Suppression of prostanoid formation and regulation of peripheral circulation after surgery using thrombin inhibitor (MD805)

We studied the effects of thrombin generation due to surgical stress on prostanoid formation and peripheral circulation in anesthetized dogs. Three experimental groups were used, consisting of a control group (group 1), a thoracotomized group (group 2), and a thoracotomized group treated with thrombin inhibitor (MD805: a synthetic arginine derivative) (group 3). The plasma concentrations of thrombin-antithrombin III complex (TAT) and prostanoids were measured along with the hemodynamic parameters. The plasma concentrations of TAT and thromboxane B2 significantly increased 1h after a thoracotomy in group 2. However, neither concentration increased after a thoracotomy in group 3. The flow ratio of the brachial and femoral arteries to cardiac output significantly decreased 1h after a thoracotomy in group 2. This study indicates that thromboxane A2 was thus synthesized by the stimulation of endogenous thrombin, while it also reduced the peripheral blood flow after surgery.     

Use of flow cytometric CD34 analysis to quantify hematopoietic progenitor cells

This review summarizes our experiments on flow cytometric analysis of CD34 positive mononuclear cells (MNC) and on colony formation of myeloid hematopoietic progenitor cells in the clonogenic assay. We examined MNC isolated by density centrifugation of bone marrow, cord blood and peripheral blood. The latter samples originated either from patients recovering from myelosuppressive treatment who received no growth factors or from patients treated with G-CSF or GM-CSF. We attempted to correlate the results obtained by CD34 analysis with the cloning efficiency determined after a 14 day culture period in the methylcellulose-based clonogenic assay. The highest cloning efficacy (60%-100%) was observed in cord blood, however, a good correlation was found in both untreated and GM-CSF treated peripheral blood samples in which a mean of 50% and 20% of the number of CD34 positive MNC gave rise to myeloid colonies. In bone marrow, the cloning efficacy was generally lower and ranged between 5% and 15%. The lowest values were observed in G-CSF treated peripheral blood in which colonies were grown from only 1%-9% of the CD34+ MNC. Due to the variable numbers of CD34+ lymphoid and/or more committed myeloid precursors which form either no colonies or only clusters, there was a greater variation and a lower cloning efficiency in the latter two cell sources. In conclusion, one colour CD34 analysis of cord blood MNC and untreated or GM-CSF treated peripheral blood MNC provides reliable results with respect to the content of myeloid progenitors. Analysis of bone marrow MNC and G-CSF treated peripheral blood MNC requires two colour staining using CD34 and CD45RA.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of flunarizine and pentoxifylline on vestibular blood flow in the guinea pig

Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear. Changes in VBF were evaluated from the posterior semicircular canal ampulla in guinea pigs using a laser Doppler flowmeter. One group of animals was infused with pentoxifylline at concentrations of 10-40 mg/ml, while a second group was treated with 0.3-1.5 mg/kg flunarizine. VBF, blood pressure (BP) and heart rate (HR) were monitored continuously. Findings showed that pentoxifylline induced a concentration-dependent increase in VBF. In contrast, no increase in VBF occurred in response to flunarizine infusions. These studies suggest that the effectiveness of pentoxifylline in the clinical treatment of vestibular disorders may be the result of improved blood flow.     

Ultrasonographic patterns of polycystic ovaries: color Doppler and hormonal correlations

Ultrasound has been used in the identification of two different morphological patterns of polycystic ovaries, namely a peripheral cystic pattern and a general cystic pattern. The aim of this study was to evaluate whether patients with the peripheral form of polycystic ovaries showed different ovarian and uterine blood flow from those with the general form, and to investigate whether there was a correlation between the forms and different hormonal parameters. Eighteen patients with the general form and 16 patients with the peripheral form of polycystic ovary underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. The parameters analyzed confirmed polycystic ovarian syndrome (PCOS) in all patients. Individual levels of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, androstenedione and estradiol did not differ between the groups. However, there was a significantly higher LH/FSH ratio and a greater stromal echodensity in the peripheral cystic group than in the general cystic group. Doppler ultrasonography demonstrated significantly lower pulsatility index values in the intraovarian arteries of the peripheral cystic group and a higher rate of visualization of these arteries than in the general cystic group. These findings suggest that, apart from the LH/FSH ratio, the different morphological types of polycystic ovary do not reflect differences in endocrine profile. The differences in blood flow demonstrated by Doppler assessment in each case, however, showed that PCOS does not predetermine a single intraovarian blood flow pattern.     

