Nifedipine Treatment Research Articles

The miR-3940-5p inhibits cell proliferation of gingival mesenchymal stem cells.

Drug-induced gingival overgrowth (DIGO) is a well-recognized side effect of nifedipine (NIF). However, the molecular mechanisms of DIGO are still unknown. Here, we explored the possible role of miR-3940-5p in DIGO using NIF-treated gingival mesenchymal stem cells (GMSCs). CFSE and cell cycle assays were used to examine cell proliferation. The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, quantitative calcium analysis, and osteogenesis-related gene expression were used to examine osteo/dentinogenic differentiation. The CFSE assay showed that NIF enhanced cell proliferation, and the over-expression of miR-3940-5p inhibited the proliferation of GMSCs with or without NIF stimulation. Cell cycle assays revealed that the cell cycle was arrested at the G0/G1 phase. Furthermore, it was found that the over-expression of miR-3940-5p upregulated p15INK4b , p18INK4c , p19INK4d , and Cyclin A and downregulated Cyclin E in GMSCs with or without NIF treatment. In addition, the over-expression of miR-3940-5p enhanced ALP activity and mineralization in vitro and increased the expression of the osteo/dentinogenic differentiation markers DSPP and DMP1 and the key transcription factor DLX5 in GMSCs. miR-3940-5p inhibited cell proliferation, enhanced the osteo/dentinogenic differentiation of GMSCs, and might play a role in DIGO as a potent agent in the treatment of nifedipine-induced gingival overgrowth.

To study the changes in fetal hemodynamics with intravenous labetalol or nifedipine in acute severe hypertension.

To compare the efficacy of intravenous labetalol or oral nifedipine in treatment of acute maternal hypertension and study the fetal hemodynamic changes using color Doppler ultrasound that follows treatment. Thirty women with severe preeclampsia having acute hypertension (more than or equal to 160/105 mmHg) were randomized in 2 groups to receive intravenous labetalol or oral nifedipine until blood pressure was lowered to less than or equal to 140/90 mmHg. Doppler vascular indices namely pulsatility index, resistance index, S/D ratio of umbilical (UA) and middle cerebral artery (MCA) were measured baseline at the time of acute severe hypertension and repeated after control of blood pressure, to assess the changes in fetal hemodynamics if any with labetalol or nifedipine. Both nifedipine and labetalol were found to be effective when used for rapid control of blood pressure. Mean age of women in both groups and mean gestational age was statistically comparable. No change in fetal heart rate before and after treatment was observed in both groups. Doppler vascular indices of UA and MCA showed no significant changes as compared to baseline values in both groups. The use of labetalol and nifedipine were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. Choice between these two drugs should be based on cost, availability respective contraindications, and clinician's experience.

Protective effects of voltage-gated calcium channel antagonists against zinc toxicity in SN56 neuroblastoma cholinergic cells.

One of the pathological site effects in excitotoxic activation is Zn2+ overload to postsynaptic neurons. Such an effect is considered to be equivalent to the glutamate component of excitotoxicity. Excessive uptake of Zn2+ by active voltage-dependent transport systems in these neurons may lead to significant neurotoxicity. The aim of this study was to investigate whether and which antagonists of the voltage gated calcium channels (VGCC) might modify this Zn2+-induced neurotoxicity in neuronal cells. Our data demonstrates that depolarized SN56 neuronal cells may take up large amounts of Zn2+ and store these in cytoplasmic and mitochondrial sub-fractions. The mitochondrial Zn2+ excess suppressed pyruvate uptake and oxidation. Such suppression was caused by inhibition of pyruvate dehydrogenase complex, aconitase and NADP-isocitrate dehydrogenase activities, resulting in the yielding of acetyl-CoA and ATP shortages. Moreover, incoming Zn2+ increased both oxidized glutathione and malondialdehyde levels, known parameters of oxidative stress. In depolarized SN56 cells, nifedipine treatment (L-type VGCC antagonist) reduced Zn2+ uptake and oxidative stress. The treatment applied prevented the activities of PDHC, aconitase and NADP-IDH enzymes, and also yielded the maintenance of acetyl-CoA and ATP levels. Apart from suppression of oxidative stress, N- and P/Q-type VGCCs presented a similar, but weaker protective influence. In conclusion, our data shows that in the course of excitotoxity, impairment to calcium homeostasis is tightly linked with an excessive neuronal Zn2+ uptake. Hence, the VGCCs types L, N and P/Q share responsibility for neuronal Zn2+ overload followed by significant energy-dependent neurotoxicity. Moreover, Zn2+ affects the target tricarboxylic acid cycle enzymes, yields acetyl-CoA and energy deficits as well.

