovery phase (before ET 0.54 s +/- 0.02 s, ET 10 min 0.46 s +/- 0.02 s, Rec 4 min 0.55 s +/- 0.03 s); LCSD could reduce such abrupt alteration of QTc during early recovery phase (after surgery: before ET 0.53 s +/- 0.03 s, ET 10 min 0.48 s +/- 0.03 s, Rec 4 min 0.53 s +/- 0.05 s). QT/RR interval slope, representing the adaptation response of QT interval to heart rate, became steeper after exercise (from 0.61 +/- 0.06 to 0.71 +/- 0.07 after exercise, P < 0.01). LCSD made the slopes become less steep both before exercise (from 0.61 +/- 0.06 before surgery to 0.55 +/- 0.07 after surgery, P = 0.013) and after exercise (from 0.71 +/- 0.07 before surgery to 0.66 +/- 0.06 after surgery, P = 0.018). Notched T wave alterations occurred in 7 patients at the end of exercise and/or during early recovery phase before surgery, and LCSD diminished such alteration in 4 patients. CONCLUSION: The slope between QT and RR both the pre-exercise and post-exercise slopes, interval becomes less steep after LCSD, which suggests that exaggerated delay in repolarization with decreasing heart rate for LQTS patients is improved by LCSD. This may be one of the mechanisms of LCSD efficacy for treating LQTS patients. Exercise test is one of tools to evaluate the effect of LCSD on LQTS patients.

Adolescent↗
PubMed2002

Solid-phase epitope recovery: a high throughput method for antigen identification and epitope optimization.

Self tolerance to MHC class I-restricted nonmutated self Ags is a significant hurdle to effective cancer immunotherapy. Compelling evidence is emerging that altered peptide ligands can be far more immunogenic than their corresponding native epitopes; however, there is no way to reliably predict which modifications will lead to enhanced native epitope-specific immune responses. We reasoned that this limitation could be overcome by devising an empirical screen in which the nearly complete combinatorial spectrum of peptides of optimal length can be rapidly assayed for reactivity with a MHC class I-restricted cytotoxic T cell clone. This method, solid-phase epitope recovery, quantitatively ranks all reactive peptides in the library and allows selection of altered peptide ligands having desirable immunogenic properties of interest. In contrast to rationally designed MHC anchor-modified peptides, peptides identified by the present method are highly substituted in predicted TCR contact residues and can reliably activate and expand effector cell populations in vitro which lyse target cells presenting the wild-type epitope. We demonstrate that solid-phase epitope recovery peptides corresponding to a poorly immunogenic epitope of the melanoma Ag, gp100, can reliably induce wild-type peptide-specific CTL using normal donor T cells in vitro. Furthermore, these peptides can complement one another to induce these responses in an overwhelming majority of normal individuals in vitro. These data provide a rationale for the design of superior vaccines comprising a mixture of structurally diverse yet functionally convergent peptides.

Antigen Presentation↗
PubMed1994

beta-Endorphin and some hormonal levels in children with acute stress hyperglycaemia.

The levels of beta-endorphin, insulin, cortisol, GH, glucagon, prolactin and TSH were measured in serum samples of 9 hyperglycaemic patients (3 female, 6 male) with a mean age of 4.1 years admitted to the pediatric emergency unit. All patients were in acute stress due to severe diseases (acute gastroenteritis, bronchopneumonia, septicaemia, etc.). Initial and repeat blood samples for hormone determination were taken at admission and in the recovery phase (after 4-6 weeks of treatment). OGTT was also performed in the recovery phase. The hyperglycaemia, monitored hourly following the initial determination, returned to normal in all patients in 1-5 h without specific treatment. Mean serum glucose values at admission and in the recovery phase were 287.0 and 84.1 mg/dl. Concomitant to the hyperglycaemia encountered in these patients in the acute phase of stress, an increase was noted in all hormone levels excluding glucagon and cortisol. All elevated hormone levels fell to normal in 4-6 weeks with significant differences from initial levels for beta-endorphin (P < 0.05) and insulin (P < 0.01). OGTT gave a normal curve. These results indicate that stress hyperglycaemia, despite high insulin levels, is associated with an increase in beta-endorphin levels. The results also show that hyperglycaemia in acute disease does not alter OGTT in short-term follow up.

Acute Disease↗
PubMed1977

Studies on cellular recovery from injury. II. Ultrastructural studies on the recovery of the pars convoluta of the proximal tubule of the rate kidney from temporary ischemia.

