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At least 1,063 records · Page 59Linked to original sources
PubMed2003

Role of aryl hydrocarbon receptor in mesencephalic circulation failure and apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and potent developmental toxicant in various animals, with developing fish being the most sensitive organisms. Although the expression of aryl hydrocarbon receptor (AHR) as well as the partner molecule, AHR nuclear translocator (ARNT) in the brain has been reported, the effect of TCDD on the brain remains to be clarified in detail. Previously, we reported local circulation failure and apoptosis in dorsal midbrain caused by TCDD in developing zebrafish. In the present experiments, we investigated the effects of morpholino antisense oligos against aryl hydrocarbon receptor 2 (zfAHR2) (AHR2-MO) on toxicological endpoints caused by TCDD in developing zebrafish. AHR2-MO but not its negative homologue (4mis-AHR2-MO) improved TCDD-evoked circulation failure in mesencephalic vein and reduced the occurrence of apoptosis in dorsal midbrain, with concomitant inhibition of CYP1A induction in vascular endothelium. Injection of bovine serum albumin (BSA) into the general circulation, followed by immunohistochemistry with anti-BSA, showed that TCDD raised vascular permeability to albumin in dorsal midbrain, which was blocked by AHR2-MO and N-acetlycystein. In the absence of TCDD, development of embryos injected with AHR2-MO appeared normal at least until 60 h after fertilization. It is concluded that AHR2 activation in the vascular endothelium of the zebrafish embryo midbrain is involved in the mesencephalic circulation failure and apoptosis elicited by TCDD. This is the further evidence that vascular endothelium is the target of TCDD in relation to local circulation failure and apoptosis in dorsal midbrain.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Effect of ultrafiltration on priming solution with preserved blood for extracorporeal circulation in infants.

In pediatric cardiac surgery, the initial priming solutions of the extracorporeal circulation include preserved blood. In an effort to eliminate unfavorable effects of preserved blood on the circulation, the authors introduced the preserved blood to ultrafiltration (UF). Seventeen infants with congenital heart defects were included in this study. UF was performed with a polysulfone ultrafiltrator before extracorporeal circulation. The 1600 ml of fluid, consisting of saline, 5% glucose, and maltose, were added to 400 ml of preserved blood, and the same amount of fluid was removed by UF. The concentrations of potassium, NH3, and bradykinin in the priming blood decreased significantly after UF. In the UF group, water balance during extracorporeal circulation and max. Creatinine-phosphokinase levels after surgery were better than controls. These data suggest that UF is able to remove some substances and result in reduction of an unfavorable effect on the circulation.

Blood Preservation↗
PubMedDate not supplied

Importance of metabolic function of the natural lung evaluated by prolonged exclusion of the pulmonary circulation.

It is generally considered that the natural lung metabolizes various vasoactive substances through the pulmonary circulation. However, the influences of bypassing or eliminating the pulmonary circulation have not been fully elucidated, especially for prolonged periods. In this study, we performed total cardiopulmonary bypass and exclusion of the pulmonary circulation for up to 336 hr in awake goats to clarify the importance of the metabolic function of the lung. In seven adult goats, biventricular bypass with a pulsatile ventricular assist system was first established. After 2 weeks, the biventricular bypass was converted to total cardiopulmonary bypass without anesthesia. Adequate gas exchange and perfusion support were achieved in all animals. However, the institution of total cardiopulmonary bypass led to marked decreases in the mean aortic pressure and systemic vascular resistance, and they remained low thereafter. The arterial levels of prostaglandin E2 and norepinephrine, which are inactivated naturally through the pulmonary circulation, increased remarkably. These results indicate that the natural lung plays an important role in controlling systemic circulation by metabolizing various vasoactive substances. Understanding the non respiratory function of the natural lung is of prime importance for advancement of lung and heart-lung support.

Animals↗
PubMed2002

Exhaled nitric oxide does not reflect the severity of acute lung injury: an experimental study in a rat model of extracorporeal circulation.