Vitamin D Enhances Efficacy of Oral Nifedipine in Treating Preeclampsia with Severe Features: A Double Blinded, Placebo-Controlled and Randomized Clinical Trial.

Vitamin D (VD) has exhibited immunomodulatory role in the pathogenesis of preeclampsia. We hypothesize VD potentiate nifedipine treatment for preeclampsia by shortened the time to control blood pressure and prolong time before subsequent hypertensive crisis. We conduct a randomized trial of 683 primigravid women with preeclampsia, who were assigned to different treatment groups, either nifedipine+placebo or nifedipine+VD orally, by random after screening. Primary endpoints include time to control hypertension and time before another hypertensive crisis. Maternal adverse effects including nausea, vomiting, chest pain, mild headache, dizziness, maternal tachycardia, hypotension or shortness of breath, and neonatal parameters including birth weight and Apgar scores, as well as the minimum number of dosages needed to control hypertension were defined as secondary endpoints. Serum levels of cytokines tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were also examined. There was a marked reduction of the time required to control hypertension and a significant lengthening (p = 0.013) of the time before a new hypertensive crisis in participants received nifedipine+VD treatments (41.8 ± 18.3 min), in comparison with the nifedipine+placebo controls (61.1 ± 15.9 min). In women treated with nifedipine+VD, the minimum number of dosages needed to control hypertension was also lower. With regard to adverse effects, no statistical difference was observed between the two treatment groups. Moreover, treatment with VD increased IL-10 and reduced TNF-α serum levels. VD possesses the potential of serving as a safe and effective adjuvant to oral nifedipine in treating women with preeclampsia against hypertension, possibly through the upregulation of IL-10 and the downregulation of TNF-α.

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

ObjectivePreeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE.Design and methodsUsing a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects.ResultsCompared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups.ConclusionOur data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.

Mechanisms of sphingosine-1-phosphate-mediated vasoconstriction of rat afferent arterioles.

Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the pre-glomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated pre-glomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway. Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation, and diameter was measured during exposure to physiological and pharmacological agents. Exogenous S1P (10-9 -10-5 mol L-1 ) evoked concentration-dependent vasoconstriction of afferent arterioles. Superfusion with nifedipine, a L-VDCC blocker, increased arteriolar diameter by 39 ± 18% of baseline and significantly attenuated the S1P-induced vasoconstriction. Superfusion with the rho kinase inhibitor, Y-27632, increased diameter by 60 ± 12% of baseline and also significantly blunted vasoconstriction by S1P. Combined nifedipine and Y-27632 treatment significantly inhibited S1P-induced vasoconstriction over the entire concentration range tested. In contrast, depletion of intracellular Ca2+ stores with the Ca2+ -ATPase inhibitors, thapsigargin or cyclopiazonic acid, did not alter the S1P-mediated vasoconstrictor profile. Scavenging reactive oxygen species (ROS) or inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity significantly attenuated S1P-mediated vasoconstriction. Exogenous S1P elicits potent vasoconstriction of rat afferent arterioles. These data also demonstrate that S1P-mediated pre-glomerular vasoconstriction involves activation of L-VDCC, the rho/rho kinase pathway and ROS. Mobilization of Ca2+ from intracellular stores is not required for S1P-mediated vasoconstriction. These studies reveal a potential role for S1P in the modulation of renal microvascular tone.