The effect of 4 years' of hypolipemic treatment on the width of the common carotid artery intima in patients with familial hyperlipidemias

Sixty-four patients with familial hyperlipoproteinaemia were treated for almost four years by dietetic treatment and various hypolipidaemic drugs. In 25 patients with familial hypercholesterolaemia who had clinical signs of ischaemic heart disease total and LDL-cholesterol declined and the width of the intima of the common carotid artery diminished from 0.78 mm to 0.69 mm (p = 0.004). In the above artery the maximal flow rate of blood declined. The increase was, however, not statistically significant. In 12 patients with familial hypercholesterolaemia who suffered from ischaemic heart disease the width of the intima of the common carotid artery and maximum flow rate did not change, however, the diameter of the artery increased (from 6.3 to 6.6 mm, p = 0.034). In 27 patients with familial combined hyperlipidaemia during the drop of cholesterol, LDL-cholesterol and triacylglycerols the width of the intima of the common carotid artery diminished (from 0.72 to 0.67 mm, p = 0.044), the diameter of the artery increased (from 6.1 to 6.4 mm, p = 0.014). The authors assume that the reduction of the width of the intima during hypolipidaemic treatment reflected the decline of cholesterol in the arterial wall and is a favourable sign which indicates possible regression of atherosclerosis.     

The spontaneous rhythm of the peripheral blood supply in diabetics needing insulin

In order to study the spontaneous rhythmics of the peripheral blood supply under diabetic metabolic onditions with the help of venous occlusion plethysmography quantitative measurings were carried out in 20 long-term diabetics treated with insulin and in an adequate control group with healthy metabolism. The results were significant differences of the sizes of blood flow in rest as well as in the behaviour of the amplitudes and in the course of time of the spontaneous rhythmical varieties of the blood supply. Influences of age and duration of diabetes could not be proved on the basis of the number of patients. As to their evidence the findings are discussed with regard to the pathogenesis and early recognition of the diabetic neuro- and angiopathy.     

Usefulness of Doppler ultrasound in predicting the effect of gonadotropin-releasing hormone agonist (GnRHa) on myoma uteri

This paper shows the value of Doppler ultrasound of the uterine blood flow in predicting the effect of GnRHa on myoma uteri. Thirty-eight patients with myoma uteri were divided into two groups by Doppler ultrasound before treatment: a group with positive arterial blood flow in or around the myoma nodule, and another group with negative arterial blood flow. Histological examinations which were performed in thirty patients demonstrated that the myoma in the negative blood flow group showed higher hyalinization with poor vascularization. In fifteen patients treated with GnRHa (Buserelin 900 micrograms/day), a significant increase (p < 0.01) in the resistance index of the uterine arteries was induced and suppressed the serum estradiol concentration in all cases during GnRHa therapy. The size of the myoma nodules also decreased in all 6 patients in the positive blood flow group, but in only 3 of the 9 patients in the negative blood flow group during GnRHa therapy. These results indicated that Doppler assessments of the arterial blood flow in myoma would be useful in predicting the effect of GnRHa on myoma uteri.     

Transurethral thermotherapy in the management of benign prostatic hyperplasia

To elucidate the intradialytic urea concentration gradients, we examined 26 hemodialysis patients wearing a double-lumen central venous catheter during their first or second fistula-punctured dialysis session. In 17 patients (group A), after 60 and 240 minutes of treatment with a mean blood flow of 196.4 +/- 9.9 mL/min, blood urea nitrogen (BUN) was measured in blood samples taken simultaneously from the central venous catheter, a vein in the arm opposite the access site, and the arterial and venous lines of the dialyzer. In 16 patients (group B), after 60 minutes of treatment with a mean blood flow rate of 197.5 +/- 12.3 mL/min, BUN was measured in blood samples taken from the dialyzer arterial line and then, after decreasing the blood flow to 50 to 60 mL/min for 1 minute, in samples taken from a vein in the arm opposite the access site, the central venous catheter, and the dialyzer arterial line. In group A, the mean BUN values in the dialyzer arterial line at 60 and 240 minutes were found to be 3.7% +/- 3.7% and 3.5% +/- 3.4% higher than the corresponding values in the central veins, respectively (P = NS between 60 and 240 minutes). In group B, after 1 minute of low blood flow, this difference was 1.5% +/- 2.4% (P = 0.06 compared with group A). The peripheral veins in group A patients at 60 and 240 minutes had 9.7% +/- 5.2% and 10.9% +/- 5.3% higher BUN values, respectively, compared with the central veins. This difference in group B patients after 1 minute of low blood flow was 6.8% +/- 4.2%. Urea access recirculation rate in group A, calculated by the classical three-samples method, was found to be 7.6% +/- 5.0% at 60 minutes and 9.9% +/- 5.8% at 240 minutes (P = NS). In group B, BUN values in the dialyzer arterial line after 1 minute of low blood flow increased significantly by 3.4% +/- 4.5% (P < 0.01). Our study shows that during conventional hemodialysis with a blood flow rate of 200 mL/min, urea concentration in the central veins is lower than in the dialyzer arterial line. This gradient after 1 minute of low-flow dialysis had a tendency to decrease. At the same time, however, the urea concentration gradient between the peripheral and central veins remained high, indicating that during conventional hemodialysis, intercompartmental disequilibrium plays a significant role in the arteriovenous gradient.     

