Effects of (±)-sotalol, (±)-propranolol, and (−)-propranolol on norepinephrine release upon hepatic nerve stimulation in the dog liver in vivo

1985 ◽  
Vol 63 (11) ◽  
pp. 1423-1428
Author(s):  
Nobuharu Yamaguchi

The study was carried out to determine whether the diminished release of norepinephrine (NE) upon sympathetic activation in the presence of sotalol can be attributed to the blockade of beta-adrenoceptors in the liver. NE release from the liver was measured in hepatic venous blood collected during direct hepatic nerve stimulation in anesthetized dogs. The mean basal NE concentration in hepatic venous and aortic blood was 0.046 ± 0.003 and 0.244 ± 0.041 ng/mL, respectively. NE release increased significantly as stimulation frequency increased, while aortic NE concentration remained unchanged. The increasing response of NE release upon stimulation in the vehicle control group remained stable during the whole experimental period. In dogs treated with sotalol (5 mg/kg, i.v.), NE release was reduced approximately by 30–43%, and the difference was statistically significant (P < 0.01) at 8 Hz. (±)-Propranolol (2.5 mg/kg, i.v.) tended to diminish it, but the difference was not significant. (−)-Propranolol (0.1 mg/kg, i.v.) did not alter NE release at any frequency tested. The beta-blocking action of these drugs in the liver, as determined by the antagonism against the hepatic arterial vasodilating response to isoproterenol, was most effective with (±)-propranolol (100%), followed by (−)-propranolol (90%) and sotalol (70%). The results suggest that the inhibitory effect of sotalol on NE release may be related to a mechanism other than its beta-blocking action in the dog liver.

Author(s):  
Ritu Bawa ◽  
Smita Tyagi

Background: The aim of present study was to determine the role of trace elements copper and zinc and impairment of infertility.Methods: The study was a randomized, comparative, clinical trial where study group included 74 patients with primary or secondary infertility and control group included 20 patients who were fertile females of reproductive age group having no gynaecological or systemic disease. Venous blood samples were taken and plasma copper and zinc concentrations were measured.Results: In the normal fertile non-pregnant healthy female’s plasma copper ranged from 98.78 - 169.2 mcg% (mean 124.72 mcg%). In patients of unexplained infertility plasma copper was found to be low. It ranged from 63.0 - 145.14 mcg% (mean 95.5 mcg%) difference being statistically significant, (P<0.001). The difference in plasma zinc concentration in both group was not statically significant (P>0.05).Conclusions: Our results show that copper deficiency might have a role to play in the etiogenesis of otherwise unexplained infertility. We can also conclude that zinc deficiency may not play a significant role in female infertility.


2020 ◽  
Vol 08 (01) ◽  
pp. 17-21
Author(s):  
Udey Singh Wirring ◽  
Tarun Kalra ◽  
Manjit Kumar ◽  
Ajay Bansal ◽  
Aquib Javaid

Abstract Introduction Marginal bone level is the criterion for implant success. Patient expectations for more natural looking implant restorations created the need to restore implants with more esthetically pleasing materials like Zirconia rather than conventional porcelain-fused to-metal (PFM) crowns. The aim of this study was to evaluate marginal bone loss around dental implants clinically and radiographically when restored with Zirconia and PFM prosthesis. Materials and Methods Two groups (control and test) were formed with 14 patients each. In the control group, the subjects were rehabilitated with PFM crowns and in the test group, the subjects were rehabilitated with Zirconia crowns. Rehabilitation was done after the healing period of 3 months. Radiographic evaluation was done at regular (baseline, 3rd, 6th, and 12th month) intervals. Results The results were statistically analyzed. Keeping in mind the limitations of the study, it was revealed that the difference in the crestal bone resorption in both the groups was not significant.


1960 ◽  
Vol 15 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Suk Ki Hong ◽  
John W. Boylan ◽  
Alf M. Tannenberg ◽  
Hermann Rahn

The total and partial gas tensions of human bladder urine were studied by a modified Krogh micromanometric method combined with fractional absorption analysis and the use of a Clark oxygen electrode. Consumption of O2 by reducing substances in urine was determined and correlated with its specific gravity and pH. Oxygen tension of bladder urine averages 50 mm Hg during air breathing and 58 mm Hg during pure O2 breathing. Pco2 ranges from 47 to 152 mm Hg and correlates best with urinary pH. The average figure for urine nitrogen tension, 550 mm Hg, agrees closely with the calculated Pn2 of alveolar air. Total gas tension of urine is typically about 60 mm Hg less than atmospheric and changes in total gas tension are shown to reflect changes in Pco2, the tensions of the other gases remaining relatively constant in an experimental period. The physiological significance of these total and partial gas tensions is discussed. A counter-current gas diffusion system is proposed to account for the difference between the oxygen tension of urine and renal venous blood. Submitted on September 24, 1959


Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM,69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.


