- Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle. [Journal Article]
- SRSci Rep 2018 Feb 15; 8(1):3114
- Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. cont...
Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+-induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH). Additionally, the ACH-induced precontraction was partly reduced by pyrazole-3 (Pyr3), a selective blocker of TRPC3 and stromal interaction molecule (STIM)/Orai channels. These channel-mediated currents were inhibited by the compounds present in P. aviculare extracts, suggesting that this inhibition was mediated by LVDCCs, TRPC3 and/or STIM/Orai channels. Moreover, these channel-mediated currents were inhibited by quercetin, which is present in P. aviculare extracts. Furthermore, quercetin inhibited ACH-induced precontraction in ASM. Overall, our data indicate that the ethyl acetate fraction of P. aviculare and quercetin can inhibit Ca2+-permeant LVDCCs, TRPC3 and STIM/Orai channels, which inhibits the precontraction of ASM. These findings suggest that P. aviculare could be used to develop new bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease.
- Comparison of intramuscular progesterone with oral nifedipine for treating threatened preterm labor: A randomized controlled trial. [Journal Article]
- MJMed J Islam Repub Iran 2017; 31:56
- Background: Threatened preterm labor (TPL) is the leading cause of hospitalization during pregnancy. Tocolytic agents are the primary therapeutic options for TPL. The aim of this ...
Background: Threatened preterm labor (TPL) is the leading cause of hospitalization during pregnancy. Tocolytic agents are the primary therapeutic options for TPL. The aim of this study is to compare intramuscular progesterone with oral nifedipine as a tocolytic agent.Methods:This randomized controlled trial was carried out in a teaching hospital (Shahid Akbarabadi) in Tehran, Iran, from December 2011 to November 2012. Three hundred and fifteen singleton pregnant women aged >18 yrs at 26-34 weeks' gestation with the diagnosis of threatened preterm labor (TPL) were randomly received either intramuscular progesterone or oral nifedipine for tocolysis. Maternal and neonatal outcomes were then compared between the two interventions. P value less than 0.05 was considered statistically significant. IRCT registration number of this study is IRCT201112198469N1Results:The success rate of progesterone and nifedipine in treating TPL were 83% and 82.7%, respectively. There was no significant difference between the two interventions with regard to gestational age at delivery, type of delivery, the time interval until the delivery, birth weight, NICU admission rate and hospital stays. Progesterone administration was associated with lower duration of NICU stay as compared with nifedipine (0.33±0.77 days vs.1.5±3.2 days, p<0.05). None of the two drugs caused any major side effects.Conclusion:Single dose intramuscular progesterone is as effective as oral nifedipine in treating TPL. It also significantly reduces the NICU stay.
- Polylactic Acid/Chitosan Nanoparticles Loading Nifedipine: Characterization Findings andIn VivoInvestigation in Animal. [Journal Article]
- JNJ Nanosci Nanotechnol 2018 Apr 01; 18(4):2294-2303
- This paper presents the results of zeta potential, water contact angle, atomic force microscopy image, in vitro solubility, and content of heavy metals in polylactic acid (PLA)/chitosan (CS) nanopart...
This paper presents the results of zeta potential, water contact angle, atomic force microscopy image, in vitro solubility, and content of heavy metals in polylactic acid (PLA)/chitosan (CS) nanoparticles loading nifedipine. In addition, the In Vivo test of the PLA/CS nanoparticles loading nifedipine in the mice is also one of highlights of this work. The Zeta potential result shows that the charged surface of the PLA/CS nanoparticles loading nifedipine is neutral, negative or complex depending on nifedipine content. Nifedipine plays a role in increase of hydrophobic property, swelling degree and regular surface as well as decrease of surface rough of the nanoparticles. The PLA/CS/nifedipine nanoparticles are dissolved in the solutions with pH 6.8, pH 4.5 and pH 1.2. The In Vivo test of PLA/CS nanoparticles loading nifedipine on mice was evaluated by the change in diastolic pressure, systolic pressure, arterial pressure and heart rate. The obtained results confirm that the PLA/CS nanoparticles loading nifedipine is suitable to apply in the treatment of hypertension patients lately.
- bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)-the active metabolite of the laxatives bisacodyl and sodium picosulfate-enhances contractility and secretion in human intestine in vitro. [Journal Article]
- NMNeurogastroenterol Motil 2018 Feb 14
- CONCLUSIONS: BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+secretion when acting luminally and a nerve-driven Cl-and HCO3-secretion once acting basolaterally after absorption.
- PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+channels with full-length CaV1.2 C-terminus. [Journal Article]
- PAPflugers Arch 2018 Feb 13
- In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, mole...
