Effects Of Calcium Antagonists Research Articles

A Review on the Chemical Properties, Plant Sources, Anti-shock Effects, Pharmacokinetics, Toxicity, and Clinical Applications of Anisodamine.

Alkaloids are natural products that occur widely in many herbal plants. Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted from the roots of the Anisodus tanguticus Maxim. It is an antagonist to M-choline receptors and exhibits diverse pharmacological effects, such as cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a range of pharmacological effects akin to those of atropine and scopolamine. owing to its low toxicity and moderate efficacy in clinical to wide applications, especially for varieties of shock treatment. However, there remains a dearth of research regarding the in vivo pharmacokinetics, mechanism of action, and toxicity of anisodamine. Consequently, this paper provides a comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic characteristics of anisodamine to increase the understanding of its medicinal value, and provide reference and inspiration for the clinical application and further in-depth research of anisodamine.

Analysis of side effects of calcium antagonists and determination of ways to minimize them

Analysis of side effects of calcium antagonists and determination of ways to minimize them

Extract of Chenopodium album lowers blood pressure in rats through endothelium-dependent and -independent vasorelaxation

To investigate the antihypertensive effect of crude extract of Chenopodium album (Ca.Cr), based on its medicinal use in hypertension. Ca.Cr and its fractions were tested in-vivo in normotensive anesthetized rats for blood pressure-lowering effect. In-vitro experiments were performed on isolated rat aortae to explore the vascular mechanism(s). In normotensive anesthetized rats, Ca.Cr produced a dose-dependent (1-300mg/kg) fall (30%mmHg) in mean arterial pressure (MAP). Among the fractions, nHexane was the most potent (46% fall). In rat aortic rings precontracted with phenylephrine (PE), Ca.Cr and its fractions (except Ca.Aq) produced endothelium-dependent vasorelaxation, which was partially reversed with endothelium removal and by pretreating intact aortic rings with L-NAME (10μM) and atropine (1μM). This relaxation to Ca.Cr and fractions (nHexane, ethylacetate and chloroform) was also eliminated with indomethacin pretreatment, however, it unmasked a vasoconstriction effect with Ca.Cr only. Surprisingly, the aqueous fraction produced a calcium sensitive strong vasoconstriction instead of vasorelaxation. The crude extract and its fractions (except Ca.Aq) also antagonized vasoconstriction induced with high K+ (80mM), suggesting calcium antagonistic effect. The aqueous fraction produced mild vasorelaxation against high K+. This effect was further confirmed when pretreatment of the aortic rings with different concentrations of crude extract and fractions suppressed CaCl2 concentration response curves, similar to verapamil. In acute toxicity test, Ca.Cr extract was found safe up to 5g/kg body weight in mice. These findings suggest that crude extract and fractions of C.album produced vasorelaxant effect through muscarinic receptors linked-NO pathway, prostaglandin (endothelium-dependent) and calcium antagonism (endothelium-independent), which explains the blood pressure lowering effect of C.album in rats.

A New Lignan from Annona squamosa L. (Annonaceae) Demonstrates Vasorelaxant Effects In Vitro.

Esquamosan, a new furofuran lignan, has been isolated by bio-guided assays from the methanolic extract of the leaves of Annona squamosa L., and its structure was elucidated by spectroscopic methods. Esquamosan inhibited the rat aortic ring contraction evoked by phenylephrine in a concentration-dependent manner and showed an inhibitory effect on vasocontraction of the depolarized aorta with high-concentration potassium. The vasorelaxant effect by esquamosan could be attributed mainly to the inhibition of calcium influx from extracellular space through voltage-dependent calcium channels or receptor-operated Ca2+ channels and also partly mediated through the increased release of NO from endothelial cells. The ability of esquamosan to modify the vascular reactivity of rat aortic rings incubated with high glucose (D-glucose 55 mM) was then evaluated, and this furofuran lignan reverted the endothelium-dependent impairment effect of high glucose in rat aortic rings. The antioxidant capacity of esquamosan was assessed using DPPH and FRAP assays. Esquamosan exhibited a similar antioxidant capacity compared to ascorbic acid, which was used as a positive control. In conclusion, this lignan showed a vasorelaxant effect, free radical scavenging capacity, and potential reductive power, suggesting its potential beneficial use to treat complex cardiometabolic diseases due to free radical-mediated diseases and its calcium antagonist effect.

