It is now clear that different pathophysiologic mechanisms have a profound influence on the extent of the functional impairment in intermittent claudication. In particular, metabolic derangements, including impaired oxygen delivery and/or extraction, reduced nitric oxide synthesis, reduced glucose oxidation, accumulation of toxic metabolites and reduction in carnitine availability are correlated with disease severity. Therefore, metabolic interventions aimed at counteracting these alterations may represent a valid therapeutic approach to the treatment of this condition. To date, verapamil and L-arginine efficacy has been proven in few patients; a large scale clinical trial, conversely, reports that propionyl-L-carnitine appears to be an effective and well tolerated drug for the treatment of intermittent claudication.
calan generic name
Expression of P-glycoprotein was examined by immunohistochemistry in surgically removed epiretinal membranes. The cellular source of P-glycoprotein was examined by colabeling for cytokeratin, glial fibrillary acidic protein, and the macrophage marker EBM-11. P-glycoprotein expression by cultured RPE cells was assessed by reverse transcription-polymerase chain reaction and immunoblot analysis. Daunomycin toxicity was quantified by crystal violet assay.
calan sr medication
Prevention of recurrent stone formation will only be possible with careful metabolic evaluation and appropriate management. In this present prospective study, a total of 95 patients with calcium oxalate (CaOx) stone disease were evaluated with respect to the effects of a calcium channel blocking agent (verapamil) therapy on stone-forming risk factors. A total of 95 patients with CaOx urolithiasis were well evaluated for the possible specific effects of verapamil administration on stone-forming risk factors during long-term follow-up. All patients had calcium-containing stones with normal renal morphology and function without any urinary tract infection. The follow-up period ranged from 12 to 36.6 months, with a mean value of 24.4 months. The age of the patients (54 male and 41 female; M/F: 1.31) ranged from 20 to 46 years (mean 34.3 years). On metabolic evaluation all patients had some kind of risk factors and patients were independently randomized into two groups, namely group 1 (n = 49): patients receiving calcium entry blocker, verapamil hydrochloride (isoptin 240 mg KKH tablets, oral t.i.d.); group 2 (n = 46): patients receiving no specific therapy (control patients) that were matched for sex and age. Follow-up results (at least 1 year) with respect to the changes in urinary stone-forming risk factors were recorded in both groups. During long-term follow-up patients undergoing no specific therapy did not show a significant change with respect to the urinary levels of stone-forming risk factors when compared with the others receiving verapamil on a regular basis. In the light of our results as well as the literature data, we believe that the pathophysiological mechanisms underlying the effect of verapamil on stone formation (as a result of enhanced crystal deposition) and on the excretion of the urinary stone-forming risk factors have to be well evaluated in further experimental as well as clinical studies. Although the exact mechanism of action is not clear; we may claim that the limitation of internal calcium shift by these agents may also well effect the tubular process related to oxalate handling which ultimately limits its excretion in urine.
calan eeze review
Development of multidrug resistance to anticancer agents is a major limitation for the success of cancer chemotherapy. The chemosensitizer verapamil increases intracellular accumulation of drugs such as adriamycin in certain multidrug-resistant cell lines. When combined with verapamil, hyperthermia should be able to alter membrane permeability to adriamycin and to enhance the cytotoxicity of the drug. Verapamil increased the cytotoxicity of adriamycin in multidrug-resistant Chinese hamster ovary cells (CH(R)C5) but not in drug-sensitive cells (AuxB1). Hyperthermia (42 degrees C) alone clearly increased the cytotoxicity of adriamycin in AuxB1 cells. There was also a small increase in CH(R)C5 cells at 42 and 43 degrees C. In drug-resistant cells, the cytotoxicity of adriamycin increased considerably when verapamil was combined with heat. This effect was dependent on temperature and increased with time of incubation. At 37 degrees C, verapamil increased the uptake of adriamycin in CH(R)C5 cells, while drug efflux decreased. When verapamil was combined with hyperthermia, drug efflux decreased even further. These results led to an overall increase in intracellular accumulation of the drug. In drug-sensitive cells, hyperthermia increased both the uptake and efflux of adriamycin, but verapamil had no effect. Verapamil plus heat increased the cytotoxicity of adriamycin in drug-resistant cells, and this was accompanied by altered permeability of the membrane to the drug. Hyperthermia combined with verapamil could be beneficial by increasing the effectiveness of adriamycin in the elimination of multidrug-resistant cells in a localized target region.
