WorldWideScience

Sample records for viagra sildenafil citrate

  1. Post Ejaculatory Effects of Sildenafil Citrate (Viagra) On Sexual ...

    African Journals Online (AJOL)

    Viagra) administration on sexual dysfunctions associated with diabetic neuropathy/ erectile impotence prevailing in the male population. Aim: To investigate whether sildenafil citrate administration maintains improved erectile functions in diabetic ...

  2. Ocular safety of Viagra, (sildenafil citrate).

    Science.gov (United States)

    Laties, A M; Fraunfelder, F T

    1999-01-01

    To date, sildenafil citrate (Viagra) gives every evidence of being a safe drug for the eye despite a series of expressed concerns. A review of how its ocular safety profile has been identified offers insights into the strengths and weaknesses of present systems and resources for judging the ocular safety of Viagra or, for that matter, of any new drug. Such insights include: The great value of careful, informed assessment of preclinical information gleaned from laboratory experiments. By and large, such assessments point the way toward appropriate clinical evaluation. For Viagra, early in its development it was noted that besides exerting a major inhibitory effect on the intended target, the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the closely related PDE6, located in the retina. For this reason, preclinical evaluation of the drug included electroretinography plus postmortem histology. In addition, an extended eye examination was incorporated into clinical protocols. The often chaotic but invaluable information stream that becomes available once marketing approval has been gained and large populations begin to use a drug. False alarms, misattribution, and erroneous information are the order of the day. Nevertheless, as information accumulates, patterns of response clarify and the true nature of special susceptibility for subpopulations, if any, becomes apparent. A role for the astute clinician remains: Subtle changes or unusual risks for subpopulations can be missed entirely for long periods of time. A manifest need for improvement in evaluation of postmarketing side-effects. This need has led to the establishment of a new discipline: pharmacoepidemiology. In ophthalmology, the National Registry of Drug Induced Ocular Side-Effects maintains a constant and invaluable surveillance. Examples are supplied to illustrate each of these major points: Our presentation will include data gleaned from

  3. Bilateral cerebral hemispheric infarction associated with sildenafil citrate (Viagra) use.

    Science.gov (United States)

    Kim, K-K; Kim, D G; Ku, Y H; Lee, Y J; Kim, W-C; Kim, O J; Kim, H S

    2008-03-01

    Sildenafil citrate (Viagra) is one of the frequently prescribed drugs for men with erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil and about 1 h later, he complained of chest discomfort, palpitation and dizziness followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic resonance imaging documented acute bilateral hemispheric infarction, and cerebral angiography showed occluded bilateral MCA. Despite significant bilateral MCA stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume that cerebral infarction was caused by cardioembolism with sildenafil use.

  4. Internet-ordered viagra (sildenafil citrate) is rarely genuine.

    Science.gov (United States)

    Campbell, Neil; Clark, John P; Stecher, Vera J; Goldstein, Irwin

    2012-11-01

    Counterfeit medication is a growing problem. This study assessed the requirement for prescription, cost, origin, and content of medications sold via the Internet and purporting to be the phosphodiesterase type 5 inhibitor Viagra (sildenafil citrate). Pfizer monitored top search results for the query "buy Viagra" on the two leading Internet search engines in March 2011. Orders were placed from 22 unique Web sites claiming to sell Viagra manufactured by Pfizer. Tablets received were assessed for chemical composition. No Web site examined required a prescription for purchase or a health screening survey; 90% offered illegal "generic Viagra." Cost per tablet ranged from $3.28-$33.00. Shipment origins of purchases were Hong Kong (N = 11), the United States (N = 6), and the United Kingdom (N = 2) as well as Canada, China, and India (N = 1 each). Notably, the four Internet pharmacies claiming to be Canadian did not ship medication from a Canadian address. Of 22 sample tablets examined, 17 (77%) were counterfeit, 4 (18%) were authentic, and 1 (5%) was an illegal generic. Counterfeit tablets were analyzed for sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra, and contents varied between 30% and 50% of the label claim. Counterfeits lacked product information leaflets, including appropriate safety warnings, and genuine Viagra formulations. Internet sites claiming to sell authentic Viagra shipped counterfeit medication 77% of the time; counterfeits usually came from non-U.S. addresses and had 30% to 50% of the labeled API claim. Caution is warranted when purchasing Viagra via the Internet. © 2012 International Society for Sexual Medicine.

  5. The effect of sildenafil citrate (Viagra) on visual sensitivity.

    Science.gov (United States)

    Stockman, Andrew; Sharpe, Lindsay T; Tufail, Adnan; Kell, Philip D; Ripamonti, Caterina; Jeffery, Glen

    2007-06-08

    The erectile dysfunction medicine sildenafil citrate (Viagra) inhibits phosphodiesterase type 6 (PDE6), an essential enzyme involved in the activation and modulation of the phototransduction cascade. Although Viagra might thus be expected to impair visual performance, reports of deficits following its ingestion have so far been largely inconclusive or anecdotal. Here, we adopt tests sensitive to the slowing of the visual response likely to result from the inhibition of PDE6. We measured temporal acuity (critical fusion frequency) and modulation sensitivity in four subjects before and after the ingestion of a 100-mg dose of Viagra under conditions chosen to isolate the responses of either their short-wavelength-sensitive (S-) cone photoreceptors or their long- and middle-wavelength-sensitive (L- and M-) cones. When vision was mediated by S-cones, all subjects exhibited some statistically significant losses in sensitivity, which varied from mild to moderate. The two individuals who showed the largest S-cone sensitivity losses also showed comparable losses when their vision was mediated by the L- and M-cones. Some of the losses appear to increase with frequency, which is broadly consistent with Viagra interfering with the ability of PDE6 to shorten the time over which the visual system integrates signals as the light level increases. However, others appear to represent a roughly frequency-independent attenuation of the visual signal, which might also be consistent with Viagra lengthening the integration time (because it has the effect of increasing the effectiveness of steady background lights), but such changes are also open to other interpretations. Even for the more affected observers, however, Viagra is unlikely to impair common visual tasks, except under conditions of reduced visibility when objects are already near visual threshold.

  6. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

    Science.gov (United States)

    Wareing, Mark; Myers, Jenny E; O'Hara, Maureen; Baker, Philip N

    2005-05-01

    Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

  7. Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

    Science.gov (United States)

    Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

    2007-12-01

    Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

  8. Effect of sildenafil citrate (Viagra) on coronary flow in normal subjects.

    Science.gov (United States)

    Ishikura, Fuminobu; Beppu, Shintaro; Ueda, Hiroaki; Nehra, Ajay; Khandheria, Bijoy K

    2008-01-01

    The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects.

  9. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  10. Studies on sildenafil citrate (Viagra) interaction with DNA using electrochemical DNA biosensor.

    Science.gov (United States)

    Rauf, Sakandar; Nawaz, Haq; Akhtar, Kalsoom; Ghauri, Muhammad A; Khalid, Ahmad M

    2007-05-15

    The interaction of sildenafil citrate (Viagra) with DNA was studied by using an electrochemical DNA biosensor. The binding mechanism of sildenafil citrate was elucidated by using constant current potentiometry and differential pulse voltammetry at DNA-modified glassy carbon electrode. The decrease in the guanine oxidation peak area or peak current was used as an indicator for the interaction in 0.2M acetate buffer (pH 5). The binding constant (K) values obtained were 2.01+/-0.05 x 10(5) and 1.97+/-0.01 x 10(5)M(-1) with constant current potentiometry and differential pulse voltammetry, respectively. A linear dependence of the guanine peak area or peak current was observed within the range of 1-40 microM sildenafil citrate with slope=-2.74 x 10(-4)s/microM, r=0.989 and slope=-2.78 x 10(-3)microA/microM, r=0.995 by using constant current potentiometry and differential pulse voltammetry, respectively. Additionally, binding constant values for sildenafil citrate-DNA interaction were determined for the pH range of 4-8 and in biological fluids (serum and urine) at pH 5. The influence of sodium and calcium ions was also studied to elucidate the mechanism of sildenafil citrate-DNA interaction under different solution conditions. The present study may prove to be helpful in extending our understanding of the anticancer activity of sildenafil citrate from cellular to DNA level.

  11. Beliefs and social norms about sildenafil citrate (Viagra) misuse and perceived consequences among Houstonian teenage males.

    Science.gov (United States)

    Peters, Ronald J; Johnson, Regina J; Kelder, Steve; Meshack, Angela F; Jefferson, Troy

    2007-09-01

    In the current study, a qualitative approach was used to investigate relevant beliefs and norms associated with sildenafil citrate (Viagra) consumption, initiation, and perceived consequences. Focus groups were conducted with 43 young men aged 18 and 19 years who identified themselves as lifetime sildenafil citrate users. The majority of focus group participants believed that "curiosity" and "peer pressure" contributed to their initial use. Most revealed that they first heard about sildenafil citrate from television advertisements, family members, friends, or sporting events, and they were able to obtain the drug from their friends and family members or they stole it from their father or grandfather. These findings may highlight the relative importance of exposure to prescription drug messages among those to whom the message is not specifically targeted, that is, young men. It is possible that the sildenafil citrate television messages are recalled by not only older male audiences but also by teenagers and younger men, producing similar cognitive processing and curiosity in both age cohorts.

  12. Colorimetric determination of sildenafil citrate (Viagra) through ion-associate complex formation.

    Science.gov (United States)

    Amin, Alaa S; Moustafa, Moustafa E; El-Dosoky, Reham

    2009-01-01

    A simple, quick, accurate, and sensitive colorimetric method is described for the determination of sildenafil citrate (SLD). The method is based on the reaction of SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate complex species; the colored products are quantitated colorimetrically at 523, 554, and 569 nm, respectively. The various experimental conditions were optimized. The stoichiometric ratio was found to be 1:1 for all ion associates; the calculated logarithmic stability constants were 8.51, 7.79, and 5.58, respectively. Beer's law was obeyed over the concentration range of 0.2-7.0 microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL. Values for molar absorptivity, Sandell sensitivity, and detection and quantification limits were also calculated. The proposed method was successfully applied to the determination of SLD in Viagra tablets and in serum samples by using the technique of standard additions with mean accuracy values of 100.06 +/- 1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60, 99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

  13. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  14. Evaluation of the effects of sildenafil citrate (viagra) on vertebral artery blood flow in patients with vertebro-basilar insufficiency.

    Science.gov (United States)

    Bozgeyik, Zulkif; Berilgen, Sait; Ozdemir, Huseyin; Tekatas, Aslan; Ogur, Erkin

    2008-01-01

    To investigate the effects of sildenafil citrate (Viagra) on the vertebral artery blood flow of patients with vertebro-basilar insufficiency (VBI) using color duplex sonography (CDS). The study included 21 patients with VBI (aged 31-76; mean 61.0 +/- 10.5 yrs). We administered a 50 mg oral dose of sildenafil citrate to all patients. Next, we measured the peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistive index (RI), pulsatility index (PI), diameter, area, and flow volume (FV) of vertebral arteries using CDS before the administration of sildenafil citrate; 45 minutes after, and 75 minutes after administration. Statistical testing was performed using SPSS for windows version 11.0. The statistical test used to determine the outcome of the analysis was the repeated measures analysis of variance (ANOVA) test. Compared to the baseline values, the vertebral artery diameter, area, and FV increased significantly following the administration of sildenafil citrate. The diameter, area and FV increased from 3.39 mm at 45 minutes to 3.64 mm at 75 minutes, 9.43 cm(2) to 10.80 cm(2) at 45 minutes and 10.81 cm(2) at 75 minutes, as well as from 0.07 L/min at baseline to 0.09 L/min at 45 minutes and unchanged at 75 minutes, respectively. Sildenafil citrate elicited a significant effect on vertebral artery diameter, area and FVs.

  15. Evaluation of the Effects of Sildenafil Citrate (Viagra) on Vertebral Artery Blood Flow in Patients with Vertebro-Basilar Insufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Bozgeyik, Zulkif; Berilgen, Sait; Ozdemir, Huseyin; Ogur, Erkin [Firat University School of Medicine, Elazig(Turkmenistan); Tekatas, Aslan [Elazig Government Hospital, Elazig (Turkmenistan)

    2008-12-15

    To investigate the effects of sildenafil citrate (Viagra) on the vertebral artery blood flow of patients with vertebro-basilar insufficiency (VBI) using color duplex sonography (CDS). The study included 21 patients with VBI (aged 31-76; mean 61.0 +- 10.5 yrs). We administered a 50 mg oral dose of sildenafil citrate to all patients. Next, we measured the peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistive index (RI), pulsatility index (PI), diameter, area, and flow volume (FV) of vertebral arteries using CDS before the administration of sildenafil citrate; 45 minutes after, and 75 minutes after administration. Statistical testing was performed using SPSS for windows version 11.0. The statistical test used to determine the outcome of the analysis was the repeated measures analysis of variance (ANOVA) test. Compared to the baseline values, the vertebral artery diameter, area, and FV increased significantly following the administration of sildenafil citrate. The diameter, area and FV increased from 3.39 mm at 45 minutes to 3.64 mm at 75 minutes, 9.43 cm{sup 2} to 10.80 cm{sup 2} at 45 minutes and 10.81 cm{sup 2} at 75 minutes, as well as from 0.07 L/min at baseline to 0.09 L/min at 45 minutes and unchanged at 75 minutes, respectively. Sildenafil citrate elicited a significant effect on vertebral artery diameter, area and FVs

  16. Voltammetric method for the determination of sildenafil citrate (Viagra) in pure form and in pharmaceutical formulations.

    Science.gov (United States)

    Tyszczuk, Katarzyna; Korolczuk, Mieczyslaw

    2010-06-01

    A highly sensitive and simple voltammetric method for the determination of sildenafil citrate (SC) was developed. The method is based on the accumulation by adsorption of SC on a lead film modified glassy carbon electrode (LF/GCE) and then the reduction of SC throughout the stripping step. During the determinations of SC at the lead film electrode three adsorptive stripping voltammetric peaks at -1.2, -1.33 and -1.45V were observed. The respective response selected for identification and quantification has been evaluated with respect to the composition and pH of the supporting electrolyte, the potential and the time of the lead film formation, the potential and the time of the SC accumulation and other variables. Experimental results indicate an excellent linear correlation between the peak current and concentration in the range of 2x10(-9)-1.5x10(-7)mol/L (for peaks 1 and 2) and 1x10(-8)-1.5x10(-7)mol/L (for the peak 3). The detection limits (LOD) for SC following 30s of accumulation time were equal to 9x10(-10)mol/L (for peaks 1 and 2) and 4.5x10(-9)mol/L (for the peak 3). The method was successfully applied to the determination of SC in the tablets (Viagra 25 and Viagra 50) and average the contents were in close agreement with those quoted by the manufacturer and with those obtained by the reported spectrophotometric method and voltammetric method using a hanging mercury drop electrode. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Hemodynamic effects of sildenafil citrate (Viagra) on segmental branches of bilateral renal arteries.

    Science.gov (United States)

    Ardicoglu, Arslan; Kocakoc, Ercan; Yuzgec, Veysel; Bozgeyik, Zulkif; Canatan, Halit; Kiris, Adem

    2005-01-01

    Erectile dysfunction (ED) is one of the most encountered male health problem and sildenafil citrate is used worldwide for treatment of ED. Aim of the present study was to determine and evaluate hemodynamic effects of sildenafil citrate on segmental branches of bilateral renal arteries of cases with ED. Total of 35 male patients aging between 34 and 56 years were recruited into study. Patients were evaluated with renal color Doppler sonography (CDS) before and after (45-75 min) peroral sildenafil citrate (50 mg) administration. Peak systolic flow rate (V(max)), end diastolic flow rate (V(min)), resistive index (RI) and pulsatility index (PI) of renal artery segmental branches were determined before and after sildenafil citrate administration. V(min) measured at right lower segment was significantly reduced after sildenafil administration (p = 0.030). Accordingly mean RI and PI of right lower segment of renal artery slightly increased after drug administration (p = 0.007 and p = 0.012, respectively). The measurements on other segments had no significant change after sildenafil treatment when compared to baseline values. On this single dose administration no side effect was recorded. Findings of the present study demonstrated that peroral sildenafil citrate usage had slight effects on hemodynamic parameters of lower segmental branch of right renal artery. This result could not be interpreted as robust evidence for hemodynamic changes of renal arteries associated with sildenafil usage nevertheless warrants more comprehensive research with larger number of patients.

  18. The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors.

    Science.gov (United States)

    Lorberboym, M; Mena, I; Wainstein, J; Boaz, M; Lampl, Y

    2010-06-01

    Sildenafil citrate is widely used for erectile dysfunction. The present study examined the short-term effects of sildenafil administration in individuals with cerebrovascular risk factors, including patients with a history of stroke. Twenty-five consecutive male patients with erectile dysfunction and vascular risk factors were included in the study. A perfusion brain SPECT study was performed at baseline and 1 h after the oral administration of sildenafil. Associations between any of the risk factors and the perfusion scores were not detected, with the exception of stroke. Stroke patients showed significantly more areas with diminished perfusion after sildenafil administration compared to baseline. In patients with diabetes or hypertension, a dose of 50 mg sildenafil does not appear to produce detrimental effects on cerebral blood flow. However, patients with a history of stroke may be at increased risk of hemodynamic impairment after the use of sildenafil.

  19. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus.

    Science.gov (United States)

    Miller, Suzanne L; Loose, Jan M; Jenkin, Graham; Wallace, Euan M

    2009-01-01

    This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra; Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being. In fetal sheep, we induced IUGR at 105-110 days (0.7 gestation) using single umbilical artery ligation (SUAL). In SUAL and control animals, we measured uterine blood flow (UBF) and blood gases before and after sildenafil administration. SUAL fetuses were hypoxemic compared with controls. Following sildenafil, UBF was significantly decreased in both SUAL and control ewes for approximately 40 minutes. In response to sildenafil, pO(2) was decreased in SUAL and control fetuses and both groups displayed significant hypotension and tachycardia. At postmortem SUAL fetal body weight was significantly reduced by 23% compared with controls. Sildenafil does not improve UBF or fetal well being in SUAL-induced IUGR pregnancies and should be used with caution in IUGR and healthy pregnancies because of its detrimental effects on uteroplacental perfusion and on the fetus.

  20. Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

    Science.gov (United States)

    Fayed, Abdel-Hasseb A; Gad, Shereen B

    2011-12-01

    As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

    Science.gov (United States)

    Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

    2009-03-01

    To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

  2. Concentration-dependent Sildenafil citrate (Viagra) effects on ROS production, energy status, and human sperm function.

    Science.gov (United States)

    Sousa, Maria Inês; Amaral, Sandra; Tavares, Renata Santos; Paiva, Carla; Ramalho-Santos, João

    2014-04-01

    Literature regarding the effects of sildenafil citrate on sperm function remains controversial. In the present study, we specifically wanted to determine if mitochondrial dysfunction, namely membrane potential, reactive oxygen species production, and changes in energy content, are involved in in vitro sildenafil-induced alterations of human sperm function. Sperm samples of healthy men were incubated in the presence of 0.03, 0.3, and 3 μM sildenafil citrate in a phosphate buffered saline (PBS)-based medium for 2, 3, 12, and 24 hours. Sperm motility and viability were evaluated and mitochondrial function, i.e., mitochondrial membrane potential and mitochondrial superoxide production were assessed using flow-cytometry. Additionally, adenosine triphosphate (ATP) levels were determined by high performance liquid chromatography (HPLC) analysis. Results show a decrease in sperm motility correlated with the level of mitochondria-generated superoxide, without a visible effect on mitochondrial membrane potential or viability upon exposure to sildenafil. The effect on both motility and superoxide production was higher for the intermediate concentration of sildenafil (0.3 µM) indicating that the in vitro effects of sildenafil on human sperm do not vary linearly with drug concentration. Adenosine triphosphate levels also decreased following sildenafil exposure, but this decrease was only detected after a decrease in motility was already evident. These results suggest that along with the level of ATP and mitochondrial function other factors are involved in the early sildenafil-mediated decline in sperm motility. However, the further decrease in ATP levels and increase in mitochondria-generated reactive oxygen species after 24 hours of exposure might further contribute towards declining sperm motility.

  3. Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy

    2010-10-01

    The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30-35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.

  4. Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

    Science.gov (United States)

    Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

    2008-02-01

    The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

  5. Central Retinal Vein Occlusion AssociatedWith Sildenafil (Viagra ...

    African Journals Online (AJOL)

    Objectives To report the occurrence of a severe, blinding and irreversible adverse effect following use of the drug sildenafil citrate (Viagra). Methods This is a case report of a 60 year old man who presented with unilateral, suddenonset, painless, visual loss following the use of sildenafil citrate 100mg twice weekly, ...

  6. Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2007-01-01

    Sildenafil citrate is a specific inhibitor of phosphodiesterase (PDE) type-5 and represents a powerful therapy for male erectile and fertility dysfunctions of different etiologies. Present study demonstrates whether sildenafil administration modifies seminal parameters in diabetic neuropathic patients. In this investigation 50 insulin dependent (IDDM) and 50 non insulin dependent (NIDDM) diabetic male patients with and without an objective evidence of neuropathy and 50 age matched non diabetic male controls were selected. Every male had age between 20 to 65 years with duration of diabetes distributed over 1 to 20 years. Treatment with 100 mg of oral sildenafil citrate on seminal parameters was evaluated by semen analysis in these patients. In both IDDM and NIDDM diabetic neuropathic patients, chronic sildenafil treatment exhibited a significant decrease in total sperm output and sperm concentration (p<0.001). On the other hand, sperm motility and semen volume were found to be increased by about 40% and 48% respectively in these patients, where as sperm morphology and quality of sperm motility remained unaffected. However both types of non neuropathic diabetics showed a non significant difference in all the above mentioned parameters when compared with the untreated groups and their respective control subjects. A comparison between IDDM and NIDDM neuropathic and non neuropathic diabetic groups further indicated a non significant difference in all the parameters of semen analysis. These findings suggest a chronic neuro physiological effect of sildenafil treatment on male fertility profile exclusively in diabetic neuropathic condition with an improvement in testicular function which was probably arrested due to some kind of testicular hyperplasia resulted by testicular necrosis and promoted spermatogenesis. Sildenafil seems to be associated with an improvement in the entire smooth musculature of reproductive tract and testicular morphology which was altered due to

  7. Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

    Science.gov (United States)

    Eltony, Sohair A; Abdelhameed, Sally Y

    2017-04-01

    Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Strategically functionalized carbon nanotubes as the ultrasensitive electrochemical probe for picomolar detection of sildenafil citrate (Viagra).

    Science.gov (United States)

    Gopalan, Anantha Iyengar; Lee, Kwang Pill; Komathi, Shanmugasundaram

    2011-02-15

    The present work demonstrates the utility of the functionalized carbon nanotubes, poly(4-aminobenzene sulfonic acid) (PABS) grafted multiwalled carbon nanotubes, MWNT-g-PABS, as an electrode modifier towards achieving ultrasensitive detection of a model drug, sildenafil citrate (SC). PABS units in MWNT-g-PABS interact with SC, pre-concentrate and accumulate at the surface. The electron transduction from SC to electrode is augmented via MWNT-g-PABS. As a result, the MWNT-g-PABS modified electrode exhibited ultrasensitive (57.7 μA/nM) and selective detection of SC with a detection limit of 4.7 pM. The present work provides scope towards targeting ultrasensitivity for the detection of biomolecules/drug through rational design and incorporation of appropriate chemical components to carbon nanotubes. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

    Science.gov (United States)

    Tsertsvadze, Alexander; Yazdi, Fatemeh; Fink, Howard A; MacDonald, Roderick; Wilt, Timothy J; Bella, Anthony J; Ansari, Mohammed T; Garritty, Chantelle; Soares-Weiser, Karla; Daniel, Raymond; Sampson, Margaret; Moher, David

    2009-10-01

    To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

  10. Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual responses in Saudi men with erectile dysfunction in routine clinical practice.