Abstract 4594: Induction of apoptosis by anti-CD20 antibodies requires the induction of EGR-1 and calcium influx

Abstract Background: Anti-CD20 monoclonal antibodies (mAbs) are an essential component of the treatment of patients with CD20-positive non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). Anti-CD20 mAbs mediate their antitumor effects by activating the immune system or by direct apoptotic signaling in target cells. In a previous preclinical study, we have shown that treatment of B-lymphoma cell lines with anti-CD20 mAbs, rituximab and obinutuzumab, resulted in upregulated expression of the transcription factor early growth factor -1 (EGR-1) (Dalle et al. 2011). However, the role of EGR-1 in response to passive immunotherapies has not been explored so far. Furthermore, EGR-1 has been described as a calcium (Ca2+) regulated transcription factor and CD20 is hypothesized to regulate transmembrane Ca2+ flux. In this study we aim to assess the role of EGR-1 and Ca2+ flux in the cytotoxic activity of anti-CD20 mAbs. Methods: EGR-1 modulation and cell death induction by anti-CD20 mAbs rituximab and obinutuzumab were investigated in cells expressing endogenous and exogenous CD20. The cytotoxic effect of anti-CD20 mAbs was evaluated in SCID mice and in B-lymphoma cell lines overexpressing EGR-1 or knocked down for EGR-1. The impact of anti-CD20 mAbs on Ca2+ flux was investigated by flow cytometry using Indo-1 AM stained cells. Ca2+ channel blocker agent nifedipine was used to investigate the role of Ca2+ flux on obinutuzumab efficacy. Results: EGR1 expression is rapidly upregulated in CD20+ cells following rituximab and obinutuzumab exposure. Decreasing EGR-1 expression by shRNA abolished the direct cytotoxic effect of obinutuzumab both in vitro and in vivo, indicating that EGR-1 is required for CD20-mediated apoptosis. Additionally, the overexpression of EGR-1 resulted in enhanced cytotoxic activity of obinutuzumab both in vitro and in vivo. Rescuing EGR-1 expression in EGR-1 knocked-down cells restored sensitivity to obinutuzumab. Moreover, our results indicate that both rituximab and obinutuzumab could induce calcium influx in the presence of suboptimal concentrations of ionomycin. Blocking Ca2+ flux with the calcium channel blocker nifedipine or the Ca2+ chelating agent EGTA abolished EGR-1 induction by anti-CD20 mAbs. In vivo, nifedipine treatment interfered with obinutuzumab antitumor activity against established Granta (a human mantle cell lymphoma line) xenografts in SCID mice. Conclusion: EGR-1 plays a major role in the direct cytotoxic activity of anti-CD20 monoclonal antibodies and should be evaluated as a new biomarker to predict response to anti-CD20 treatment. Our data also show that calcium channel blockers interfere with the antitumor activity of obinutuzumab in preclinical models. Citation Format: Ivana Spasevska, Jade Villé, Kamel Chettab, Eva-Laure Matera, Charles Dumontet. Induction of apoptosis by anti-CD20 antibodies requires the induction of EGR-1 and calcium influx [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4594. doi:10.1158/1538-7445.AM2017-4594

White coat effect in hypertensive patients: the role of hospital environment or physician presence

This study was to evaluate the role of hospital environment or physician presence for white coat effect (WCE) in hypertensive patients. At first, 54 hypertensive outpatients diagnosed on office blood pressure (OBP) were included for 2-week placebo run in. During the second week of the run in period, home BP was measured using electronic BP monitors for 5–7 days. Finally, 26 sustained hypertensive patients with home systolic BP/diastolic BP over 135/85 (but <180/110) mm Hg were enrolled for 8-week treatment of nifedipine controlled–release tablet. In the visit day, BP was measured by patient-self (OBP-p) or by doctor (OBP-d) according to order determined with randomization method. The self-BP measurement was performed in a reception room of hospital. The differences between home BP and OBP-d or OBP-p were calculated as WCE calculated on doctor-measurement (WCE-d) or WCE calculated on patient-measurement (WCE-p), respectively. The home and OBP were measured with the same BP device for each patient during the study period. In the total 54 outpatients received placebo, the WCE-d was similar to the WCE-p (for systolic BP 6.6 ± 14.4 vs. 6.8 ± 15.8 mm Hg, NS; for diastolic BP 3.3 ± 8.8 vs. 2.9 ± 9.2 mm Hg, NS). Meanwhile, the 26 sustained hypertensive patients had similar systolic WCE-d and WCE-p (4.8 ± 10.3 vs. 5.0 ± 12.2 mm Hg, NS) at placebo stage. Similarly, these values were comparable (3.0 ± 14.0 vs. 2.2 ± 14.4 mm Hg, NS) in treatment stage. Hospital environment plays a main role for the WCE in hypertensive patients.