Сomparative effectiveness of calcium antagonists of prolonged action in patients with stable angina pectoris

The article is devoted to investigation the comparative efficacy of therapy with drugs of calcium antagonists with prolong action — dilren and altiasem PP in old patients, suffering from ischemic heart disease, stable stenocardia 2–3 functional class. There were established more efficacy of therapy with dilren then altiasem PP in the relation to clinical symptoms, hemodynamical parameters and their circadian chronostructure. These data manifested by more essential antianginal, antiischemic and vasodilated effects of dilren then of altiasem PP. There were more essential the increase of tolerance to physical loading, promotion of pumping myocardial function under the influence of dilren and tendency to normalization in circadian organization of hemodynamic parameters.

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases.

This review aimed to identify preclinical and clinical studies examining the effects of rosmarinic acid (RA), carnosic acid (CaA), rosmanol (RO), carnosol (CA), and ursolic acid (UA) against allergic and immunologic disorders. Various online databases, including PubMed, Science Direct, EMBASE, Web of Sciences, Cochrane trials, and Scopus, were searched from inception until October 2022. Due to the suppression of the nuclear factor-κB (NF-κB) pathway, the main factor in allergic asthma, RA may be a promising candidate for the treatment of asthma. The other ingredients comprising CA and UA reduce the expression of interleukin (IL)-4, IL-5, and IL-13 and improve airway inflammation. Rosemary's anti-cancer effect is mediated by several mechanisms, including DNA fragmentation, apoptosis induction, inhibition of astrocyte-upregulated gene-1 expression, and obstruction of cell cycle progression in the G1 phase. The compounds, essentially found in Rosemary essential oil, prevent smooth muscle contraction through its calcium antagonistic effects, inhibiting acetylcholine (ACH), histamine, and norepinephrine stimulation. Additionally, CA exhibits a substantially greater interaction with the nicotinic ACH receptor than a family of medications that relax the smooth muscles, making it a potent antispasmodic treatment. The components have demonstrated therapeutic effects on the immune, allergy, and respiratory disorders.

Cardioprotective Potential of Aqueous Extract of Fumaria indica on Isoproterenol-Induced Myocardial Infarction in SD Rats.

Ischemic heart disease (IHD) treatments and preventions by using plant extract and its phytochemical constituents have achieved considerable attention globally due to its cardioprotective effects. This study is aimed at investigating the cardioprotective and vascular effects of Fumaria indica (F. indica) crude extract on isoproterenol- (ISO-) induced myocardial infarction (MI) in Sprague-Dawley (SD) rats. Rats treated with isoproterenol (85 mg/kg, s.c), administered. Twice at an interval of 24 h showed a significant ST-segment elevation in ECG, edema, and necrosis in histopathology and also in troponin I (cTnI), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Pretreatment with F. indica (10, 30, and 100 mg/kg, p.o) for 21 days significantly reversed the effects of isoproterenol-induced ischemic changes in the ECG, levels of cTnI, CPK, LDH, and AST, and histopathological changes. In isolated rat atrial strips, F. indica induced negative chronotropic and inotropic effects which were not affected by pretreatment with atropine, excluding role of cardiac muscarinic receptors. Cumulative addition of the extract induced a vasorelaxant effect on phenylephrine-evoked contractions in isolated rat aortic rings, which remained unchanged when challenged with L-NAME, excluding role of endothelial NO. However, extract of F. indica concentration dependently reversed contractions evoked with high K+, indicating calcium entry blocking effect. In conclusion, the F. indica extract is a cardioprotective remedy that ameliorates the isoproterenol-induced cardiotoxic effects and reverses cardiac ischemia, and the calcium antagonistic effect might be of useful in the treatment of MI.

Effect of Hibiscus Sabdariffa Calyx Extract on Derived Haematologic Indices in Sickle Cell Anaemia In-vitro