    Science.gov (United States)

    Ali, Syed Tabrez

    2008-07-01

    Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction, yet enhanced satisfaction has been infrequently assessed in the sexual trials. We evaluated the efficacy of sildenafil vs. tadalafil, in Saudi men with erectile dysfunction and determined the self-based rating of medicinal preference. Sildenafil citrate (Viagra) is a potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Whereas cGMP is a second messenger for the vasodilator effects of nitric oxide causing smooth muscle relaxation, which in turn leads to penile erection; however the mechanism by which cGMP stimulates relaxation of the smooth muscles remains to be elucidated. Both sildenafil and tadalafil have a rapid onset with the effectiveness up to 4 hours and 36 hours respectively. In this study subjects treated with 100 mg oral dose of sildenafil / 20 mg tadalafil were found to be associated with higher mean scores for the questions of the International Index of Erectile Function (IIEF). Frequency of penetration and maintenance of erection after sexual penetration and/or during masturbation were found to be enhanced significantly (p<0.001) in both sildenafil/tadalafil treated men. Similarly mean domain of erectile function, orgasmic function, and intercourse satisfaction also showed a significantly positive improvement (p/0.001) in both the treated groups in comparison with their age matched untreated controls. Interestingly in all the cases, tadalafil group showed considerably greater positive responses than the sildenafil group but within the same significant levels. Strikingly the sexual-desire domain in sildenafil treated men with respect to their aged matched controls

  11. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

    Science.gov (United States)

    Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

    2001-01-01

    OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

  12. Novel synthesis of nanocomposite for the extraction of Sildenafil Citrate (Viagra) from water and urine samples: Process screening and optimization.

    Science.gov (United States)

    Asfaram, Arash; Ghaedi, Mehrorang; Purkait, Mihir Kumar

    2017-09-01

    A sensitive analytical method is investigated to concentrate and determine trace level of Sildenafil Citrate (SLC) present in water and urine samples. The method is based on a sample treatment using dispersive solid-phase micro-extraction (DSPME) with laboratory-made Mn@ CuS/ZnS nanocomposite loaded on activated carbon (Mn@ CuS/ZnS-NCs-AC) as a sorbent for the target analyte. The efficiency was enhanced by ultrasound-assisted (UA) with dispersive nanocomposite solid-phase micro-extraction (UA-DNSPME). Four significant variables affecting SLC recovery like; pH, eluent volume, sonication time and adsorbent mass were selected by the Plackett-Burman design (PBD) experiments. These selected factors were optimized by the central composite design (CCD) to maximize extraction of SLC. The results exhibited that the optimum conditions for maximizing extraction of SLC were 6.0 pH, 300μL eluent (acetonitrile) volume, 10mg of adsorbent and 6min sonication time. Under optimized conditions, virtuous linearity of SLC was ranged from 30 to 4000ngmL -1 with R 2 of 0.99. The limit of detection (LOD) was 2.50ngmL -1 and the recoveries at two spiked levels were ranged from 97.37 to 103.21% with the relative standard deviation (RSD) less than 4.50% (n=15). The enhancement factor (EF) was 81.91. The results show that the combination UAE with DNSPME is a suitable method for the determination of SLC in water and urine samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A systematic review assessing the economic impact of sildenafil citrate (Viagra) in the treatment of erectile dysfunction.

    Science.gov (United States)

    Martin, Amber L; Huelin, Rachel; Wilson, David; Foster, Talia S; Mould, Joaquin F

    2013-05-01

    Sildenafil was the first oral phosphodiesterase type 5 (PDE5) inhibitor introduced as primary therapy for erectile dysfunction (ED). In the 7 years following its market launch, sildenafil was prescribed by more than 750,000 physicians to more than 23 million men worldwide. To date, few studies have evaluated the economic impact of sildenafil in treating ED. To evaluate the cost-effectiveness and impact of sildenafil on health care costs for patients with ED in multiple countries. Economic outcomes including cost, cost-effectiveness, cost of illness, cost consequence, resource use, productivity, work loss, and willingness to pay (WTP) were investigated. Using keywords related to economic outcomes and sildenafil, we systematically searched literature published between July 2001 and July 2011 using MEDLINE and EMBASE. Included articles pertained to costs, WTP, and economic evaluations. In the last 10 years, 12 studies assessed economic outcomes associated with sildenafil for ED. Most studies were conducted in the United States and the United Kingdom, with one study identified in Canada and one from Mexico. Six studies evaluated cost of illness, cost consequence, or cost of care, and four studies evaluated WTP or drug pricing by country in the United States and the United Kingdom. In the United States and the United Kingdom, costs to health care systems have increased with demand for treatment. Cost analyses suggested that sildenafil would lower direct costs compared with other PDE5 inhibitors. U.S. and U.K. studies found that patients exhibited WTP for sildenafil. The two cost-effectiveness models we identified examined ED sub-groups, those with spinal cord injury and those with diabetes or hypertension. These models indicated favorable cost-effectiveness profiles for sildenafil compared with other active-treatment options in both Mexico and Canada. The relative value of sildenafil vs. surgically implanted prosthetic devices and other PDE5 inhibitors, is underscored

  14. Modeling and simulation of sexual activity daily diary data of patients with female sexual arousal disorder treated with sildenafil citrate (Viagra).

    Science.gov (United States)

    Claret, Laurent; Cox, Eugene H; McFadyen, Lynn; Pidgen, Alwyn; Johnson, Patrick J; Haughie, Scott; Boolell, Mitra; Bruno, Rene

    2006-08-01

    To develop a model to explore the dose-response of sildenafil citrate in patients with female sexual arousal disorder (FSAD) based on telephone sexual activity daily diary (TSADD) data obtained in double-blind, placebo controlled clinical studies. Data were available on 614 patients with FSAD. A parametric model (Weibull distribution) was developed to describe the probability density function of the time between sexual events. Orgasm satisfaction scores and overall sexual satisfaction scores were simultaneously modeled as ordered categorical variables. Simulations were performed to evaluate the expected clinical response in patients with FSAD. The expected time between sexual events was approximately 3.5 days. Satisfaction scores increased with time to achieve a plateau after 3 to 4 weeks on treatment. The expected probability of satisfying orgasm (score of 3 and higher) ranged from 34.7% for placebo to 41.6% for 100 mg sildenafil citrate. Treatment effect (difference from placebo) was 6.9% for 100 mg sildenafil citrate, ranging from 0.6 to 24.7% for testosterone levels of 0.1 to 4.0 pg/ml. The treatment effect in postmenopausal women was larger than in premenopausal women. A modeling and simulation framework to support drug development in FSAD was developed. Sildenafil citrate demonstrated a dose-dependent effect in patients with FSAD.

  15. Estudo da circulação retrobulbar e do campo visual após dose única oral de citrato de sildenafil (Viagra® The effects of a single dose of sildenafil citrate (Viagra® on the retrobulbar circulation and visual field

    Directory of Open Access Journals (Sweden)

    Alessandra Kurahashi

    2001-08-01

    Full Text Available Objetivo: Estudar os efeitos na circulação retrobulbar e no campo visual de uma dose oral única de 100 mg de citrato de sildenafil (Viagra®. Métodos: Um estudo duplo-mascarado e controlado por placebo foi realizado em 10 voluntários do sexo masculino, com idade média de 27,7 + 5,68 anos. O olho direito de cada voluntário foi submetido aos exames de Doppler colorido de órbita e análise de campo visual por meio de perimetria computadorizada (Humphrey, programa 30-2, estratégia "Full Threshold" em 3 ocasiões: "baseline", 1 hora após placebo e 1 hora após 100 mg de sildenafil via oral. No campo visual, analisaram-se o limiar foveal e o "mean deviation" (MD nas 3 ocasiões. No Doppler colorido, medimos a velocidade sistólica máxima (VSM, a velocidade diastólica final (VDF e o índice de resistência (IR da artéria central da retina (ACR e da artéria oftálmica (AO nas 3 ocasiões. Resultados: A administração do sildenafil não alterou significativamente o limiar foveal e o "mean deviation" em relação ao "baseline" e ao placebo. Houve um aumento significativo da velocidade sistólica máxima e velocidade diastólica final na artéria oftálmica após a administração do citrato de sildenafil (pPurpose: To analyze the effects of 100 mg of sildenafil citrate (Viagra® on the retrobulbar circulation and visual field. Methods: A double masked, placebo controlled study was conducted in 10 males with a mean age of 27.7 + 5.68 years. The right eye of each volunteer underwent orbital color Doppler imaging and automated perimetry (Humphrey, program 30-2, Full-Threshold Strategy at 3 occasions: baseline, 1 hour after placebo and 1 hour after 100 mg of sildenafil. The foveal threshold and the mean deviation (MD were analyzed by automated perimetry on the three occasions. Color Doppler imaging allowed the measurement of the peak systolic velocity (PSV, end diastolic velocity (EDV and Pourcelot index (PI in the central retinal artery and

  16. SILDENAFIL (VIAGRA) IN THE TREATMENT OF MALE ERECTILE ...

    African Journals Online (AJOL)

    hi-tech

    2000-02-02

    Feb 2, 2000 ... facial flushing and nausea and vomiting in one patient, respectively. Conclusion: Oral sildenafil (Viagra) ... the Massachusetts male ageing study has been carried out, .... Facial flushing. 1. 0.46. Seven patients (3.2%) had adverse effects related to viagra administration (Table 6). The adverse effects include.

  17. Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra®) on the fertilisation biology of broadcast spawning marine invertebrates.

    Science.gov (United States)

    Mohd Zanuri, Norlaila Binti; Bentley, Matthew G; Caldwell, Gary S

    2017-06-01

    Exposure to synthetic chemicals is a key environmental challenge faced by aquatic organisms. The time and dose effects of the pharmaceuticals diclofenac, ibuprofen, and sildenafil citrate on sperm motility and successful fertilisation are studied using the echinoderms, Asterias rubens and Psammechinus miliaris, and the polychaete worm Arenicola marina, all important components of the marine benthos. Motility was reduced for all species when exposed to diclofenac concentrations ≥0.1 μg/L. Exposure to ≥1.0 μg/L of ibuprofen affected only P. miliaris gametes and fertilisation success of A. marina. A. rubens and P. miliaris sperm increased in both percentage motility and swimming velocity when exposed to sildenafil citrate at concentrations ≥18 and ≥ 50 ng/L, respectively. Pre-incubation of sperm with sildenafil citrate significantly increased fertilisation success in A. rubens and P. miliaris but not in A. marina. Pre-incubated A. rubens oocytes fertilised successfully in ibuprofen. According to EU Directive 93/67/EEC, diclofenac is classified as a very toxic substance to gametes of A. rubens, P. miliaris, and A. marina (EC 50  = 100-1000 μg/L) while ibuprofen is classified as very toxic to gametes of P. miliaris but non-toxic to gametes of A. marina (EC 50  > 10,000 μg/L). The present study indicates that diclofenac exposure may have negative impacts on invertebrate reproductive success, whereas ibuprofen potentially may compromise P. miliaris reproduction. This study provides a valuable insight into the mechanisms that allow marine invertebrates to survive and reproduce in contaminated and changing habitats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Probable neuro sexual mode of action of Casimiroa edulis seed extract versus [correction of verses] sildenafil citrate (Viagra(tm)) on mating behavior in normal male rats.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2008-01-01

    The present study deals with the aphrodisiac actions of the aqueous extract of the seeds of the hypotensive plant Casimiroa edulis on the sexual behavior of normal male rats. In this investigation 30 healthy male Wister strain white albino rats showing the brisk sexual activity age 15 weeks, weighing 400-450 grams were included. Female rats were artificially brought into estrous by hormonal treatment. Receptivity was checked by exposing them to the male rats and the most receptive females were selected for the stud The mating responses including Mounting Frequency (MF), Intromission Frequency (IF), Mounting Latency (ML), Intromission Latency (IL), Ejaculatory Latency in first and second series (EL1 and EL2) and Post Ejaculatory Interval (PEI) were recorded after treating the animals with 250 mg/kg casimiroa edulis extract (test reference) and 5 mg/kg sildenafil citrate (standard reference) respectively orally per day for 7 days. Both the groups exhibited a significant increase in Mounting Frequency, Intromission Frequency, and first and second ejaculatory latencies, where as Mounting and Intromission latencies and the Post Ejaculatory Interval showed a significant reduction than the controls. Although a similar pattern of mating behavior was observed among the test and the standard groups, however in all the cases as expected, sildenafil produced greater activity than the casimiroa edulis extract. These results suggest the possibility of a similar mode of action of casimiroa edulis and sildenafil citrate on mating behavior in these animals. Our work reported in this research thus provide preliminary evidence that the aqueous seed extract of casimiroa edulis possesses alphrodisiac activity and may be used as an alternative drug therapy to restore sexual functions probably via a neurogenic mode of action.

  19. Molecular characterization of microbial population dynamics during sildenafil citrate degradation.

    Science.gov (United States)

    De Felice, Bruna; Argenziano, Carolina; Guida, Marco; Trifuoggi, Marco; Russo, Francesca; Condorelli, Valerio; Inglese, Mafalda

    2009-02-01

    Little is known about pharmaceutical and personal care products pollutants (PPCPs), but there is a growing interest in how they might impact the environment and microbial communities. The widespread use of Viagra (sildenafil citrate) has attracted great attention because of the high usage rate, the unpredictable disposal and the unknown potential effects on wildlife and the environment. Until now information regarding the impact of Viagra on microbial community in water environment has not been reported. In this research, for the first time, the genetic profile of the microbial community, developing in a Viagra polluted water environment, was evaluated by means of the 16S and 18S rRNA genes, for bacteria and fungi, respectively, amplified by polymerase chain reaction (PCR) and separated using the denaturing gradient gel electrophoresis (DGGE) technique. The DGGE results revealed a complex microbial community structure with most of the population persisting throughout the experimental period. DNA sequences from bands observed in the different denaturing gradient gel electrophoresis profiles exhibited the highest degree of identity to uncultured bacteria and fungi found previously mainly in polluted environmental and treating bioreactors. Biotransformation ability of sildenafil citrate by the microbial pool was studied and the capability of these microorganisms to detoxify a polluted water ecosystem was assessed. The bacterial and fungal population was able to degrade sildenafil citrate entirely. Additionally, assays conducted on Daphnia magna, algal growth inhibition assay and cell viability determination on HepG2 human cells showed that biotransformation products obtained from the bacterial growth was not toxic. The higher removal efficiency for sildenafil citrate and the lack of toxicity by the biotransformation products obtained showed that the microbial community identified here represented a composite population that might have biotechnological relevance to

  20. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases.

    Science.gov (United States)

    Pomeranz, Howard D; Bhavsar, Abdhish R

    2005-03-01

    Seven patients, aged between 50 and 69 years, had typical features of nonarteritic anterior ischemic optic neuropathy (NAION) within 36 hours after ingestion of sildenafil citrate (Viagra) for erectile dysfunction. Six patients had vision loss within 24 hours after use of the agent. Final visual acuity in the affected eye ranged from 20/20 to light perception. Both eyes were affected in one individual. All affected individuals had pre-existing hypertension, diabetes, elevated cholesterol, or hyperlipidemia. Seven similar cases have been previously reported. Sildenafil may provoke NAION in individuals with an arteriosclerotic risk profile.

  1. Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra) for erectile dysfunction: a multicentre, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Heiman, J R; Talley, D R; Bailen, J L; Oskin, T A; Rosenberg, S J; Pace, C R; Creanga, D L; Bavendam, T

    2007-04-01

    To investigate the effect of improvement in erectile dysfunction (ED) on sexual function and satisfaction measures in heterosexual couples in which the woman reports that sexual intercourse is unsatisfactory at least half of the time. Multicentre, double-blind, placebo-controlled study. Outpatient medical clinics. Hundred and eighty men with ED and their female partners in whom sexual intercourse was satisfactory about half the time or less (score of Self-Esteem And Relationship questionnaire, and EDITS. Secondary, partners and men: Dyadic Adjustment Scale. The intention-to-treat population included 85 sildenafil recipients (mean age 59 +/- 12 years) and 91 placebo recipients (mean age 57 +/- 11 years). Most partners (aged 20-79 years; mean, 54 years) were postmenopausal. Sildenafil compared with placebo couples had greater improvement in the primary outcome (FePEDS Q3 [P < 0.0001]) and in sexual function, intercourse success rates, and secondary sexual satisfaction measures (FSFI satisfaction domain [P < 0.0001] and IIEF satisfaction domains [P < 0.001]) and had higher treatment satisfaction (EDITS and EDITS-Partner; P < 0.0001). Several predictors of improvement were identified, and improvement in one member of the couple correlated positively with improvement in the other member. The interdependence of sexual function and sexual satisfaction measures between members of couples consisting of men with ED and sexually healthy women reporting infrequent satisfactory sexual intercourse underscores the importance of including partners in ED treatment discussions.

  2. Results of double-blind placebo-controlled crossover study of sildenafil citrate (Viagra) in women suffering from obstructed voiding or retention associated with the primary disorder of sphincter relaxation (Fowler's Syndrome).

    Science.gov (United States)

    Datta, Soumendra N; Kavia, Rajesh B C; Gonzales, Gwen; Fowler, Clare J

    2007-02-01

    Women with the primary disorder of sphincter relaxation find voiding difficult. Studies have identified neuronal nitric oxide synthase in the female urethral sphincter, and nitric oxide donors have been shown to decrease sphincter pressures. The aim of our study was to determine if sildenafil could improve sphincter relaxation and thereby increase flow rates and improve bladder emptying. Twenty women with complete (5), partial retention or obstructed voiding (15) with a maximum flow rate (Qmax) of less than 15 ml/min with an elevated maximal urethral closure pressure (92--age cm H(2)O) and sphincter volume (>1.6 cm(3)) were included in the study. The study was a double-blind, randomised, placebo-control, crossover design, with patients taking sildenafil or placebo, and with measurement of flow rate and residual volume at baseline and after each treatment phase. Voiding diary, quality of life, and International Prostate Symptom Score (IPSS) data were also collected. No statistical significant difference was seen in any voiding parameters and diaries when sildenafil citrate was compared with placebo. There was a significant mean decrease in IPSS of 3.64 between baseline and the sildenafil phase (p=0.0083), but not when compared with placebo. In the subgroup of women with partial retention and obstructed voiding (15/20), there was a statistically significant increase in Qmax of 4.7 ml/sec (p=0.025) between sildenafil and baseline; however this difference was not seen when compared with placebo. This is the first study looking at sildenafil in voiding dysfunction in women. Clinical improvements with sildenafil were not significant when compared with placebo. Sildenafil was not effective as a therapeutic pharmacologic agent in this group of patients.

  3. Women taking the “blue pill” (sildenafil citrate: such a big deal?

    Directory of Open Access Journals (Sweden)

    Lo Monte G

    2014-11-01

    Full Text Available Giuseppe Lo Monte, Angela Graziano, Isabella Piva, Roberto Marci Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy Abstract: For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra® in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate should be kept as the last option. Keywords: phosphodiesterase type 5 inhibitors, female sexual arousal disorder (FSAD, sildenafil citrate

  4. Measurement of Choroidal Perfusion and Thickness Following Systemic Sildenafil (Viagra®)

    Science.gov (United States)

    Kim, David Y.; Silverman, Ronald H.; Chan, R.V. Paul; Khanifar, Aziz A.; Rondeau, Mark; Lloyd, Harriet; Schlegel, Peter; Coleman, D. Jackson

    2011-01-01

    Objective To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (ViagraR) using enhanced depth imaging spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high frequency digital ultrasound. Methods Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and two hours after ingesting 50 mg of sildenafil. Swept-scan high frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyze differences in choroidal flow and thickness at baseline and two hours after ingestion of sildenafil. Results Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47 to 7.80 times baseline (p=0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea, and 10.7% underneath the fovea (p<0.001 for all values). Conclusions Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms, and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow. PMID:22974308

  5. Fracture penis : A complication of sildenafil citrate!

    Directory of Open Access Journals (Sweden)

    Anup Kumar Kundu

    2002-01-01

    Full Text Available Our experience with 6 consecutive cases of fracture penis, a rare urological injury, in normal male without any erectile dysfunction, who consumed Sildenafil Citrate for prolonged sexual enjoyment out of curiosity. All of them were properly worked up and treated surgi-cally resulting in excellent recovery of function.

  6. An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents.

    Science.gov (United States)

    Park, Hyun Jun; Park, Nam Cheol; Shim, Hong Bang; Park, Jong Kwan; Lee, Sung Won; Park, Kwangsung; Kim, Sae Woong; Moon, Ki Hak; Lee, Dong Hyeon; Yoon, Sang Jin

    2008-10-01

    Erectile dysfunction (ED) is common among men taking antihypertensive agents to control blood pressure. We evaluated the efficacy and safety of sildenafil citrate in men with ED taking antihypertensive agents. A total of 198 male subjects, aged 20 years and older were enrolled. This study was conducted for 10 weeks as an open-label, multicenter and flexible dose trial with a 2-week screening period and an 8-week treatment phase. Subjects were asked to complete Event Log Worksheets, as well as the International Index of Erectile Function (IIEF) and the Global Efficacy Assessment Questions (GEAQ) questionnaires during the study period. The average age among the 167 subjects who completed the study was 55.8 (31.7 to 77.1). The scores for questions 3 and 4 of IIEF improved from 2.3 and 1.8 at baseline to 3.7 and 3.4 at week 4 and 3.8 and 3.4 at week 8, respectively. There were 86.3% of the patients reported improved erectile function at week 8; 88.3% of the patients reported improved ability to achieve sexual intercourse at week 8. There were no significant differences observed in the responses to questions 3 and 4 of IIEF and GEAQ by the number of antihypertensive agents taken. The adverse events were facial flushing (20.1%), headache (11.7%), palpitation (5.0%), rhinitis (2.8%), URI (2.8%), dizziness (2.2%), dyspnea (2.2%), and nausea (1.7%). Sildenafil citrate is an effective treatment for ED; it is safe and well tolerated by patients with ED taking multiple antihypertensive agents for arterial hypertension.

  7. Women taking the "blue pill" (sildenafil citrate): such a big deal?

    Science.gov (United States)

    Lo Monte, Giuseppe; Graziano, Angela; Piva, Isabella; Marci, Roberto

    2014-01-01

    For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra(®)) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option.

  8. Women taking the “blue pill” (sildenafil citrate): such a big deal?

    Science.gov (United States)

    Lo Monte, Giuseppe; Graziano, Angela; Piva, Isabella; Marci, Roberto

    2014-01-01

    For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra®) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option. PMID:25422584

  9. Enhanced dissolution of sildenafil citrate as dry foam tablets.

    Science.gov (United States)

    Sawatdee, Somchai; Atipairin, Apichart; Sae Yoon, Attawadee; Srichana, Teerapol; Changsan, Narumon

    2017-01-30

    Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

  10. Characterization of sildenafil citrate tablets of different sources by near infrared chemical imaging and chemometric tools.

    Science.gov (United States)

    Sabin, Guilherme P; Lozano, Valeria A; Rocha, Werickson F C; Romão, Wanderson; Ortiz, Rafael S; Poppi, Ronei J

    2013-11-01

    The chemical imaging technique by near infrared spectroscopy was applied for characterization of formulations in tablets of sildenafil citrate of six different sources. Five formulations were provided by Brazilian Federal Police and correspond to several trademarks of prohibited marketing and one was an authentic sample of Viagra. In a first step of the study, multivariate curve resolution was properly chosen for the estimation of the distribution map of concentration of the active ingredient in tablets of different sources, where the chemical composition of all excipients constituents was not truly known. In such cases, it is very difficult to establish an appropriate calibration technique, so that only the information of sildenafil is considered independently of the excipients. This determination was possible only by reaching the second-order advantage, where the analyte quantification can be performed in the presence of unknown interferences. In a second step, the normalized histograms of images from active ingredient were grouped according to their similarities by hierarchical cluster analysis. Finally it was possible to recognize the patterns of distribution maps of concentration of sildenafil citrate, distinguishing the true formulation of Viagra. This concept can be used to improve the knowledge of industrial products and processes, as well as, for characterization of counterfeit drugs. Copyright © 2013. Published by Elsevier B.V.

