Direct Effects of α1-and α2-AdrenergicAgonists on Spinal and Cerebral Pial Vessels in Dogs 

1999 ◽  
Vol 91 (2) ◽  
pp. 479-485 ◽  
Author(s):  
Hiroki Iida ◽  
Hiroto Ohata ◽  
Mami Iida ◽  
Yukinaga Watanabe ◽  
Shuji Dohi
Keyword(s):  
Topical Administration ◽  
Vessel Diameter ◽  
Dependent Manner ◽  
Adrenergic Agonists ◽  
Concentration Dependent Manner ◽  
Cranial Window ◽  
Pial Vessels ◽  
Cerebral Arterioles ◽  
Pial Vessel

Background The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of alpha2- and alpha1-adrenergic agonists on spinal and cerebral pial vessels in vivo. Methods Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 microg/ml; [2.1, 1.9, 2.5, and 2.3] x [10(-6), 10(-5), and 10(-4)] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window. Results On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 microg/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels). Conclusion Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.

Isoflurane and Sevoflurane Induce Vasodilation of Cerebral Vessels via ATP-sensitive K+Channel Activation 

1998 ◽  
Vol 89 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Hiroki Iida ◽  
Hiroto Ohata ◽  
Mami Iida ◽  
Yukinaga Watanabe ◽  
Shuji Dohi
Keyword(s):  
Adenosine Triphosphate ◽  
Volatile Anesthetic ◽  
Vessel Diameter ◽  
Cerebral Vessels ◽  
K Channel ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Cranial Window ◽  
Cerebral Vasodilation

Background Activation of adenosine triphosphate-sensitive K+ channels causes cerebral vasodilation. To assess their contribution to volatile anesthetic-induced cerebral vasodilation, the effects of glibenclamide, an adenosine triphosphate-sensitive K+ channel blocker, on the cerebral vasodilation induced by isoflurane and sevoflurane were studied. Methods Pentobarbital-anesthetized dogs (n = 24) assigned to one of two groups were prepared for measurement of pial vessel diameter using a cranial window preparation. Each dog received three minimum alveolar concentrations (MAC; 0.5, 1, and 1.5 MAC) of either isoflurane or sevoflurane, and the pial arteriolar diameters were measured in the presence or absence of glibenclamide (10(-5) M) infused continuously into the window. Mean arterial pressure was maintained with phenylephrine. Furthermore, to assess the direct effect of isoflurane and sevoflurane on cerebral vessels, artificial cerebrospinal fluid was administered topically by being bubbled with isoflurane or sevoflurane. The blocking effect of glibenclamide on the vasoactive effects of these anesthetics also were evaluated. Results Isoflurane and sevoflurane both significantly dilated large (> or = 100 microm) and small (< 100 microm) pial arterioles in a concentration-dependent manner (6% and 10%, 3% and 8% for 0.5 MAC; 10% and 19%, 7% and 14% for 1 MAC; 17% and 28%, 13% and 25% for 1.5 MAC). Glibenclamide attenuated the arteriolar dilation induced by these anesthetics (not significant in isoflurane). Topical application of isoflurane or sevoflurane dilated large and small arterioles both in a concentration-dependent manner. Such vasodilation was inhibited completely by glibenclamide. Conclusion The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane appears to be mediated, at least in part, via activation of adenosine triphosphate-sensitive K+ channels.

Direct Effects of Ropivacaine and Bupivacaine on Spinal Pial Vessels in Canine 

1997 ◽  
Vol 87 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Hiroki Iida ◽  
Yukinaga Watanabe ◽  
Shuji Dohi ◽  
Tadahiko Ishiyama
Keyword(s):  
Topical Application ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Beta Adrenoceptor ◽  
Pial Vessels ◽  
Arterial Blood ◽  
Before And After ◽  
Pial Arterioles ◽  
Anesthetized Dogs ◽  
Pial Vessel

Background Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. Methods Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. Results Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. Conclusions The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.

scholarly journals Effects of Bradykinin on Permeability and Diameter of Pial Vessels In vivo

1984 ◽  
Vol 4 (4) ◽  
pp. 574-585 ◽  
Author(s):  
Andreas Unterberg ◽  
Michael Wahl ◽  
Alexander Baethmann
Keyword(s):  
Blood Brain Barrier ◽  
Topical Administration ◽  
Vessel Diameter ◽  
Brain Barrier ◽  
Maximal Response ◽  
Barrier Dysfunction ◽  
Kinin System ◽  
Pial Vessels ◽  
Blood Brain