Salbutamol Versus Nifedipine Dans Le Traitement De La Menace D’accouchement Premature A La Maternite Du Centre Hospitalier Universitaire Et Departemental Du Borgou

Introduction: The threat of the premature birth (TPB) raises a problem of public health in Benin in general and in Parakou in particular. Objective: The aim of this research paper is to compare the efficiency of salbutamol and nifedipine in the treatment of the threat of premature birth at the maternity hospital of CHUD-Borgou. Framework and methodological approach: It is about a comparative prospective study with analytical view, within a period of six (06) months, going from 1, March 2016 to 1, September 2016. The target population is composed of all the pregnant women admitted to the maternity hospital of CHUD-B during the period of the study. Results: The 60 pregnant women have been divided into two groups of 30 pregnant women. The average age of the pregnant women is 26.50 years with the extremes of 16 years and 38 years. The women who have between two and three pregnancies are the most represented with 56.67% of the cases; just as much as the women who have between two and three deliveries with 36.67%. From the total number, 21. 67% had antecedents of spontaneous miscarriages and 6, 67% antecedents of premature birth delivery. With 90% of the cases, the gestational age is between 28 weeks of amenorrhoea and 33weeks of amenorrhoea plus six (06) days. The pregnancy is twin in 16.67% of the cases. At the admission, 90% of the cases after assessment of the Coefficient of Risk of Premature birth Delivery. (CRPD), had a potential risk of prematurity and 85% had a score of Baumgarten between 3 and 6. The most discovered aetiology is malaria with 46.67% of the pregnant women. The side effect of usage of nifedipine, in order to relieve the uterus, has been noticed with 16.67% pregnant women who have received nifedipine treatment against 30% pregnant women who have received the treatment of Salbutamol. There is no difference statistically significant. For the nifedipine, there is 90% of success against 10% of failure. For salbutamol, there is respectively 56.67% and 43.33%. We have no case of intolerance. Conclusion: The study shows neat efficiency of nifedipine in relation to salbutamol during the treatment of the threats of premature birth delivery.

Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1

The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model. These data suggest that inhibitors of PP2A, as well as calcium channel blockers, might be used in broader MPNST preclinical studies as single agents or in combinatorial therapeutic strategies.

Effect of nifedipine on fertility of male lesser bandicoot rat (Bandicota bengalensis)

Current study was designed to evaluate the antifertility effects of nifedipine, a pharmaceutical medicament for high blood pressure. Mature and healthy male lesser Bandicoot rats, Bandicota bengalensis Gray and Hardwicke, were fed on bait (cracked wheat, powdered sugar, groundnut oil 98:2:2) containing 0.1 and 0.05% nifedipine for 12 days in no-choice feeding test to record antifertility effects of nifedipine. The factors studied were the effect on weight of reproductive organs, sperm parameters in cauda epididymal fluid, breeding performance and histomorphology of testis. Nifedipine treatment significantly (P <0.05) reduced the weight of seminal vesicles and prostate gland in treated groups as compared to untreated group. Sperm motility, live sperm count, sperm density and sperm morphology differed significantly between untreated and treated groups. The breeding performance of treated male rats was found reduced by 40–60% as compared to untreated ones. A significant effect of nifedipine treatment was observed on the number of germinal cells in seminiferous tubules. The study indicates the effect of nifedipine on fertility of male rats.

Soluble vascular cell adhesion molecule-1 and magnesium sulfate with nifedipine treatment in Indonesian women with severe pre-eclampsia.