We hypothesised that the calyx extract of Hibiscus sabdariffa (HS) may have antisickling potential on account of its calcium antagonistic and antioxidants effects. Five ml of blood was collected from sickle cell anaemia (SCA) patients (n=11). 50µL ofblood was incubated with 50µL each of 0.l, 1 and 10mg/ml of HS before adding 50µL of 2% sodium metabisulphite (Na2S2O5) (protective assay). Also, 50µL Na2S2O5 was added to 50µL of blood and then incubated with 50µL each of 0.l, 1 and 10mg/ml of HS (reversal assay). In parallel, 50µL of blood each was incubated with 50µL of 5 mg/ml hydroxyurea and 50µL of 0.9% NaCl (control) respectively. The mean cell haemoglobin concentration (MCHC), mean cell volume (MCV) and mean platelet volume (MPV) were determined. In both the protective and reversal assays, a significant (p<0.01 and p<0.05 respectively) decrease in MCHC was observed in the presence of HS. However, there was a significant (P<0.05) increase in MCV in the presence of HS in the reversal assay only. In the protective and reversal assays the MPV increased significantly (P<0.05 and P<0.01 respectively) in the presence of HS. These parameters showed no significant change in the presence of hydroxyurea. These results suggest that in the reversal assay HS may have antisickling properties by lowering the MCHC and increasing MCV and thereby reducing haemoglobin S concentration and polymerization. This further suggests that HS may have a Gardos channel inhibitory effect. However, the increase in MPV suggests that HS may be toxic at these concentrations

Effect of Rythmol (propafenone HCl) administration during pregnancy in Wistar rats.

Propafenone is a well-known Class 1C antiarrhythmic agent that has sodium channel blocking properties as well as the ability to block 13 other channels and a modest calcium antagonistic effect. Propafenone has a profound electrophysiologic effect on auxiliary atrioventricular circuits and in patients with atrioventricular nodal reentry tachycardia can obstruct conduction in the fast conducting pathway. Furthermore, propafenone is less likely than other Class 1C drugs to cause proarrhythmia. However, although this medicine can pass through the placenta, the effects during pregnancy remain unknown. Here, we investigated the potential teratogenic and genotoxic effects of Rythmol during rat development. Pregnant Wistar rats received 46.25 mg/kg body weight of propafenone daily by gavage from Gestation Day (GD) 5 to GD 19. At GD 20, the dams were dissected, and their fetuses were assessed via morphologic, skeletal, and histologic investigation. In addition, a comet assay was used to measure DNA impairment of fetal skull osteocytes and hepatic cells. The study showed that propafenone treatment of pregnant rats led to a marked decrease in gravid uterine weight, number of implants/litter, number of viable fetuses, and bodyweight of fetuses but a clear increase in placental weight and placental index in the treated group. Frequent morphologic abnormalities and severe ossification deficiency in the cranium bones were observed in the treatment group. Various histopathological changes were observed in the liver, kidney, and brain tissues of maternally treated fetuses. Similarly, propafenone induced DNA damage to examined samples. Thus, our study indicates that propafenone may be embryotoxic in humans.

Констеляція артеріальної гіпертензії та стабільної стенокардії, вплив адипокінів та запалення, місце амлодипіну

У роботі досліджено динаміку показників С-реактивного білка й лептину в пацієнтів з артеріальною гіпертензією й стабільною стенокардією, розглянуто ефекти антагоністів кальцію.

Choosing an antianginal therapy strategy in patients with stable coronary artery disease in real clinical practice: the advantages of trimetazidine

Cardiovascular diseases (CVD) are the leading cause of death among adults worldwide, including in the Russian Federation. At the same time, the leading position in the structure of causes of death from CVD is occupied by coronary heart disease (CHD) (16% of the total number of deaths in the world per year). The new clinical guidelines of the Ministry of Health of the Russian Federation for the management of patients with stable coronary heart disease in 2020 identify two main goals of conservative therapy – the elimination of symptoms of the disease and the prevention of cardiovascular complications (CVD). In this connection, when choosing antianginal therapy in patients with stable angina, it is necessary to consider the possibility of using combinations of both first-line and second-line drugs in order to really improve the effectiveness of treatment and achieve the goals set. It is advisable and justified to use more widely 2-line drugs, in particular trimetazidine, at any stage of therapy to enhance the antianginal effectiveness of b-blockers, calcium antagonists and prolonged-acting nitrates, especially in patients with hemodynamic features (arterial hypotension, rhythm and conduction disorders), which is demonstrated in the given clinical example. The effective addition of tremetazidine to the arsenal of traditional antianginal drugs is legislated in practice and is reflected in the new clinical recommendations of the Ministry of Health of the Russian Federation in 2020. The accumulated experience of using trimetazidine allows a pathogenetically sound approach to the treatment of stable CHD, restoring the balance between the need and delivery of oxygen to the heart muscle, and the safety profile expands the possibilities of use in patients with comorbid pathology.