In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a CaV1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased CaV1.2 channel currents without altering CaV1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of CaV1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length CaV1.2 (CaV1.2FL) is expressed much more abundantly than truncated CaV1.2. In a heterologous expression system, c-Src activated CaV1.2 channels composed of CaV1.2FL but not truncated CaV1.2 (CaV1.2Δ1763) or CaV1.2Δ1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of CaV1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with CaV1.2Δ1763, c-Src could more efficiently bind to and phosphorylate CaV1.2FL irrespective of the presence or absence of clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational CaV1.2 modifications.
- Variable Contribution of TMEM16A to Tone in Murine Arterial Vasculature. [Journal Article]
- BCBasic Clin Pharmacol Toxicol 2018 Feb 13
- TMEM16A is essential for Ca2+-activated Cl-channel conductance in vascular smooth muscle. The importance of TMEM16A for agonist-induced vascular constriction and blood pressure control is, however, u...
TMEM16A is essential for Ca2+-activated Cl-channel conductance in vascular smooth muscle. The importance of TMEM16A for agonist-induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM16A might have a complex cellular function beyond being essential for the Ca2+-activated Cl-conductance, e.g. modulation of Ca2+channel expression. Mice with constitutive, smooth muscle-specific expression of siRNA directed against Tmem16a (transgenic mice, TG) were generated. Isometric constrictions of isolated aorta, mesenteric, femoral and tail arteries from TG mice were compared with wild-types. Protein expression was analysed by western blots. Blood pressure and heart rate were studied telemetrically. Significant TMEM16A down-regulation was seen in aorta and tail arteries while no changes were detected in mesenteric and femoral arteries. Contractile responses of mesenteric and femoral arteries from TG and wild-type mice were not different. Aorta from TG mice showed reduced agonist-induced constriction while their responses to elevated K+were unchanged. Tail arteries from TG mice also constricted less to adrenergic stimulation than wild-types. Surprisingly, tail arteries from TG mice constricted less to elevated K+too, and were more sensitive to nifedipine-induced relaxation. Consistently, TMEM16A down-regulation in tail arteries was associated with reduction in CACNA1C protein (i.e. vascular L-type Ca2+channel) expression. No differences in blood pressure and heart rate between the groups were seen. This study suggests a complex contribution of TMEM16A in vascular function. We suggest that TMEM16A modulates arterial contractility, at least in part, indirectly via regulation of CACNA1C expression. This article is protected by copyright. All rights reserved.
- Influence of Dutasteride and Nifedipine on CatSper gene expression in epididymis of mice. [Journal Article]
- RReproduction 2018 Feb 06
- Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular C...
Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca2 + through CatSper (sperm specific cation channel). The CatSper channel complex contains four pore forming α subunits (CatSper1-4 ) and five accessory subunits called β, δ, ε, γ and ζ . Genetic deletion of any of the four CatSper genes in mice results in loss of hyperactivated motility and male infertility. Despite their vital role in male fertility, almost very little is known about influence of anti-fertility agents on CatSper gene expression in epididymis and epididymal spermatozoa. Therefore, we performed quantitative real time q-PCR analysis for CatSper expression in the epididymis and epididymal sperm of BALB/c mice after treatment with Dutasteride (DS), a dual 5-α reductase inhibitor and Nifedipine (NF) a calcium channel blocker as positive control. We observed that treatment with anti-fertility agents Dutasteride and Nifedipine induced significant decreases in the caput and cauda epididymal sperm counts, motility and fertility which could partly be attributed to alteration in the normal morphology of the sperm associated with downregulation/ up-regulation of CatSper mRNAs in epididymis and epididymal spermatozoa of male BALB/c mice. These can be explained on the basis of interference with mechanisms affecting calcium ion signaling resulting in changes in intracellular calcium required for sperm activity, finally affecting sperm maturation and fertility of male BALB/c mice. These studies provide some novel avenues for developing new male contraceptives in future.
- Codonopsis lanceolata extract prevents hypertension in rats. [Journal Article]
- PPhytomedicine 2018 Jan 15; 39:119-124
- CONCLUSIONS: These results suggest that ECL is effective in reducing SBP and inflammation in hypertensive conditions.
- Formulation development and Evaluation of nifedipine as pylorospasm inhibitor. [Journal Article]
- DDDrug Dev Ind Pharm 2018 Feb 12; :1-40
- CONCLUSIONS: Results strongly suggest that nifedipine loaded mucoadhesive formulation has a targeting potential which accelerates gastric emptying process in gastroparesis patients, and thus the formulation might prove useful as a potent prokinetic agent.
New Search Next
- Drugs in Pregnancy and Lactation - Medications Used in Swiss Obstetrics. [Journal Article]
- ZGZ Geburtshilfe Neonatol 2018 Feb 08
- CONCLUSIONS: The same active constituents of medications are consistently used in Swiss perinatal centres for the main indications in pregnant women. Despite the existing experience and available evidence, they are mainly used off-label. Official authorisations for frequently or consistently used active ingredients should be granted.