1979 ◽  
Vol 237 (3) ◽  
pp. H326-H331
Author(s):  
N. W. Robie

Experiments were performed in anesthetized dogs to determine whether previously reported in vitro inhibition of sympathetic neurotransmitter release by acetylcholine could be demonstrated in the renal vasculature of the intact animal. Vasoconstrictor responses to renal sympathetic nerve stimulation at varying frequencies were compared to intra-arterial injections of norepinephrine before and during intra-arterial infusions of acetylcholine, 2.5--80 micrograms/min. The vasoconstrictor responses to nerve stimulation were inhibited to a greater extent than were responses to norepinephrine during infusions of acetylcholine. The inhibitory effects of acetylcholine on nerve stimulation were dose and frequency dependent. The inhibition was blocked by atropine but not altered by physostigmine. Changes in renal blood flow per se did not contribute to the inhibitory effect of acetylcholine, since another vasodilator agent, sodium acetate, did not affect the nerve stimulation-norepinephrine vasocontriction relationship. Thus, acetylcholine produced inhibition of in vivo renal sympathetic vasoconstrictor responses, and the receptor involved appears to be muscarinic.


Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093942
Author(s):  
Muhammad Younus ◽  
Muhammad Mohtasheem ul Hasan ◽  
Khalil Ahmad ◽  
Ali Sharif ◽  
Hafiz Muhammad Asif ◽  
...  

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.


1986 ◽  
Vol 64 (8) ◽  
pp. 1076-1084 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Michel Naud ◽  
Daniel Lamontagne ◽  
Reginald Nadeau ◽  
Jacques de Champlain

Effect of sotalol (STL) was compared with that of (±)-propranolol, (+)-propranolol (PPL), and acebutolol (ABL) on noradrenaline (NA) release as measured in coronary sinus (CS) blood during postganglionic stimulation (2 Hz, 30 s) of the left cardiac sympathetic nerves in anesthetized dogs. In control dogs receiving saline, increasing responses of CS-NA concentration, mean CS blood flow, and CS-NA output to repetitive stimulation were relatively stable throughout a given experimental period. Both STL (1, 2.5, and 5 mg/kg, i.v.) and (±)-PPL (0.5 and 2.5 mg/kg, i.v.) diminished the increased CS-NA concentration by approximately 35 (P < 0.05) to 60% (P < 0.01) in a dose-dependent fashion. However, (+)-PPL (0.02–2.5 mg/kg, i.v.) and ABL (0.5–5 mg/kg, i.v.) did not significantly alter the increasing response of CS-NA concentration upon stimulation. STL, (±)-PPL, and ABL markedly inhibited the CS blood flow response to stimulation at all doses tested, while (+)-PPL did not significantly diminish the flow response even at the highest dose tested. Consequently, CS-NA output decreased significantly (p < 0.01) in the presence of STL, (±)-PPL, and ABL at all doses tested but not with (+)-PPL at any dose tested. The inhibitory effect of STL and (±)-PPL on the increasing response of CS-NA concentration upon stimulation could be related to their beta-blocking effect, which exerts presumably on postulated presynaptic β-adrenoceptors, as (+)-PPL did not at all diminish the response. On the other hand, ABL does not seem to exert a similar presynaptic inhibitory effect, owing presumably either to its β-1 selectivity or to its intrinsic sympathetic activity. The results support the existence of facilitatory presynaptic β-adrenoceptors in the normal dog heart under in vivo conditions. The findings also suggest that NA release upon cardiac sympathetic nerve stimulation may be reflected more precisely by CS-NA concentration than by NA output.