Endothelial cell activation in pre-eclampsia is associated with elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) levels. The objective of the study was to determine whether sVCAM-1 levels in Indonesian women with pre-eclampsia were similar to other ethnic studies and to determine the effects of magnesium sulfate with nifedipine on blood pressure. A total of 61 pregnant women were admitted, who had normal pregnancy (n = 25) and severe pre-eclampsia (n = 36). Blood sampling was performed at admission to the study, 1h after placental separation, and 24h postpartum. sVCAM-1 and blood pressure levels were determined. The mean ages in normal pregnancy (n = 25) and in severe pre-eclampsia (n = 36) are 30.0 ± 3.4 years and 27.1 ± 6.1 years, respectively. Significantly elevated sVCAM-1 was seen in pre-eclampsia. No significant variation in sVCAM-1 levels during the study periods was seen in both groups of cohorts. Magnesium sulfate infusion and nifedipine significantly lowered the blood pressure level. Elevated sVCAM-1 levels were also seen in Indonesian women with severe pre-eclampsia. The placenta may not be the only source of elevated sVCAM-1 and that endothelial dysfunction persists beyond the postpartum period. Magnesium sulfate together with nifedipine significantly lowered blood pressure. The determination of elevated sVCAM-1 in pregnancy as a risk marker for endothelial dysfunction is therefore suggested.

Nifedipine increases fetoplacental perfusion.

Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6±2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the "continuity equation", to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166±73.81 beat.cm3/min to 220±83.3 beat.cm3/min. Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP.

Triterpene derivative: A potential signaling pathway for the fern-9(11)-ene-2α,3β-diol on insulin secretion in pancreatic islet

AimTriterpenes and their derivatives influence on carbohydrate metabolism. In vivo and in vitro treatment investigated the effect of the natural triterpene fern-9(11)-ene-2α,3β-diol (1), isolated from Croton heterodoxus, and a derivative triterpene (2) on glucose homeostasis. Main methodsThe antidiabetic effect of the crude extract from C. heterodoxus leaves, the natural triterpene (1) as well as the derivative triterpene (2) were assayed on glucose tolerance. The effect and the mechanism of action on in vivo treatment with triterpene 2 on glycaemia and insulin secretion were studied. In addition, in vitro studies investigated the mechanism of triterpene 2 on glucose uptake and calcium influx on insulin secretion in pancreatic islets. Key findingsThe results show the extract slightly reduced the glycaemia when compared with hyperglycemic group. However, the presence of the substituent electron-withdrawing 4-nitrobenzoyl group in the A-ring of triterpene 2 powered the serum glucose lowering compared to triterpene 1. In addition, in vivo treatment with triterpene 2 significantly increased the insulin secretion induced by glucose and stimulated the glucose uptake and calcium influx in pancreatic islet. The effect of triterpene on calcium influx was completely inhibited by diazoxide, nifedipine and stearoylcarnitine treatment. SignificanceThe stimulatory effect of triterpene 2 on glucose uptake, calcium influx, regulation of potassium (K+-ATP) and calcium (L-VDCCs) channels activity as well as the pathway of PKC highlights the mechanism of action of the compound in pancreatic islets on insulin secretion and glucose homeostasis. In addition, this compound did not induce toxicity in this experimental condition.

切迫早産治療薬としてニフェジピンが奏功した一例

We report the case of a 35-year-old pregnant woman treated with the calcium channel blocker, nifedipine, for maintenance tocolysis. She was hospitalized due to preterm labor at 21 weeks of gestation by her previous physician. A rash appeared following ritodrine hydrochloride administration for maintenance tocolysis. After changing to magnesium sulfate, a rash appeared again. As these rashes were suspected to have been induced by ritodrine hydrochloride and magnesium sulfate independently, consecutive treatment with these drugs was difficult. Therefore, she was transferred to our hospital for follow-up. At 28 weeks 6 days of gestation, treatment with nifedipine for maintenance tocolysis was started after receiving written informed consent, and the medication was approved by the institutional review board of our hospital. The attending pharmacist considered fetal/neonatal adverse effects of nifedipine, such as teratogenicity, fetotoxicity, and neonatal complications, as well as maternal side effects, such as headache, constipation, and excessive blood pressure drop. The pharmacist provided drug information about nifedipine to the attending physicians and nurses, and gave medication counseling to the patient. Following oral administration of 80 mg of nifedipine daily (20 mg every 6 hours), headache and constipation were evident but gradually improved. Neither excessive blood pressure drop nor exacerbated uterine contraction was observed throughout the period of nifedipine treatment. This medication was finished at 34 weeks 5 days of gestation and the patient was discharged at 36 weeks 2 days of gestation. She delivered a baby at 40 weeks 3 days of gestation.