OBJECTIVE: This study was undertaken to determine whether an increase in exhaled nitric oxide would reflect the severity of the acute lung injury caused by extracorporeal circulation. DESIGN: Prospective, controlled animal laboratory investigation. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Wistar rats (n = 34). INTERVENTIONS: Twenty-three Wistar rats underwent a partial (100 mL.kg(-1).min(-1)) femoro-femoral extracorporeal circulation in normothermia for 90 mins. Eleven time-matched rats formed the sham group. MEASUREMENTS AND MAIN RESULTS: Exhaled nitric oxide was monitored with a chemiluminescence analyzer. Acute lung injury was assessed by blood gas analysis and lung water content. Lung Evans blue dye content, lung myeloperoxidase, and heme oxygenase activities were determined. Compared with the sham rats, extracorporeal circulation was responsible for acute lung injury characterized by an increased lung water content (82.4 +/- 1.3% vs. 77.9 +/- 1.1%; p<.05), an increased Evans blue dye content (191.8 +/- 15.8 vs. 112.5 +/- 16.8 mg/g tissue wet weight; <.01), and an increased pulmonary heme oxygenase activity (332.9 +/- 107 vs. 113.7 +/- 46.5 pmol. hr(-1).mg of protein(-1); p<.05). Exhaled nitric oxide remained stable throughout the experiment in all sham rats. Among the 23 rats that underwent extracorporeal circulation, eight rats (35%) experienced an increase in exhaled nitric oxide concentration (16.9 +/- 12.7 ppb). There was no significant difference between rats that did or did not experience an increase in exhaled nitric oxide regarding each index of acute lung injury. CONCLUSIONS: An increase in exhaled nitric oxide did not reflect the severity of the acute lung injury caused by extracorporeal circulation. Its significance remains to be determined.

Animals↗
PubMed2003

Anesthetic management for clipping a giant basilar artery aneurysm with moderate hypothermia, extracorporeal circulation assistance, and propofol infusion.

A 65-year-old female patient underwent surgery to clip a giant basilar artery aneurysm with closed-chest extracorporeal circulation using femorofemoral bypass. Moderate hypothermia (27 degrees C-30 degrees C), retention of spontaneous circulation, and propofol infusion (3-5 mg. kg(-1). h(-1)) were used under general anesthesia. Blood outflow via femoral vein was sufficient to maintain cardiopulmonary bypass and to induce hypothermia. Hemodynamics were controlled with dopamine and noradrenaline. In this case, extracorporeal circulation under moderate hypothermia was used to assist rather than substitute for spontaneous circulation, and spontaneous circulation was maintained at all times. We think that this method had advantages over deep hypothermic circulatory arrest with regard to intraoperative risks and postoperative complications.

Aged↗
PubMed1998

Dose-dependent effect of diaspirin cross-linked hemoglobin on regional blood circulation of severely hemorrhaged rats.

Diaspirin cross-linked hemoglobin (DCLHb), a hemoglobin-based blood substitute, has been found to improve systemic hemodynamics, cutaneous oxygen tension, and normalization of blood lactate levels and acid-base equilibrium after hemorrhage in animals. The present study was conducted to determine the dose-dependent effect of a 10% solution of DCLHb (20, 50, and 100% of shed blood volume; SBV) on regional blood circulation in hemorrhaged rats. Hemorrhage was induced in urethane-anesthetized rats by bleeding them at a rate of approximately .5 to 1 mL/min until a mean arterial pressure of 35-40 mmHg was achieved. This was maintained for up to 90 min to reach a base deficit of more than -12 mmol/L. Hemorrhage significantly decreased oxygen consumption, mean arterial pressure, cardiac output, stroke volume, and regional blood circulation, but increased total peripheral resistance. The vehicle Ringer's lactate (RL at 20% of SBV, intravenously) did not produce any improvements in oxygen consumption, base deficit, systemic hemodynamics, and regional blood circulation. DCLHb increased oxygen consumption, decreased base deficit, and produced significant improvements in systemic hemodynamics and regional blood flow in a dose-dependent manner. The increase in blood flow was highly significant until 60 min, but was less marked at 120 min, after resuscitation with DCLHb. Resuscitation with RL (300% of SBV) significantly improved systemic and regional blood circulation. However, the improvement was greater after resuscitation with DCLHb (50 or 100% of SBV) as compared with RL at 300% SBV. DCLHb in the dose of 50% of SBV produced maximal resuscitative effects, which were comparable to a DCLHb dose of 100% of SBV. The effect of DCLHb at 50% of SBV on renal cortical blood perfusion, concentration of moving red blood cells (CMBC), and blood velocity was also studied using laser Doppler flowmetry. Hemorrhage produced a decrease in renal cortical blood perfusion (85.3%), which was due to a decrease in the CMBC (61.0%) and their velocity (64.2%). Resuscitation with the RL did not produce any improvement in renal cortical perfusion. However, resuscitation with DCLHb significantly increased renal cortical perfusion (364.7%) due to an increase in both CMBC (123.4%) and their velocity (109.9%). It is concluded that DCLHb in a dose of 50% of SBV produces maximal improvement in regional blood circulation of hemorrhaged rats.