Possible role for nitric oxide releasing nerves in the regulation of ocular blood flow in the rat

AIM: To investigate the role of nitrergic nerves in the regulation of ocular blood flow. METHODS: Conscious, lightly restrained rats were treated with either the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI), or the nonselective inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and ocular blood flow was measured ex vivo from tissue samples, using the fully quantitative [14C]-iodoantipyrine technique. RESULTS: In the peripheral circulation, L-NAME produced an increase in arterial blood pressure (+22%) while 7-NI had no effect. In contrast, both 7-NI and L-NAME produced significant decreases in ocular blood flow (-31% and -59% respectively). The ocular vascular resistance calculated from ocular blood flow and mean arterial blood pressure increased by 29% following 7-NI, but by 130% following L-NAME. CONCLUSIONS: Nitric oxide releasing neurons may play an important contributory role in regulating ocular blood flow.     

Blink reflex recovery cycle in patients with blepharospasm unilaterally treated with botulinum toxin

To study the role of arterial blood dynamics in the thrombogenesis of thrombin-induced experimental retinal vein obstruction, the retinal blood flow velocity was evaluated using scanning laser ophthalmoscopic fluorescein videoangiography in an experimental rabbit retinal vein obstruction model. Retinal vein obstruction was made by transadventitial direct instillation of thrombin to the retinal vessels from the vitreous side. The blood flow velocity in the retinal artery and vein was estimated by measuring the passing velocity of the flow head of the dye bolus and venous filling time, respectively. 23 animals were treated with thrombin and compared with 18 controls not treated. In the control group retinal artery blood flow velocity and retinal venous fluorescein filling time was 5.3 +/- 1.1 mm/sec (mean +/- standard deviation) and 6.2 +/- 1.2 sec, respectively. In the treated group the values were 5.7 +/- 1.3 mm/sec and 5.8 +/- 1.0 sec before the thrombin administration, and 3.0 +/- 0.9 mm/sec at 24 hours after its administration, and 5.7 +/- 2.0 sec and 4.0 +/- 1.5 mm/sec and 4.5 +/- 1.4 sec at 48 hours after the administration. These results indicate that a decrease in retinal artery blood flow velocity is strongly involved in the thrombogenesis in thrombin-induced experimental retinal vein obstruction.     

Cardiovascular correlates of attention in normal and psychiatrically disturbed children. Blood pressure, peripheral blood flow, and peripheral vascular resistance

Blood pressure, peripheral blood flow, and peripheral vascular resistance were measured in normal adults and children and in children with autism and severe disturbances in personality development while the individuals were engaged in a variety of attentional tasks. The tasks were designed to elicit outward direction of attention (and intake of sensory input) or inward direction of attention (and relative rejection of external sensory input). During tasks involving sensory rejection, normal adults and normal children showed increased blood flow and decreased peripheral vascular resistance; with sensory intake, blood flow was decreased and resistance was increased. The most severely impaired children showed little alteration in their physiological response to task requirements. Autistic children had higher mean blood flow and lower peripheral vascular resistance than normal children and adults. Some autistic children characteristically may be in a state of sensory rejection associated with generally higher levels of arousal or defense against environmental bombardment.     

Cardiovascular effects of Althesin. Changes in systolic time intervals and peripheral tissue blood flow

Systolic time intervals were studied and peripheral blood flow measurements made in twelve healthy patients before and after intravenous induction of anaesthesia with Althesin 0.05 ml per kg. The changes in systolic time intervals observed were considered to reflect the cardio-depressive properties of the drug. The reduction in peripheral blood flow which occurs in Althesin anaesthesia was confirmed. Measurement of systolic time intervals and peripheral blood flow constitute a simple and sensitive method for the evaluation of the effects of drugs on the cardiovascular system.     