  11. Effect of sildenafil citrate on secondary healing in full thickness skin defects in experiment.

    Science.gov (United States)

    Cakmak, E; Karasoy Yesilada, A; Sevim, K Z; Sumer, O; Tatlidede, H S; Sakiz, D

    2014-01-01

    An acceleration of the wound healing process expedites chronic wound patient's return to normal social environments significantly. Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phosphodiesterase- 5 inhibitor has been shown to be a potent stimulator of angiogenesis through upregulation of cGMP. In our study, sildenafil was administered orally as a cost-effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity. Randomly selected 72 Wistar-Albino rats were divided into the two groups, 36 rats in each group. Control group (n =36) was divided further into a secondary healing group consisting of 9 rats and a pathology group consisting of 27 rats (pathology group 1: 9 rats, 4th and 7th day of wound healing, pathology group 2: 9 rats, 10th and 14th day of wound healing, pathology group 3: 9 rats, 21st and 28th day of wound healing. Experimental group consisted of 36 rats which received sildenafil citrate (Viagra® Pfizer, Germany) for secondary wound healing to proceed. The average wound healing period in the control group was 17.89 days and in the sildenafil citrate administered group 14.56 days. The difference of the epithelialisation on full thickness defects were more prominent on days 5 and 11 postoperatively. In the sildenafil citrate applied group, on the 7th day, the defect was 25% smaller and on the 13th day, the defect contracted by 38%. In conclusion, we believe that sildenafil citrate administered orally is a cost- effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity (Tab. 4, Fig. 7, Ref. 34).

  12. Sildenafil (Viagra). Verträglichkeit, Kontraindikationen, Arzneimittelinteraktionen

    NARCIS (Netherlands)

    Sperling, H.; Michel, M. C.; Rübben, H.

    1999-01-01

    Placebo-controlled studies have clearly demonstrated the efficacy of sildenafil in the treatment of erectile dysfunction. It's tolerability cannot yet be judged definitively based on the available information. Some findings indicate that in addition to established contraindications (allergy against

  13. Central Retinal Vein Occlusion AssociatedWith Sildenafil (Viagra

    Directory of Open Access Journals (Sweden)

    H C Obiudu

    2010-01-01

    Conclusion - Central retinal vein occlusion is a possible adverse effect of sildenafil use. Physicians should be vigilant while prescribing thismedication and avoid its use in patients with elevated intraocular pressure

  14. Adsorption and inhibitive properties of sildenafil (Viagra for zinc in hydrochloric acid solution

    Directory of Open Access Journals (Sweden)

    A.S. Fouda

    Full Text Available Sildenafil (Viagra was investigated as corrosion inhibitor for Zn in 1 M HCl solution using chemical and electrochemical methods at 25 °C. Electrochemical results showed that this drug is efficient inhibitor for Zn in HCl and the inhibition efficiency (IE reached to 91% at 300 ppm. The IE increases with the drug concentration and decreases with increasing temperature. The adsorption of this drug on Zn surface follows Langmuir adsorption isotherm. The polarization plots revealed that Sildenafil acts as a mixed-type inhibitor. The thermodynamic parameters of activation and adsorption were calculated and discussed. The surface morphology of the Zn specimens was evaluated using scanning electron microscope (SEM, energy dispersive X-ray (EDX, atomic force microscopy (AFM and Fourier transform infrared spectroscopy (FTIR techniques. Keywords: Zn, Corrosion inhibition, HCl, SEM, EDX, AFM, FTIR, Sildenafil drug

  15. Effect of sildenafil citrate on intraocular pressure and blood pressure in human volunteers.

    Science.gov (United States)

    Gerometta, Rosana; Alvarez, Lawrence J; Candia, Oscar A

    2011-07-01

    Anecdotal reports have suggested that the vasodilator, sildenafil citrate, which evokes its effect via a select inhibition of PDE5, has the potential to increase intraocular pressure (IOP) in some individuals. An ocular hypertensive effect by sildenafil was also recently described in a sheep animal model. In contrast, clinical studies have not found a direct association between sildenafil ingestion (commonly consumed as Viagra) and changes in IOP. However, some such studies also reported no effects of sildenafil on systemic blood pressure (BP) at the time of the IOP determination. Given this surprising result, our purpose was to repeat a study in human volunteers in the city of Corrientes, Argentina to corroborate the effects of sildenafil on human IOP and systemic BP. For the present study, 9 healthy volunteers (male and female, 18-74 years old) were selected as subjects after ophthalmic and cardiovascular evaluation indicated that they exhibited normal parameters for their age. In a masked, placebo-controlled study, the subjects ingested 100 mg sildenafil citrate (provided as Vorst from Laboratorios Bernabo, Argentina) in one session, and a placebo on a second separate occasion. IOP was measured with a Goldman applanation tonometer by an ophthalmologist, and BP by a second physician, neither of whom witnessed the tablet ingestion by the volunteers, nor provided with information on the nature of the test compounds. A third individual administered the tablets. The average baseline IOP of this group of 9 was 13.1 ± 0.6 mm Hg. Subsequent to sildenafil ingestion, IOP increased by 26% to 16.5 ± 0.8 mm Hg 60 min later (P < 0.005, as paired data), and returned to control values within 2 h. Both systolic and diastolic BP were significantly reduced by sildenafil ingestion. At the point of maximal systemic hypotension (90 min), the systolic and diastolic pressures declined by 15% and 13%, respectively. No significant changes in IOP or BP were recorded after

  16. Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet.

    Science.gov (United States)

    Veronin, Michael A; Nutan, Mohammad T; Dodla, Uday Krishna Reddy

    2014-10-01

    The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug products compared with the US innovator product are not

  17. Adsorption and inhibitive properties of sildenafil (Viagra) for zinc in hydrochloric acid solution

    Science.gov (United States)

    Fouda, A. S.; Ibrahim, H.; Atef, M.

    Sildenafil (Viagra) was investigated as corrosion inhibitor for Zn in 1 M HCl solution using chemical and electrochemical methods at 25 °C. Electrochemical results showed that this drug is efficient inhibitor for Zn in HCl and the inhibition efficiency (IE) reached to 91% at 300 ppm. The IE increases with the drug concentration and decreases with increasing temperature. The adsorption of this drug on Zn surface follows Langmuir adsorption isotherm. The polarization plots revealed that Sildenafil acts as a mixed-type inhibitor. The thermodynamic parameters of activation and adsorption were calculated and discussed. The surface morphology of the Zn specimens was evaluated using scanning electron microscope (SEM), energy dispersive X-ray (EDX), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) techniques.

  18. Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer.

    Science.gov (United States)

    Greish, Khaled; Fateel, Maryam; Abdelghany, Sara; Rachel, Nanitha; Alimoradi, Houman; Bakhiet, Moiz; Alsaie, Ahmed

    2017-11-21

    Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of sildenafil on tumour vasculatures could result in an improvement of anticancer drug concentration in tumour tissues and hence improves its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro. Adding 1, 30 and 100 μM of Viagra to 1 μM of doxorubicin resulted in 1.8-fold, 6.2-fold and 21-fold statistically significant increases in its cytotoxic effect, respectively. As a result, 4T1 tumour-bearing mice showed up to 2.7-fold increase in drug concentrations of the fluorescent Dye DiI and doxorubicin in tumour tissues, as well as their nanoformulations. Animals treated with the combinations of both Sildenafil citrate and doxorubicin showed a statistically significant 4.7-fold reduction in tumour size compared to doxorubicin alone. This work highlights the effect of Sildenafil on tumour vasculatures and provides a rational for further testing the combination on breast cancer patients.

  19. Effect of sildenafil citrate on interleukin-1β-induced nitric oxide synthesis and iNOS expression in SW982 cells

    Science.gov (United States)

    Kim, Kyung-Ok; Park, Shin-Young; Han, Chang-Woo; Chung, Hyun Kee; Ryu, Dae-Hyun

    2008-01-01

    The purpose of this study was to identify the effect of sildenafil citrate on IL-1β-induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1β stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1β-induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1β treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1β-induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1β-induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines. PMID:18587266

  20. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

  1. Fingerprinting of sildenafil citrate and tadalafil tablets in pharmaceutical formulations via X-ray fluorescence (XRF) spectrometry.

    Science.gov (United States)

    Ortiz, Rafael S; Mariotti, Kristiane C; Schwab, Nicolas V; Sabin, Guilherme P; Rocha, Werickson F C; de Castro, Eustáquio V R; Limberger, Renata P; Mayorga, Paulo; Bueno, Maria Izabel M S; Romão, Wanderson

    2012-01-25

    The production of counterfeited drugs is a criminal problem that carries serious risks to public health in the worldwide. In Brazil, Viagra and Cialis are the most counterfeit medicines, being used to inhibit the phosphodiesterase type 5 (PDE-5), treating thus, problems related to erectile dysfunction. X-ray fluorescence (XRF) is a suitable technique to control the quality of new pharmaceutical formulations and distinguish between authentic and counterfeit tablets. XRF has advantageous features like multielemental capability, good detectivity, high precision, short analysis times, and is nondestructive, which makes it suitable to be extended to a great variety of samples. In this work, the inorganic fingerprinting chemical of forty-one commercial samples (Viagra, Cialis, Lazar, Libiden, Maxfil, Plenovit, Potent 75, Rigix, V-50, Vimax and Pramil) and fifty-six counterfeit samples (Viagra and Cialis) were obtained from XRF data. XRF presented an excellent analytical methodology for semi-quantitative determination of active ingredient (in case of sildenafil citrate that presents S in its structure) and excipients such as calcium phosphate, titanium oxide and iron oxide (P, Ca, Ti and Fe). The matrix data were allied to chemometric methods (Principal Component Analysis and Hierarchical Cluster Analysis) to classify the tablets investigated between authentic and counterfeit, grouping the samples into of seven groups: A, B, C, D and E (counterfeit group) and F and G (authentic group). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  2. Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

    Science.gov (United States)

    Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

    2010-02-01

    Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

  3. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

    Directory of Open Access Journals (Sweden)

    Lynch Tadhg

    2009-04-01

    Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  4. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

    LENUS (Irish Health Repository)

    Maharaj, Chrisen H

    2009-01-01

    OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  5. Stable Isotope Profiling of Internet-Sourced Viagra® and 'generic- Viagra' Tablets

    Science.gov (United States)

    Kemp, Helen; Meier-Augenstein, Wolfram

    2013-04-01

    Viagra® manufactured by Pfizer was the first prescription drug for the treatment of erectile dysfunction (ED), a condition that is estimated to affect 1 in 10 men at some stage in their lives (1). Viagra® contains the active pharmaceutical ingredient (API) sildenafil, as the citrate salt. Sildenafil, along with Tadalafil and Vardenafil belong to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. Since its first production in 1998, Viagra® has generated well in excess of 10 billion US dollars in sales (2) and with Pfizers' patent extended to April 2020 (3) it still remains the only sildenafil-based treatment option for sufferers of ED in the US. There are no legal 'generic-Viagra' formulations available in the US. However, formulations containing sildenafil citrate as API are widely available over the internet and often sold as 'generic Viagra'. These cheaper alternatives are often manufactured under less than ideal conditions with little or no QA/QC procedures in place. The World Health Organisation recognised the scale of the problem in its 2010 bulletin "Growing threat from counterfeit medicines" (4) and quotes a Dutch study cited in the International Journal of Clinical Practice in which from a cohort of 370 seized Viagra® samples, only 10 were genuine. We sourced a variety of tablets sold for the treatment of ED which claimed to have sildenafil citrate as API. Viagra®, 'generic-Viagra', Kamagra, Silagra and Filagra tablets were ordered via the internet and supplied from both UK-based pharmacies as well as overseas suppliers (Hong Kong, India, Vanuata). In this small-scale pilot study, we present results from bulk 2H/18O and 13C/15N stable isotope analysis performed on crushed tablets from 23 samples of internet-sourced tablets sold for the treatment of ED and purported to contain sildenafil citrate as API. References 1. www.healthcare.org.uk 2. www.moneynews.com 3. US Patent & trademark office (www.uspto.gov) 4. WHO bulletin 2010; 88:247-248

  6. Intranasal Microemulsion of Sildenafil Citrate: In Vitro Evaluation and In Vivo Pharmacokinetic Study in Rabbits

    National Research Council Canada - National Science Library

    Elshafeey, Ahmed H; Bendas, Ehab R; Mohamed, Osama H

    2009-01-01

    The purpose of the present study was to prepare intranasal delivery system of sildenafil citrate and estimate its relative bioavailability after nasal administration in rabbits to attain rapid onset...

  7. Comparison of Elaeagnus angustifolia Extract and Sildenafil Citrate on Female Orgasmic Disorders: A Randomized Clinical Trial

    OpenAIRE

    Akbarzadeh, Marzieh; Zeinalzadeh, Sanaz; Zolghadri, Jaleh; Mohagheghzadeh, Abdolali; Faridi, Pouya; Sayadi, Mehrab

    2014-01-01

    Background Orgasmic disorder can create a feeling of deprivation and failure and provide mental problems, incompatibility and marital discord. This study aimed to compare the effects of Elaeagnus angustifolia flower extract and sildenafil citrate on female orgasmic disorder in women in 2013. Methods In this randomized clinical trial, 125 women between 18-40 years old who suffered from orgasmic disorder were divided into three E. angustifolia, sildenafil citrate and control groups. The data we...

  8. Effect of topically applied sildenafil citrate on wound healing: experimental study

    Directory of Open Access Journals (Sweden)

    Koray Gürsoy

    2014-08-01

    Full Text Available Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention.This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels.Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day.

  9. Effect of topically applied sildenafil citrate on wound healing: experimental study

    Science.gov (United States)

    Gürsoy, Koray; Oruç, Melike; Kankaya, Yüksel; Ulusoy, M. Gürhan; Koçer, Uğur; Kankaya, Duygu; Gürsoy, R. Neslihan; Çevik, Özge; Öğüş, Elmas; Fidanci, Vildan

    2014-01-01

    Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention. This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total) were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels. Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day. PMID:25172969

  10. Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate.

    Science.gov (United States)

    El-Sayed, Mohamed Adel; Saleh, Said Abdel-Aty; Maher, Mohammad Ahmed; Khidre, Asmaa Mohamed

    2018-04-01

    To assess efficacy and tolerability of sildenafil citrate on utero-placental blood flow and fetal growth in pregnancies complicated by fetal growth restriction (FGR). From March 2015, a randomized controlled trial of 54 patients at 24 weeks or more complicated by FGR and abnormal Doppler indices were randomly allocated 1:1 into an intervention arm (receive sildenafil citrate, 50 mg) or a control arm (receive placebo). The primary outcomes were changes occurred in the Doppler parameters 2 h following drug administration. Baseline characteristics were similar between groups. Significant difference was observed in the Delta uterine and umbilical Doppler indices among sildenafil group as compared to placebo group (p Doppler indices, however, decreased significantly after sildenafil, which could be the result of shifting more blood to improve the utero-placental perfusion. No difference regarding Delta cerebro-placental ratio among both groups (p = 0.979). Sildenafil was also associated with pregnancy prolongation (p = .0001), increased gestational age at delivery (p = .004), improved neonatal weight (p = .0001), and less admission to neonatal intensive care unit (p = .03). No adverse effects reported in both treatment arms. Sildenafil citrate, by its vasodilator effect, can improve utero-placental blood flow in pregnancies complicated by FGR and abnormal Doppler. gov Registry: NCT02362399.

  11. Comparison of Elaeagnus angustifolia Extract and Sildenafil Citrate on Female Orgasmic Disorders: A Randomized Clinical Trial.

    Science.gov (United States)

    Akbarzadeh, Marzieh; Zeinalzadeh, Sanaz; Zolghadri, Jaleh; Mohagheghzadeh, Abdolali; Faridi, Pouya; Sayadi, Mehrab

    2014-10-01

    Orgasmic disorder can create a feeling of deprivation and failure and provide mental problems, incompatibility and marital discord. This study aimed to compare the effects of Elaeagnus angustifolia flower extract and sildenafil citrate on female orgasmic disorder in women in 2013. In this randomized clinical trial, 125 women between 18-40 years old who suffered from orgasmic disorder were divided into three E. angustifolia, sildenafil citrate and control groups. The data were gathered using Female Sexual Function Index and through measurement of TSH and prolactin. The first intervention group had to consume 4.5 gr E. angustifolia extract in two divided doses for 35 days and the second one had to use 50 mg sildenafil citrate tablets for 4 weeks one hour before their sexual relationship. However, the control group had to consume the placebo. The data were analyzed using paired t-test, one-way ANOVA, and Bonferroni posthoc test and porgasmic disorder before the intervention was 41.5%, 40.5%, and 57.1% in E. angustifolia, sildenafil citrate, and control groups, respectively (p=0.23). However, these measures were respectively 29.3%, 16.7%, and 50% after the intervention (p=0.004). A significant difference between the two groups regarding sexual satisfaction after the intervention (p=0.003) compared to the beginning of the study (p=0.356). Besides, the highest reduction of changes after the intervention (58.82%) was observed in the sildenafil citrate group. Both E. angustifolia extract and sildenafil citrate were effective in reduction of the frequency of orgasmic disorder in women.

  12. Haematological changes and wound healing effects of sildenafil ...

    African Journals Online (AJOL)

    ADEYEYE

    2016-12-07

    Dec 7, 2016 ... The effects of sildenafil citrate (Viagra) in the early phase of healing process in open wounds in dogs, Acta. Veterinarians, 72:273-277. Weller R, Ormerod AD, Hobson RP & Benjamin NJ. (1998). A randomized trial of acidified nitrite cream in the treatment of tinea pedis. Journal of the American Academy of.

  13. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  14. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  15. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios

    Directory of Open Access Journals (Sweden)

    Choudhary R

    2016-08-01

    Full Text Available Rana Choudhary,1 Kavita Desai,2 Hetal Parekh,3 Kedar Ganla1 1Department of Reproductive Medicine, Ankoor Fertility Clinic, 2Department of Radiology, Dadar Imaging and Diagnostic Centre, 3IVF Department, Hiranandani Hospital, Mumbai, India Abstract: Fetal growth restriction (FGR and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. Keywords: sildenafil citrate, fetal growth restriction, oligohydramnios, thin endometrium

  16. Sildenafil (Viagra(®)) prevents and restores LPS-induced inflammation in astrocytes.

    Science.gov (United States)

    de Santana Nunes, Ana Karolina; Rapôso, Catarina; Björklund, Ulrika; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves; Hansson, Elisabeth

    2016-09-06

    Astrocytes are effectively involved in the pathophysiological processes in the central nervous system (CNS) and may contribute to or protect against development of inflammatory and degenerative diseases. Sildenafil is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor, which induces cyclic GMP accumulation. However, the mechanisms of actions on glial cells are not clear. The aim of the present work is to evaluate the role of sildenafil in lipopolysaccharide (LPS)-stimulated astrocytes. The cytoskeleton integrity and Ca(2+) waves were assessed as indicators of inflammatory state. Two main groups were done: (A) one prevention and (B) one restoration. Each of these groups: A1: control; A2: LPS for 24h; A3: sildenafil 1 or 10μM for 4h and then sildenafil 1 or 10μM+LPS for 24h. B1: control; B2: LPS for 24h; B3: LPS for 24h and then LPS+sildenafil 1 or 10μM for 24h. Cytoskeleton integrity was analyzed through GFAP immunolabeling and actin labeling with an Alexa 488-conjugated phalloidin probe. Calcium responses were assessed through a Ca(2+)-sensitive fluorophore Fura-2/AM. The results show that both preventive and restorative treatments with sildenafil (in both concentrations) reduced the Ca(2+) responses in intensity and induced a more organized actin fiber pattern, compared to LPS treated cells. This work demonstrated for the first time that astrocytes are a key part of the sildenafil protective effects in the CNS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Erectile Dysfunction: Viagra and Other Oral Medications

    Science.gov (United States)

    Erectile dysfunction: Viagra and other oral medications By Mayo Clinic Staff Oral medications are often the first line of treatment for ... medications work well and cause few side effects. Sildenafil (Viagra), vardenafil (Levitra, Staxyn), tadalafil (Cialis) and avanafil ( ...

  18. Electroretinography and immunohistochemistry of retina in rabbits treated with sildenafil citrate

    Directory of Open Access Journals (Sweden)

    A.V.C. Amaral

    2015-12-01

    Full Text Available Sildenafil citrate is a type-5 phosphodiesterase inhibitor (PDE-5, able to inhibit type-6 phosphodiesterase (PDE-6 as well, providing clinical benefits and paraeffects, some of them potentially related to the retina. The effects of the sildenafil on the retrobulbar and retinal circulation were studied in 27 adult male rabbits of the White New Zealand breed. The electric activity of the retina was evaluated before and at the end of the treatments, and immunohistochemistry studies were conducted. An amplitude increase of the b wave was found in the mixed response of cones and rods after 7 days of treatment with sildenafil citrate. However, in the other evaluations and periods, the values did not differ from the basal ones. Through immunohistochemistry, no significant decrease of the expression of PDE-5 and PDE-6 proteins was observed. Based on the results obtained, it is possible to admit that the sildenafil citrate did not change the expression of PDE-5 and PDE-6, neither the electroretinographic activity of the retina of male rabbits of the White New Zealand breed.

  19. Sildenafil (Viagra for male erectile dysfunction: a meta-analysis of clinical trial reports

    Directory of Open Access Journals (Sweden)

    McQuay HJ

    2002-05-01

    Full Text Available Abstract Background Evaluation of company clinical trial reports could provide information for meta-analysis at the commercial introduction of a new technology. Methods Clinical trial reports of sildenafil for erectile dysfunction from September 1997 were used for meta-analysis of randomised trials (at least four weeks duration and using fixed or dose optimisation regimens. The main outcome sought was an erection, sufficiently rigid for penetration, followed by successful intercourse, and conducted at home. Results Ten randomised controlled trials fulfilled the inclusion criteria (2123 men given sildenafil and 1131 placebo. NNT or NNH were calculated for important efficacy, adverse event and discontinuation outcomes. Dose optimisation led to at least 60% of attempts at sexual intercourse being successful in 49% of men, compared with 11% with placebo; the NNT was 2.7 (95% confidence interval 2.3 to 3.3. For global improvement in erections the NNT was 1.7 (1.6 to 1.9. Treatment-related adverse events occurred in 30% of men on dose optimised sildenafil compared with 11% on placebo; the NNH was 5.4 (4.3 to 7.3. All cause discontinuations were less frequent with sildenafil (10% than with placebo (20%. Sildenafil dose optimisation gave efficacy equivalent to the highest fixed doses, and adverse events equivalent to the lowest fixed doses. Conclusion This review of clinical trial reports available at the time of licensing agreed with later reviews that had many more trials and patients. Making reports submitted for marketing approval available publicly would provide better information when it was most needed, and would improve evidence-based introduction of new technologies.