Author(s):  
Heydar Sadeghi ◽  
Hesam Fazlali ◽  
Saba Sadeghi ◽  
Seyedmojtaba Seyedmojtaba Ojaghi

Background: In athletes with anterior cruciate ligament (ACL) deficiencies could assess functional capabilities with different instruments such as use of a camera in vivo situation. However, these methods have suffered from a large number of limitations such as inability to be repeatable and complexity in technique. Objective: The main purpose of this study was to compare gait pattern of the athletes with ACL injury and able-bodied subjects using an accelerometer. Method: A three-dimensional accelerometer was placed over the tibia tuberosity of 20 healthy and 20 individuals with ACL-deficiencies (ACLD). After walking on the treadmill, the principal components of the acceleration data were calculated using MATLAB software. Results: In this study, Principle Component analysis was used for statistical analysis. The results indicated that subjects with ACL deficiency have different gait pattern compared to the control group. The major differences between stride trajectories of the two groups were at the end of mid-swing and the beginning of terminal swing phases in vertical axis. ACL deficient subjects exhibited different gait patterns during mid and terminal stance phases in anterior- posterior axis compared with normal controls. Conclusions: The difference in gait between subjects with ACL deficiency and healthy subjects are depends on variation in the amount of knee flexion and tibia rotation that could be altered to motor recruitment.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 509-509 ◽  
Author(s):  
Angela Pennisi ◽  
Wen Ling ◽  
Paul Perkins ◽  
Rinku Saha ◽  
Xin Li ◽  
...  

Abstract We have recently demonstrated the inhibitory effect of osteoblasts on myeloma (MM) ex vivo and in vivo (Yaccoby et al., Haematologica 2006) and that anti-MM response of bortezomib is associated with osteoblast activation in patients with MM (Zangari et al., BJH 2005). The aims of this study were to investigate the effect of intermittent PTH and bortezomib on bone remodeling and tumor growth, and the consequences of PTH pretreatment on MM progression in our SCID-rab model for primary MM (Yata & Yaccoby, Leukemia 2004). In nonmyelomatous hosts, both PTH and bortezomib significantly increased bone mineral density (BMD) of the implanted bone. SCID-rab mice were engrafted with MM cells from 13 patients. Following establishment of MM growth, as monitored by bi-weekly measurement of human monoclonal immunoglobulins (hIg) in mice sera and by x-rays, mice were injected subcutaneously with bortezomib (0.5 mg/kg twice a week, n=10), PTH (0.3 mg/kg/day, n=5) or PBS for 4–8 weeks. Whereas all PBS-treated mice had increased hIg levels during the experimental period, bortezomib treatment resulted in marked reduction of hIg in 5/10 experiments by 73±10% from pretreatment levels (responding hosts) and stabilized or delayed growth in additional 5 experiments. Overall, tumor burden in control- and bortezomib-treated mice was increased by 447±118% and 157±97% from pretreatment levels, respectively (p&lt;0.02). Whereas in control mice the BMD of the implanted bone was reduced by 17±5% from pretreatment, it increased in bortezomib-treated hosts by 4±10% from pretreatment (p&lt;0.03). While in bortezomib-responding hosts BMD increased by 20±14% (n=5), it decreased in partial/non-responding hosts (n=5) by 13±12% (n=5) from pretreatment (p&lt;0.047). This bone anabolic effect was unique to bortezomib and was not observed in hosts responding to dexamethasone. Histological examination revealed that myelomatous bones from bortezomib-treated hosts had increased numbers of osteocalcin-expressing osteoblasts (34±7 vs. 13±3 per mm bone in control mice, p&lt;0.03) and reduced numbers of multinucleated TRAP-expressing osteoclasts (10±3 vs. 28±7 per mm bone in control mice, p&lt;0.02). We further demonstrated that bortezomib suppresses osteoclastogenesis through downregulation of NF-κB activity in osteoclast precursors. Since bortezomib also directly inhibits MM cell growth we further studied the association between increased bone formation and MM growth by treating hosts engrafted with MM cells from 5 patients with PTH, a bone anabolic agent with no known direct apoptotic effect on MM cells. Whereas PTH treatment resulted in increased BMD of the implanted bone by 19±5%, BMD in control hosts was reduced by 5±8% from pre-treatment (p&lt;0.05). The bone anabolic effect of PTH was associated with inhibition of MM progression in 4/5 experiments. Overall, hIg in PBS- and PTH-treated mice was increased by 947±247% and 391±217% from pretreatment levels, respectively (p&lt;0.04). In additional set of experiments hosts received PTH or PBS, 4 weeks prior to inoculation of MM cells from 3 patients and thereafter. In all experiments, PTH pretreatment, which increased implanted BMD by 48±11%, resulted in slower growth of MM cells as compared to control hosts. We conclude that increased bone formation by PTH and bortezomib contributes to controlling MM growth and that pretreatment with PTH, in addition to improving skeletal complications, may be a promising approach to prevent MM progression.


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