The effect of bradykinin on the permeability and vasomotor response of pial vessels has been studied to enhance our understanding of the pathophysiological role of the kallikrein–kinin system in cerebral tissue. Intravital fluorescence microscopy of the pia arachnoidea was conducted using Na+-fluorescein, FITC-dextran, and FITC-albumin as low and high molecular weight blood–brain barrier indicators. Massive arterial dilatation evolved immediately upon administration of bradykinin by superfusion of the exposed cerebral surface. An increase of the arterial diameter by 40% was the maximal response found at bradykinin concentrations of 4 × 10−5 M. Arterial dilatation became attenuated with continuous superfusion of the preparation with bradykinin. In pial veins, a moderate reduction of the vessel diameter was observed, however, only after prolonged superfusion of the preparation. Bradykinin led to selective opening of the blood–brain barrier for Na+-fluorescein at super-fusate concentrations of ⩾4 × 10−7 M, but not for FITC-dextran or FITC-albumin. Topical administration of l-isoproterenol (10−4 M) was found to prevent extravasation of Na+-fluorescein in the presence of bradykinin concentrations of 4 × 10−6 M. Protection of the blood–brain barrier by isoproterenol was not observed when higher concentrations of bradykinin were employed. Intracarotid infusion of bradykinin led also to a selective opening of the blood–brain barrier for Na+-fluorescein, but not for FITC-dextran or FITC-albumin. In contrast to superfusion, this route of administration did not induce changes of the vasomotor behavior of the arteries or veins. Additional experiments with B1-agonists and -antagonists suggest that bradykinin causes the opening of the blood–brain barrier through an interaction with B2-receptors on endothelial cells, and arterial dilatation via interaction with B2-receptors on vascular smooth muscle cells. Our findings support the concept that the release of kinins in the brain during an acute cerebral lesion mediates secondary damaging processes by the enhancement of blood–brain barrier dysfunction.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

scholarly journals Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Natalia K. Kordulewska ◽  
Justyna Topa ◽  
Małgorzata Tańska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Reaction ◽  
Wide Spectrum ◽  
Cell Monolayer ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

Fibrinogen binding to the integrin αIIbβ3 modulates store-mediated calcium entry in human platelets

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2648-2656 ◽  
Author(s):  
Juan A. Rosado ◽  
Else M. Y. Meijer ◽  
Karly Hamulyak ◽  
Irena Novakova ◽  
Johan W. M. Heemskerk ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Integrin Αiibβ3 ◽  
Fibrinogen Binding

Abstract Effects of the occupation of integrin αIIbβ3 by fibrinogen on Ca++signaling in fura-2–loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to αIIbβ3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin αIIbβ3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo.

Vasomotion of basilar arteries in vivo

1990 ◽  
Vol 258 (6) ◽  
pp. H1829-H1834 ◽  
Author(s):  
K. Fujii ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
Moderate Hypertension ◽  
Vessel Diameter ◽  
Base Line ◽  
Large Artery ◽  
Cranial Window ◽  
Basilar Arteries ◽  
The Mean ◽  
Rhythmic Change ◽  
The Brain

Vasomotion is a rhythmic change in vascular caliber that has been described in vivo mainly in peripheral arterioles. In this study, we have characterized vasomotion in a large artery of the brain in vivo. In anesthetized rats, spontaneous vasomotion was observed in 38 of 47 basilar arteries visualized through a cranial window. Base-line arterial diameter was 259 +/- 9 (means +/- SE) microns. Under control conditions, the frequency of vasomotion was 4.8 +/- 0.2 cycles/min, and the amplitude was 19 +/- 2% of the mean diameter. Vasomotion usually occurred simultaneously along the entire length of the vessel, but in some arteries it propagated in either direction. Moderate hypertension (phenylephrine) or vasoconstriction induced by topical application of serotonin, vasopressin, or the thromboxane analogue U 46619 increased the frequency of vasomotion. Moderate hypotension or vasodilation induced by nitroglycerin, adenosine, or acetylcholine decreased the frequency. Marked hypertension, hypotension, or vasodilatation abolished vasomotion. Thus vasomotion of the basilar artery in vivo 1) is common and of relatively large amplitude, 2) does not seem to be driven by a single pacemaker, and 3) is dependent on vessel diameter or vasomotor tone.