At baseline, the maximum DF among the PVs (6.9 +/- 0.9 Hz) was significantly higher than the DF in the RAFW (6.2 +/- 0.7 Hz), CS (5.7 +/- 0.5 Hz), or LAA (5.9 +/- 0.7 Hz) (P<.01); there was a substantial PV-to-atrial DF gradient (RAFW 0.7 +/- 0.9, CS 1.1 +/- 0.7, LAA 0.7 +/- 0.9 Hz). Verapamil increased the atrial DF to 6.9 +/- 0.8, 6.6 +/- 0.7, and 7.2 +/- 1.0 Hz in the RAFW, CS, and LAA, respectively (P<.0001) but did not affect the maximum PV DF (7.1 +/- 0.7 Hz). The PV-to-atrial DF gradient was eliminated after verapamil (RAFW 0.2 +/- 0.8, CS 0.5 +/- 0.6, LAA -0.4 +/- 0.8 Hz; P<.01 vs. baseline).
calan drug classification
Angiotensin II (Ang II)-induced apoptosis was demonstrated for the first time in cultured adult rat ventricular myocytes (ARVMs) isolated by retrograde heart perfusion with Krebs-Henseleit bicarbonate (KHB) buffer containing collagenase and hyaluronidase. ARVMs incubated with 10 mumol/L Ang II for 48 h showed morphological features of apoptosis (cellular shrinkage, condensation of cytoplasm) and a characteristic "ladder" of DNA bands representing integer multiples of the internucleosomal DNA length about 180-200 bp, which became more evident with further incubation up to 72 h. With shorter incubation time (< or = 24 h) or at a lower Ang II concentration (< 10 mumol/L), such changes failed to occur. This effect of Ang II could be abolished by losartan (10 mumol/L), verapamil (1 mumol/L) or staurosporine (10 nmol/L). The above results indicate that Ang II-induced apoptosis in ARVMs may be mainly mediated by Ang II type I (AT1) receptors with [Ca2+]i and protein kinase C (PKC) playing a critical role.
calan dosage forms
(11)C-7 is a novel tracer of P-gp function with higher baseline uptake than (11)C-verapamil. Upregulation of P-gp function in response to treatment (which is hard to detect with (11)C-verapamil) may be detectable using (11)C-7 and PET. Because (11)C-6 shows specific binding in target organs, this compound is the first PET tracer allowing measurement of P-gp expression.
calan 120 mg
Transient adverse drug reactions, vomiting and abdominal pain, were associated with WBI. Polyethylene glycol plus electrolyte lavage solution (PEG-ELS) was more frequently administered through the nasogastric tube. Patients who underwent WBI through nasogastric tube received higher doses of PEG-ELS.
calan 240 mg
This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration-response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration-response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.
Preparations of individual cells from either whole mucosa or epithelium of mouse jejunum were stained with Hoechst 33342 and propidium iodide and then sorted using fluorescence-activated cell sorting. Cells were characterized using fluorochrome-labeled antibodies to surface markers, intracellular markers, and annexin V to detect early apoptosis. Total RNA was isolated from sorted fractions and used for quantitative real-time reverse-transcription polymerase chain reaction to evaluate the expression of cell lineage markers and the intestinal stem-cell marker, Musashi-1.
calan 180 mg
Calpain was generally believed to exist and function only in the cytoplasm. However, m-calpain has now been detected in the extracellular spaces of some kinds of tissue. In this study, we demonstrated the existence of m-calpain in the medium surrounding MC3T3-E1 cultures, and its activity by zymography. At the same time, the amount of lactate dehydrogenase in medium of MC3T3-E1 culture was extremely low compared with other cell cultures, suggesting that m-calpain found in the culture medium of MC3T3-E1 cells originated mainly from active secretion. Moreover, the secretion of m-calpain was not blocked by brefeldin A, implying that m-calpain may be secreted by a nonclassical pathway. Recently, MC3T3-E1 has been reported to produce matrix vesicles and media vesicles, and we demonstrated m-calpain in these vesicles produced by MC3T3-E1 cultures. We therefore concluded that these vesicles are partly responsible for the secretion of m-calpain into the culture medium of MC3T3-E1 cells.
