Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the...Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the other hand,drug brain delivery via the BBB is a big challenge in glioma therapy.The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development.Here,we present in vrivo and er vrivo study of the BBB disruption and glioma cells(GCs)migration in rats using fuorescence and confocal microscopy.We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells,where the BBB was impermeable for high weight molecules.The migr ation of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration.The mechanisms underlying glioma progression remain umknown but there is an evidence that the sympathetic nervous system(SNS)via activation of vascular beta2-adrenoreceptors(B2-ADRs)can play an important role in tumor metastasis.Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta arrestin-1-co-factor of B2-ADRs signaling pathway in rats with glioma.Pharmacological blockade of B2-ADRs reduces the BBB disruption,macrophages infiltration,GCs migration and increases survival rate.These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis。展开更多
To explore the relationship of β adrenoreceptor density and function with the condition of patients with essential hypertension Methods In the present study, 69 male patients with essential hypertension at differe...To explore the relationship of β adrenoreceptor density and function with the condition of patients with essential hypertension Methods In the present study, 69 male patients with essential hypertension at different stages were compared with a group of age matched normotensive controls β adrenoreceptor maximum bound volume (B max ) in peripheral lymphocytes was measured by 3 H dihydroalprenolol ( 3 H DHA) radio ligand binding β adrenoreceptor responsiveness was determined by Salbutamol (injection) Results In patients with essential hypertension at stages Ⅰ and Ⅱ, B max was significantly higher ( P <0 01 and P <0 001, respectively) and the chronotropic doses of Salbutamol required to increase the heart rate by 30 beats/min (CD 30 ) were significantly lower ( P <0 01 and P <0 001, respectively) than in age matched normotensive control subjects In patients with essential hypertension at stage Ⅲ, B max was significantly lower and CD 30 was significantly higher (both P <0 01) than those in the age matched normotensive control subjects B max was significantly higher and CD 30 was significantly lower (both P <0 001) in patients with essential hypertension and with left ventricular hypertrophy (LVH) than that in patients with essential hypertension but without LVH In patients with essential hypertension and heart failure, B max was significantly lower and CD 30 was significantly higher (both P <0 001) than those in patients with essential hypertension without heart failure Conclusions The changes of β adrenoreceptor density and function were related to hypertension, hypertension complicated with ventricular hypertrophy, and heart failure They may be viewed as indexes of the condition in the patients with essential hypertension展开更多
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants o...Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).展开更多
基金Grant of Russian Science Foundation No.17-75-20069.
文摘Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the other hand,drug brain delivery via the BBB is a big challenge in glioma therapy.The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development.Here,we present in vrivo and er vrivo study of the BBB disruption and glioma cells(GCs)migration in rats using fuorescence and confocal microscopy.We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells,where the BBB was impermeable for high weight molecules.The migr ation of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration.The mechanisms underlying glioma progression remain umknown but there is an evidence that the sympathetic nervous system(SNS)via activation of vascular beta2-adrenoreceptors(B2-ADRs)can play an important role in tumor metastasis.Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta arrestin-1-co-factor of B2-ADRs signaling pathway in rats with glioma.Pharmacological blockade of B2-ADRs reduces the BBB disruption,macrophages infiltration,GCs migration and increases survival rate.These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis。
文摘To explore the relationship of β adrenoreceptor density and function with the condition of patients with essential hypertension Methods In the present study, 69 male patients with essential hypertension at different stages were compared with a group of age matched normotensive controls β adrenoreceptor maximum bound volume (B max ) in peripheral lymphocytes was measured by 3 H dihydroalprenolol ( 3 H DHA) radio ligand binding β adrenoreceptor responsiveness was determined by Salbutamol (injection) Results In patients with essential hypertension at stages Ⅰ and Ⅱ, B max was significantly higher ( P <0 01 and P <0 001, respectively) and the chronotropic doses of Salbutamol required to increase the heart rate by 30 beats/min (CD 30 ) were significantly lower ( P <0 01 and P <0 001, respectively) than in age matched normotensive control subjects In patients with essential hypertension at stage Ⅲ, B max was significantly lower and CD 30 was significantly higher (both P <0 01) than those in the age matched normotensive control subjects B max was significantly higher and CD 30 was significantly lower (both P <0 001) in patients with essential hypertension and with left ventricular hypertrophy (LVH) than that in patients with essential hypertension but without LVH In patients with essential hypertension and heart failure, B max was significantly lower and CD 30 was significantly higher (both P <0 001) than those in patients with essential hypertension without heart failure Conclusions The changes of β adrenoreceptor density and function were related to hypertension, hypertension complicated with ventricular hypertrophy, and heart failure They may be viewed as indexes of the condition in the patients with essential hypertension
文摘Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).