Acid-Base Equilibrium↗
PubMed2003

Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure.

OBJECTIVE: To assess whether postoperative detection of circulating tumor cells in peripheral blood influenced the prognosis of patients with colorectal cancer after radical surgery. SUMMARY BACKGROUND DATA: In a previous study, the authors demonstrated that baseline detection of blood circulating tumor cells does not have prognostic significance in patients with colorectal cancer. However, surgical procedures may increase tumor cell detachment and mobilization. METHODS: Sixty-six patients with histologically confirmed colorectal cancer operated on for cure were included in this study. Circulating tumor cells were detected by means of reverse transcriptase-polymerase chain reaction targeting to carcinoembryonic antigen messenger RNA in peripheral blood samples obtained 24 hours after surgery. Endpoints of the study were tumor recurrence, overall survival, and cancer-related survival. Univariate (Kaplan-Meier method) and multivariate (Cox regression model) analyses were performed. RESULTS: After a median follow-up of 36 months, 15 patients (23%) had tumor relapse and 14 had died (21%), 8 of them from a cancer-related cause. Cox regression analysis identified lymph node metastases and gender as independent predictors of tumor recurrence and cancer-related survival, whereas overall survival was dependent on the degree of differentiation of the primary tumor. More importantly, the presence of circulating tumor cells after surgery had no prognostic influence on tumor recurrence, overall survival, or cancer-related survival. CONCLUSIONS: Postoperative detection of blood circulating tumor cells had no prognostic significance in patients with colorectal cancer operated on for cure.

Aged↗
PubMed2003

Evaluation of change of cerebral circulation by SpO2 in preterm infants with apneic episodes using near infrared spectroscopy.

BACKGROUND: In the neonatal intensive care unit (NICU), hemodynamics in very low-birthweight infants are generally examined for oxygen saturation (SpO2), heart rate, respiration rate, and blood pressure. The present study examined how changes in cerebral circulation in preterm infants can be evaluated by the SpO2 monitoring method with near infrared spectroscopy (NIRS) to detect the cerebral circulation. METHODS: The study was conducted in 11 low-birthweight neonates with a mean weight of 1252 g (940-1948 g), mean post-conceptional age of 28.9 weeks (28-31 weeks) and in whom a total of 145 apneic episodes were examined. Changes in cerebral circulation at the apneic attack were evaluated by two parameters of Delta HbD ( micro mol/L) for reduction in cerebral oxygenation and Delta cHb (mL/100 g brain) for variation in cerebral blood volume using the near infrared spectroscopy (NIRS). RESULTS: There was a tendency for a reduction in cerebral oxygenation and a change in cerebral blood volume as SpO2 was reduced. In the event of apneic attacks where SpO2 was reduced to <85%, cerebral oxygen saturation was extensively reduced. In addition, cerebral blood volume was also greatly changed when the SpO2 was reduced to <85%, and changed further still when SpO2 was reduced again to < or =75%. CONCLUSION: Reduction in SpO2 (<85%) was suggested to be an effective indication to changes in cerebral circulation. In the case of apneic attacks where SpO2 was < or =85%, the cerebral circulation in preterm low-birthweight neonates was extensively changed and, therefore, attention should be paid to changes in the concentration of SpO2 when managing apnea of prematurity in NICU.

Apnea↗
PubMed2005

Impaired coronary circulation in patients with apical hypertrophic cardiomyopathy: noninvasive analysis by transthoracic Doppler echocardiography.