The pars convoluta of the proximal tubule of the rat kidney was studied by light and electron microscopy during the recovery phase from transient ischemia. The left kidney was made ischemic by clamping the aorta just above the left renal artery leaving the blood supply to the right kidney and the intestine intact. The pars convoluta (P1 and P2 segments) of the proximal tubule was examined both immediately after various periods of ischemia (15, 30, 60 and 120 min) and after the same ischemic periods followed by 3, 6, 12 and 24 h of blood reflow (= recovery phase). It was found that ischemia for periods up to 60 min were compatible with cell survival whereas 120 min of ischemia gave rise to irreversible cellular changes. Before regaining a normal conformation during the recovery phase, cells made ischemic for 15 min were characterized by slightly decreased cell height, dispersed nuclear chromatin, mitochondria in orthodox conformation and increased numbers of digestive vacuoles and of lipid droplets (stage A2). Most cells made ischemic for 15 min appeared normal when examined after 24 h of reflow. Cells made ischemic for 30 min were also characterized by stage A2 changes after 3 h of reflow and remained in this stage during all recovery periods studied. Cells made ischemic for 60 min first passed into a stage designated A1 and then later during the recovery phase into stage A2. Stage A1 cells were characterized by decreased height, condensed mitochondria, apparently increased numbers and sizes of secondary lysosomes and slightly dilated rough surfaced endoplasmic reticulum; 120 min of ischemia followed by reflow was not compatible with cell survival. Cells made ischemic for 120 min showed the following alterations denoted as stages C and D: shrunken with pyknotic nuclei, swollen mitochondria with large flocculent densities, and filled with different sized vesicles in the apical portion (stage C). Stage D included cells which had undergone necrosis, i.e., phasma membranes and organelles were fragmented and occurred as debris in the tubule lumens.

Animals↗
PubMed1996

Regulation of the thrombin receptor response in human endothelial cells.

At present only little information is available about the regulation of the thrombin receptor activity in human endothelial cells. The study presented was performed to clarify the problem of thrombin receptor regulation in human endothelial cells. Endothelial cells were isolated from the vein or artery of human umbilical cords. These cells were stimulated with thrombin or with the thrombin receptor activation peptides (TRAP) SFLLRN or SFLLRNPNDKYEPF and subsequently the von Willebrand factor (vWf) release was measured as a physiologically significant response regarding the thrombin receptor activation. Shortly after the first activation by thrombin or SFLLRN, the cells were desensitised to a second stimulation. After a recovery phase of 10 min, merely 35% of the receptor response was obtained by subsequent stimulation. Expanding the recovery time to 90 min resulted in a vWf release of nearly 100% of the amount measured after the first stimulation. The resensitisation rate was similar for thrombin and SFLLRN stimulated cells. Adding RNA synthesis inhibitors or protein synthesis inhibitors had no effect on the recovery of the receptor response. Therefore, a de novo synthesis of receptor protein must be excluded as a means of resensitising endothelial cells to thrombin. It was shown that the dephosphorylation of tyrosine kinase inactivated receptors is also not responsible for receptor regeneration. These results prove that endothelial cells are capable of developing full thrombin receptor activity after a relatively short recovery phase of only 60-90 min as compared to the recovery phase of 16-24 h in megacaryoblastic cell lines. Desensitisation is similar in thrombin and TRAP stimulated cells. We assumed a transport mechanism for intracellular stored vesicles for receptor resensitisation; a co-localisation with vWf in the Weibel-Palade bodies is improbable.

Amino Acid Sequence↗
PubMed1987

Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in men: effects of long term treatment with GnRH agonist infusion and androgen.

Constant infusion of GnRH agonist (GnRH-A) leads to far greater suppression of spermatogenesis and gonadotropins in the monkey than its intermittent administration. We assessed if greater suppression of gonadotropins and spermatogenesis could also be achieved in man by continuous GnRH-A administration. Seven normal men were given 400 micrograms GnRH-A daily by constant sc infusion using a mechanical pump device and bimonthly injections of 200 mg testosterone (T) enanthate for 16 weeks. Basal serum LH, FSH, T, and estradiol concentrations were measured every week during a 5-week control period, daily on treatment days 0, 1-11, 14, 18, 22, 26, 28, and every week thereafter until day 56, and every 2 weeks thereafter during the remainder of the treatment phase and during the 14-week recovery phase. Detailed analysis of LH and FSH secretion during the 24-h period was performed by multiple blood sampling on days 0, 1, 10, 28, 56, 84, and 112. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. The mean sperm count declined by 93% to a nadir of 6 +/- 3 (+/- SE) million/mL between weeks 14-16. Four men had sperm counts less than 1 million/mL, and three subjects were azoospermic during treatment. Basal serum immunoreactive LH concentrations, after an early increase, declined to near baseline by day 14. The basal and 24-h integrated serum LH concentrations and 24-h urinary LH excretion were not significantly lowered by treatment. Bioassayable serum LH concentrations, however, after an early rise, declined significantly below baseline by day 28 and remained low thereafter. The frequency and amplitude of LH pulses were reduced by GnRH agonist infusion. Basal and 24-h integrated serum FSH concentrations, after a brief initial increase, declined to baseline by day 10, but were not significantly below baseline by day 112. Serum T concentrations did not fall into the hypogonadal range at any time during the treatment period. After discontinuation of treatment, serum LH and FSH and sperm counts returned to normal in all men. Thus, this regimen, employing constant infusion of 400 micrograms GnRH agonist daily plus T led to a greater suppression of spermatogenesis than the previous regimen employing single daily injections of 200 micrograms of the same agonist plus T. Whether the higher dose or the constant infusion was responsible for the greater inhibition of spermatogenesis is not clear. It is conceivable that a still higher dose of the agonist, given by constant infusion, might induce azoospermia in all men.

Adult↗