  20. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

    Science.gov (United States)

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

    2010-01-01

    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

  1. Sildenafil citrate in the treatment of pain in primary dysmenorrhea: a randomized controlled trial.

    Science.gov (United States)

    Dmitrovic, R; Kunselman, A R; Legro, R S

    2013-11-01

    Is a vaginal preparation of sildenafil citrate capable of alleviating acute menstrual pain in patients with primary dysmenorrhea (PD)? A vaginal preparation of sildenafil citrate is capable of alleviating acute menstrual pain in patients with PD with no observed adverse effects. Oral preparations of nitric oxide (NO) donor drugs augment relaxant effects of NO on myometrial cells, reverse the vasoconstriction caused by prostaglandins and successfully alleviate pain, but the incidence of side effects is too high for routine clinical use. Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Therefore, by inhibiting PDE5, the tissue remains relaxed and more blood can circulate through. It has been used previously in a vaginal form with no observed side effects, and it enhances endometrial blood flow. A double-blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 PD patients at the time of painful menstruation was conducted. The primary outcome was total pain relief over 4 consecutive hours (TOPAR4) comparing sildenafil citrate to placebo, where higher TOPAR4 scores represent better pain relief. Secondary outcomes were pain relief as measured by the visual analog scale (VAS) and uterine artery pulsatility index (PI). Subjects were recruited from December 2007 to January 2011. The trial was stopped due to closeout of the funding for the study. Participants were women in good health, were aged 18-35 years and suffered from moderate to severe PD. They were randomized to either vaginal placebo or 100 mg vaginal sildenafil citrate in a 1:1 ratio using random permuted blocks having a block size of 4. At baseline and 1, 2, 3, and 4 h post-treatment, patients were asked to provide assessment of their degree of pain using two scales: (i) pain on the 5-level

  2. THERMODYNAMIC PARAMETERS OF SOLUTIONS OF SILDENAFIL CITRATE IN SOME ORGANIC SOLVENTS AT DIFFERENT TEMPERATURES

    Directory of Open Access Journals (Sweden)

    S. Baluja

    2014-06-01

    Full Text Available The solubility of Sildenafil citrate in some organic solvents; hexane, toluene,1-butanol and 1,2 dichloroethane has been determined using gravimetric method over different temperature range (298.15 K to 328.15 K at one atmospheric pressure. The modified Apelblat and Buchowski-Ksiazczak λh equations were used to correlate the experimental solubility data. Further, various thermodynamic parameters have been evaluated from these solubility data.

  3. THERMODYNAMIC PARAMETERS OF SOLUTIONS OF SILDENAFIL CITRATE IN SOME ORGANIC SOLVENTS AT DIFFERENT TEMPERATURES

    Directory of Open Access Journals (Sweden)

    S. Baluja

    2015-07-01

    Full Text Available The solubility of Sildenafil citrate in some organic solvents; hexane, toluene,1-butanol and 1,2 dichloroethane has been determined using gravimetric method over different temperature range (298.15 K to 328.15 K at one atmospheric pressure. The modified Apelblat and Buchowski-Ksiazczak λh equations were used to correlate the experimental solubility data. Further, various thermodynamic parameters have been evaluated from these solubility data.

  4. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

    Directory of Open Access Journals (Sweden)

    Dinani Matoso Fialho de Oliveira Armstrong

    2013-04-01

    Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

  5. The enhancement of vaginal vasocongestion by sildenafil in healthy premenopausal women

    NARCIS (Netherlands)

    Laan, Ellen; van Lunsen, Rik H. W.; Everaerd, Walter; Riley, Alan; Scott, Elizabeth; Boolell, Mitradev

    2002-01-01

    Objective: This study examined the effect of a single oral dose of sildenafil citrate (Viagra(R) Pfizer, Inc., New York, NY) on vaginal vasocongestion and subjective sexual arousal in healthy premenopausal women. Methods: Twelve women without sexual dysfunction were randomly assigned to receive

  6. A Case of Recurrent Transient Monocular Visual Loss after Receiving Sildenafil

    Directory of Open Access Journals (Sweden)

    Asaad Ghanem Ghanem

    2011-01-01

    Full Text Available A 53-year-old man was attended to the Clinic Ophthalmic Center, Mansoura University, Egypt, with recurrent transient monocular visual loss after receiving sildenafil citrate (Viagra for erectile dysfunction. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral nonarteritic anterior ischemic optic neuropathy (NAION. Physicians might look for arteriosclerotic risk factors and family history of NAION among predisposing risk factors before prescribing sildenafil erectile dysfunction drugs.

  7. A new electrochemical sensor containing a film of chitosan-supported ruthenium: detection and quantification of sildenafil citrate and acetaminophen

    Energy Technology Data Exchange (ETDEWEB)

    Delolo, Fabio Godoy; Rodrigues, Claudia; Silva, Monize Martins da; Batista, Alzir Azevedo, E-mail: fabiodelolo@hotmail.com, E-mail: daab@power.ufscar.br [Universidade Federal de Sao Carlos (UFSCar), SP (Brazil). Departamento de Quimica. Lab. de Estrutura e Reatividade de Compostos Inorganicos; Dinelli, Luis Rogerio [Universidade Federal de Uberlandia (UFU), Ituiutaba, MG (Brazil). Faculdade de Ciencias Integradas do Pontal; Delling, Felix Nicolai; Zukerman-Schpector, Julio, E-mail: fabiodelolo@hotmail.com, E-mail: daab@power.ufscar.br [Universidade Federal de Sao Carlos (UFSCar), SP (Brazil). Departamento de Quimica. Lab. de Cristalografia Estereodinamica e Modelagem Molecular

    2014-03-15

    This work presents the construction of a novel electrochemical sensor for detection of organic analytes, using a glassy carbon electrode (GCE) modified with a chitosan-supported ruthenium film. The ruthenium-chitosan film was obtained starting from the mer-[RuCl{sub 3}(dppb)(H{sub 2}O)] complex as a [1,4-bis(diphenylphosphine)butane] (dppb) precursor, and chitosan (QT). The structure of the chitosan-supported ruthenium film on the surface of the glassy carbon electrode was characterized by UV-Vis spectroscopy, electron paramagnetic resonance (EPR), scanning electron microscopy (SEM), atomic force microscopy (AFM), powder X-ray diffraction (XRD) and atomic absorption spectroscopy (AAS) techniques. The glassy carbon electrode was modified with a film formed from the evaporation of 5 μL of a solution composed of 5 mg chitosan-supported ruthenium (RuQT) in 10 mL of 0.1 mol L{sup -1} acetic acid. The modified electrode was tested as a sensor for sildenafil citrate (Viagra® 50 mg) and acetaminophen (Tylenol®) detection. The technique utilized for these analyses was differential pulse voltammetry (DPV) in 0.1 mol L{sup -1} H{sub 2}SO{sub 4} (pH 1.0) and 0.1 mol L{sup -1} CH{sub 3}COOK (pH 6.5) as supporting electrolyte. All analyses were carried out during a month using the same electrode. The electrode was washed only with water in between the analyses, keeping it in the refrigerator when it was not in use. This electrode was stable during the period utilized showing no degradation and presenting a linear response over the evaluated concentration interval (1.25 × 10{sup -5} to 4.99 × 10{sup -4} mol L{sup -1}). (author)

  8. Spectrophotometric determination of sildenafil citrate in pure form and in pharmaceutical formulation using some chromotropic acid azo dyes

    Science.gov (United States)

    Issa, Y. M.; El-Hawary, W. F.; Youssef, A. F. A.; Senosy, A. R.

    2010-04-01

    Two simple and highly sensitive spectrophotometric methods were developed for the quantitative determination of the drug sildenafil citrate (SC), Viagra, in pure form and in pharmaceutical formulations, through ion-associate formation reactions (method A) with mono-chromotropic acid azo dyes, chromotrope 2B (I) and chromotrope 2R (II) and ion-pair reactions (method B) with bi-chromotropic acid azo dyes, 3-phenylazo-6-o-carboxyphenylazo-chromotropic acid (III), bis-3,6-(o-hydroxyphenylazo)-chromotropic acid (IV), bis-3,6-(p-N,N-dimethylphenylazo)-chromotropic acid (V) and 3-phenylazo-6-o-hydroxyphenylazo-chromotorpic acid (VI). The reaction products, extractable in methylene chloride, were quantitatively measured at 540, 520, 540, 570, 600 and 575 nm using reagents, I-VI, respectively. The reaction conditions were studied and optimized. Beer's plots were linear in the concentration ranges 3.3-87.0, 3.3-96.0, 5.0-115.0, 2.5-125.0, 8.3-166.7 and 0.8-15.0 μg mL -1 with corresponding molar absorptivities 1.02 × 10 4, 8.34 × 10 3, 6.86 × 10 3, 5.42 × 10 3, 3.35 × 10 3 and 2.32 × 10 4 L mol -1 cm -1 using reagents I-VI, respectively. The limits of detection and Sandell's sensitivities were calculated. The methods were successfully applied to the analysis of commercial tablets (Vigoran) and the recovery study reveals that there is no interference from the common excipients that are present in tablets. Statistical comparison of the results was performed with regard to accuracy and precision using Student's t- and F-tests at 95% confidence level. There is no significant difference between the reported and proposed methods with regard to accuracy and precision.

  9. Ups and downs of Viagra: revisiting ototoxicity in the mouse model.

    Science.gov (United States)

    Au, Adrian; Stuyt, John Gerka; Chen, Daniel; Alagramam, Kumar

    2013-01-01

    Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra

  10. Ups and downs of Viagra: revisiting ototoxicity in the mouse model.

    Directory of Open Access Journals (Sweden)

    Adrian Au

    Full Text Available Sildenafil citrate (Viagra, a phosphodiesterase 5 inhibitor (PDE5i, is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008 reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012 showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day or saline for 30 days. Auditory brainstem responses (ABRs were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue

  11. Intravaginal Administration of Sildenafil Citrate Increases Blood Flow in the Bovine Uterus

    Directory of Open Access Journals (Sweden)

    Dzięcioł Michał

    2015-04-01

    Full Text Available The aim of the study was to evaluate the influence of sildenafil citrate administrated intravaginaly on the blood flow in the bovine uterus during dioestrus. Uterine blood flow was examined in six healthy adult cows. Sildenafil was administrated intravaginaly to each co w between the 6th and 8th d of the ovarian cycle, in the form of vaginal suppositories containing 100 mg of active substance at a dose of 100, 200, or 300 mg per animal. Uterine perfusion was estimated by the colour Doppler examination, and obtained results were analysed with the Pixel Flux Software (Chameleon, Germany. Moreover, cardiovascular parameters were also evaluated. Animals were examined before and five times after drug application (two times at 15 min intervals, and three times at 2 h intervals. A placebo suppository was also given to the cows. The analysis of the intensity and velocity of blood flow in the uterus proved that sildenafil administrated intravaginaly significantly increased blood flow in the uterus and the effect of increased perfusion was observed for 4 h and 30 min after administration. The effect of increased uterine perfusion was observed after low as well as high doses of sildenafil. Significant changes in the cardio-vascular parameters were not detected. There were no changes in the uterine perfusion as well as in cardiovascular parameters after placebo administration.

  12. Effect of sildenafil citrate on women affected by sexual dysfunction referred to health clinics

    Directory of Open Access Journals (Sweden)

    Sanaz Zeinalzadeh

    2017-06-01

    Full Text Available Background. Female sexual dysfunction is a serious, multifactorial problem which affects women’s quality of life. Objectives. This study aimed at assessing the effect of sildenafil citrate on sexual dysfunction among women of reproductive age. Materials and methods. The present randomized clinical trial was conducted on 84 married women between 18 and 40 years old who suffered from sexual dysfunction. The inclusion criteria of the study were being married and between 18–40 years old, obtaining scores ≥ 22 in FSFI, not having a history of hypothyroidism or hyperprolactinemia, and not suffering from dyspareunia or vaginismus. The intervention group was required to consume 50 mg sildenafil citrate 1 hour before sexual intercourse for 5 weeks, and the control group received placebo. FSFI was completed by both study groups before and 5 weeks after the treatment. The data were analyzed through SPSS (v. 18 and paired t-test and independent t-test. Results . Most of the women (67.2% were between 30 and 40 years old. The study results revealed a significant difference between the two groups regarding the mean scores of sexual desire (p = 0.011, sexual arousal (p = 0.001, lubrication (p = 0.026, orgasm and sexual satisfaction (p < 0.001, and the whole dimension (p < 0.001. Besides, total mean sexual function before and after for the intervention and control groups was 21.1 ± 3.28 vs. 17.22 ± 5.9 (p < 0.001. Conclusion . In this study, sildenafil citrate was effective in enhancing sexual desire, arousal, orgasm, and sexual satisfaction. Of course, more studies need to be conducted on this issue.

  13. Viagra for Women: Why Doesn't It Exist?

    Science.gov (United States)

    ... Lifestyle Sexual health Is there an equivalent of Viagra for women? Answers from Yvonne Butler Tobah, M. ... of drugs to treat erectile dysfunction, such as sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra), drug companies ...

  14. Physicochemical and Microbiological Stability of the Extemporaneous Sildenafil Citrate Oral Suspension

    Science.gov (United States)

    Sae Yoon, Attawadee; Sawatdee, Somchai; Woradechakul, Chuthamas; Sae Chee, Kridsada; Atipairin, Apichart

    2015-01-01

    Sildenafil is a potent and selective phosphodiesterase-5 inhibitor that is effectively used in the treatment of pulmonary arterial hypertension. In several countries, hospital pharmacists prepare the drug in an extemporaneous liquid preparation as there are no liquid formulations available for pediatric and adult uses. The purpose of this study was to evaluate the stability of an extemporaneous sildenafil citrate oral suspension for 90 days, according to the ASEAN guideline on stability studies of drug products. The results showed that the preparation was a white suspension with a sweet taste. It was a viscous and weakly acidic mixture with pseudoplastic behavior. The drug content was in the range between 99.23% and 102.23%, and the microbial examination met the general requirements throughout the study period. Therefore, the extemporaneously compounded sildenafil suspensions were physically, chemically, and microbiologically stable for at least 90 days when stored at 30° and 40°C. Furthermore, the in-use stability study showed that the preparations had acceptable attributes at least 14 days after the first-time use. This might provide an alternative option when the commercial suspension is unavailable. PMID:26839846

  15. Self-Esteem, Confidence, and Relationships in Men Treated with Sildenafil Citrate for Erectile Dysfunction

    Science.gov (United States)

    Althof, Stanley E; O' Leary, Michael P; Cappelleri, Joseph C; Glina, Sidney; King, Rosie; Tseng, Li-Jung; Bowler, Jessica L

    2006-01-01

    BACKGROUND Men with erectile dysfunction (ED) often have low self-esteem, confidence, and sexual relationship satisfaction. OBJECTIVE We evaluated the impact of sildenafil citrate and its generalizability across cultures on self-esteem, confidence, and sexual relationship satisfaction in men with ED using the Self-Esteem And Relationship (SEAR) questionnaire. DESIGN Pooled analysis of 2 double-blind, placebo-controlled, flexible-dose trials of sildenafil with identical protocols: 1 was conducted in the United States and the other in Mexico, Brazil, Australia, and Japan. PATIENTS Men ≥18 years old with ED. MEASUREMENTS The impact of treatment on psychosocial factors associated with ED was determined by patient responses to the SEAR questionnaire. Erectile function was determined using the International Index of Erectile Function (IIEF) and a global efficacy question. Successful sexual intercourse attempts were derived from event logs of sexual activity. Treatment effect sizes were calculated for all study outcomes. RESULTS Compared with patients who received placebo (n = 274), patients who received sildenafil (n = 279) reported significantly greater improvements (Pcrossculturally and correlated significantly and tangibly with improvements in erectile function. PMID:16836626

  16. Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation.

    Science.gov (United States)

    Soliman, Ghareb M; Fetih, Gihan; Abbas, Ahmed M

    2017-03-01

    The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness. Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic® (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (Tsol-gel), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725). The Tsol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28-37 °C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration. Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

  17. Sildenafil (Viagra Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

    Directory of Open Access Journals (Sweden)

    Catarina Raposo

    2013-01-01

    Full Text Available We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi, and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

  18. Effect of sildenafil (Viagra® on the genital reflexes of paradoxical sleep-deprived male rats

    Directory of Open Access Journals (Sweden)

    M.L. Andersen

    2007-11-01

    Full Text Available Since there is evidence that paradoxical sleep deprivation (PSD elicits penile erection (PE and ejaculation (EJ, and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group. The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL than in controls (365 ± 38 ng/dL, whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

  19. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    Science.gov (United States)

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  20. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  1. Prevention of valproic acid-induced neural tube defects by sildenafil citrate.

    Science.gov (United States)

    Tiboni, Gian Mario; Ponzano, Adalisa

    2015-08-15

    This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: a geographical comparison from a single arm, open-label study.

    Science.gov (United States)

    Rubio-Aurioles, Eusebio; Glina, Sidney; Abdo, Carmita H N; Hernandez-Serrano, Ruben; Rampazzo, Claudia; Sotomayor, Mariano; West, Teena M; Gallagher, Gabrielle L; Lenero, Enrique

    2009-10-01

    Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.

  3. Effect of sildenafil citrate on penile weight and physiology of cavernous smooth muscle in a post-radical prostatectomy model of erectile dysfunction in rats.

    Science.gov (United States)

    Özden, Ender; Öztürk, Bülent; Koşan, Murat; Tezel, Gaye Güler; Aki, Fazil Tuncay; Gür, Serap; Ergen, Ali; Özen, Haluk

    2011-03-01

    To evaluate the gross morphometric changes and in vitro responses of the corpus cavernosus of rats treated with sildenafil citrate after cavernous neurotomy. The animals were divided into 3 groups. Group 1 consisted of sham-operated rats (n = 16); group 2 consisted of rats that underwent bilateral cavernous neurotomy (BCN) (n = 16); and group 3 consisted of rats that underwent unilateral cavernous neurotomy (UCN) (n = 16). Each group of rats was further classified into 2 subgroups according to whether or not they received sildenafil treatment. The rats were killed on postoperative day 14, and penectomy was performed. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL), and organ-bath studies were evaluated by Phenylephrine (Phe), acetylcholine (Ach), sodium nitroprusside (SNP), and electrical field stimulation (EFS) responses. Penile weight in the BCN group was significantly lower than that of sham-treated group. UCN allowed much more preservation of penile weight compared with that in the sham-treated group. Sildenafil citrate treatment had positive effects on penile weight of both BCN (P = .003) and UCN (P = .004) groups. BCN increased smooth muscle apoptosis when compared with the sham or UCN group. Sildenafil citrate had a positive effect on the apoptotic index. In the BCN group, responses to Phe, Ach, SNP, and EFS decreased significantly, and sildenafil treatment corrected the responses to Phe, Ach, and SNP. Our experimental study results support that early and daily sildenafil citrate treatment has a protective affect on the adrenergic and cholinergic systems, which play a role in erectile function. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer.

    Science.gov (United States)

    Kalayci, Mehmet; Kocdor, Mehmet Ali; Kuloglu, Tuncay; Sahin, İbrahim; Sarac, Mehmet; Aksoy, Aziz; Yardim, Meltem; Dalkilic, Semih; Gursu, Onur; Aydin, Suna; Akkoc, Ramazan Fazil; Ugras, Meltem; Artas, Gokhan; Ozercan, İbrahim Hanifi; Ugur, Kader; Aydin, Suleyman

    2017-10-01

    The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer+NS); Group III (5mg/kg sildenafil citrate, low dose); Group IV (10mg/kg sildenafil citrate, high dose); Group V (0.6mg/kg heparin, low dose); Group VI (6mg/kg heparin, high dose); Group VII (20nmol/kg des-acyl ghrelin); Group VIII (40nmol/kg des-acyl ghrelin); Group IX (4nmol/kg acyl ghrelin); Group X (8nmol/kg acly ghrelin); Group XI (20pmol/kg Nesfatin-1); Group XII (15nmol/kg Obestatin) and Group XIII (5nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Impact of erectile dysfunction on confidence, self-esteem and relationship satisfaction after 9 months of sildenafil citrate treatment.

    Science.gov (United States)

    Althof, Stanley E; O'Leary, Michael P; Cappelleri, Joseph C; Crowley, Arthur R; Tseng, Li-Jung; Collins, Suzanne

    2006-11-01

    The first double-blind, placebo controlled trial in the United States of the Self-Esteem And Relationship questionnaire revealed that treatment with sildenafil citrate improves erectile function and measures of quality of life in men with erectile dysfunction. We investigated long-term improvement, and correlations between improved erectile function and confidence, self-esteem and sexual relationship satisfaction in men with erectile dysfunction. This was a 36-week open label extension of the double-blind, placebo controlled trial. The blind was not broken. Patients were 18 years or older with clinically diagnosed erectile dysfunction. Erectile function was assessed using the International Index of Erectile Function. Self-esteem, confidence and relationship satisfaction were assessed using the Self-Esteem And Relationship questionnaire. Correlations were determined using Pearson's product moment coefficients. A total of 204 participants were enrolled in the open label extension, including 108 on placebo and 96 on sildenafil. In men who received placebo in the double-blind, placebo controlled phase mean erectile function scores and self-esteem, confidence and relationship satisfaction scores were increased significantly at week 36 of the open label extension (p self-esteem, confidence and relationship satisfaction were strong and positive (p self-esteem, confidence and relationship satisfaction. Following an initial 12 weeks of double-blind, placebo controlled sildenafil therapy for erectile dysfunction improvements were sustained an additional 9 months. Positive correlations between erectile function, and self-esteem, confidence and relationship satisfaction suggest that improved erectile quality can improve long-term psychosocial quality of life.

  6. Sildenafil citrate in combination with tamsulosin versus tamsulosin monotherapy for management of male lower urinary tract symptoms due to benign prostatic hyperplasia: A randomised, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Amr Fawzi

    2017-03-01

    Conclusion: Sildenafil citrate combined with tamsulosin improved LUTS, erectile function, and patient QoL more than tamsulosin monotherapy with the merit of a comparable safety profile in patients with LUTS/BPH.

  7. Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy after Ingestion of Sildenafil for Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Tarantini

    2012-01-01

    Full Text Available Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION after ingestion of Sildenafil citrate (Viagra for erectile dysfunction. Methods. Observational case report. Results. A 60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours after his third consecutive 50 mg daily Sildenafil ingestion. A diagnosis of bilateral NAION was made and he was treated for three days with methylprednisolone 1 g/d intravenously, followed by oral prednisone 75 mg/d. Final visual acuity was 20/50 right eye (OD and 20/20 left eye (OS. He had preexisting diabetes. Conclusion. This is the first reported case of simultaneous bilateral NAION occurred in a diabetic patient early after Sildenafil intake. Patients with predisposing conditions such as diabetes have to be warned against the use of PDE inhibitors.

  8. Sildenafil-associated hepatoxicity: a review of the literature.

    Science.gov (United States)

    Graziano, S; Montana, A; Zaami, S; Rotolo, M C; Minutillo, A; Busardò, F P; Marinelli, E

    2017-03-01

    Sildenafil citrate (Viagra®) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.

  9. Sildenafil (Viagra®) blocks inflammatory injury in LPS-induced mouse abortion: A potential prophylactic treatment against acute pregnancy loss?