EFFECTS OF CALCIUM CHANNEL BLOCKERS ON SYMPATHETIC NERVE FUNCTION IN THE ELDERLY WERE EVALUATED WITH PUPILLARY FUNCTION

Objective: Pupillary function test is used to evaluate the sympathetic and parasympathetic activity in diabetic and autonomic dysfunction patients. Mydriatic velocity is used as a marker of sympathetic activity. Pupillary function test and power spectrum analysis were performed during handgrip test in hypertensive patients taking calcium antagonist, amlodipine (M) and azelnidipine (Z) to clarify the effects of calcium antagonists on sympathetic nerves between the group under 70 years (young group) and the group above 70 years (elderly group). Design and method: Young Z group (n = 11, 65.2 ± 9.3 y.o., mean ± SD) and elderly Z group (n = 14, 74.6 ± 4.2 y.o.), young M group (n = 10, 58.1 ± 9.3 y.o.) and elderly M group (n = 10, 77.4 ± 3.9 y.o.) are enrolled in this study. Hand grip test were performed for 1 minute at 70% of grip strength and changes of blood pressure, pulse rate, mydriatic velocity and LF/HF by power spectrum analysis were measured before and after handgrip test. Results: Changes in blood pressure (young: 137.0 ± 8.6 to142.4 ± 16.8mmHg, elderly; 137.3 ± 8.6 to143.9 ± 14.6mmHg) pulse rate (young: 67.1 ± 9.4 to 69.0 ± 8.4/min., elderly; 66.4 ± 7.3 to 67.6 ± 10.5/min.), mydriatic velocity (young: 1.8 ± 0.4to1.9 ± 0.3ms, elderly; 1.4 ± 0.3 to 1.6 ± 0.6ms), and LF / HF (young: 3.5 ± 2.2 to 2.7 ± 2.3, elderly; 3.4 ± 3.2 to 2.9 ± 2.3) due to hand grip load showed no significant change in young and elderly Z group. In young M group, blood pressure increased significantly (132.4 ± 11.4mmHg to144.94 ± 12.3mmHg), but pulse rate (68.3 ± 10.7 to 72.5 ± 11.5/min.), mydriatic velocity (1.8 ± 0.6 to 2.18 ± 0.6ms) and LF / HF (2.8 ± 1.9 to 4.1 ± 3.3) did not change significantly. On the other hand, blood pressure (134.2 ± 11.5 to 144.2 ± 14.1mmHg) and pulse rate (66.9 ± 8.5 to 72.8 ± 8.7/min.) were not changed, but mydriatic velocity (1.8 ± 0.6ms to 2.18 ± 0.6ms, p < 0.01) and LF / HF (1.7 ± 1.9 to 5.8 ± 5.2, p < 0.05) increased significantly in the elderly M group. Conclusions: Pupillary function during static exercise can be used to evaluate the sympathetic activity in hypertension. Azelnidipine suppress sympathetic activity compared with amlodipine. Elderly patient shows hyper-sympathetic response by handgrip test. Azelnidipine is safe to use even in elderly patients under static exercise.

Influence of the potential dependent calcium channel blockers to the development of carrageenan-induced aseptic inflammation

Background: A number of patients with diseases of the cardiovascular system simultaneously take anti-inflammatory medicines due to the presence of concomitant chronic inflammatory diseases such as rheumatism, arthritis, and podagra. Considering the above, it seems important to study the effect of calcium antagonists (CA) on the course of the inflammatory process. Aim and Objectives: The purpose of the study was an investigation of the effect of amlodipine, diltiazem, and cinnarizine in comparison with diclofenac sodium on the course of carrageenan-induced aseptic arthritis. Materials and Methods: The experiments were carried out on outbred white rats, males, and weigh 150–170 g. The inflammation was induced by the subplantary injection of a 1% aqueous solution of carrageenan in a volume of 0.1 ml. The studied medicines diclofenac sodium at a dose of 10 mg/kg, amlodipine and diltiazem at doses of 20 mg/kg, and cinnarizine at doses of 50 mg/kg were intragastrically administered to experimental animals 1 h before the injection of carrageenan. Measurement of the paw volume of animals was carried out using a plethysmometer Results: The anti-inflammatory activity of amlodipine in the indicated hours of observation was 34.1, 36.8, 37.8, and 39.7%, respectively. Сinnarizine also had a distinct anti-exudative effect, after 1, 2, 3, and 4 h of the experiment value of anti-inflammatory activity of it were as following: 38.6, 40.3, 41.9, and 44.0%, respectively. Conclusion: Blockers of potential-dependent calcium channels clearly suppress the exudative phase of aseptic inflammation. The studied medicines are arranged in a descending order by their pharmacological activity in the following row: diclofenac sodium = diltiazem> cinnarizine> amlodipine.