Flexor carpi ulnaris (humeral head) muscle flap for reconstruction of distal forelimb injuries in two dogs

BACKGROUND: It is difficult to predict ischemic cerebrovascular diseases by noninvasive methods before overt symptoms develop. Advanced carotid and cerebral atherosclerosis reduce common carotid blood flow volume due to increased resistance of peripheral circulation. According to a study in which clinical and pathological specimens were compared, the lower threshold for the flow volume in normal individuals has been confirmed to be 6.5 ml/s. We investigated the possibility that the development of ischemic cerebrovascular diseases can be predicted based on blood flow volume. METHOD: We conducted a retrospective study on 314 patients who were available for determination of common carotid blood flow volume with an ultrasonic quantitative flowmeter. RESULTS: Thirty-three patients developed ischemic cerebrovascular attacks during the observation period (onset group), while the remaining 281 did not develop attacks (non-onset group). The discriminating value for common carotid blood flow volume between the onset and non-onset groups was 6.8 ml/s. Based on an odds ratio of 6.7, it was concluded that a common carotid blood flow volume of less than 6.8 ml/s is highly likely to predict the onset of ischemic cerebrovascular accidents.     

The hemodynamic effects of mechanical prosthetic valve type and orientation on fluid mechanical energy loss and pressure drop in in vitro models of ventricular hypertrophy

A bolus injection of theophylline produced a significant increase in peripheral blood flow in anesthetized rat ear, monitored by laser-Doppler flowmetry, with increases in arterial blood pressure and heart rate. These effects were attenuated by previous treatment with reserpine, but reserpine had no effect on the blood flow increase produced by acetylcholine. A dose of propranolol, which caused attenuation of the theophylline-induced increase in heart rate, did not change the peripheral blood flow. The higher dose of propranolol, which nearly canceled the increases in blood pressure and heart rate, caused attenuation of the blood flow increase but did not cancel it. However, the theophylline-induced flow increase was completely reversed by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, which alone had no effect, without any change in arterial blood pressure and heart rate. Treatment of the rats with the dose of inhibitor slightly and significantly reduced the response of peripheral blood flow to acetylcholine. The other isomer, NG-nitro-D-arginine methyl ester, and the other inhibitor, NG-monomethyl-L-arginine, did not have such an effect. These results suggest that the flow increase is due to an independent effect on the heart with modification by autonomic reflexes and involves the adrenergic and nitrergic pathways.     

Telomere length, telomerase activity and telomerase RNA expression during mouse mammary tumor progression

The effects of intraportal administration of prostaglandin E1 (PGE1) on portal venous flow, hepatic arterial flow, peripheral tissue blood flow, and systemic arterial flow before and after 60 min total liver ischemia followed by 70% partial hepatectomy in rats were investigated. Total liver ischemia was induced by occluding the hepatoduodenal ligament for 60 min. PGE1 at a dose of 0.5 microg/kg/min was infused intraportally for 15 min before inducing hepatic ischemia (preischemic period) and for 60 min after ischemia (postischemic reperfusion period) in the treatment group. Normal saline was infused in the control group. Seventy percent partial hepatectomy was performed during ischemia. Serum biochemical analysis and liver tissue histology were carried out 1, 3, and 24 h, and 1 and 24 h after reperfusion respectively. One-week survival of the PGE1 group was improved to 70% compared to that of the control group of 30%. Postischemia reperfusion values of portal and peripheral tissue blood flows in the PGE1 group were 6.33 +/- 0.600 ml/min and 27.2 +/- 23.5 (arbitrary), and were significantly different from those of the control group of 4.34 +/- 0.400 ml/min and 23.5 +/- 5.54 (arbitrary), respectively. There was no significant difference in hepatic arterial flow between the two groups. Serum alkaline phosphatase decreased significantly in the prostaglandin group. Histological examination revealed a significant portal venous congestion in the control group 1 and 24 h after reperfusion. The extent of the sinusoidal congestion was also severe in the control group 24 h after reperfusion. It was concluded that PGE1 has a protective effect against liver damage when the liver was injured by warm ischemia and reperfusion followed by partial resection.     