    Science.gov (United States)

    Luna, R L; Nunes, A K S; Oliveira, A G V; Araujo, S M R; Lemos, A J J M; Rocha, S W S; Croy, B A; Peixoto, C A

    2015-10-01

    Recurrent pregnancy losses (RPL) are common women's health issues. Inflammatory and thrombotic events have been associated with RPL including excessive production of cytokines, in particular TNF-α. However, mechanisms behind gestational losses are not yet fully understood. Sildenafil inhibits phosphodiesterase Type-5 (PDE5). This drug increases intracellular cyclic guanosine monophosphate, having vasodilatory and, more recently described, anti-inflammatory properties. PDE5 is present in murine and human uterus and placenta. Sildenafil is already used clinically for treatment of human fetal growth restriction (FGR). Our objective was to determine if Sildenafil alone or in combination with Heparin had protective effects in pregnant Swiss albino challenged to abort by lipopolysaccharide (LPS). Treatments (Sildenafil (50 mg/kg/day), Heparin (500 IU/Kg/day) or Sildenafil + Heparin at the same doses) were initiated the morning of copulation plug detection (gestational day (gd0)). On the 15th day of pregnancy, an intra-peritoneal injection of LPS (100 μg/kg) was administered. Untreated, pregnant mice challenged by LPS served as controls. Assessments at 48 h after LPS revealed that Sildenafil + Heparin prevented fetal loss. Early assessments at 2 h after LPS indicated that the pretreatments prevented induction of inflammatory cytokine production (TNF-α, IL-1β/NF-κβ) and preserved placental histopathology. Combined Sildenafil + Heparin therapy was superior to either treatment alone in most analyses. The known safety of Sildenafil and Heparin in human pregnancy suggests that usage of these combined agents may be of value for treatment of patients with impending pregnancy loss or prophylactically in women with a history of recurrent miscarriages. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. The Effects of Administrated Sildenafil Citrate on Uterine Luminal Epithelium Height Associated with Ovarian Angiogenesis: An Experimental Animal Study

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Golkar

    2017-01-01

    Full Text Available Background: Ovarian angiogenesis (OA remains in lifetime and normal ovarian function depends to this continual remodeling of a complex vascular system. Endometrial thickness (ET is one of the strongest predictors of successful implantation and pregnancy. Appropriate OA effects on ET by facilitating of ovarian hormone delivery. Materials and Methods: Thirty adult female mice and twenty adult male mice were purchased. The female mice were divided into three groups: (1 control group without any intervention (n = 10, (2 gonadotropin group: receiving human menopausal gonadotropin (HMG and human chorionic gonadotropin (n = 10, and (3 gonadotropin and sildenafil citrate (SC group: receiving HMG and SC administration (n = 10. After mating, animals were deeply anesthetized, and the ovary and uterus was rapidly removed for histology and immunohistochemistry process. Results: Four days after ovarian induction, all three layers of the uterus with specified thickness can be clearly seen. The heights of endometrial epithelial cells in gonadotropin group were not significantly different than those in control group. In gonadotropin and SC group, heights of the cells were significantly (P 0.05 each. Our results of immunohistochemistry survey for ovarian CD31 demonstrated that administrated SC increased OA but not significantly (P > 0.05 each. Conclusion: It may finally conclude that administration of SC does not cause notable alterations in OA and ET; although for realistic decision about the SC effects on aforementioned parameters, more molecular investigations and longer drug consumption period are necessary.

  11. Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

    Science.gov (United States)

    Hsu, Lewis L.; Berkowitz, Dan E.; Champion, Hunter C.; Burnett, Arthur L.

    2013-01-01

    Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders. PMID:23844149

  12. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress.

    Directory of Open Access Journals (Sweden)

    Trinity J Bivalacqua

    Full Text Available Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.

  13. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress.

    Science.gov (United States)

    Bivalacqua, Trinity J; Musicki, Biljana; Hsu, Lewis L; Berkowitz, Dan E; Champion, Hunter C; Burnett, Arthur L

    2013-01-01

    Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.

  14. Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies.

    Science.gov (United States)

    Tripathi, Alok Shiomurti; Timiri, Ajay Kumar; Mazumder, Papiya Mitra; Chandewar, Anil

    2015-10-01

    The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies.

  15. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

    Directory of Open Access Journals (Sweden)

    Mark Robert Dilworth

    Full Text Available Fetal growth restriction (FGR is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th centile of customised growth charts. Sildenafil citrate (SC, Viagra™, a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8% in P0 mice following maternal SC treatment (0.4 mg/ml via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056. Additionally, 75% of the P0 fetal weights were below the 5(th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

  16. Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

    Science.gov (United States)

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

  17. Self-esteem, confidence, and relationships in men treated with sildenafil citrate for erectile dysfunction: results of two double-blind, placebo-controlled trials.

    Science.gov (United States)

    Althof, Stanley E; O' Leary, Michael P; Cappelleri, Joseph C; Glina, Sidney; King, Rosie; Tseng, Li-Jung; Bowler, Jessica L

    2006-10-01

    Men with erectile dysfunction (ED) often have low self-esteem, confidence, and sexual relationship satisfaction. We evaluated the impact of sildenafil citrate and its generalizability across cultures on self-esteem, confidence, and sexual relationship satisfaction in men with ED using the Self-Esteem And Relationship (SEAR) questionnaire. Pooled analysis of 2 double-blind, placebo-controlled, flexible-dose trials of sildenafil with identical protocols: 1 was conducted in the United States and the other in Mexico, Brazil, Australia, and Japan. Men > or = 18 years old with ED. The impact of treatment on psychosocial factors associated with ED was determined by patient responses to the SEAR questionnaire. Erectile function was determined using the International Index of Erectile Function (IIEF) and a global efficacy question. Successful sexual intercourse attempts were derived from event logs of sexual activity. Treatment effect sizes were calculated for all study outcomes. Compared with patients who received placebo (n = 274), patients who received sildenafil (n = 279) reported significantly greater improvements (P self-esteem, confidence, sexual relationship satisfaction, and in all sexual function domains of the IIEF. Treatment effect sizes were large (range, 0.7 to 1.2) for all SEAR components, and improvement in psychosocial measures showed moderate to high correlations (range, 0.50 to 0.83, P self-esteem, confidence, and sexual relationship satisfaction. Improvements in these psychosocial factors were observed crossculturally and correlated significantly and tangibly with improvements in erectile function.

  18. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  19. Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy

    OpenAIRE

    Al-Adl, Ahmed M.; Abdel-Wahab, Osama; El-Karamany, Tarek; Aal, Ashraf A.

    2011-01-01

    Objective To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). Patients and methods The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, pen...

  20. Soy polysaccharide as a novel superdisintegrant in sildenafil citrate sublingual tablets: preparation, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Hosny KM

    2015-01-01

    Full Text Available Khaled Mohamed Hosny,1,2 Hisham Ahmed Mosli,3 Ali Habiballah Hassan4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 3Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Sildenafil citrate (SC, a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays inadequate aqueous solubility, which delays the onset of its action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40% bioavailability. Third, the gastrointestinal effects of SC include dyspepsia and a burning sensation. The aim of this research was to prepare SC as a sublingual tablet utilizing soy polysaccharide as novel superdisintegrant to mitigate the abovementioned problems. The solubility of SC in various hydrophilic carrier solutions was estimated in order to prepare the drug as a coprecipitate. Sublingual tablets were prepared and evaluated for hardness, friability, drug content, wetting time, water absorption ratio, in vitro dispersion time, dissolution rate, and stability study. The pharmacokinetic study of the tablets was carried out on healthy volunteers. The results indicated that the co-precipitation of SC with polyvinylpyrollidone K30 enhanced the solubility of SC by more than eight folds. The tablet contained 8% soy polysaccharide as a superdisintegrant and provided a wetting time of 25 seconds, and in vitro dispersion times of 55 seconds. The drug release was found to be 95.6%. The prepared SC sublingual tablet also exhibited a rapid onset of action, and its bioavailability was enhanced 1.68-fold compared with that of the marketed tablets. It

  1. Ação do citrato de sildenafil sobre a função uretral de ratas com desnervação vesical Effect of sildenafil citrate in the urethral function in rats with denervated bladder

    Directory of Open Access Journals (Sweden)

    Haylton Jorge Suaid

    2003-01-01

    Full Text Available O óxido nítrico atua como neurotransmissor não adrenérgico e não colinérgico na bexiga e na uretra. Sua forma de ação se faz pela ativação da guanilatociclase responsável pela transformação de GMP em GMPc que promove o relaxamento da fibra muscular lisa. O citrato de sildenafil causa aumento do GMPc, através da inibição de fosfodiesterases, que hidrolisam o GMPc. Assim, o objetivo do experimento foi verificar sua ação na uretra. MÉTODOS: Estudou-se 6 ratas com peso aproximado de 200g. A anestesia foi com uretana na dose de 1,25 mg/kg. As cistometrias, em número de 3, foram realizadas através de cistostomia com cateter P50. A primeira logo após a cistostomia; a segunda depois da desnervação cirúrgica da bexiga e a terceira uma hora após a infusão gástrica do citrato de sildenafil. O sistema de registro das pressões constou de uma bomba de infusão contínua regulada para 0,3ml/minuto conectada em Y com o cateter P50 e a um polígrafo Narco-Bioystem. Nas cistometrias avaliou-se as pressões vesicais máxima e mínima nos momentos: normais-(I; desnervadas (II e desnervadas com citrato de sildenafil na dose de 1 mg/kg (III. A análise estatística foi feita pelo método de Wilcoxon. RESULTADOS: As médias das pressões máximas (pma foram: momentos I (x=86,6 - SD=10,1 ; momentos II (x=42,6 - SD=15,0 e momentos III (x=30,8 - SD=12,4. As médias das pressões mínimas (pmi foram: momentos I (x=72,1 - SD=18,9; momentos II (x=31,1 - SD=9,8; momentos III ( x=14,5 - SD=9,5. A análise estatística entre as pma e pmi no mesmo grupo mostrou pBACKGROUND: Nitric oxide acts as a non-adrenergic and non-cholinergic neurotransmitter in the bladder and urethra. It activates the guanilatocyclase that transforms GMP in cGMP which promotes muscle relaxation. Sildenafil citrate increases the cGMP concentration by inhibiting the phosphodiesterase responsible for its hydrolysis. METHODS: 6 female rats weighing 200g were anesthetized with

  2. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    Science.gov (United States)

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency. © 2016 American Heart Association, Inc.

  3. Sorption and Transport of Sildenafil in Natural Soils

    Science.gov (United States)

    Boudinot, F. G.; Vulava, V. M.

    2013-12-01

    Pharmaceutical Chemicals (PCs) mainly enter our ecosystems from discharges of treated wastewater and have direct effects on the ecological health of that area. Sildenafil citrate (Viagra) is one such PC, whose presence has been reported in stream waters. Although one study has shown that sildenafil is not harmful in bacterial and fungal environments, there remains much unknown about its fate elsewhere in ecosystems. Sildenafil is a complex organic molecule with two amino functional groups that result in pKa's of 7.27 and 5.97. It also has a high solubility of 3.5 g/L. Given that sildenafil consumption (and concurrently disposal) is on the rise, it is essential that its behavior in the natural environment be better understood. The goal of this study was to quantify the sorption and transport behavior of sildenafil in differing natural soils with varying compositions. Pristine A- and B- horizon soil samples from several soil series were collected in a managed forest near Charleston, SC and used for these studies. The soils were characterized for physical and chemical properties: soil organic matter content ranged between 0.6-7.6%, clay content between 6-20%, and soil pH between 4-5. These soils were then used to perform kinetic reaction, sorption, and column transport experiments. Batch kinetic experiments showed a fast reaction rate in both clay-rich and organic-rich soils and an equilibration time of less than 24 hours. Batch reactor sorption experiments provided data for sorption isotherms (plot of sildenafil in solution, C vs. sildenafil sorbed in soil, q) which were nonlinear. The isotherms were fit using Freundlich model (q=KfCn, where Kf and n are fitting parameters). Sildenafil sorbed more strongly to clay-rich soils compared with organic-rich soils with less clay. It is hypothesized that permanent negative charge on clay mineral surfaces form ionic bonds with positively charged amines in sildenafil in acidic pHs. Transport experiments were conducted using

  4. A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil

    Directory of Open Access Journals (Sweden)

    Felekis T

    2011-10-01

    Full Text Available T Felekis1, I Asproudis1, K Katsanos2, EV Tsianos21University Eye Clinic of Ioannina, Ioannina, Greece; 2First Department of Internal Medicine, University Hospital of Ioannina, Ioannina, GreeceAbstract: A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION 12 hours after receiving sildenafil citrate (Viagra®. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs.Keywords: sildenafil, nonarteritic anterior ischemic optic neuropathy, erectile dysfunction drugs, family history

  5. Psychosocial outcomes after initial treatment of erectile dysfunction with tadalafil once daily, tadalafil on demand or sildenafil citrate on demand: results from a randomized, open-label study.

    Science.gov (United States)

    Hatzimouratidis, K; Buvat, J; Büttner, H; Vendeira, P A S; Moncada, I; Boehmer, M; Henneges, C; Boess, F G

    2014-01-01

    Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N = 252) or sildenafil-citrate (sildenafil) 50 mg PRN (N = 261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P = 0.044 and P = 0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups.

  6. Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy.

    Science.gov (United States)

    Al-Adl, Ahmed M; Abdel-Wahab, Osama; El-Karamany, Tarek; Aal, Ashraf A

    2011-06-01

    To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25 mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25 mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25 mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed. The mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%). Chronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy.

  7. Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014.

    Science.gov (United States)

    Kellihan, Heidi B; Waller, Kenneth R; Pinkos, Alyssa; Steinberg, Howard; Bates, Melissa L

    2015-09-01

    To describe clinical canine patients with naturally occurring pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and after treatment with sildenafil. Ten client-owned dogs. A retrospective analysis of dogs with echocardiographically-determined pulmonary hypertension and pulmonary alveolar infiltrates on thoracic radiographs was performed before (PRE) and after (POST) sildenafil therapy. Clinical scores, pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were analyzed PRE and POST sildenafil. Pulmonary alveolar infiltrates associated with pulmonary hypertension developed in a diffusely patchy distribution (10/10). Sixty percent of dogs had a suspected diagnosis of interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p = 0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). A subset of dogs with moderate to severe pulmonary hypertension present with diffuse, patchy alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical clinical presentation is acute dyspnea and syncope, often in conjunction with heart murmurs suggestive of valvular insufficiency. This constellation of signs may lead to an initial misdiagnosis of congestive heart failure or pneumonia; however, these dogs clinically and radiographically improve with the initiation of sildenafil. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Testing of complementarity of PDA and MS detectors using chromatographic fingerprinting of genuine and counterfeit samples containing sildenafil citrate.

    Science.gov (United States)

    Custers, Deborah; Krakowska, Barbara; De Beer, Jacques O; Courselle, Patricia; Daszykowski, Michal; Apers, Sandra; Deconinck, Eric

    2016-02-01

    Counterfeit medicines are a global threat to public health. High amounts enter the European market, which is why characterization of these products is a very important issue. In this study, a high-performance liquid chromatography-photodiode array (HPLC-PDA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) method were developed for the analysis of genuine Viagra®, generic products of Viagra®, and counterfeit samples in order to obtain different types of fingerprints. These data were included in the chemometric data analysis, aiming to test whether PDA and MS are complementary detection techniques. The MS data comprise both MS1 and MS2 fingerprints; the PDA data consist of fingerprints measured at three different wavelengths, i.e., 254, 270, and 290 nm, and all possible combinations of these wavelengths. First, it was verified if both groups of fingerprints can discriminate between genuine, generic, and counterfeit medicines separately; next, it was studied if the obtained results could be ameliorated by combining both fingerprint types. This data analysis showed that MS1 does not provide suitable classification models since several genuines and generics are classified as counterfeits and vice versa. However, when analyzing the MS1_MS2 data in combination with partial least squares-discriminant analysis (PLS-DA), a perfect discrimination was obtained. When only using data measured at 254 nm, good classification models can be obtained by k nearest neighbors (kNN) and soft independent modelling of class analogy (SIMCA), which might be interesting for the characterization of counterfeit drugs in developing countries. However, in general, the combination of PDA and MS data (254 nm_MS1) is preferred due to less classification errors between the genuines/generics and counterfeits compared to PDA and MS data separately.

  9. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress: Possible Role for Nitric Oxide Activation of 3',5'-cyclic Guanosine Monophosphate Signaling.

    Science.gov (United States)

    Bolnick, Jay M; Kilburn, Brian A; Bolnick, Alan D; Diamond, Michael P; Singh, Manvinder; Hertz, Michael; Dai, Jing; Armant, D Randall

    2015-06-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-N(G)-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. © The Author(s) 2014.

  10. The blue pill (sildenafil and its descendants: an overview

    Directory of Open Access Journals (Sweden)

    Krzanowski Tomasz

    2017-09-01

    Full Text Available An increasing number of men around the world suffer from erectile dysfunction (ED. Indeed, according to the sexuality study conducted by Professor Izdebski, 1 out of 10 men in Poland suffers from ED. The problem is found among men of any age, however, 60% of all patients are between 40 and 60 years old, thus in their prime, and who still want to fully enjoy life. Not only do the effects of ED affect a man, but they have influence on his relationship and partner as well. In spite of a growing awareness within society, the problem remains perceived as embarrassing, which leads patients to treat themselves on their own, delaying a visit to their doctors. Meanwhile, in many cases, ED may be the first symptom of more serious diseases, such as diabetes, or result from the sideeffects of applied drugs. A breakthrough in the oral medication treatment of ED was observed when a new phosphodiesterase type 5 inhibitor (PDE-5-inhibitor - sildenafil citrate (Viagra® - was introduced. Nowadays, 5 active substances from this group are being applied. The current medical guidelines recommend PDE-5 inhibitors as the firstline therapy for most men with ED, irrespective of the cause and severity of the disease. Recently, sildenafil at the dose of 25 mg came into the market without prescription. This paper presents an overview and update of the PDE-5 inhibitors.

  11. Analysis of single items on the Self-Esteem and Relationship questionnaire in men treated with sildenafil citrate for erectile dysfunction: results of two double-blind, placebo-controlled trials.

    Science.gov (United States)

    Cappelleri, Joseph C; Althof, Stanley E; O'Leary, Michael P; Tseng, Li-Jung

    2008-04-01

    To evaluate the effect of sildenafil citrate on each item of the 14-item Self-Esteem And Relationship (SEAR) questionnaire, which is used to measure self-esteem, confidence, satisfaction with sexual relationship, and overall relationship satisfaction in men with erectile dysfunction (ED). Data were combined from two 12-week, double-blind, placebo-controlled, flexible-dose sildenafil trials having identical protocols, one conducted in the USA and the other in Mexico, Brazil, Australia and Japan. All men had ED and were aged >or=18 years. Response categories of each SEAR item used a 4-week reference period and were based on a five-point scale (1, almost never/never; 2, a few times; 3, sometimes; 4, most times; 5, almost always/always). The difference (sildenafil vs placebo) in the change from baseline to week 12 was evaluated with a Wilcoxon rank sum test using ridit analysis, and an analysis of covariance model that included treatment group, centre, study and baseline item score. Compared with the 274 patients receiving placebo, the 279 receiving sildenafil reported significantly greater mean and median improvements (P self-esteem, confidence and relationship satisfaction.

  12. ALERT: Revatio is another brand name for sildenafil.

    Science.gov (United States)

    Koczmara, Christine; Hyland, Sylvia; Greenall, Julie

    2009-01-01

    In this column, the authors highlight a medication incident that occurred with Revatio (sildenafil), along with the learnings and recommendations from a previously published ISMP Canada Safety Bulletin. It is well-known to health care practitioners that use of nitroglycerin therapy is contraindicated in patients taking sildenafil (commonly known as Viagra). Many health care practitioners may be unaware that sildenafil is also marketed under the brand name Revatio for treatment of primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disease. The following incident signals the need to heighten the awareness that Revatio is a brand name for sildenafil.

  13. Application of narrow-bore HPLC columns in rapid determination of sildenafil citrate in its pharmaceutical dosage forms.

    Science.gov (United States)

    Ghodsi, Razieh; Kobarfard, Farzad; Tabatabai, Sayyed Abbas

    2012-01-01

    A special type of silica-based columns has been recently introduced into the market which is called narrow-bore columns. They have lower internal volume than the standard high-performance liquid chromatography (HPLC) columns and thus reduce the solvent consumption by almost 80%. A simple, accurate and environmentally friendly reversed phase- HPLC (RP-HPLC method) which could be used in fast and high throughput analyses has been developed for the purpose of determining the sildenafil in bulk and pharmaceutical dosage forms, using narrow-bore C18 column (50 × 3.2 mm, 5 µm particle size) in isocratic mode, with mobile phase comprising of buffer (pH = 3) and acetonitrile in the ratio of 75:25 v/v. The flow rate was 0.7 mL/min and the detection was monitored through Ultraviolet detector (UV detector) at 292 nm. Clonazepam was used as the internal standard and the run time was 4 min. The proposed method has permitted the quantification of sildenafil over the linearity in the range of 30-4000 ng/mL and its percentage recovery was found to be 99-105%. Limit of quantitation (LOQ) is determined as 30 ng/mL. The intra-day and inter-day precisions were found 1.2-2.2% and 1.56-3.4% respectively. The solvent consumption was 2.8 mL per sample of which ca 0.7 mL was acetonitrile. This study shows that the application of narrow-bore column instead of the conventional reversed phase column in HPLC analyses has the advantages of shorter run time and less organic solvent consumption. This method is highly sensitive with excellent recoveries and precision and there is no need for special column and pre-column or post-column treatment of the sample. Moreover, the method is free from interference by common additives and excipients, suggesting applications in routine quality control analyses.

  14. Phosphodiesterase 5 and effects of sildenafil on cerebral arteries of man and guinea pig

    DEFF Research Database (Denmark)

    Kruuse, Christina; Khurana, Tejvir S; Rybalkin, Sergei D

    2005-01-01

    Sildenafil (Viagra), a selective inhibitor of phosphodiesterase 5 (PDE5), induces headache and migraine. Although previously supposed to be a "vascular" headache, no significant cerebral artery dilatation was found in vivo. Thus, we hypothesised that PDE5 may not be present or that sildenafil...

  15. Cerebral haemodynamic response or excitability is not affected by sildenafil

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Hansen, Adam E; Larsson, Henrik B W

    2009-01-01

    Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70...

  16. The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus- A histological study

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-07-01

    Full Text Available The histological effect of oral administration of sildenafil citrate (Viagra, commonly used as an aphrodisiac and for the treatment of erectile dysfunction on one of the visual relay centres namely the lateral geniculate body (LGB of adult Wistar rat was carefully studied. The rats of both sexes (n=24, average weight of 202g were randomly assigned into three treatment (n=18 and control (n=6 groups. The rats in the treatment groups ‘A’, ‘B’ and ‘C’ received respectively, 0.25mg/kg, 0.70mg/kg and 1.43mg/kg body weight of sildenafil citrate base dissolved in distilled water daily for 30 days, through orogastric feeding tube, while that of the control group D, received equal volume of distilled water daily during the period of the experiment. The rats were fed with growers’ mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria and were given water liberally. The rats were sacrificed on day thirty-one of the experiment. The lateral geniculate body (LGB was carefully dissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after H&E method indicated that the treated section of the lateral geniculate body (LGB showed some varying degree of reduced cellular population based on its sparse distribution, degenerative changes, cellular hypertrophy, and intercellular vacuolations appearing in the stroma. Varying dosage and long administration of sildenafil citrate may have some deleterious effects on the neurons of the intracranial visual relay centre and this may probably have some adverse effects on visual sensibilities by its deleterious effects on the cells of the lateral geniculate body (LGB of adult Wistar rats. It is therefore recommended that further studies aimed at corroborating these observations be carried out.

  17. Sildenafil citrate improves self-esteem, confidence, and relationships in men with erectile dysfunction: Results from an international, multi-center, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Althof, Stanley E; O'leary, Michael P; Cappelleri, Joseph C; Hvidsten, Kyle; Stecher, Vera J; Glina, Sidney; King, Rosie; Siegel, Richard L

    2006-05-01

    Erectile dysfunction (ED) can significantly impact a man's relationships and well-being. We assessed changes in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction in men with ED using the validated Self-Esteem And Relationship questionnaire (SEAR). This was a 12-week, double-blind, placebo-controlled, flexible-dose (25, 50, 100 mg, as needed) international study of sildenafil in men > or =18 years of age in Mexico, Brazil, Australia, and Japan. The primary study outcome was change in self-esteem from baseline to the end of treatment. Secondary study measures were changes in other SEAR components, International Index of Erectile Function (IIEF) domains, percentage of intercourse attempts that were successful, and the response to a global efficacy question at the end of treatment. Patients were well balanced for age and duration of ED (placebo = 149 and sildenafil = 151). Compared with placebo, sildenafil significantly improved self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction (P self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction after treatment of ED with sildenafil were consistent among countries. These data suggest a substantial cross-cultural improvement in well-being after successful treatment of ED with sildenafil.