OBJECTIVES: We designed this study to examine the characteristics of coronary circulation in patients with apical hypertrophic cardiomyopathy (ApHCM) using noninvasive transthoracic Doppler echocardiography (TTDE). BACKGROUND: Recent advances in TTDE have allowed noninvasive assessment of coronary circulation by the measurement of coronary flow velocity (CFV) patterns and coronary flow velocity reserve (CFVR). However, there have been no previous studies evaluating coronary circulation in ApHCM. METHODS: We analyzed CFV and CFVR in the left anterior descending coronary artery (LAD), and apical wall thickness in the left ventricle, in 10 ApHCM subjects and 10 control subjects. Mean diastolic velocity (MDV) and time from the beginning of diastole to peak velocity (TPV), and CFVR, defined as a ratio of drug-induced hyperemic to basal MDV, were measured. RESULTS: At baseline, MDV was higher, and TPV was longer, in ApHCM subjects than in control subjects (29 +/- 5.7 versus 19 +/- 6.5 cm/sec; p < 0.01 and 5.2 +/- 1.0 versus 3.5 +/- 0.6 msec; p < 0.005, respectively). CFVR in ApHCM subjects was significantly lower than in control subjects (1.9 +/- 0.4 versus 3.1 +/- 0.8; p < 0.005). CFVR and basal MDV in ApHCM subjects showed significant correlations with apical/posterior wall thickness ratio [CFVR; r =-0.84, p < 0.01 and MDV; r = 0.74, p < 0.05, respectively]. CONCLUSION: Noninvasive coronary flow assessment by TTDE revealed an impaired coronary circulation with reduced CFVR, high MDV at baseline and prolonged TPV. These results suggest that these characteristics of coronary circulation may provide an additional index for the assessment of ApHCM.

Adenosine Triphosphate↗
PubMed1981

Biliary secretion in conscious rabbits: role of the enterohepatic circulation of bile salts and of the gall bladder.

The role of enterohepatic circulation of bile salts in biliary secretion in conscious rabbits has been investigated before and after cholecystectomy. Bile flow was higher and bile salt concentration lower in cholecystectomized than in intact rabbits: this could have been caused by a negative feed-back effect on bile salt synthesis as the circulating bile salt pool increased. The effects of cholecystectomy on flow and bile salt concentration balanced each other. Bile flow and bile salt concentration declined after interruption of the enterohepatic circulation in both cholecystectomized and intact rabbits. Furthermore, the percentage of the flow of bile independent of bile salt secretion increased, while that independent of total analysed solutes decreased after the enterohepatic circulation was broken. These results confirm that the decrease in bile flow after interruption of the enterohepatic circulation is due to loss of bile salts and not of electrolytes.

Animals↗
PubMed1975

Adrenergic mechanisms in canine gastric circulation.

The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are "mixed" adrenergic agonists and isoproterenol is a "pure" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right.

Adrenergic Agonists↗
PubMed2004

Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.

Antibodies, Monoclonal↗
PubMed2004

Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support.

BACKGROUND: The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation. METHODS AND RESULTS: Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI <0.25) compared with those with adequate (CFI > or =0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (r=-0.61, P<0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor165, or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (r=0.75, P<0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (P<0.05) and 70% (P<0.05), respectively. CONCLUSIONS: In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.

Aged↗
PubMed2002

Mesencephalic and associated posterior circulation infarcts.

BACKGROUND AND PURPOSE: The purposes of this study were to evaluate and review the risk factors and clinical features of patients with posterior circulation stroke involving mesencephalon and neighboring structures and to describe the clinical syndromes according to the mesencephalic arterial territory involved. METHODS: We studied all patients with acute posterior circulation stroke involving mesencephalon who were admitted consecutively to our stroke unit over a 6-year period. We selected these patients (3%) from 1296 patients with posterior circulation infarct. Neurological and radiological investigations, including MRI and angiography, were performed in all cases. We classified patients into 4 groups on the basis of MRI findings: (1) isolated mesencephalic infarcts (9 patients); (2) distal territory infarcts (19 patients), including mesencephalon, thalamus, medial temporal and occipital lobes, and cerebellum; (3) middle territory infarcts (12 patients), including the pons and anterior inferior cerebellar artery territory; and (4) proximal territory infarcts (1 patient), including the medulla and posterior inferior cerebellar artery territory. RESULTS: Middle mesencephalon involvement was the most common in all groups, and the anteromedial territory was frequently affected, depending on the direct perforators of basilar artery. In patients with isolated mesencephalic infarct, the clinical picture was dominated by nuclear or fascicular third-nerve palsy and contralateral motor deficits. The distal territory involvement was the most common and associated with consciousness disturbances, gait ataxia, ocular motor disturbances, and visual field deficits. The neurological picture of middle territory infarcts was dominated by consciousness disturbances with dysarthria, horizontal ocular motor disorders, and hemiparesis. Proximal territory involvement was rare and associated with acute unsteadiness, vertigo, dysphagia, dysphonia, tetra-ataxia, and motor weakness. The most common cause of stroke was large-artery disease in 16 patients (39%), cardioembolism in 8 (20%), and small-artery disease with lacunar mesencephalic infarct in 10 (24%). Bilateral mesencephalic infarcts were not uncommon (27%), mainly in patients with multiple and extended infarcts in the posterior circulation, and were associated with poor outcome compared with unilateral infarct. CONCLUSIONS: Our study highlights the topographic and clinical heterogeneity of the acute posterior circulation infarcts involving mesencephalon. The variety of the underlying potential causes of stroke requires detailed investigations of the extra and intracranial arteries and the heart.

