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Thirty-eight patients with ET affecting upper limbs underwent a randomized, crossover study with olanzapine (20 mg/day) and propranolol (120 mg/day). Evaluation (baseline and 1 month after each drug) was done by using the tremor clinical rating scale and a self-reported disability scale.
Variceal obliteration was achieved in 16 of 20 patients (80%) in the SG group and in 16 of 18 patients (88%) in the SPG group. Time required for variceal obliteration was significantly shorter in the SPG group compared with the SG group (4.1 +/- 1.4 vs 3.2 +/- 0.9 months; P < 0.05). The variceal recurrence rate was 65 and 38.8% in the SG and SPG groups, respectively. Compared with the SG group, less variceal rebleeding was observed during EST in the SPG group (25 vs 16.6%, respectively).However, these differences were not statistically significant.
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In mammalian heart, connexin43 (Cx43) represents the predominant connexin in the working myocardium. As the beta-adrenoceptor is involved in many cardiac diseases, we wanted to clarify the pathway by which beta-adrenoceptor stimulation may control Cx43 expression.
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We report a 15-year-old girl with a recent diagnosis of type 2 diabetes mellitus who presented in malignant hypertensive crisis (BP 210/120 mm Hg). Abdominal CT showed an 8.2 x 4.7 x 7.0 cm mass in the region of the organ of Zuckerkandl. MIBG scan showed a single paraganglioma without metastatic foci. Plasma total metanephrines were 232,176.4 pmol/l [263-1052] with normetanephrine predominance. Pre-operative course was complicated by ischemic stroke in the left MCA and right thalamic regions, acute renal failure, rhabdomyolysis and congestive heart failure. She required massive doses of propranolol, phenoxybenzamine, doxazosin and metyrosine prior to surgery.
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The progressive shortening of the atrial effective refractory period (ERP) during atrial fibrillation (AF) might be due to the activation of the KATP channels by rapid atrial rates. We tested the hypothesis that the cardioselective, sarcolemmal KATP channel blocker HMR 1098 would prevent atrial ERP shortening during AF.
Presenting age, treating institution, syndrome presence, presenting AIH stage, endoscopy status, propranolol initiation location/dose/duration, time to stridor resolution, adjunctive medical and surgical therapy, and treatment-associated complications.
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The interaction between drugs and human serum albumin (HSA) was investigated by capillary electrophoresis (CE). It involves stereoselectivity, drug displacement and synergism effects. Under protein-drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by frontal analysis (FA). The stereoselectivity of verapamil (VER) binding to HSA was proved by the different free fractions of two enantiomers. In physiological pH (7.4, ionic strength 0.17 phosphate buffer) when 300 microM (+/-) VER were equilibrated with 500 microM HSA, the concentration of unbound S-VER was about 1.7 times its antipode. The binding constants of two enantiomers, K(R-VER) and K(S-VER), were 2670 and 850 M(-1), respectively. However, no obvious stereoselective binding of propranolol (PRO) to HSA was observed. Trimethyl-beta-cyclodextrin (45 mM) was used as a chiral selector in pH 2.5 phosphate buffer. Several drug systems were studied by the method. When ibuprofen (IBU) was added into VER-HSA solution. R-VER was partially displaced while S-VER was not displaced at all. A binding synergism effect between bupivacaine (BUP) and verapamil was observed and further study suggested that verapamil and bupivacaine occupy different binding site of HSA (site II and site III, respectively).
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Sterile-male-release technique is currently used to control the sea lamprey (Petromyzon marinus) population in the Great Lakes. The chemosterilant (bisazir) used in this program is extremely hazardous; special safety measures are necessary when handling this chemical. Therefore, replacement of bisazir with safer agents is desirable. In this study, we examined the effects of low-toxicity compounds with previously described spermicidal activity (mainly against mammalian sperm) on motility and fertilizing ability of sea lamprey spermatozoa. Nonoxynol-9, benzalkonium chloride, zinc acetate, cupric chloride, cysteamine, tannic acid and propranolol were able to inhibit both sperm motility and fertilizing ability. Effective concentrations of these spermicides ranged from 0.15 to 1%. Therefore, they can be potentially used in further study directed at in vivo sterilization of male sea lampreys.