  18. Self-esteem, confidence and relationship satisfaction of men with erectile dysfunction treated with sildenafil citrate: a multicenter, randomized, parallel group, double-blind, placebo controlled study in the United States.

    Science.gov (United States)

    O'Leary, Michael P; Althof, Stanley E; Cappelleri, Joseph C; Crowley, Arthur; Sherman, Nancy; Duttagupta, Sandeep

    2006-03-01

    We assessed the change in confidence, relationships and self-esteem, and its correlation with erectile function in men with ED treated with sildenafil citrate in the first United States based, double-blind, placebo controlled, randomized trial assessed by the validated SEAR. This 12-week flexible dose (25, 50 or 100 mg) trial determined change scores from baseline to end of treatment for the 5 SEAR components (Sexual Relationship domain, Confidence domain, Self-Esteem subscale [prespecified as the primary end point], Overall Relationship subscale and Overall score), and their correlations with the IIEF and event log data, as well as correlations between SEAR components and a general efficacy question at the end of treatment. Compared with the placebo group (125 patients, mean age +/- SD 55 +/- 13 years, mean years ED 3.8 +/- 4.2), the sildenafil group (128 patients, mean age +/- SD 56 +/- 12, mean years ED 4.6 +/- 4.3) had significantly greater improvements in all 5 SEAR components (p self-esteem, confidence and relationship satisfaction as measured by SEAR scores, which showed moderate to high positive correlations with IIEF scores.

  19. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial.

    Science.gov (United States)

    Basson, Rosemary; Brotto, Lori A

    2003-11-01

    Some postmenopausal women lose genital sexual responsivity despite preserved subjective sexual arousal from non-genital stimuli. When oestrogen replacement is without benefit, both the underlying pathophysiology and management of this acquired genital female sexual arousal disorder are unclear. We aimed to study the effect of sildenafil on sexual arousal and orgasmic functioning of such women. Secondly, we aimed to explore the concordance between a detailed historical assessment of genital response in real life, with laboratory vaginal photoplethysmographic assessment of genital vasocongestion. Session one consisted of a semi-structured clinical interview to assess real life sexual arousal. Session two employed vaginal pulse amplitude and self-report questionnaire assessment of erotica-induced sexual arousal. Sessions three and four were a randomised, double-blind, placebo-controlled crossover administration of sildenafil on orgasm latency, intensity, perception of genital congestion and subjective arousal to erotica plus clitoral vibrostimulation. University associated Sexual Medicine Clinic and Psychophysiology Laboratory. Volunteer sample of 34 oestrogenised postmenopausal women with acquired genital female sexual arousal disorder and impaired orgasm. Sildenafil (50 mg) or placebo administered over two laboratory sessions. Orgasm latency and intensity during drug sessions; subjective and psychophysiological sexual arousal during photoplethysmography session. The erotic video significantly increased subjective sexual arousal in all women. Vaginal pulse amplitude responses varied from robust to absent. Although across all women, sildenafil improved neither arousal nor orgasm, subsequent analyses comparing high versus low vaginal pulse amplitude responders revealed significantly reduced latency to orgasm, and increased subjective sexual arousal and perception of genital arousal in the latter group of women. The data suggest that oestrogenised postmenopausal women

  20. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    . METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure...

  1. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Thomsen, Lars Lykke; Birk, Steffen

    2003-01-01

    GMP)-mediated vasodilatation. We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo...

  2. Stability of sildenafil in combination with heparin and dopamine.

    Science.gov (United States)

    Luu, Yao; Thigpen, Jim; Brown, Stacy D

    2017-01-01

    The stability of sildenafil in combination with heparin and dopamine was evaluated. A stability-indicating high-performance liquid chromatography method with ultraviolet detection was developed for sildenafil citrate and validated. The method was applied to the investigation of sildenafil alone, sildenafil with heparin, sildenafil with dopamine, and sildenafil with heparin and with dopamine, all in 5% dextrose injection at room temperature and under refrigeration for 30 days. Samples of 100 μL were pulled from each storage bottle on each sampling day, diluted in mobile phase, and assayed in duplicate. Samples were tested on days 0, 1, 2, 3, 4, 5, 7, 9, 12, 14, 21, and 30. Each preparation was visually inspected for precipitation and color change. The percent recovery in each study sample was determined by comparing the peak area of sildenafil in the sample with the peak area of sildenafil from a freshly prepared 100-μg/mL standard in mobile phase. The sildenafil alone, sildenafil with heparin, and sildenafil with dopamine remained within 90-110% of the expected sildenafil potency for at least 30 days at both temperatures. The preparation of sildenafil with both heparin and dopamine fell below 90% potency after 3 days at room temperature and 21 days in the refrigerator. Sildenafil prepared in 5% dextrose injection alone, with heparin, and with dopamine retained over 90% potency after 30 days of storage at room temperature and under refrigeration. Sildenafil prepared with both heparin and dopamine had a potency of <90% after 3 days of storage at room temperature and 21 days of storage under refrigeration. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  3. Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

    Science.gov (United States)

    Nivison-Smith, Lisa; Zhu, Yuan; Whatham, Andrew; Bui, Bang V; Fletcher, Erica L; Acosta, Monica L; Kalloniatis, Michael

    2014-11-01

    Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Determination of sildenafil by preconcentration on surfactant coated polymeric resin followed by spectrofluorimetry

    Directory of Open Access Journals (Sweden)

    Chien C. Wang

    2013-06-01

    Full Text Available The illicit addition of phosphodiesterase type-5 (PDE-5 inhibitors like sildenafil (Viagra in product offered as herbal medicine or dietary supplement for male erectile dysfunction has concerned authorities in recent times. In this paper, we proposed a sensitive surfactant-coated Amberlite XAD™ resin for sildenafil preconcentration method with spectrofluorimetric detection. Retention capacity of micellar coated XAD resin for sildenafil was studied and the obtained eluate was measured by spectrofluorometer at excitation and emission wavelengths of 350 and 430nm, respectively. This method allowed the detection of sildenafil at 0.15ng/mL with linear range of 0.0003–7.0μg/mL. The method has been successfully applied to the analysis of some local commercially available herbal medicines and urine. Keywords: Sildenafil, Herbal medicines, Spectrofluorimetric analysis, Surfactant

  5. Screening suspected counterfeit Viagra and imitations of Viagra with near-infrared spectroscopy.

    NARCIS (Netherlands)

    Vredenbregt, M J; Blok-Tip, L; Hoogerbrugge, Ronald; Barends, D M; Kaste, D de

    2006-01-01

    We describe a near-infrared spectroscopy (NIRS) method for fast-screening Viagra tablets, counterfeit Viagra tablets, and imitations of Viagra. The method can (1) check the homogeneity of a batch; (2) distinguish counterfeits and imitations from authentic Viagra; (3) screen for the presence of

  6. Effect of sildenafil in cavernous arteries of patients with erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Joaquim A Claro

    2003-08-01

    Full Text Available INTRODUCTION: Sildenafil citrate is a type 5 phosphodiesterase inhibitor, which has demonstrated excellent results in the treatment of erectile dysfunction. The effect of sildenafil citrate in the cavernous arteries of patients with erectile dysfunction has not been established yet. The objective of this study was to assess the effect of sildenafil citrate in the cavernous arteries of patients with erectile dysfunction, following an intracavernous injection of alprostadil. MATERIALS AND METHODS: 29 male patients, with mean age of 53.8 years (32 to 75 years, were prospectively evaluated. The mean time with complaint of erectile dysfunction was 50.5 months (6 to 168 months. Each patient was his own control. Patients underwent a measurement of peak systolic velocity before and after use of sildenafil citrate associated with 5 micrograms of alprostadil, through ultrasonic velocitometry Knoll/MIDUS® system. In the interval between measurements, approximately 15 days, patients used 3 tablets of sildenafil at home with their partners. RESULTS: Using only 5 mcg of alprostadil, average peak systolic velocity was 23.9 cm/s, and when associated to 50 mg of sildenafil it was 24.8 cm/s. Despite the increase in the flow rate caused by sildenafil, the difference was not statistically significant, Zcalculated = - 0.695 NS (Wilcoxon test. Twenty one of the 29 patients (72.4% showed global improvement in sexual performance with the use of sildenafil citrate at home. There was not a statistically significant correlation between the global response to sildenafil citrate and the increase in the peak systolic velocity. CONCLUSION: We concluded that, even though the use of 50 mg of sildenafil citrate associated with 5 mcg of alprostadil provides an increase in the peak systolic velocity of the cavernous arteries, there was no statistic difference in relation to alprostadil alone. There was no correlation between the global response to sildenafil and the increase in

  7. Oral sildenafil (Viagra™ in male erectile dysfunction: use, efficacy and safety profile in an unselected cohort presenting to a British district general hospital.

    Directory of Open Access Journals (Sweden)

    Boustead Gregory

    2002-04-01

    Full Text Available Abstract Introduction Sildenafil (Viagra® is one of the drugs used in the first line therapy of male erectile dysfunction (MED. We have recorded outcomes, adverse events and acceptability of Sildenafil (Viagra therapy in an unselected group of men presenting with ED to a British district general hospital. Methods In this prospective observational study, 147 men with ED were seen since Oct 1999. Study patients were reviewed at 4, 12 and 52 weeks. All the patients filled the International Index of Erectile Function (IIEF questionnaire and were asked about their willingness to pay (WTP for treatment. Results All suitable men accepted Viagra as first line therapy. 91% of our patients found sildenafil treatment successful. 80% of these patients were willing to continue with sildenafil therapy. Side effect profile of sildenafil was different in this study with much higher incidence of headache, dyspepsia, flushing and abnormal vision. 92% of men with ED expect to be treated by the NHS. Of those men eligible for treatment in the NHS, 30% qualify under the clinical categories and 18% under the 'distress' category. Only 55% of those with cardiovascular risk factors qualify for NHS treatment. Conclusions Sildenafil is widely accepted as first line therapy among British men with ED and has a success rate of 91%. Nearly half of men with ED qualify for NHS treatment. Nearly half of those with vascular risk factors do not qualify for NHS treatment. Most men with ED could possibly be managed in primary care.

  8. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan

    2004-01-01

    . METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  9. Visual field defect as a presenting sign for hemorrhagic stroke caused by sildenafil

    Directory of Open Access Journals (Sweden)

    Mehdizadeh Morteza

    2008-01-01

    Full Text Available Herein, we describe the presenting symptoms, history, ophthalmic examination, visual fields and brain magnetic resonance imaging of a patient who developed left homonymous hemianopia due to right occipital lobe hemorrhage after ingestion of sildenafil citrate (Novagra Forte. To the best of our knowledge, association of homonymous hemianopia with sildenafil usage has not been reported before.

  10. Self-esteem, confidence, and relationships in Brazilian men with erectile dysfunction receiving sildenafil citrate: a randomized, parallel-group, double-blind, placebo-controlled study in Brazil.

    Science.gov (United States)

    Glina, Sidney; Damião, Ronaldo; Abdo, Carmita; Afif-Abdo, João; Tseng, Li-Jung; Stecher, Vera

    2009-01-01

    Psychosocial manifestations of erectile dysfunction (ED) differ across cultures. Understanding the treatment response to ED medications within cultural groups can aid in resource allocation and in developing treatment strategies. Evaluate the effect of sildenafil treatment on self-esteem, confidence, and sexual relationship satisfaction in Brazilian men with ED. The Self-Esteem and Relationship (SEAR) questionnaire, a validated, 14-question instrument developed to specifically address self-esteem and relationship issues within the context of ED. Men aged 18 years or older with a clinical diagnosis of ED (self-esteem subscale of the SEAR questionnaire. Thirteen Brazilian sites participated in a randomized, double-blind, placebo-controlled trial of sildenafil treatment for ED. Patients were randomized to receive either 50 mg of sildenafil (adjustable to 25 mg or 100 mg based on patient response) or matching placebo approximately 1 hour before anticipated sexual activity but not more than once a day. At the end of double-blind treatment, 63 and 66 patients in the placebo and sildenafil groups, respectively, from 13 Brazilian sites were assessed for efficacy. Brazilian patients receiving sildenafil had significantly greater improvements in their scores on the SEAR self-esteem subscale (42.9 [95% confidence interval 35.7-50.0]) compared with placebo (21.1 [95% confidence interval 13.7-28.6]; P self-esteem, confidence, and relationships after treatment with sildenafil.

  11. [Role of psychiatry and psychotherapy in sexual medicine after introductory marketing of viagra].

    Science.gov (United States)

    Weig, W

    2000-03-01

    Sildenafil (Viagra) is a substance for the treatment of erectile dysfunction. Great expectations are connected with its introduction into the market. In this situation the multidimensionality in the control-mechanismus of the sexual reaction and of the satisfaction in the sexual experience are pointed out. These aspects affect the diagnostic and therapeutic competence of psychiatry and psychotherapy in a high degree. Efficient psycho-educative and psychotherapeutic ways of treatment for sexual dysfunction are available. Increased specific knowledge in this area is required by psychiatrists, medical psychotherapists and neuropsychiatrists.

  12. [Identification system for Sildenafil in health foods].

    Science.gov (United States)

    Moriyasu, T; Shigeoka, S; Kishimoto, K; Ishikawa, F; Nakajima, J; Kamimura, H; Yasuda, I

    2001-10-01

    A substantially available identification system for Sildenafil in health foods was established using 3 different analytical methods; i.e. TLC, preparative TLC/MS and HPLC/photo-diode array. Sildenafil in health foods was extracted with ethyl acetate under alkaline conditions as sample solutions for TLC and preparative TLC, and also extracted with 50% methanol and then diluted with solution of HPLC mobile phase for HPLC. The sample solution for TLC was applied to Silica gel 60 F254 plates with chloroform/methanol/28% ammonia (90:1:5, under layer) as mobile phase. Spots were located under UV radiation at 254 nm and 366 nm, and spraying dragendorff reagent. The conditions for preparative TLC were the same as these of TLC method, and samples abtained from preparative TLC were determined by MS with APCI interface, under both positive and negative modes. The HPLC analysis was carried out on a column of Cosmosil 5C18-AR (4.6 mm x 150 mm, 5 microns) with 0.05 mol/l phosphate buffer pH 3.0/acetonitrile(73:27) as mobile phase and the eluate was monitored by a photo-diode array detector. The quantitative analysis was available, when the peak of this sample on HPLC was detected at 290 nm. When this system was applied to commercial health foods, Sildenafil was identified and their contents were 25 mg-45 mg/tablet or bottle. These contents nearly correspond to that in Viagra, 25 mg, 50 mg/tablet. Therefore, there is a fear of side effects for Sildenafil, when it is taken as health foods.

  13. Nexavar/Stivarga and Viagra Interact to Kill Tumor Cells

    Science.gov (United States)

    Tavallai, Mehrad; Hamed, Hossein A.; Roberts, Jane L.; Cruickshanks, Nichola; Chuckalovcak, John; Poklepovic, Andrew; Booth, Laurence

    2015-01-01

    We determined whether the multi‐kinase inhibitor sorafenib or its derivative regorafenib interacted with phosphodiesterase 5 (PDE5) inhibitors such as Viagra (sildenafil) to kill tumor cells. PDE5 and PDGFRα/β were over‐expressed in liver tumors compared to normal liver tissue. In multiple cell types in vitro sorafenib/regorafenib and PDE5 inhibitors interacted in a greater than additive fashion to cause tumor cell death, regardless of whether cells were grown in 10 or 100% human serum. Knock down of PDE5 or of PDGFRα/β recapitulated the effects of the individual drugs. The drug combination increased ROS/RNS levels that were causal in cell killing. Inhibition of CD95/FADD/caspase 8 signaling suppressed drug combination toxicity. Knock down of ULK‐1, Beclin1, or ATG5 suppressed drug combination lethality. The drug combination inactivated ERK, AKT, p70 S6K, and mTOR and activated JNK. The drug combination also reduced mTOR protein expression. Activation of ERK or AKT was modestly protective whereas re‐expression of an activated mTOR protein or inhibition of JNK signaling almost abolished drug combination toxicity. Sildenafil and sorafenib/regorafenib interacted in vivo to suppress xenograft tumor growth using liver and colon cancer cells. From multiplex assays on tumor tissue and plasma, we discovered that increased FGF levels and ERBB1 and AKT phosphorylation were biomarkers that were directly associated with lower levels of cell killing by ‘rafenib + sildenafil. Our data are now being translated into the clinic for further determination as to whether this drug combination is a useful anti‐tumor therapy for solid tumor patients. J. Cell. Physiol. 230: 2281–2298, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25704960

  14. Determinação de citrato de sildenafila e de tadalafila por cromatografia líquida de ultraeficiência com detecção por arranjo de diodos (CLUE-DAD Determination of sildenafil citrate and tadalafil by ultra performance liquid chromatography with diode-array detection (UPLC-DAD

    Directory of Open Access Journals (Sweden)

    Rafael Scorsatto Ortiz

    2010-01-01

    Full Text Available A simple ultra-performance liquid chromatographic method for the simultaneous determination of sildenafil citrate and tadalafil was developed and validated. Sample preparation was dissolution in methanol, followed by centrifugation and dilution (1:10 with methanol. Analysis was performed in an Acquity® UPLC system with Acquity® BEH C18 column (2.1 x 50 mm, with 1.7 μm particles. The elution was isocratic with phosphate buffer pH 2.3 and acetonitrile (65:35, v/v at a flow rate of 0.7 mL/min. The method presented adequate specificity, linearity, precision and accuracy and allowed the determination of the drugs in seized forensic samples.

  15. Viagra: : A success story for rationing?

    NARCIS (Netherlands)

    Klein, R.; Sturm, H.

    2002-01-01

    The 1998 launch of Viagra prompted widespread fears about the budgetary consequences for insurers and governments, all the more so since Viagra was only the first of a new wave of so-called lifestyle drugs. The fears have turned out to be greatly exaggerated. This paper analyzes the rationing

  16. Haematological changes and wound healing effects of sildenafil ...

    African Journals Online (AJOL)

    This study presents baseline data on the effect of sildenafil citrate on some of the haematological and biochemical parameters in wistar rats with diabetes and wound formation. Forty two albino rats weighing between 139 and 225 g were separated at random into seven groups (A, B, C, D, E, F and G) of six rats per group.

  17. Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

    Directory of Open Access Journals (Sweden)

    Balarini Camille M

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS and nitric oxide (NO. Sildenafil, a selective phosphodiesterase-5 (PDE5 inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/− mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage were compared to the untreated apoE−/− and the wild-type (WT mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor or apocynin (NADPH oxidase inhibitor. In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous

  18. Sildenafil Stimulates Aqueous Humor Turnover in Rabbits

    Science.gov (United States)

    Alvarez, Lawrence J.; Zamudio, Aldo C.; Candia, Oscar A.

    2013-01-01

    Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈ 2 hrs of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈ 45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90–120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 μL/min to 3.14 μL/min (PViagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation. PMID:23562660

  19. The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction.

    Science.gov (United States)

    Gumrah, Abdulkadir; Tanidir, Yiloren; Tinay, Ilker; Ozyurek, Mustafa; Tarcan, Tufan

    2017-08-01

    Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO). Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA. Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups. Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS. © 2016 Wiley Periodicals, Inc.

  20. Effect of sildenafil on ocular hemodynamics in 3 months regular use.

    Science.gov (United States)

    Dündar, S O; Dayanir, Y; Topaloğlu, A; Dündar, M; Koçak, I

    2006-01-01

    The aim of this study was to evaluate the effect of sildenafil on ocular hemodynamics in a group of men with erectile dysfunction in 3 months regular use. A total of 15 patients with erectile dysfunction were included in this prospective study. All patients received 50 mg doses of sildenafil (Viagra, Pfizer) two times per week regularly for 3 months. The following examinations were performed on both eyes before and after sildenafil treatment: best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision, anterior segment, and fundus examination. Using color Doppler imaging, we measured hemodynamic variables in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA). No significant changes in BCVA, color vision and IOP were found after sildenafil treatment. The anterior segment and fundus examinations showed no abnormalities. All Doppler parameters of OA, CRA, and SPCA remained nonsignificant for both eyes after sildenafil treatment. Oral sildenafil in 3 months regular use seems to have no effect on ocular hemodynamics.

  1. A nanohybrid system for taste masking of sildenafil

    Science.gov (United States)

    Lee, Ji-Hee; Choi, Goeun; Oh, Yeon-Ji; Park, Je Won; Choy, Young Bin; Park, Mung Chul; Yoon, Yeo Joon; Lee, Hwa Jeong; Chang, Hee Chul; Choy, Jin-Ho

    2012-01-01

    A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN–MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN–MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN–MMT and Viagra®, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN–MMT during the first 2 hours while almost 100% of drug was released from Viagra®. However, an in vivo experiment showed that the AEA-coated SDN–MMT exhibited higher drug exposure than Viagra®. For the AEA-coated SDN–MMT, the area under the plasma concentration– time curve from 0 hours to infinity (AUC0-∞) and maximum concentration (Cmax) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra® (AUC0-∞ = 69.2 ± 3.19 μg · hour/mL; Cmax = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure. PMID:22619517

  2. Study Refutes Viagra-Melanoma Link

    Science.gov (United States)

    ... for sexually active older men: Viagra and related erectile dysfunction drugs do not increase the risk of ... large-scale studies of more than 866,000 erectile medication users. While men who used the drugs ...

  3. An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment.

    Science.gov (United States)

    Safarinejad, M R; Shafiei, N; Safarinejad, S

    2010-01-01

    Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.

  4. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-01-01

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

  5. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  6. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Science.gov (United States)

    Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

    2017-01-01

    A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

  7. OSU‐03012 and Viagra Treatment Inhibits the Activity of Multiple Chaperone Proteins and Disrupts the Blood–Brain Barrier: Implications for Anti‐Cancer Therapies

    Science.gov (United States)

    Booth, Laurence; Roberts, Jane L.; Tavallai, Mehrad; Nourbakhsh, Aida; Chuckalovcak, John; Carter, Jori; Poklepovic, Andrew

    2015-01-01

    We examined the interaction between OSU‐03012 (also called AR‐12) with phosphodiesterase 5 (PDE5) inhibitors to determine the role of the chaperone glucose‐regulated protein (GRP78)/BiP/HSPA5 in the cellular response. Sildenafil (Viagra) interacted in a greater than additive fashion with OSU‐03012 to kill stem‐like GBM cells. Treatment of cells with OSU‐03012/sildenafil: abolished the expression of multiple oncogenic growth factor receptors and plasma membrane drug efflux pumps and caused a rapid degradation of GRP78 and other HSP70 and HSP90 family chaperone proteins. Decreased expression of plasma membrane receptors and drug efflux pumps was dependent upon enhanced PERK‐eIF2α‐ATF4‐CHOP signaling and was blocked by GRP78 over‐expression. In vivo OSU‐03012/sildenafil was more efficacious than treatment with celecoxib and sildenafil at killing tumor cells without damaging normal tissues and in parallel reduced expression of ABCB1 and ABCG2 in the normal brain. The combination of OSU‐03012/sildenafil synergized with low concentrations of sorafenib to kill tumor cells, and with lapatinib to kill ERBB1 over‐expressing tumor cells. In multiplex assays on plasma and human tumor tissue from an OSU‐03012/sildenafil treated mouse, we noted a profound reduction in uPA signaling and identified FGF and JAK1/2 as response biomarkers for potentially suppressing the killing response. Inhibition of FGFR signaling and to a lesser extent JAK1/2 signaling profoundly enhanced OSU‐03012/sildenafil lethality. J. Cell. Physiol. 230: 1982–1998, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25736380

  8. [3H]sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous, and stimulated by cGMP.