scholarly journals Sequestration of erythrocytes infected with Plasmodium berghei ANKA in BALB/c mice treated with goat bile

2020 ◽  
Vol 4 (2) ◽  
pp. 179
Author(s):  
Kartika Arum Wardani ◽  
Kholida Nur Aini ◽  
Heny Arwati ◽  
Willy Sandhika
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Control Group ◽  
Dependent Manner ◽  
Plasmodium Berghei Anka ◽  
Concentration Dependent Manner ◽  
Control Group Design ◽  
Bile Concentration

Abstract Sequestration of Plasmodium berghei ANKA-infected erythrocytes occurs in BALB/c mice as characteristic of  Plasmodium falciparum infection in humans. Animals’ bile has been widely used for centuries in Traditional Chinese Medicine. Goat bile has been used in healing infectious and non-infectious diseases; however, no report on the use of goat bile against malaria infection and sequestration. The purpose of this study was to analyze the correlation between parasitemia and sequestration in the liver of P.berghei ANKA-infected BALB/c mice treated with goat bile. This research was an in vivo experimental study using the post-test control group design. The male BALB/c mice aged ± 6 weeks, body weight 20-25 g were used. The mice were divided into five groups where Group 1-3 were mice treated with goat bile 25%, 50%, and 100%, respectively. Group 4-5 were negative (sterile water) and positive controls (DHP). Parasitemia was observed daily from each mouse and the number of sequestered infected erythrocytes on the endothelium of sinusoids. The data were analyzed using t independent test. Antimalarial activity of goat bile was shown by the lower parasitemia in goat bile-treated mice compared with the negative control. The average number of sequestration was goat bile concentration-dependent manner. The higher the concentration, the lower the number of sequestration. Sequestration was correlated with parasitemia (p=0,0001). Sequestration of P.berghei ANKA-infected erythrocytes correlated with parasitemia, and was goat bile concentration-dependent manner. Keywords: Malaria, parasitemia, sequestration, goat bileCorrespondence: [email protected]

scholarly journals Inhibition of HepG-2 Cells (Liver Cancer Cell Line) Viability by 3-Hydroxypyridine-2-Carboxaldehyde N(4)-Methylthiosemicarbazone

2021 ◽  
Vol 8 (2) ◽  
pp. 88-97
Author(s):  
Edrees Khan Rahmatzada ◽  
Prof. Paras Nath Yadav ◽  
Dr. Yuba Raj Pokharel
Keyword(s):  
Cancer Cell Line ◽  
Mapk Signaling ◽  
In Vivo Model ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Concentration Dependent Manner ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Colony Number

Thiosemicarbazone have the antiviral, antibacterial, antifungal, and anticancer effects. 3-OH-Me-TSC inhibited the cell viability of HepG-2 cells by CV assay in a concentration dependent manner (control, 1μM, 3μM, 10μM, 30μM, and 100μM) with IC50 value of 9.587622μM. Further colony formation assay demonstrated that 3-OH-Me-TSC inhibits colony number and size of HepG-2. Wound healing assay exhibited that 3-OH-Me-TSC inhibit the migration of HepG-2 cells. DAPI staining showed that 3-OH-Me-TSC inhibited proliferation of HepG-2 cells in 30μM and 100μM concentrations respectively. 3-OH-Me-TSC inhibited VEGF, p38 alpha, C-JUN, BECN-1, ERK, NF-KB, in HepG-2 cells. We found that 3-OH-Me-TSC inhibit proliferation of HepG-2 cells by inhibiting MAPK signaling pathway, 3-OH-Me-TSC can be developed as future chemotherapeutic agent for treatment of hepatocellular carcinoma after the evaluation of this compounds in more cancer cells an in vivo model.

Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza Shiran ◽  
Elham Mahmoudian ◽  
Abolghasem Ajami ◽  
Seyed Mostafa Hosseini ◽  
Ayjamal Khojasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Animal Model ◽  
Protein Expression ◽  
Western Blot ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Abstract Objectives Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1. Conclusions Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

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