Adrenergic responses are crucial for hypoglycemic recovery. Epinephrine increases glucose production, lipolysis, and peripheral insulin resistance as well as blood flow and glucose delivery. Sympathetic activation causes vasoconstriction and reduces glucose delivery. To determine the effects of alpha- and beta-adrenergic activity on muscle glucose uptake during hypoglycemia, we studied forearm blood flow (FBF) (plethysmography), arteriovenous glucose difference (AV-diff), and forearm glucose uptake (FGU) during insulin infusion with 60 min of euglycemia followed by 60 min of hypoglycemia. Twelve healthy subjects (27 plus minus 5 years of age) were randomized to intravenous propranolol (IV PROP, 80 microg/min), intravenous phentolamine (IV PHEN, 500 microg/min), intra-arterial propranolol (IA PROP, 25 microg/min), intra-arterial phentolamine (IA PHEN, 12 microg/min per 100 ml forearm tissue), and saline (SAL). FBF increased during hypoglycemia with SAL (P < 0.001) but not with IA or IV PROP. FGU (P = 0.015) and AV-diff (P = 0.099) fell during hypoglycemia with IA PROP but not with IV PROP. FBF increased during hypoglycemia with IA and IV PHEN (P < 0.005). AV-diff fell during hypoglycemia with IA and IV PHEN (P < 0.01), but FGU was unchanged. Blood pressure fell (P < 0.001), and adrenergic and neuroglycopenic symptoms increased with IV PHEN (P < 0.01). Thus, systemic but not local propranolol prevents a decrease in forearm glucose extraction during hypoglycemia, suggesting that epinephrine increases peripheral muscular insulin resistance through systemic effects. alpha-Adrenergic activation inhibits vasodilation and helps maintain brain glucose delivery.
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Based on previous studies we hypothesize that under stress conditions catecholamine-induced hyperglycemia contributes to enhance cortisol production in head kidney of rainbow trout. Therefore, treatment with propranolol (β-adrenoceptor blocker) should reduce the hyperglycemia elicited by stress and, therefore, we expected reduced glucosensing response and cortisol production in head kidney. Propranolol treatment was effective in blocking most of the effects of catecholamines in liver energy metabolism resulting in a lower glycemia in stressed fish. The decreased glycemia of stressed fish treated with propranolol was observed along with reduced transcription of genes involved in the cortisol synthetic pathway, which supports our hypothesis. However, changes in putative glucosensing parameters assessed in head kidney were scarce and in general did not follow changes noted in glucose levels in plasma. Furthermore, circulating cortisol levels did not change in parallel with changes in glycemia. As a whole, the present results suggest that glycemia could participate in the regulation of cortisol synthetic pathways but other factors are also likely involved. Propranolol effects on trout stress response were different depending on time passed after stress onset; the direct or indirect involvement of catecholaminergic response in the regulation of cortisol production and release deserves further investigation.
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Patients with mild-to-moderate irreversible COPD and AHR.
We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P < 0.05 versus precooling). Hypoxia caused vasodilatation prior to cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P < 0.05 versus precooling; both P < 0.05 versus normoxia). Core cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.
To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress.
To evaluate the effects of left ventricular contractility on the changes of average image intensity (AII) of the myocardial integrated backscatter (IB) and cyclic variation in IB (CVIB), 7 adult mongrel dogs were studied. The magnitude of AII and CVIB were measured from myocardial IB carves before and after dobatamine or propranolol infusion. Dobutamine or propranolol did not affect the magnitude of AII (13.8 +/- 0.7 vs 14.7 +/- 0.5, P > 0.05 or 14.3 +/- 0.5 vs 14.2 +/- 0.4, P > 0.05). However, dobutamine produced a significant increase in the magnitude of CVIB (6.8 +/- 0.3 vs 9.5 +/- 0.6, P < 0.001) and propranolol induced significant decrease in the magnitude of CVIB (7.1 +/- 0.2 vs 5.2 +/- 0.3, P < 0.001). The changes of the magnitude of AII and CVIB in the myocardium have been demonstrated to reflect different myocardial physiological and pathological changes respectively. The alteration of contractility did not affect the magnitude of AII but induced significant change in CVIB. The increase of left ventricular contractility resulted in a significant rise of the magnitude of CVIB and the decrease of left ventricular contractility resulted in a significant fall of the magnitude of CVIB.
In the present study, we examined the effect of vasopressin on the induction of the low-molecular-weight heat shock proteins heat shock protein 27 (HSP27) and alphaB-crystallin in an aortic smooth muscle cell line, A10 cells. Vasopressin induced a time-dependent accumulation of HSP27 and alphaB-crystallin. The stimulatory effects of vasopressin were dose-dependent over the range 0.1 nmol/L to 0.1 micromol/L. The EC50 values for vasopressin were 2 (HSP27) and 4 nmol/L (alphaB-crystallin). Vasopressin induced increases in the levels of the mRNAs for HSP27 and alphaB-crystallin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, induced an accumulation of HSP27 (EC50, 20 nmol/L) and alphaB-crystallin (EC50, 2 nmol/L). In contrast, 4alpha-phorbol 12,13-didecanoate, a non-PKC-activating phorbol ester, had no such effect. Staurosporine and calphostin C, inhibitors of PKC, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin as well as that induced by TPA. BAPTA/AM and TMB-8, inhibitors of intracellular Ca2+ mobilization, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin. These results strongly suggest that vasopressin stimulates the induction of HSP27 and alphaB-crystallin via PKC activation in vascular smooth muscle cells and that this effect of vasopressin is dependent on intracellular Ca2+ mobilization.