The changes of cytosolic Ca(2+) fluorescence intensity and the activities of calcium channel of primary maize root tip cells induced by PEG6000 or abscisic acid (ABA) were studied by both confocal techniques and the whole-cell patch clamping in this study. The Ca(2+) fluorescence intensity increased while treated with PEG or ABA within 10 min, illuminating that Ca(2+) participated in the process of ABA signal transduction. For further proving the mechanism and origin of cytosolic Ca(2+) increase induced by PEG treatments, N,N,N',N'-tetraacetic acid (EGTA), Verapamil (VP) and Trifluoperazine (TFP) were added to the PEG solution in the experiments separately. The results showed that Ca(2+) fluorescence intensity induced by PEG was suppressed by both EGTA and VP obviously in the root tip cells. The Ca(2+) fluorescence intensity of plants changed after the addition of CaM inhibitor TFP while subjected to osmotic stress, which seemed to show that CaM participated in the process of signal transduction of osmotic stress too. The mechanism about it is unknown today. Further, a hyperpolarization-activated calcium permeable channel was recorded in plasma membrane of maize root tip cells. The Ca(2+) current (I(Ca)) intensity increased remarkably after PEG treatment, and the open voltage of the calcium conductance increased. Similar changes could be observed after ABA treatment, but the channel opened earlier and the current intensity was stronger than that of PEG treatment. The activation of calcium channel initiated by PEG strongly was inhibited by EGTA, VP or TFP respectively. The results revealed that Ca(2+) participated in the signals transduction process of osmotic stress, and the cytosolic free Ca(2+) increase by osmotic stress mainly came from the extracellular, and some came from the release of cytoplasmic calcium pool.
Vincristine (VCR)-resistant gastric cancer cell line SGC7901/VCR is a typical multidrug resistant (MDR) cell line with high expression of P-glycoprotein (P-gp). However, verapamil (VRP), the inhibitor of P-gp, can not totally reverse the drug resistance, indicating that additional mechanisms must contribute to the MDR phenotype. Our previous study showed that sorcin, a calcium-binding protein, is significantly up-regulated in SGC7901/VCR cells. This study was to explore the role of sorcin in the development of MDR in human gastric cancer cell line SGC7901.
calan 80 mg
The pharmacokinetic parameters of verapamil and one of its metabolites, norverapamil, were compared in 14 healthy male Korean volunteers (age range 22-28 years) who had been administered verapamil (60 mg) orally in the presence or absence of oral lovastatin (20 mg). The design of the experiment was a standard 2 x 2 crossover model in random order.
calan 40 mg
The effect of three different stereoisomer pairs of CNS (central nervous system) active compounds was studied on the activity of human mdr1 p-glycoprotein. The methotrimeprazine, clopenthixol and butaclamol isomers had an antiproliferative effect (ID50) on the mdr1 expressing cells at 0.250 microgram/ml, while the parental cells were less sensitive having ID50 at 0.37-0.69 microgram/ml. Enantiomers of methotrimeprazine and clopenthixol had similar effectivity on the drug efflux of mdr cells. However, (-)butaclamol was found to inhibit mdr efflux-pump activity much more than the CNS active (+) isomer. Based on these results, tricyclic compounds does not seem to have stereoselectivity in methotrimeprazine and clopenthixol on the mdr reversal effect. In general, both active and inactive members of stereoisomers had a similar effect on the drug accumulation of the mdr cells. Therefore, hypothetically the CNS inactive member of stereoisomer pairs can be used as a resistance modifier without any risk in patients suffering from drug resistant cancer.
calan sr dosage
The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P < 0.01). However, the generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.
L-type calcium channel (LTCC) and Na(+)/Ca(2+) exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate calcium and contractility. Although LTCC inhibition is negative inotropic, NCX inhibition has the opposite effect. Combined block may, therefore, offer an advantage for hemodynamics and antiarrhythmic efficiency, particularly in diseased hearts. In a model of proarrhythmia, the dog with chronic atrioventricular block, we investigated whether combined inhibition of NCX and LTCC with SEA-0400 is effective against dofetilide-induced torsade de pointes arrhythmias (TdP), while maintaining calcium homeostasis and hemodynamics.
calan 5 mg
Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF.