    Science.gov (United States)

    Corbin, Jackie D; Blount, Mitsi A; Weeks, James L; Beasley, Alfreda; Kuhn, Karl P; Ho, Yew S J; Saidi, Layla F; Hurley, James H; Kotera, Jun; Francis, Sharron H

    2003-06-01

    Sildenafil (Viagra) potentiates penile erection by acting as a nonhydrolyzable analog of cGMP and competing with this nucleotide for catalysis by phosphodiesterase-5 (PDE5), but the characteristics of direct binding of radiolabeled sildenafil to PDE5 have not been determined. [3H]Sildenafil binding to PDE5 was retained when filtered through nitrocellulose or glass-fiber membranes. Binding was inhibited by excess sildenafil, 2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl)-8-(pyrimidin-2-yl)methoxy-1,2-dihydro-1-oxo-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride (T-0156), 3-isobutyl-1-methylxanthine, EDTA, or cGMP, but not by cAMP or 5'-GMP. PDE5 was the only [3H]sildenafil binding protein detected in human lung extract. Using purified recombinant PDE5, [3H]sildenafil exchange dissociation yielded two components with t1/2 values of 1 and 14 min and corresponding calculated KD values of 12 and 0.83 nM, respectively. This implied the existence of two conformers of the PDE5 catalytic site. [3H]Sildenafil binding isotherm of PDE5 indicated KD was 8.3 to 13.3 nM, and low cGMP decreased the KD to 4.8 nM but only slightly increased Bmax to a maximum of 0.61 mol/mol-subunit. Results suggest that these effects occur via cGMP binding to the allosteric cGMP binding sites of PDE5. Results imply that by inhibiting PDE5 and thereby increasing cGMP, sildenafil accentuates its own binding affinity for PDE5, which further elevates cGMP. The data also indicate that after physiological elevation, cGMP may directly stimulate the catalytic site by binding to the allosteric cGMP-binding sites of PDE5, thus causing negative feedback on this pathway.

  9. Impact of erectile dysfunction and its subsequent treatment with sildenafil: qualitative study.

    Science.gov (United States)

    Tomlinson, John; Wright, David

    2004-05-01

    To determine the effects of erectile dysfunction and to explore the impact of treatment with sildenafil (Viagra). An exploratory qualitative study with semistructured interviews. Men's health clinic in NHS hospital. 40 men who had had erectile dysfunction and had attended the clinic during the year before interview. Impact of erectile dysfunction on men, their expectations of sildenafil, and impact of treatment on men and their relationships. Issues explored with exploratory qualitative approach. Erectile dysfunction caused serious distress to all those men who experienced it, with marked effects on their self esteem and their relationships. Sildenafil, when it worked, caused a great improvement in wellbeing. The expectations raised by media hyperbole with the launch of sildenafil had an adverse effect on the morale of those who found it did not work. When, according to the patient, treatment did not work, the distress was severe and for many confirmed their lack of self worth. Further study is needed to explore the feelings of men affected by erectile dysfunction and their perception of treatment. Health professionals should be aware of the extreme distress erectile dysfunction can cause.

  10. USE OF SILDENAFIL (VIAGRA® FOR ERECTILE DYSFUNCTION IN DIALYSIS PATIENTS – OUR FIRST EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Bojan Vujkovac

    2002-01-01

    Full Text Available Background. Male patients with end stage renal disease often report erectile dysfunction, which is very common especially in younger males. Impotence is reported to exceed 50% in male chronic renal failure patients, and is present in 65% of such patients undergoing hemodialysis. Numerous etiological factors have been reported as possible cause for sexual dysfunction. Sildenafil (Viagra®, a potent specific inhibitor of cGMP phosphodiesterase, was used in this case study to improve erectile dysfunction in dialysis male patients.Methods and results. During 12 weeks we treated 4 dialysis patients. 2 patients were treated with peritoneal dialysis and 2 patients were in the program of chronic hemodialysis. All patients were in the program of dialysis for more than 24 months, and reported erectile dysfunction and impotence after they had started with dialysis treatment. Sildenafil was used in the treatment. The dosage schedule for sildenafil was 50mg/ week orally for 2 weeks followed by 100 mg/week for the next 10 weeks if there was no effect on initial dosage. Efficacy of treatment was evaluated by means of the International Index of Erectile Dysfunction. All 4 patients reported no significant effect on initial dose. With higher dose of sildenafil treatment was overwhelmingly successful, with reported prolonged improvement of erectile dysfunction for 42 to 72 hours. Side effects were present only in 1 patient who had severe headaches after higher dose. No patients experienced priapism.Conclusions. There have been only few reports in the literature on the use of sildenafil in dialysis patients. Our small case study suggests that sildenafil could be successfully and safely used for treatment of erectile dysfunction also in dialysis patients. A large trial would be necessary to confirm the efficacy of the drug for this specific group of patients.

  11. A nanohybrid system for taste masking of sildenafil.

    Science.gov (United States)

    Lee, Ji-Hee; Choi, Goeun; Oh, Yeon-Ji; Park, Je Won; Choy, Young Bin; Park, Mung Chul; Yoon, Yeo Joon; Lee, Hwa Jeong; Chang, Hee Chul; Choy, Jin-Ho

    2012-01-01

    A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN-MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN-MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN-MMT and Viagra(®), an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN-MMT during the first 2 hours while almost 100% of drug was released from Viagra(®). However, an in vivo experiment showed that the AEA-coated SDN-MMT exhibited higher drug exposure than Viagra(®). For the AEA-coated SDN-MMT, the area under the plasma concentration- time curve from 0 hours to infinity (AUC(0-∞)) and maximum concentration (C(max)) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra(®) (AUC(0-∞) = 69.2 ± 3.19 μg · hour/mL; C(max) = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure.

  12. [Clinical efficacy of Viagra with behavior therapy against premature ejaculation].

    Science.gov (United States)

    Tang, Wenhao; Ma, Lulin; Zhao, Lianming; Liu, Yuqing; Chen, Zhenwen

    2004-05-01

    To study the efficacy of Viagra combined with behavior therapy against premature ejaculation (PE). Sixty PE patients were divided into two groups randomly: control group (behavior therapy alone) and the group of Viagra combined with behavior therapy. Intra-vaginal ejaculation latency time (IELT) and the coitus satisfaction of the patient and the partner were recorded before and after treatment. The IELTs of the two groups were 0.80 +/- 0.20 and 0.73 +/- 0.24 minutes respectively before treatment, and 1.82 +/- 0.54 and 3.63 +/- 0.55 minutes respectively after treatment. As for IELT and satisfaction degree, Viagra produced better result than behavior therapy. During this clinical trial, Viagra combined with behavior therapy prolonged IELT, which suggests that Viagra may be helpful for the treatment of premature ejaculation.

  13. NJS July - Dec 2010.cdr (cynt...

    African Journals Online (AJOL)

    NAM

    following use of the drug sildenafil citrate (Viagra). This is a case report of a 60 year old man who presented with unilateral, sudden- onset, painless, visual loss following the use of sildenafil citrate 100mg twice weekly, prescribed for his erectile dysfunction. Examination revealed a visual acuity of 6/6 in the right eye and ...

  14. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Radicioni M

    2017-04-01

    Full Text Available Milko Radicioni,1 Chiara Castiglioni,1 Andrea Giori,2 Irma Cupone,3 Valeria Frangione,4 Stefano Rovati4 1CROSS Research S.A., Phase I Unit, Arzo, Switzerland; 2IBSA Farmaceutici Italia, Lodi, Italy; 3Bouty S.p.A., Strada Padana Superiore, Cassina De’ Pecchi, Italy; 4IBSA Institut Biochimique S.A., Pambio-Noranco, Switzerland Abstract: A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra® after single-dose administration to 53 healthy male volunteers (aged 18–51 years in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg

  15. The South Australian couples sildenafil study: double-blind, parallel-group randomized controlled study to examine the psychological and relationship consequences of sildenafil use in couples.

    Science.gov (United States)

    Hundertmark, James; Esterman, Adrian; Ben-Tovim, David; Austin, Mary-Anne; Dougherty, Melissa

    2007-07-01

    The South Australian Couples Sildenafil (SACS) study sought to look more closely at the role of sexual functioning in couples by exploring the impact of treatment for erectile dysfunction (ED) with sildenafil. The SACS study investigated the individual and dyadic impact of the drug sildenafil (Viagra) on couples over a 6-month period. A range of outcome measures were utilized including the Dyadic Adjustment Scale (DAS), the International Index of Erectile Function (IIEF), and the Erectile Dysfunction Inventory of Treatment Satisfaction. Couples were recruited through the use of local media and general practitioners. Couples were randomly allocated to placebo or active drug with the option of using up to one study tablet per day for 6 months. Couples were reviewed at 2 weeks, 4 weeks, 8 weeks, 3 months, and 6 months. There were 108 couples who were eligible for the study with the eventual analysis including 49 couples in the active treatment group and 47 in the placebo group with similar demographic and background profiles found in both groups. A large number of psychosocial, quality-of-life, and sexual measures were recorded at the end of the trial for both male subjects and their female partners. Predictably, the erectile response in the active treatment group showed a significant improvement as measured by the IIEF although no change was found between the active and placebo groups in relationship functioning as measured by the DAS scores. The SACS study found no difference between treatment arms with regard to relationship functioning after the use of sildenafil for ED. Potential contributing factors to a "no change" result are discussed. The SACS study adds to the available literature on psychological and interpersonal factors in the treatment of ED which have not been sufficiently investigated until recently.

  16. Total Testosterone Levels and the Effect of Sildenafil on Type 2 Diabetics with Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Nabeel Najib Fadhil Hadeed

    2014-01-01

    Full Text Available Objectives: Hypotestosteronemia has been reported in approximately half of type 2 diabetic men in general. This study aims to assess serum total testosterone levels in type 2 diabetics with erectile dysfunction and to correlate the degree of improvement between sildenafil citrate and testosterone levels. Methods: A cross sectional and prospective comparative interventional study was conducted at the Diabetic Clinic of Assalam Teaching Hospital in Mosul, during the period from January 1, 2009 through to December 31, 2011. The study enrolled 120 type 2 diabetic males with erectile dysfunction who were analyzed with regard to age, duration of diabetes, duration and severity of erectile dysfunction, serum total testosteron levels and the degree of response to sildenafil citrate in terms of testosterone levels. The data were statistically analyzed using the independent two-sample Student t test, χ2 test and Pearson correlation test. A p-value of <0.05 was considered statistically significant. Results: Thirty six percent of type 2 diabetic males with erectile dysfunction were found to have low serum testosterone levels. The hypotestosteronemic and normotestosteronemic subgroups were not significantly different in terms of mean age, duration of diabetes, reduction of libido, and reduction in erectile function. The rate and the degree of improvement of erection by sildenafil in the normo-and-hypotestosteronemic respondents were not significantly different, but the degree of improvement by sildenafil was significantly correlated to testosterone levels among the hypotestosteronemic group. Conclusion: Hypotestosteronemia was found in 36% of type 2 diabetic males with erectile dysfunction. The degree of improvement of erectile dysfunction by sildenafil was directly proportional to the serum testosterone levels among the hypotestosteronemic group. Therapeutic supplement with testosterone preparation in the hypotestosteronemic diabetics with erectile

  17. Thermodynamic Parameters of Solutions of Sildenafil Citrate in ...

    African Journals Online (AJOL)

    butanol and 1,2 dichloroethane has been determined using gravimetric method over different temperature range (298.15 K to 328.15 K) at one atmospheric pressure. The modified Apelblat and Buchowski-Ksiazczak λh equations were used to ...

  18. Sildenafil citrate (VIAGRA™) in the treatment of male Erectile ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction (ED) is a major health concern which in some communities has been estimated to affect about half of men aged 40 years and above. Due to the high social stigma and its co-morbid nature, ED still remains highly under-diagnosed and hence untreated. Equally important is the lack of ...

  19. Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients.

    Science.gov (United States)

    De Santo, L S; Mastroianni, C; Romano, G; Amarelli, C; Marra, C; Maiello, C; Galdieri, N; Della Corte, A; Cotrufo, M; Caianiello, G

    2008-01-01

    Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

  20. L-Arginine

    Science.gov (United States)

    ... with this combination.Talk with your health provider.Sildenafil (Viagra)Sildenafil (Viagra) can lower blood pressure. L-arginine can also lower blood pressure. Taking sildenafil (Viagra) and L-arginine together might cause the ...

  1. Vertebral artery dissection associated with sildenafil abuse.

    Science.gov (United States)

    Dersch, Rick; Anastasopoulos, Constantin; Hader, Claudia; Stich, Oliver

    2013-05-01

    We present a 49-year-old male who suffered a cerebellar infarction due to a vertebral artery dissection. The patient had taken sildenafil daily for at least 2 years for sexual enhancement. There was no sexual intercourse or traumatic event prior to symptom onset. Sildenafil intake has been associated with aortic dissection and, in the light of this report, we suggest that chronic sildenafil intake could be a risk factor for arterial dissection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Geochemical Fate and Transport of Sildenafil and Vardenafil

    Science.gov (United States)

    Richter, L.; Boudinot, G.; Vulava, V. M.; Cory, W. C.

    2015-12-01

    The geochemical fate of pharmaceuticals and their degradation products is a developing environmental field. The geologic, chemical, and biological fate of these pollutants has become very relevant with the increase in human population and the resulting increase in pollutant concentrations in the environment. In this study, we focus on sildenafil (SDF) and vardenafil (VDF), active compounds in Viagra and Levitra, respectively, two commonly used erectile dysfunction drugs. The main objective is to determine the sorption potential and transport behavior of these two compounds in natural soils. Both SDF and VDF are complex organic molecules with multiple amine functional groups in their structures. Two types of natural acidic soils (pH≈4.5), an organic-rich soil (7.6% OM) and clay-rich soil (5.1% clay) were used in this study to determine which soil components influence sorption behavior of both compounds. Sorption isotherms measured using batch reactors were nearly linear, but sorption was stronger in soil that contained higher clay content. Both compounds have multiple pKas due to the amine functional groups, the relevant pKas of SDF are 5.97 and 7.27, and those of VDF's are 4.72 and 6.21. These values indicate that these compounds likely behave as cations in soil suspensions and hence were strongly sorbed to negatively-charged clay minerals present in both soils. The clay composition in both soils is predominantly kaolinite with smaller amount of montmorillonite, both of which have a predominantly negative surface charge. Transport experiments using glass chromatography columns indicated that both compounds were more strongly retarded in the clay-rich soils. Breakthrough curves from the transport experiments were modeled using convection-dispersion transport equations. The organic matter in the soil seemed to play a less dominant role in the geochemistry in this study, but is likely to transform both compounds into derivative compounds as seen in other studies.

  3. The cost-utility of Viagra® in The Netherlands

    NARCIS (Netherlands)

    E.A. Stolk (Elly); J.J. van Busschbach (Jan); M. Caffa; E.J.H. Meuleman; F.F.H. Rutten (Frans)

    1999-01-01

    textabstractOBJECTIVE: Clinical trials suggest that sildenafil is an effective treatment for erectile dysfunction. Nevertheless, reimbursement is controversial: sildenafil is expected to be more effective than conservative therapy (papaverine/ phentolamine injections), but also more costly to

  4. Citrat og nyresten

    DEFF Research Database (Denmark)

    Osther, P J

    1993-01-01

    Citrate is an important naturally occurring inhibitor of calcium stone formation in urine. Urinary citrate excretion was examined in 43 consecutive patients with recurrent idiopathic calcium nephrolithiasis and in 50 normal controls by a specific enzymatic technique. Hypocitraturia (<1.6 mmol/24h...

  5. Comparative Evaluation of the Aphrodisiac efficacy of Sildenafil and Carpolobia lutea Root Extract in Male Rabbits

    Directory of Open Access Journals (Sweden)

    Ayobami Dare

    2015-12-01

    Full Text Available Aims: In spite of folkloric use of the root of Carpolobia lutea as sexual stimulant in man, there has been limited scientific proof of its efficacy. This study evaluates efficacy of methanol extract of Carpolobia lutea root (MECLR on sexual activity of male rabbits. Methods: Twenty adult male rabbits were grouped into four of five rabbits each. Groups 1-4 were treated orally for 28 days with 2ml/kg 1% tween 20 (vehicle, 40mg/kg MECLR, 80mg/kg MECLR, and 0.5mg/kg sildenafil citrate respectively. Sexual activities of males from each group was assessed by cohabiting them with sexually receptive female at estrus on days 0,1,3 and 5 using digital camera mounted on mating arena. Serum testosterone and nitric oxide concentration of the corpora cavernosa homogenates were also determined. Results: MECLR caused a dose dependent significant increase in mount frequency, intromission frequency and ejaculatory latency, while it reduced mount latency, intromission latency and post ejaculatory latency (similar to sildenafil citrate when compared with the control. MECLR also caused a significant increase in nitric oxide concentration in corpora cavernosa but no change in serum testosterone concentration. Conclusions: Results suggest that MECLR enhances male sexual activity possibly by augmenting nitric oxide concentration. This study thus provides novel scientific rationale for the use of Carpolobia lutea in the management of penile erectile dysfunction and impaired libido. [J Intercult Ethnopharmacol 2015; 4(4.000: 302-307

  6. Sildenafil

    Science.gov (United States)

    ... the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV). ... you smoke, if you have ever had an erection that lasted for several hours, ... the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease); ...

  7. Trisilver(I citrate

    Directory of Open Access Journals (Sweden)

    Andreas Fischer

    2011-02-01

    Full Text Available Trisilver(I citrate, 3Ag+·C6H5O73−, was obtained by evaporation of a saturated aqueous solution of the raw material that had been obtained from sodium dihydrogen citrate and silver nitrate. It features one formula unit in the asymmetric unit. There is an intramolecular O—H...O hydrogen bond between the OH group and one of the terminal carboxylate groups. Different citrate groups are linked via the three Ag+ ions, yielding a three-dimensional network with rather irregular [AgO4] polyhedra.

  8. Viagra selfhood: pharmaceutical advertising and the visual formation of Swedish masculinity.

    Science.gov (United States)

    Asberg, Cecilia; Johnson, Ericka

    2009-06-01

    Using material from the Pfizer sponsored website providing health information on erectile dysfunction to potential Swedish Viagra customers (www.potenslinjen.se), this article explores the public image of masculinity in relation to sexual health and the cultural techniques for creating pharmaceutical appeal. We zoom in on the targeted ideal users of Viagra, and the nationalized, racialized and sexualized identities they are assigned. As part of Pfizer's marketing strategy of adjustments to fit the local consumer base, the ways in which Viagra is promoted for the Swedish setting is telling of what concepts of masculinity are so stable and unassailable that they can withstand the association with a drug that is, in essence, an acknowledgement of 'failed' masculinity and 'dysfunctional' sexuality. With comparative national examples, this study presents an interdisciplinary take on the 'glocalized' cultural imaginary of Viagra, and the masculine subject positions it engenders.

  9. Recent developments in counterfeits and imitations of Viagra, Cialis and Levitra. A 2005-2006 update

    NARCIS (Netherlands)

    Venhuis BJ; Barends DM; Zwaagstra ME; Kaste D de; Douane Laboratorium; KCF

    2007-01-01

    A strong trend is observed towards increasingly professional counterfeits and imitations of Viagra, Cialis and Levitra, with regard to the appearance of tablets, capsules and packaging. The professional presentation will deceive potential consumers into assuming these products are legal, efficacious

  10. The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

    Science.gov (United States)

    Korkmaz, Mehmet Fatih; Parlakpınar, Hakan; Ceylan, Mehmet Fethi; Ediz, Levent; Şamdancı, Emine; Kekilli, Ersoy; Sağır, Mustafa

    2016-01-01

    Background: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. Aims: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. Study Design: Animal experiment. Methods: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. Results: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42nd day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of

  11. Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents--initial experience.

    Science.gov (United States)

    Copel, Laurian; Katz, Ran; Blachar, Arye; Sosna, Jacob; Sheiman, Robert G

    2005-12-01

    To prospectively evaluate the clinical response and hemodynamic changes in cavernosal arteries after oral administration of sildenafil without and with audiovisual sexual stimulation and to compare those responses with responses from intracavernosal injections of vasoactive agents. Institutional review board approval and written informed consent were obtained. Thirteen consecutive patients (age range, 22-77 years; mean, 60.4 years) with erectile dysfunction were evaluated with clinical assessment and cavernosal duplex ultrasonography (US). The patients were examined at two sessions 3 weeks apart. First, each patient received 100 mg of sildenafil citrate orally and was examined 60 minutes later without any sexual stimulation. Each patient then underwent repeat clinical and duplex US assessment after audiovisual sexual stimulation. Three weeks later, the patients underwent identical clinical evaluation and duplex US after intracavernosal injection of a commercially available combination of papaverine, prostaglandin E1, and phentolamine. Clinical and duplex US data (ie, peak systolic velocity [PSV]) were examined by using the Wilcoxon signed rank test for matched pairs. At rest, the overall mean cavernosal artery PSV was 1.08 cm/sec and remained unchanged after intake of sildenafil without any audiovisual stimulation, with no clinical evidence of erection. With the addition of audiovisual sexual stimulation, eight (62%) of 13 patients had penile congestion or erection, and six (46%) had a PSV greater than 25 cm/sec. With intracavernosal injection of the combination of three drugs, all 13 patients achieved congestion or erection, and 10 (77%) had a PSV greater than 25 cm/sec. Both clinical and duplex US responses to intracavernosal injection were significantly greater than they were to sildenafil with audiovisual sexual stimulation (P = .04 and .003, respectively). Oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment

  12. Sudan Journal of Medical Sciences - Vol 2, No 4 (2007)

    African Journals Online (AJOL)

    Serum calcium level as a marker of pregnancy-induced hypertension · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT ... Post Ejaculatory Effects of Sildenafil Citrate (Viagra) On Sexual Responses In Diabetic Neuropathic Men · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT ...

  13. Erectile Dysfunction Among Men Attending Surgical Outpatients ...

    African Journals Online (AJOL)

    2016-04-05

    Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in Nigerian men. Int J Impot Res. 2003;15 Suppl 1:S15‑8. 19. Heidelbaugh JJ. Management of erectile dysfunction. Am Fam. Physician 2010;81:305‑12. [Downloaded free from http://www.nigerianjsurg.com on Tuesday, April 05, 2016, IP: 41.132.79.253

  14. Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate

    NARCIS (Netherlands)

    Uckert, Stefan; Oelke, Matthias; Stief, Christian G.; Andersson, K.-E.; Jonas, Udo; Hedlund, Petter

    2006-01-01

    With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate.

  15. 2018-02-23T08:31:55Z https://www.ajol.info/index.php/all/oai oai:ojs ...

    African Journals Online (AJOL)

    article/38499 2018-02-23T08:31:55Z sjms:ART Post Ejaculatory Effects of Sildenafil Citrate (Viagra) On Sexual Responses In Diabetic Neuropathic Men Ali, S T Background: Erectile dysfunctions in diabetes are important signs probably due to ...

  16. Sexual function of males with chronic liver disease

    African Journals Online (AJOL)

    experience with sildenafil citrate (Viagra). Int J Impot. Res 2003;15(Suppl 1):S1‑2. 6. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J,. Mishra A. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822‑30. 7. Ali S, Hussain S, Hair M, ...