Tamsulosin versus nifedipine for the management of lower ureteral stones: a meta-analysis

Objective To compare the efficacy and safety of tamsulosin with nifedipine for medical expulsive therapy (MET) in patients with lower ureteral stones (LUS). Methods Randomized controlled trials(RCTs)in comparison of tamsulosin and nifedipine in treatment of LUS published in Pubmed, Cochrane Library, Embase, CNKI, CBM, Wanfang and VIP from databases establishment to July 2015 were retrieved. According to Cochrane handbook, the quality of included RCTs were assessed, and the relevant data including the number of participants, stone size, stone expulsion rate, time to stone expulsion, drug-related side effect, the incidence of ESWL or ureteroscopy lithotripsy (URSL) after MET and analgesic dose were extracted by two reviewers independently. The statistical software RevMan 5.2 was used for meta-analysis with regard to the stone expulsion rate, the incidence of ESWL or URSL and adverse effects. This study lasted more than one month from June to July 2015. Results A total of 13 RCTs with 4 831 patients were eligible. The results showed that the stone expulsion rate and the incidence rate of ESWL or URSL after MET were 92%(2 221/2 423) and 8%(27/333) in the tamsulosin group, and 73%(1 748/2 408) and 20%(67/328) in the nifedipine group. There are statistically significant differences(RR=1.24, 95% CI 1.13-1.37, P<0.05; RR=0.40, 95% CI 0.27-0.60, P<0.05, respectively). The subgroup analysis indicated no statistically significant differences in drug-related adverse effects between tamsulosin and nifedipine with 5%(99/1 804)and 7% (117/1 796) minor adverse effects respectively and less than 1% severe adverse effects in both groups(RR=0.85, 95% CI 0.65-1.10, P=0.21; RR=0.49, 95% CI 0.09-2.59, P= 0.40). Conclusion Compared to nifedipine, tamsulosin has higher stone expulsion rate and lower incidence rates for ESWL or URSL. Since there was no obvious adverse effects, tamsulosin could be considered as a preferable option for patients with LUS. Key words: Tamsulosin; Nifedipine; Medical expulsive therapy; Ureteral stones; Meta-analysis

Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications

Rupture of abdominal aortic aneurysm (AAA) is a lethal event. No oral medicine has been available to prevent or treat AAA. We have recently identified a novel mechanism of eNOS uncoupling by which AAA develops, in angiotensin II (Ang II) infused hyperphenylalaninemia 1 (hph-1) mice. Using this unique model we investigated effects on AAA formation of the L-type calcium channel blocker nifedipine, in view of the unclear relationship between hypertension and AAA, and unclear mechanisms of aneurysm protective effects of some blood pressure lowering drugs. Six-month old hph-1 mice were infused with Ang II (0.7mg/kg/day) for 2weeks, and fed nifedipine chow at two different doses (5 and 20mg/kg/day). While the high dose of nifedipine reduced blood pressure, the lower dose had no effect. Interestingly, the incidence rate of AAA dropped from 71% to 7 and 12.5% for low and high dose nifedipine, respectively. Expansion of abdominal aorta, determined by ultrasound imaging, was abolished by both doses of nifedipine, which recoupled eNOS completely to improve NO bioavailability. Both also abrogated aortic superoxide production. Of note, Ang II activation of NADPH oxidase in vascular smooth muscle cells and endothelial cells, known to uncouple eNOS, was also attenuated by nifedipine. Although low dose was a sub-pressor while the high dose reduced blood pressure via inhibition of calcium channels, both doses were highly effective in preventing AAA by preserving eNOS coupling activity to eliminate sustained oxidative stress from uncoupled eNOS. These data demonstrate that oral treatment of nifedipine is highly effective in preserving eNOS function to attenuate AAA formation. Nifedipine may be used for AAA prevention either at low dose in AAA risk group, or at high dose in patients with co-existing hypertension.

Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies.