Regulation of Human Monocyte Surface Antigen Expression. I. Up-Modulation of Mo3e Antigen Expression on U-937 and HL-60 Cells Stimulated by Pharmacologic Activators of Protein Kinase C

Mo3e is a protein (p 50,80) that is expressed on the surface of human monocytic cells after exposure in vitro to soluble activating factors that include bacterial lipopolysaccharide, muramyl dipeptide, and phorbol myristate acetate (PMA). The surface expression of Mo3e may represent a cellular event that occurs in response to the formation of "secondary messengers" that include diacylglycerol, inositol trisphosphate, and calcium ions. This postulate is based on the stimulatory effect of agents that can mimic the activity of endogenous diacylglycerol (PMA and other biologically active phorbol compounds, mezerein, and L-alpha-1,2 dioctanoylglycerol) and inositol trisphosphate (ionomycin) on Mo3e expression by U-937 and HL-60 cells. The inhibitory effect of phospholipid-active calmodulin inhibitors (trifluoperazine, chlorpromazine, and dibucaine), calcium antagonists (nicardipine and TMB-8), and EGTA further support the involvement of phospholipid- and calcium-dependent protein kinase (protein kinase C) and calcium ions in the up-modulation of Mo3e surface expression.

β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study.

AimsThe effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain.Methods and resultsWe analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality.ConclusionIn this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI.

Calcium antagonists for acute ischemic stroke.

The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes. The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers. Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke. Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures. We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available. We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.

Ишемические и реперфузионные повреждения сердца: роль Ca 2+ -каналов L-типа и Na + /H + -обменника. Анализ экспериментальных и клинических данных

The most published data suggest that L-type Ca2+ channel blockers, when administered prior to coronary occlusion or after the onset of ischemia, delay the occurrence of irreversible damage to cardiomyocytes. Verapamil is able to prevent reperfusion injury of the heart. The cardioprotective effect of calcium antagonists disappears with the duration of ischemia more than 3 h. L-type Ca2+ channel plays an important role in the pathogenesis of ischemic and reperfusion injury of the heart if the duration of ischemia is less than 3 h. Nifedipine increased the risk of death among patients with acute myocardial infarction (AMI). Verapamil with intracoronary administration to patients with AMI reduces the incidence of microvascular obstruction. The results of clinical studies do not allow us to judge with confidence the role of L-type Ca2+ channel in the pathogenesis of AMI. Experimental studies have shown that Na+/H+-exchange (NHE) inhibitors are able to prevent both ischemic and reperfusion injury of the heart. NHE plays an important role in ischemic and reperfusion injury of the heart. NHE inhibitors may be effective in the therapy of AMI in the case of early admission of patients with AMI. The published data does not allow to draw a conclusion about the role of NHE in ischemic and reperfusion injury of the human heart.

Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 14 - effects of different classes of antihypertensive drugs in older and younger patients: overview and meta-analysis.

The five major classes of blood pressure (BP)-lowering drugs have all been shown to significantly reduce the risk of major cardiovascular events when compared with placebo, and when directly (head-to-head) compared, no significant differences in their overall effectiveness have been detected, except for minor differences in cause-specific events. It is unknown, however, whether age-related differences exist and if some classes of drugs are differently effective in older or younger individuals. This clinically relevant question has been the object of a systematic search and meta-analysis of all available data. Two databases we had previously identified [72 placebo-controlled BP-lowering randomized clinical trials (RCTs) in 260 210 individuals and 50 RCTs head-to-head comparing treatments with BP-lowering drugs of different classes in 247 006 individuals) were searched for separately reported data on patients older or younger than 65 years, and the data were further stratified according to the class of drug [diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers] compared with placebo or with other drug classes. Seven fatal and nonfatal outcomes were considered for benefits. Adverse events were investigated as permanent treatment discontinuations for adverse events. Risk ratios and absolute risk changes were calculated by a random effects model. Effects at older and younger ages were compared by heterogeneity test. We identified 20 placebo-controlled RCTs on 55 645 older individuals and 21 on 99 621 younger individuals, and 21 head-to-head drug comparison RCTs on 94 228 older individuals and 27 on 100 232 younger individuals (for a total of 349 726 individuals). When compared with placebo, all five classes of BP-lowering drugs significantly reduced the risk of major cardiovascular events or stroke, with no significant difference between older and younger patients. However, in head-to-head comparisons, no significant difference was found between older and younger patients in the effects of diuretics, calcium antagonists, ACE inhibitors and angiotensin receptor blockers on all cardiovascular outcomes, whereas beta-blockers revealed an age-dependent effectiveness, being equally effective as the other agents at an age below 65 years, but less effective at an older age. Most BP-lowering classes are equally effective in preventing risk of fatal and nonfatal cardiovascular events both in older and younger patients, whereas beta-blockers, though being equally effective as the other agents in patients younger than 65, loose some of their effectiveness at an older age.