Myocardial infarction has been reported with ephedrine and pseudoephedrine use. It has been suggested that these agents may induce coronary artery spasm, hypercoagulable states, or oxygen demand imbalance. We report a 25-year-old male with myocardial infarction after receiving a diet pill containing ephedra. Coronary angiography revealed normal coronary arteries with very slow flow, suggestive of microcirculation abnormalities. The flow responded promptly to intracoronary verapamil.
An involvement of signal transduction other than phosphatidylinositol turnover in thromboxane A(2) receptor (TP receptor)-mediated vascular contraction was investigated in rat aorta. The contraction induced by U46619, a TP receptor agonist, at low concentrations (≤ 30 nM) was partially inhibited by verapamil, an inhibitor of voltage-dependent Ca(2+) channels (VDCC), and was further diminished in Ca(2+)-free solution. Twenty nanomolar of U46619 induced contraction and elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)), which were consisted of two phases; slowly developing first phase followed by quickly rising second phase. The second phase was inhibited by verapamil, and all the [Ca(2+)](i) response was abolished in Ca(2+)-free solution. The contraction and [Ca(2+)](i) elevation induced by 20 nM U46619 were not inhibited by U73122, an inhibitor of phosphatidylinositol-specific phospholipase C, or GF109203X, a protein kinase C inhibitor, but were abolished by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). However, D609 had no effect on those induced by 1 μM phenylephrine. The U46619-induced responses were also partially inhibited by cation channel blockers, 2-APB and LOE908. The inhibition by LOE908 was abolished in the presence of verapamil, suggesting that LOE908-sensitive cation channels lead to the activation of VDCC by depolarizing plasma membrane. In contrast, 2-APB further diminished the U46619-induced [Ca(2+)](i) elevation in the presence of verapamil. In conclusion, TP receptor stimulation is suggested to be coupled with PC-PLC. Diacylglycerol produced by PC-PLC seems to activate two types of cation channels independently of PKC, which in turn leads to VDCC-dependent and independent Ca(2+) influx, thereby eliciting contraction.
Our data demonstrate that the cardiogenic potential of iPS cells is comparable to that of ES cells and that iPS-CMs possess all fundamental functional elements of a typical cardiac cell, including spontaneous beating, hormonal regulation, cardiac ion channel expression and contractility. Therefore, iPS-CMs can be regarded as a potentially valuable source of cells for in vitro studies and cellular cardiomyoplasty.
calan generic name
Tumour resistance to anticancer agents remains a challenge in oncological practice, because it results in exposure to toxicities, unnecessary costs and, most importantly, delay of a potentially more effective treatment. Drug uptake by tumours may be impaired by several resistance pathways. Reasons for primary resistance may be that the drug is not delivered to the tumour or that its uptake by the tumour is not sufficient. Drug delivery depends on its distribution within the body, its bioavailability in the circulation and its transport to the tumour. Binding of drugs to circulating cells and proteins, formation of inactive metabolites as well as a rapid drug clearance may limit bioavailability. Furthermore, drug delivery to tumours is regulated by tumour vascularisation. Finally, tumour targets such as hormone receptors and efflux pumps also influence drug uptake by tumours. The use of specific PET tracers such as radiolabelled anticancer drugs (e.g. [(18)F]fluoropaclitaxel and [(18)F]5-fluorouracil) provide a unique means for individualized treatment planning and drug development. Combining these specific tracers with other less specific tracers, such as tracers for blood flow (e.g. [(15)O]H(2)O) and efflux (e.g. [(11)C]verapamil), may provide additional information on drug resistance mechanisms. Furthermore, radiolabelled anticancer agents may be valuable to evaluate the optimal timing of combination therapies. This review will focus on how PET can reveal different mechanisms of tumour resistance and thus may play a role in drug development and prediction of tumour response.
calan sr medication
28 Sprague-Dawley rats.
calan eeze review
SAH induced 23% constriction of the basilar artery. Ca(2+)-free solution and 1 mumol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, relaxed in response to Ca(2+)-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni2+, which is known to block SOCs, induced a combined relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca(2+)-free solution, verapamil, and verapamil plus Ni2+ by 69%, 20%, and 50%, respectively (P > .05) versus respective values in SAH vessels). In contrast, control vessels challenged with 2 to 8 mumol/L serotonin, which induced a magnitude of constriction similar to those of SAH and ET-1 (22%), completely relaxed in response to Ca(2+)-free solution and verapamil.