The purpose of the present study was to analyze the changes in blood pressure, left ventricular (LV) wall thickness and LV systolic function of aged spontaneously hypertensive rats (SHRs) either with or without antihypertensive therapy. Twenty-one SHRs aged 60.5±0.25 weeks were investigated over 22 weeks. They were divided into the following three groups (7 per group): untreated controls (CTRL), treatment with captopril (CAP, 60 mg kg(-1) daily) and treatment with captopril plus nifedipine (CAP+NIF, 60+10 mg kg(-1) daily). Systolic blood pressure (SBP) was regularly measured using the tail cuff method, and an echocardiogram was repeatedly obtained to examine the LV systolic and diastolic area, LV systolic fractional area change, cardiac output and LV myocardial wall thickness. Finally, heart catheterization was performed. While SBP remained stable in the CTRL animals over the experimental period, both of the antihypertensive treatments significantly reduced SBP by 20% in the treated animals (P<0.001). Echocardiography demonstrated that both the systolic and the diastolic LV function of the untreated SHRs deteriorated over time, whereas both types of antihypertensive treatments attenuated and delayed but did not completely prevent the decline in LV systolic function. Cardiac output, as determined by pulsed wave Doppler echocardiography, remained significantly higher in the treated animals than in CTRLs until week 20, but it then decreased. Heart catheterization showed a significant decrease in LV function, as reflected by the LV systolic pressure and contractility, in the CTRLs but not in treated animals. These findings clearly indicate that late-onset antihypertensive treatment with CAP or CAP+NIF is beneficial with respect to blood pressure reduction, LV hypertrophy attenuation and LV systolic function preservation.

Comparison of effects of nifedipine and ritodrine on maternal and fetal blood flow patterns in preterm labor.

The aim of this study was to investigate and compare the effects of nifedipine and ritodrine treatment on fetomaternal blood flow parameters in women with preterm labor. Sixty women with gestational age between 24 and 36 weeks admitted to the obstetrics clinic for preterm labor were enrolled in this study. Patients were randomly assigned to receive either nifedipine (n=30) or ritodrine (n=30) treatment. Demographic features, clinic and laboratory parameters, fetal and maternal side effects, and Doppler ultrasound indices of the umbilical artery (UA), uterine arteries (UtA), and middle cerebral artery (MCA) before, 2 hours after, and 48 hours after the initiation of tocolytic treatments were compared between the two groups. In both the groups, early- and late-onset changes in the pulsatility index (PI) and other Doppler indices for UA, UtA, and MCA were similar. In addition, time elapsed till delivery, fetal mortality, and maternal morbidity in both the groups were not statistically significant (p>0.05). However, maternal side effects such as tachycardia was more frequent (p<0.05) in the ritodrine group. Besides, in the ritodrine group, anxiety was only minimally observed. Nifedipine and ritodrine used as tocolytic agents did not significantly alter early- and late-onset changes in Doppler ultrasonography parameters in fetal and fetomaternal circulation.

The reduction of circulating levels of IL-6 in pregnant women with preeclampsia by magnesium sulphate and nifedipine: In vitro evidence for potential mechanisms

IntroductionWomen with preeclampsia have elevated levels of inflammatory cytokines including IL-6. IL-6, which is known to activate endothelial cells and induce the production of necrotic trophoblastic debris from the placenta, may be important in the pathogenesis of preeclampsia. MgSO4 is a major therapy for the prevention of seizures in preeclampsia but it has been suggested to also have anti-inflammatory and vasodilatory properties. Methods22 pregnant women with preeclampsia and 68 normotensive controls were recruited and circulating IL-6 levels in these women were measured before MgSO4 and nifedipine treatment and after delivery. In addition, endothelial cells were treated with IL-6 or necrotic trophoblastic debris, generated from first trimester placental explants in the presence or absence of MgSO4 in vitro, and cell-surface ICAM-1 was measured by ELISA. The levels of IL-6 in the culture medium were also measured. Furthermore nitric oxide synthetase activity in endothelial cells that had been treated with IL-6 was measured using l-NAME. ResultsCirculating levels of IL-6 in preeclampsia were reduced significantly following administration of MgSO4. In vitro, MgSO4 reversed the activation of endothelial cells induced by IL-6 but not by necrotic trophoblastic debris. The effect of MgSO4 in reversing the IL-6 induced activation of endothelial cells was not dependent upon nitric oxide synthetase. Treating placental explants with MgSO4 prevented the production of necrotic trophoblastic debris induced by IL-6. Discussionwe demonstrated that IL-6 levels drop following treatment with MgSO4 and nifedipine in vivo, and have identified several mechanisms by which this positive effect on IL-6 may occur in vitro.