Acute Disease↗
PubMed1976

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.

Adenosine Triphosphatases↗
PubMed1990

Characteristics of the limb circulation in hypertension.

The aim of this study was to investigate the effect of hypertension on the regulation of limb circulation. The study group consisted of 50 patients suffering from hypertension; in 21 cases the peripheral circulation was intact, while 29 patients had peripheral obliterative arterial disease (POAD) (clinical symptoms: intermittent claudication or rest pain). The control group consisted of 67 normotensive patients. In 33 subjects of the control group the peripheral circulation was intact, while 34 patients suffered from POAD (clinical symptoms: intermittent claudication or rest pain). The total limb blood flow (LBF) was measured by using venous isotope dilution technique. In hypertensive patients the limb vascular resistance (LVR) was markedly elevated, but the LBF remained in the normal range. In patients suffering from both hypertension and POAD the LVR was pathologically elevated and the LBF markedly diminished. After acute vasodilator therapy the LBF significantly increased, despite the drop in blood pressure owing to the extensive decrease of the LVR. It appears that in hypertension the elevation of the LVR is the most characteristic change of the limb circulation. The elevation of the arterial blood pressure has no favorable effect on the limb circulation, and the LBF compared with the blood pressure is relatively low.

Adolescent↗
PubMedDate not supplied

Extracorporeal circulation as a new experimental pathway for myoblast implantation in mdx mice.

The deficiency of dystrophin, a sarcolemmal associated protein, is responsible for Duchenne muscular dystrophy (DMD). Gene replacement is attractive as a potential therapy. In this article, we describe a new method for myoblast transplantation and expression of dystrophin in skeletal muscle tissue of dystrophin-deficient mdx mouse through iliac vessels extracorporeal circulation. We evaluated the extracorporeal circulation as an alternative route of delivering myoblasts to the target tissue. Two series of experiments were performed with the extracorporeal circulation. In a first series, L6 rat myoblasts, transfected with LacZ reporter gene, were perfused in limbs of 15 rats. In the second series, the muscle limbs of three 6-8-week-old mdx were perfused with myoblasts of donor C57BL10J mice. Before these perfusions, the right tibialis anterior (TA) muscle of the rats and mdx was injected three times at several sites with bupivacaine (BPVC) and hyaluronidase. The ability of injected cells to migrate in the host tissue was assessed in rats by technetium-99m cell labeling. No radioactivity was detected in the lungs, bowels, and liver of animals treated with extracorporeal circulation. The tissue integration and viability of the myoblasts were ultimately confirmed by genetic and histochemical analysis of LacZ reporter gene. Following a single extracorporeal perfusion of myoblasts from donor C57BL10J, sarcolemmal expression of dystrophin was observed in clusters of myofibers in tibialis anterior muscles previously treated with BPVC and hyaluronidase. Furthermore, large clusters of dystrophin-positive fibers were observed in muscles up to 21 days after repeated treatments. These clusters represented an average of 4.2% of the total muscle fibers. These results demonstrate that the extracorporeal circulation allows selective myoblast-mediated gene transfer to muscles, opening new perspectives in muscular dystrophy gene therapy.

Animals↗
PubMed2005

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring.

INTRODUCTION: In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting. METHOD: We used MAINTRAC analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients. RESULTS: MAINTRAC analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy. CONCLUSION: The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.

Antineoplastic Combined Chemotherapy Protocols↗