Ganciclovir (GCV), like other nucleoside analogs such as trifluridine and acyclovir (ACV), is hydrophilic, poorly permeable across membranes and orally low-bioavailable. In the present studies, Labrasol was evaluated for improving intestinal absorption of GCV through in vitro and in vivo experiments. The effect of Labrasol on absorption of GCV in rat small intestine was investigated using an in situ single-pass perfusion technique. The apparent absorptive clearance (PeA) of GCV with Labrasol in the duodenum, jejunum and ileum was 1.01, 1.28, and 1.49 mL/min/cm (n = 6), respectively, and significant regional differences of GCV absorption among the three segments were observed p jejunum, p duodenum (p > 0.05). The effects of EDTA, verapamil on the permeability of GCV were conducted. The permeability of GCV was increased by EDTA, verapamil, respectively. The results indicated that paracellular absorption and efflux played important roles in GCV absorption. In vivo absorption GCV in rats was conducted. When GCV at 1 mg/kg dose was administered with Labrasol (10%, v/v), the mean AUC of was determined as 14.45 ± 3.88 μg*h/mL, compared to 8.05 ± 1.52 µg*h/mL without Labrasol. Based on the results, we could conclude that the absorption of GCV through GI lumen would be enhanced by Labrasol. The effect of Labrasol maybe ascribed to both (i) inhibit efflux of GCV from the enterocytes to the GI lumen; and (ii) enhance GCV absorption from the GI lumen through paracellular pathway.
calan drug classification
Various studies have shown that calcium channel blockers (CCB) affect the release of central neurotransmitters including noradrenaline (NA) and 5-hydroxytryptamine (5-HT), which are involved in depression. The behavioural despair test was used to investigate the effect of CCB on depression. The mice were treated acutely with CCB. Verapamil (5, 10, 20, and 40 mgkg(-1), i.p.) and diltiazem (10, 20, and 40 mgkg(-1), i.p.) produced a dose-dependent increase in immobility time, indicating the facilitation of depression, while nifedipine (12.5, 25, and 50 mgkg(-1), i.p.) significantly decreased the immobility time, indicating an antidepressant activity. Verapamil ( 40 mgkg(-1), i.p.) and diltiazem ( 40 mgkg(-1), i.p.) blocked the antidepressant effect of desipramine, clomipramine, mianserin, and tranylcypromine, indicating the involvement of various mechanisms in the facilitatory effect of verapamil and diltiazem on depression. The antidepressant effect of nifedipine may be attributed to the blockade of presynaptic alpha -2-receptors (autoreceptors), as nifedipine blocked the clonidine-induced facilitation of depression.
calan dosage forms
1. The herbal products Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic were investigated for in vitro inhibitory potential on P-glycoprotein (P-gp)-mediated transport of digoxin (30 nM) in differentiated and polarized Caco-2 cells. 2. Satisfactory cell functionality was demonstrated through measurements of assay linearity, transepithelial electric resistance (TEER), cytotoxicity, mannitol permeability, and inclusion of the positive inhibition control verapamil. 3. The most potent inhibitors of the net digoxin flux (IC(50)) were mistletoe > Natto K2 > Agaricus > green tea (0.022, 0.62, 3.81, >4.5 mg ml(-1), respectively). Mistletoe also showed the lowest IC(25) value, close to that obtained by verapamil (1.0 and 0.5 microg ml(-1), respectively). The IC(50)/IC(25) ratio was found to be a good parameter for the determination of inhibition profiles. Garlic and noni juice were classified as non-inhibitors. 4. This study shows that mistletoe, Natto K2, Agaricus and green tea inhibit P-gp in vitro. Special attention should be paid to mistletoe due to very low IC(50) and IC(25) values and to Natto K2 due to a low IC(50) value and a low IC(50)/IC(25) ratio.
calan 120 mg
Of mammary epithelial cells isolated from both the human and mouse mammary epithelia, 0.2-0.45% formed a distinct SP. The SP was relatively undifferentiated but grew as typical differentiated epithelial clones when cultured. Transplantation of murine SP cells at limiting dilution into cleared mammary fat pads generated epithelial ductal and lobuloalveolar structures.