Hyperin Enhances the Sensitivity of HCT8/VCR Colon Cancer Cell Line to Vincristine by Down-Regulating P-Glycoprotein.

Long-term chemotherapy reduces the sensitivity of colon cancer cells to chemotherapeutics like vincristine (VCR) and lead to drug resistance, which has become a major barrier for colon cancer treatment. Calcium antagonists are used as clinical tumor multidrug resistance reversal agents to regulate the P-glycoprotein (P-gp) level and block efflux pump function now, but they have significant side effects. Hyperin as active component with low toxicity in traditional Chinese medicine has calcium antagonistic effect. Thus, the purpose of this study was to evaluate the inhibitory effect of hyperin on the growth of HCT8/VCR colon cancer cell line (vincristine-resistant) and analyze the enhancing effect of hyperin on the sensitivity of cancer cells to VCR and its relationship to the expression and function of P-gp. Using the MTT method, we investigated the influence of hyperin, VCR alone, and hyperin plus VCR on the growth of HCT8/VCR cells. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the fluorescence intensity of intracellular Rho123. The inhibitory effect of hyperin at the dose of 12.5 μM on HCT8/VCR cell growth was not enhanced as time progressed and no significant inhibitory effect was found for VCR-treated cells at the dose of 2 μM. But the inhibition of cell growth was observed after the combined treatment of hyperin (12.5 μM) and VCR (2 μM). P-gp expression levels in HCT8/VCR cells treated with hyperin plus VCR were markedly lower than the levels in control cells and those treated with VCR. In addition, the intensity of Rho123 fluorescence of HCT8/VCR cells treated with hyperin plus VCR or hyperin alone was significantly higher than intensity observed in control cells and those treated with VCR alone. Hyperin synergistically augments the growth inhibitory effect of vincristine. The underlying mechanism most probably involves down-regulation of P-gp expression and inhibiting the function of the P-gp pump in HCT8/VCR cells.

Pharmacological basis for medicinal use of Ziziphyus nummularia (Rhamnaceae) leaves in gastrointestinal disorders

Purpose: To explore the pharmacological basis for the folkloric use of Ziziphus nummularia for treating diarrhea and gastrointestinal spasm.Methods: Ziziphus nummularia crude extract (Zn.Cr) was investigated for antidiarrheal activity (50, 100 and 300 mg/kg) in terms of reduction diarrhea droppings as well as for antisecretory activity (300 and 1000 mg/kg) in castor-oil induced model in mice. The effect of the extract on potassium chloride (KCl, 80 mM)-induced contractions in isolated rabbit jejunum tissues were was also examined. Furthermore, the antiulcer properties of the extract was assessed in an ethanol-induced gastrointestinal ulcer model.Results: Zn.Cr (50 – 1000 mg/kg) exhibited protective effect against castor oil-induced diarrhea (p <0.05, p < 0.01 vs saline group) and intestinal fluid accumulation (p < 0.001 vs. castor oil group) in mice. In isolated rabbit jejunum model, Zn.Cr concentration-dependently (0.01, 0.1, 0.3, 0.5, 1 and 3 mg/mL) caused relaxation of spontaneous and KCl-induced contractions, similar to verapamil. Calcium antagonistic effect was indicated, as pretreatment of intestinal tissues with Zn.Cr (0.3, 0.5 and 1.0 mg/mL) produced a rightward shift in Ca2+ concentration-response curves, with suppression of maximum contraction. In ethanol-induced gastric ulceration assay, Zn.Cr (300 and 1000 mg/kg) caused52.5 and 93.6 % inhibition, respectively (p < 0.001 vs. saline group).Conclusion: These results reveal that Ziziphus nummularia possesses anti-diarrheal, anti-secretory, anti-spasmodic and anti-ulcer actions, mediated possibly through voltage-gated Ca2+channel blockade.Keywords: Ziziphus nummularia, Anti-diarrheal, Anti-secretory, Anti-spasmodic, Anti-ulcer