Dispensability of p53 degradation for tumorigenicity and decreased serum requirement of human papillomavirus type 16 E6

Tonsils and adenoids are secondary lymphoid organs exposed to the environment. The most important classifications of AIDS include the lymphocyte subsets of peripheral blood. We have studied the lymphocyte subsets in peripheral blood and secondary lymphoid organs in a control group of children suffering adenotonsillar pathology and in five children with AIDS and the same adenotonsillar pathology. The antigen surface markers were determined by flow cytometry in lymphocytes isolated from peripheral blood, and from tonsils and adenoids after tonsillectomy and adenoidectomy, in the control group and in children diagnosed with AIDS. The most important findings in tonsils and adenoids were a decrease of the total T lymphocytes, helper T lymphocytes and CD4/CD8 ratio; an increase of cytotoxic T lymphocytes and B lymphocytes, as well as a 200% increase in monocytes of AIDS-affected children. These observations show the value of analyzing the lymphocyte subsets of the tonsils and adenoids of AIDS-affected children, and establishing an earlier relation to clinical symptoms.     

10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I

BACKGROUND: Several retrospective studies have claimed that extracorporeal photopheresis (ECP) prolongs survival in patients with erythrodermic cutaneous T-cell lymphoma. In a retrospective study of 44 patients with Sézary syndrome, we compared survival in patients treated with ECP with that of patients treated conventionally at the same institute. All patients had genotypic evidence of a peripheral blood T-cell clone. OBSERVATIONS: Twenty-nine patients received ECP (group 1); 15 patients did not receive ECP, 8 patients when ECP was available (group 2) and 7 before ECP was available (group 3). Forty-three of 44 patients received other conventional treatments. Median survival from diagnosis of Sézary syndrome was 39 months in group 1, 22 months in group 2, and 27.5 months in group 3 (Kaplan-Meier analysis). Cox regression analysis showed no significant difference between the 3 groups after correcting for age, sex, and initial Sézary cell count (hazard ratio, 0.56; 95% confidence interval, 0.26-1.17; P = .12). CONCLUSIONS: This study does not support the contention that ECP prolongs survival in patients with Sézary syndrome. The median survival in the ECP-treated group is considerably less than that reported in other published series, possibly because genotypic evidence of clonality in the peripheral blood was required for inclusion in this study. We believe that a randomized trial comparing ECP with standard chemotherapy is urgently needed.     

Clinical study on treating asthma of cold type with wenyang tongluo mixture

Sixty-eight asthma patients of Cold type were randomly divided into two groups, 34 for each group. The treated group was treated with Chinese herbal medicine Wenyang Tongluo Mixture (WYTLM), the control group was treated with Salbutamol orally and beclomethasone dipropionate aerosol. After 8 weeks of treatment, the results showed that there was no significant difference between the short-term total effective rate of the two groups (P > 0.05). Results of followup 1 year after withdrawal of treatment, showed that 9 patients (26.47%) in the treated group and 2 (5.88%) in the control group were cured clinically, it indicated that the long-term curative rate of the former group was higher than that of the latter group significantly (P < 0.05). And the effect of treated group on eliminating Asthenia-Cold symptoms, improving pulmonary ventilation function, regulating adrenergic beta-receptors of peripheral blood lymphocyte and decreasing the serum level of 5-hydroxytryptamine was more superior to that of control group (P < 0.05-0.01). This study provided some objective basis for using WYTLM in preventing and treating asthma of Cold type.     

Portal and peripheral blood immunoreactive insulin concentrations after glucose infusion during gastrectomy

We evaluated portal and peripheral blood immunoreactive insulin concentrations (IRI) after glucose infusion in patients undergoing gastrectomy. Seventy-four patients were divided into following two groups: 68 received 25g glucose infusion in an hour (glucose group), and the remainder received no glucose (control group). Portal blood IRI level in glucose group was about thirty-fold higher than that in control group. However, peripheral blood IRI did not correlate with portal blood IRI in glucose group. In addition, significant negative correlation between portal blood IRI and blood glucose was observed in glucose group. Our results reveal that adequate pancreatic insulin secretion occurs after glucose infusion during gastrectomy, but peripheral blood IRI does not reflect this pancreatic insulin secretion. The results also suggest that blood glucose may be regulated by the liver under these conditions.     

The effect of an infusion of low molecular weight dextran on peripheral resistance in patients with arteriosclerosis

Low molecular weight dextran is frequently given to improve the flow of blood to the periphery, but its mode of action is uncertain. We measured the effect of an infusion of 500 ml of Dextran 40 on the peripheral resistance in 12 patients undergoing reconstructive surgery for atherosclerotic occlusion of the superficial femoral artery. After the infusion, values of packed cell volume and blood viscosity indicated haemodilution. There was a consistent increase in mean flow and a fall in peripheral resistance. There was no correlation between change in viscosity and change in peripheral resistance, but there was a good correlation between the percentage change in resistance and the initial resistance. This suggests that the increase in flow of blood was due to reflex vasodilatation rather than to any reduction in viscosity.