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A total of 60 patients undergoing bimaxillary surgery were studied in a prospective, randomized, and double-blind study of oral propranolol 10 mg or placebo as premedication before hypotensive anesthesia with sodium nitroprusside. Hemodynamic variables, the amount of sodium nitroprusside used, and blood loss were statistically analyzed.
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A strong correlation was found between the actual LV volume and that calculated from RT3D echocardiography (r=0.96, p<0.001). Propranolol (0.1 mg/kg/10 min, n=5) caused an increase in ESV, but not EDV, resulting in a decrease in EF and SV, while verapamil produced increases in both EDV and ESV. Dobutamine (0.01 mg/kg/5 min, n=5) produced decreases in both EDV and ESV and thereby the increased CO resulted from the increased SV.
Molecularly imprinted polymers (MIPs) were synthesized in 24-well glass fiber membrane filter plates to obtain a novel type of solid phase extraction device for the cleanup of propranolol. Sample processing parameters like residence time during sample loading, sample volume, pH, sample solvent, type and amount of washing and elution solvents were investigated and optimized. Important differences from the traditional molecularly imprinted solid phase extraction (MISPE) cartridges have been identified. The MIP modified composite membrane suits well for the sample preparation of low volume biological samples. A protocol has been elaborated for the quantitation of propranolol from urine and plasma samples in the clinically relevant concentration ranges. Preliminary validation results indicate that the composite MIP membrane filter plates offer a viable alternative to existing MISPE cartridges and at the same time have advantages like much easier and faster synthesis method and high-throughput analysis.
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Adenosine infusion can potentially be used as a diagnostic test for sick sinus syndrome (SSS) based on its negative chronotropic effects. Whether autonomic tone underlies adenosine's negative chronotropic effects remains unknown. This study was to investigate the bradycardiac response of sinus node to ATP in patients with and without clinical SSS by measuring atrial cycle length (ACL) before and after bolus of ATP in different states of autonomic tone. The negative chronotropic effect of ATP was assessed by comparing the mean ACL before ATP administration with the longest ACL after a bolus of ATP infusion (Delta ACL). Our results showed that Delta ACL in patients with SSS were significantly greater than that without SSS (P<.001) in all 4 states, and IHR in patients with SSS were significantly lower than calculated IHR (P<.0001). Moreover, there was no significant difference in Delta ACL between the 4 states in patients with SSS (P = .99). However, Delta ACL was significantly greater during isoproterenol infusion and after propranolol administration in patients without sinus node dysfunction, comparing with baseline state (P<.01), but not after combination of atropine (P = .33). Our results indicate that the negative chronotropic effect of ATP on sinus node is much more dramatic in patients with SSS, in which the intrinsic disease of sinus node is responsible for the abnormal adenosine-mediated sinus arrest, and this effect is influenced by autonomic tone in patients without sinus node dysfunction but not in patients with SSS.
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There were no statistically significant differences between the two groups with respect to the HUTT pattern (P=0.25) and requirement for sublingual NTG during test (P=0.20). After one month of treatment, oral beta-blockers prevented the occurrence of syncope during second HUTT in 11 patients (35.5%) in the Group I and 9 (29%) patients in the Group II (P=0.58) and delayed the occurrence of symptoms in 9 Group I patients (29%) and 8 Group II patients (16%) (P=0.77). During the 16-months follow-up, 53 patients (85.5%) remained free of syncope. No statistically significant difference was observed between the two groups with respect to recurrence of syncope (P=0.47). In both groups, the patients in whom treatment efficacy was proved by a negative tilt test had similar recurrence of syncope as those patients who had a positive tilt test (Both P>0.05).
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Twelve chiral derivatizing reagents (CDRs) were synthesized by substituting one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene (DFDNB) with three optically pure amines [(R)-(-)-1-cyclohexylethylamine, (+)-dehydroabietylamine and (S)-(-)-alpha,4-dimethylbenzylamine], six amino acid amides [L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg-NH(2)] and three amino acids [L-Ala, L-Val and L-Leu]. In addition, dinitrophenyl-L-Pro-N-hydroxysuccinimide ester and N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate were also synthesized and used as CDR. Keeping in view the presence of an amino group, diastereomers of six beta-blockers (atenolol, propranolol, bisoprolol, metoprolol, salbutamol, and carvedilol) were synthesized by reaction with these 14 CDRs. The diastereomers were separated by RP-HPLC. The method was validated for linearity, accuracy, limit of detection and limit of quantification.