  17. Sex, tensions and pills : Young people’s use of contemporary reproductive and sexual health technologies in Addis Ababa, Ethiopia

    NARCIS (Netherlands)

    Both, R.E.C.

    2017-01-01

    This study sheds light on why some young men and women from diverse backgrounds in Addis Ababa use emergency contraceptive pills (ECs) and sildenafil citrate (Viagra) repeatedly, sometimes in a routinized manner. It unravels the reasons behind the frequent yet secretive purchasing of these two

  18. Sildenafil dilates ophthalmic artery in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Akeel AMH Zwain

    2013-08-01

    Full Text Available Background: Conflicting reports exist on the effect of sildenafil on ophthalmic artery blood flow; many visual disturbances due to vascular insult were reported with the use of sildenafil in diabetic patients like nonarteritic ischemic optic neuropathy. Objectives: The present work aimed to investigate whether sildenafil modulates ophthalmic artery vasoreactivity in patients with type 2 diabetes mellitus. Literature reports on this aspect are lacking. Methods: A total of 35 male subjects were enrolled in this study, 18 with type 2 diabetes mellitus matched with 17 normal individuals. Ophthalmic artery was insonated through a transorbital window using colored Doppler equipment with transcranial Doppler facility. Ophthalmic artery reactivity was assessed using breath holding/hyperventilation test, before and after giving 50 mg oral sildenafil. Results: It was found that in both normal subjects and diabetic patients, sildenafil increased baseline control of mean flow velocity of ophthalmic artery significantly (p 0.05 after sildenafil, in normal and diabetic groups. There was a significant increase of resistive index of ophthalmic artery flow in diabetic patients compared with that of normal subject (p < 0.05. Sildenafil decreased resistive index of ophthalmic artery flow significantly only in diabetic patients (p < 0.05. Conclusion: Sildenafil increased MFVopa, but had no significant effect on vasoreactivity of ophthalmic artery; sildenafil decreased resistive index only in type 2 diabetic patients.

  19. Recent developments in counterfeits and imitations of Viagra, Cialis and Levitra. A 2005-2006 update

    NARCIS (Netherlands)

    Venhuis BJ; Barends DM; Zwaagstra ME; de Kaste D; KCF

    2007-01-01

    Er wordt een sterke trend waargenomen naar steeds professionelere vervalsingen en imitaties van Viagra, Cialis en Levitra ten aanzien van het uiterlijk van de tabletten, capsules en verpakking. Deze toenemende professionele presentatie zal potentiele gebruikers misleiden aan te nemen dat deze

  20. Geochemical Fate and Transport of Sildenafil in Natural Soils

    Science.gov (United States)

    Turner, A. E.; Vulava, V. M.

    2016-12-01

    In recent years, pharmaceutical drugs have become of increasing concern to the health of our environment. As a result of wastewater treatment plant discharge and various sources of surface runoff, pharmaceuticals can be found in trace amounts in our most common water resources. Sildenafil, a drug marketed to treat erectile dysfunction, is amongst the top 20 most prescribed pharmaceutical products in the U.S. Sildenafil is a complex polar organic molecule with multiple amine functional groups, which gives it acid-base functionality. The most common pKa of this molecule is approximately 6.0 and water solubility ranges from 3.5 to 4.6 mg/L. The goal of this project is to examine the sorption and transport behavior of sildenafil in natural organic matter- (OM) and clay-rich soils. Soils used for this study were collected from undisturbed forested areas in Francis Marion National Forest, Charleston, SC. A series of batch sorption isotherm and column transport experiments were conducted with these soils. Sildenafil was analyzed using high performance liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LC-MS) techniques. Batch sorption isotherm experiments produced nonlinear data for both OM- and clay-rich soil types. The data shows that sildenafil sorbs more strongly to the clay-rich soils than to the OM-rich soils. This suggests that sildenafil behaved as a cation and preferentially sorbed with the negatively-charged clay minerals. The transport behavior of sildenafil as determined by experiments with soil-packed glass chromatography columns confirmed this behavior. The resulting breakthrough curves show that sildenafil is strongly retarded in clay-rich soils. Our studies do not show degradation or transformation of sildenafil in soils. The results from this study have strong implications for environmental management of pharmaceutical chemical effluents and disposal.

  1. Clinical deterioration after sildenafil cessation in patients with pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Anne M Keogh

    2008-10-01

    Full Text Available Anne M Keogh, Andrew Jabbour, Christopher S Hayward, Peter S MacdonaldHeart Lung Transplant Unit, St Vincent’s Hospital, Sydney, New South Wales, AustraliaAbstract: Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE-5. Its chronic administration has been shown to improve exercise capacity, World Health Organization functional class, and haemodynamics in patients with symptomatic pulmonary arterial hypertension (PAH. There is however, no data describing the clinical consequences of sudden cessation of sildenafil treatment. In this series, 9 patients with NYHA Class II–IV PAH who were stable on 2 months of sildenafil monotherapy, had their sildenafil ceased to accommodate a 2-week washout period, required for enrollment in research involving an endothelin receptor antagonist. Six minute walk distance (SMWD and clinical assessments were performed before cessation of sildenafil, and again 2 weeks later. Over the course of this 2-week washout period, 6 of the 9 patients reported increased breathlessness and fatigue, 1 of these was hospitalized with worsening right heart failure. The SMWD fell in 6 patients, with falls of greater than 100 m recorded in 4 patients. This was accompanied by a worsening of NYHA Class from 2.5 ± 0.2 to 3.1 ± 0.1 (mean ± SEM, p = 0.01. These data indicate that sudden cessation of sildenafil monotherapy, in patients with PAH, carries with it a significant and unpredictable risk of rapid clinical deterioration. We recommend that if sildenafil needs to be ceased, it would be more prudent to consider concurrent vasodilator therapy before the gradual cessation of sildenafil.Keywords: sildenafil, pulmonary hypertension, phosphodiesterase inhibitor

  2. Autonomic cerebral vascular response to sildenafil in diabetic patient

    Directory of Open Access Journals (Sweden)

    Al-Amran Fadhil G

    2012-01-01

    Full Text Available Abstract Background Erectile dysfunction is a common problem in type 2 diabetic patients who are at higher risk of cerebrovascular events, and it's recorded with sildenafil, a drug which is primarily used for erectile dysfunction. Objectives We tested the hypothesis whether or not sildenafil modulates cerebrovascular reactivity (CVR in patients with type 2 diabetes mellitus. Methods A total of 35 male participants were enrolled; eighteen with type 2 diabetes mellitus matched with seventeen normal individuals. Transcranial Doppler Ultrasonographic examination (TCD was performed for all participants to insonate the middle cerebral artery (MCA through a trans-temporal window. CVR was assessed by using breath holding (BH-hyperventilation (HV test, before and after oral 50 mg sildenafil; recordings were analyzed by using SPSS program version 12. Results In normal individuals, sildenafil did not result in statistically significant change in breath holding index (BHI from 0.91 ± 0.11 to 0.81 ± 0.09 and full range of vasodilatation (FVD from (59.4% ± 6.3% to (53.7% ± 4.9%. In diabetic patients, giving sildenafil resulted in significant increase in BHI (from 0.74 ± 0.14 to 1.03 ± 0.14 and FVD (from 60.2% ± 4.96% to 74% ± 4.8%, (p Conclusion Sildenafil significantly improves CVR in type 2 diabetic patients but not in normal subjects.

  3. Clinical predictive factors of sildenafil response: a penile hemodynamic study.

    Science.gov (United States)

    Elhanbly, S M; Elkholy, A A-M; Alghobary, M; Abou Al-Ghar, M

    2015-03-01

    Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing. © 2015 American Society of Andrology and European Academy of Andrology.

  4. Cost utility analysis of sildenafil compared with papaverine-phentolamine injections

    NARCIS (Netherlands)

    E.A. Stolk (Elly); M. Caffa; E.J. Meuleman; F.F.H. Rutten (Frans); J.J. van Busschbach (Jan)

    2000-01-01

    textabstractOBJECTIVE: To compare the cost effectiveness of sildenafil and papaverine-phentolamine injections for treating erectile dysfunction. DESIGN: Cost utility analysis comparing treatment with sildenafil (allowing a switch to injection therapy) and treatment

  5. Analisa Sildenafil Sitrat Pada Obat Tradisional Gali-Gali Dengan Metode Kromatografi Lapis Tipis

    OpenAIRE

    Arista, Indri

    2010-01-01

    Have done identification sildenafil sitrat in traditional medicine gali – gali. For determination this contained is sildenafil sitrat analysis with thin layer cromatography method, with comparison volume etil acetate : methanol : amonia (85 : 10 : 5) as mobile phase and sildenafil sitrat as solution standart. From result analysis traditional medicine gali – gali contained sildenafil sitrat. Was know that in all traditional medicine not permission contained chemical materials. So that traditi...

  6. Gaddafi vägedel lasub kahtlus massivägistamistes Viagra abil / Evelyn Kaldoja

    Index Scriptorium Estoniae

    Kaldoja, Evelyn, 1980-

    2011-01-01

    Venemaa välisministeerium teatas Moskvat külastanud Liibüa liidri Muammar Gaddafi esindajale Muhammad Ahmed al-Sharifile, et Liibüa peab järgima ÜRO Julgeolekunõukogu otsuseid ja lõpetama sõjalise jõu kasutamise tsiviilisikute vastu. Liibüast lahkus naftaminister Shukuri Ghanem. Gaddafit kahtlustatakse oma vägedele massivägistamisteks potentsiravimi Viagra jagamises. Tagaotsitavad

  7. Sildenafil normalizes bowel transit in preclinical models of constipation.

    Directory of Open Access Journals (Sweden)

    Sarah K Sharman

    Full Text Available Guanylyl cyclase-C (GC-C agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC and irritable bowel syndrome with constipation (IBS-C. Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.

  8. Viagra: la panacea para la disfunción eréctil?

    Directory of Open Access Journals (Sweden)

    María Luisa Cárdenas Muñoz

    1998-04-01

    Full Text Available En este momento se lanza al mercado un producto nuevo: el Sildenafil, Pero, hasta qué punto es segura, como para permitir asumir el costo-beneficio? EI citrato de sildenafil, es un inhibidor selectivo del monofosfato de guanosina cíclico (GMPc en los cuerpos cavernosos, De tal manera que, cuando ocurre la estimulaci6n sexual se produce un incremento del oxido nítrico, por la inhibición que ejerce el sildenafil sobre la fosfodiesterasa tipo 5 impidiendo la degradaci6n del GMPc, permitiendo la relajación del musculo liso y facilitando por lo tanto el llenado sanguíneo de los cuerpos cavernosos. Se absorbe por vía oral, logrando una biodisponibilidad del 40%. Las concentraciones máximas se logran en un tiempo que oscila entre los 30 y los 120 minutos con un promedio de 60 minutos.

  9. The Magic Pill: The Branding of Impotence and the Positioning of Viagra as Its Solution through Edutainment.

    Science.gov (United States)

    Gesser-Edelsburg, Anat; Hijazi, Rana

    2018-02-13

    Product placement can be presented through edutainment. A drug such as Viagra is introduced or impotence is branded in movies and TV series in different ways to raise awareness of impotence disorder and Viagra as a solution. This study aims to analyze strategies of framing and branding Viagra and impotence disorder, based on a qualitative method analysis of 40 movies and TV series. Findings show that Viagra is shown as not only for older men but also for young and healthy men. Out of 40 movies and TV series in the study sample, in 14 (32.5%), the age of the target audience ranged from 20 to 40 years, in 12 (31.6%) movies and series, the age of the target audience was over 40, and in 12 (31.6%) movies and series, the target audience was very old (over 70). Viagra is shown as not only treating impotence but is presented as a wonder drug that provides a solution for psychological and social needs. The movies show usage instructions, side effects, and risks, and how to store the drug. We recommend that the viewing audience be educated for critical viewing of movies/series in order to empower viewers and give them tools for their decision-making processes concerning their health.

  10. Hepatic histological alterations and biochemical changes induced by sildenafil overdoses.

    Science.gov (United States)

    Jarrar, Bashir Mahmoud; Almansour, Mansour Ibrahim

    2015-11-01

    Sildenafil is used for the treatment of erectile dysfunction and is helping millions of men around the world to achieve and maintain a long lasting erection. Fifty healthy male rabbits (Oryctolagus cuniculus) were used in the present study and exposed daily to sildenafil (0, 1, 3, 6, 9 mg/kg) for 5 days per week for 7 weeks to investigate the biochemical changes and alterations in the hepatic tissues induced by this drug overdosing. In comparison with respective control rabbits, sildenafil overdoses elevated significantly (p-value<0.05, ANOVA test) alanine aminotransferase (ALT), aspartate aminotransferase (AST), testosterone, follicular stimulating hormone and total protein, while creatinine and urea were lowered with no significant alteration was observed in uric acid and luteinizing hormone concentration. Also sildenafil provoked hepatocytes nuclear alterations, necrosis, hydropic degeneration, bile duct hyperplasia, Kupffer cells hyperplasia, inflammatory cells infiltration, hepatic vessels congestion and evident partial depletion of glycogen content. The results show that subchronic exposure to sildenafil overdoses exhibits significant biochemical and alterations in the hepatic tissues that might affect the functions of the liver and other vital organs.

  11. Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Gupta, Saurabh; Nilsson, Elisabeth

    2012-01-01

    Phosphodiesterase 5 (PDE5) is associated with migraine pathophysiology, stroke recovery and vasospasm treatment. The potential vascular interplay of PDE5 inhibitors sildenafil, tadalafil and UK-114,542 was studied by intra- versus extra-luminal administration in rat middle cerebral arteries...... in vitro and on middle meningeal arteries in vivo. By Western blot PDE5 was detected in both cerebral and meningeal arteries, though with minor variations in band intensity between vascular beds. Rat middle cerebral artery diameter was investigated using pressurised arteriography, applying UK-114......,542, sildenafil, and tadalafil intra- or extra-luminally. Effects on the dural middle meningeal artery were studied in the in vivo closed cranial window model. At high concentrations, abluminal sildenafil and UK-114,542, but not tadalafil, induced dilatation of the middle cerebral artery. Luminal application...

  12. Physical profile of counterfeit tablets Viagra® and Cialis®

    Directory of Open Access Journals (Sweden)

    Rafael Scorsatto Ortiz

    2012-09-01

    Full Text Available The profile of tablets containing an active pharmacological ingredient can be obtained using different sets of properties, including physical and chemical aspects. The first measurements carried out on tablets are the physical characteristics also called post-tabletting batch (post-TB characteristics. These data may be valuable to assist in the detection of pharmaceutical product forgery and may also be used in a forensic intelligence perspective when inserted into databases. This work is focused on the physical characteristics of Cialis® and Viagra® tablets seized by the Brazilian Federal Police in the Rio Grande do Sul state. Using the F-test (ANOVA, all samples of counterfeit Viagra® (n = 28 and Cialis® (n = 40 were well distinguished from authentic samples by the following post-TB characteristics: length (major and minor, thickness, and mass. Using the exploratory statistical technique of Hierarchical Cluster Analysis (HCA, tablets with similar physical profiles were grouped. This result may indicate a common illicit production. We observed the validity of using post-TB properties to generate - in a fast and reliable manner and with no sample preparation - a technological profile that joins itself to the other analytical methods assisting in routine forensic detection of counterfeit Viagra® and Cialis®.Perfil para medicamentos na forma farmacêutica comprimidos contendo uma substância ativa pode ser obtido usando diferentes conjuntos de propriedades, incluindo aspectos físicos e químicos. As primeiras medições realizadas em comprimidos são de características físicas, também chamadas características pós-compressão. Tais dados podem ser valiosos para auxiliar na detecção de falsificações de medicamentos e ser utilizados em uma perspectiva de inteligência forense, quando inseridos em bancos de dados. Este trabalho está focado nas características físicas dos comprimidos de Cialis® e Viagra® apreendidos pela Pol

  13. 21 CFR 582.5449 - Manganese citrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  14. 21 CFR 184.1449 - Manganese citrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Manganese citrate. 184.1449 Section 184.1449 Food... Specific Substances Affirmed as GRAS § 184.1449 Manganese citrate. (a) Manganese citrate (Mn3(C6H5O7)2, CAS... manganese carbonate from manganese sulfate and sodium carbonate solutions. The filtered and washed...

  15. In vitro assessment of mouse fetal abdominal aortic vascular function

    OpenAIRE

    Renshall, Lewis J.; Dilworth, Mark R.; Greenwood, Susan L.; Sibley, Colin P.; Wareing, Mark

    2014-01-01

    Fetal growth restriction (FGR) affects 3?8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivit...

  16. Determination of mirodenafil and sildenafil in the plasma and corpus cavernous of SD male rats.

    Science.gov (United States)

    Lee, Sang Kyu; Kim, Yoon; Kim, Tae Kon; Im, Guang-Jin; Lee, Bong-Yong; Kim, Dong-Hyun; Jin, Changbae; Yoo, Hye Hyun

    2009-02-20

    The purpose of the present study was to determine sildenafil and a novel PDE-5 inhibitor, mirodenafil in the plasma and corpus cavernosum tissue of rats to compare their pharmacokinetic properties. The concentrations of mirodenafil and sildenafil in the rat plasma and corpus cavernosum tissue samples were analyzed using LC-MS/MS after a single oral administration at a dose of 40mg/kg to rats. Although the T(max), Tlambda(1/2) and MRT were not different between mirodenafil and sildenafil, the C(max) and AUC of mirodenafil were significantly higher than those of sildenafil in the plasma and corpus cavernosum tissue. Consequently mirodenafil remained longer than sildenafil in the plasma and tissue. This may provide pharmacokinetic evidence for assessment of the in vivo efficacy of mirodenafil and sildenafil.

  17. From cellulite to smooth skin: is Viagra the new dream cream?

    Science.gov (United States)

    Altabas, Karmela; Altabas, Velimir; Berković, Maja Cigrovski; Rotkvić, Vanja Zjacić

    2009-07-01

    In this article, we provide a hypothesis considering the potential effect of phosphodiesterase 5a inhibitors on cellulite. Cellulite is a significant cosmetic problem for many post-adolescent women. Its pathophysiology is complex and involves the presence of excess subcutaneous fat, the microcirculatory system, lymphatics and the extracellular matrix. Many diverse treatments have been tested to treat cellulite like iontophoresis, ultrasound, thermotherapy, pressotherapy, lymphatic drainage and electrolipophoresis which all enhance skin microcirculation. There have been several attempts to treat cellulite with drugs, but results were insufficient. Phosphodiesterases (PDE) are a superfamily of enzymes degrading adenosine monophosphate (cAMP) and cyclic guanosine monophoshpate (cGMP). Human fat cell lipolysis is mediated by both cAMP- and cGMP-dependent protein kinases. Indeed, high dose sildenafil pretreatment led to increased lipolysis in adipocyte cultures. That effect could not be attributed exclusively to either PDE3b or PDE5a inhibition, since sildenafil inhibited about 50% of the PDE3b activity in pretreated adipocytes. Sildenafil has a potential beneficial effect on skin microcirculation, as well as on tissue hypoxia. Transdermal or local route of administration should be considered.

  18. Cerebral venous sinus thrombosis following sildenafil administration; a case report

    Directory of Open Access Journals (Sweden)

    Daryoosh Afshari

    2010-09-01

    Full Text Available Background: Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5 which currently used for the treatment of erection dysfunction (ED. Medicine approved by the FDA for treatment of pulmonary hypertension. Although there is no evidence of hypercoagulation states being associated with the use of PDE5 inhibitors, several animal studies suggest that PDE5 inhibitors may cause arterial and venous thrombotic or embolic events. Case report: The patient was a 37 year old man who had suffered sever headache and tonic- clonic generalized seizure. In neurological examination, he had decreased level of consciousness and he had no other positive finding in examination. The patient has been constantly taken 100 mg of Sildenafil once a day without medical supervision over the last month. Brain computerized tomography (CT showed a small hemorrhage in left frontal lobe with suspicious to cerebral venous sinus thrombosis (CVST lumbar puncture was performed. Increased cerebrospinal fluid pressure suggested the probability of CVST. Brain MRI result confirmed superior sagittal sinus thrombosis. Conclusion: Cerebral venous sinus thromboses need to be considered a potential side effect of Sildenafil administration.

  19. Sildenafil During Pregnancy A Preclinical Meta-Analysis on Fetal Growth and Maternal Blood Pressure

    NARCIS (Netherlands)

    Paauw, Nina D.; Terstappen, Fieke; Ganzevoort, Wessel; Joles, Jaap A.; Gremmels, Hendrik; Lely, A. Titia

    2017-01-01

    Sildenafil is a new approach to treat fetal growth restriction (FGR) and preeclampsia. We performed a systematic meta-analysis to evaluate effects of sildenafil. Our search identified 22 animal studies (mouse, rat, rabbit, sheep, and guinea pigs) and 2 human randomized controlled trials. Data were

  20. Sildenafil during Pregnancy : A Preclinical Meta-Analysis on Fetal Growth and Maternal Blood Pressure

    NARCIS (Netherlands)

    Paauw, Nina D.|info:eu-repo/dai/nl/413968596; Terstappen, Fieke; Ganzevoort, Wessel; Joles, Jaap A.|info:eu-repo/dai/nl/070114595; Gremmels, Hendrik|info:eu-repo/dai/nl/345485076; Lely, A. Titia|info:eu-repo/dai/nl/30474719X

    2017-01-01

    Sildenafil is a new approach to treat fetal growth restriction (FGR) and preeclampsia. We performed a systematic meta-analysis to evaluate effects of sildenafil. Our search identified 22 animal studies (mouse, rat, rabbit, sheep, and guinea pigs) and 2 human randomized controlled trials. Data were

  1. Oxytocin is involved in the proconvulsant effects of Sildenafil: Possible role of CREB.

    Science.gov (United States)

    Khoshneviszadeh, Mahsima; Rahimian, Reza; Fakhfouri, Gohar; Payandemehr, Borna; Khodagholi, Fariba; Ejtemaei Mehr, Shahram; Dehpour, Ahmad Reza

    2016-08-10

    Sildenafil is a phosphodiesterase type 5 inhibitor mainly used for male erectile dysfunction. One of rare yet serious adverse effects of Sildenafil is its potential to decrease seizure threshold. Ample evidence suggests that Sildenafil exerts central effects through induction of Oxytocin (OT) secretion and CREB phosphorylation. The aim of the present study is to evaluate potential roles of OT and CREB in the proconvulsant effects of Sildenafil. The Pentylenetetrazole-induced seizure was used as a standard convulsion model in this study. OT release and pCREB expression were evaluated in the hippocampus of mice using ELISA and western blot assays, respectively. Our results showed that Sildenafil at the dose of 10mgkg(-1) or higher, significantly decreased seizure threshold. Pretreatment with a non-effective dose of OT, potentiated while OT receptor antagonist, Atosiban, reversed fully the proconvulsant effects of Sildenafil (5mgkg(-1)). At biochemical inspection, Sildenafil markedly increased CREB which was attenuated by coadministration of Atosiban. The present study shows for the first time that OT release and the subsequent CREB phosphorylation are involved in the proconvulsant effects of acute Sildenafil treatment in an experimental model of seizure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Ranitidine bismuth citrate: A review

    Directory of Open Access Journals (Sweden)

    N Chiba

    2001-01-01

    Full Text Available Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC, a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.

  3. The Emergence of Viagra in the Brazilian Public Scenario: Discourses on Body, Gender and Sexuality in the Media

    Directory of Open Access Journals (Sweden)

    Mauro Brigeiro

    2009-01-01

    Full Text Available This work proposes an anthropological reflection on the images and discourses of the body and the sexuality in the Brazilian society, focusing on a particular social phenomenon: the emergence of the Viagra in the national public scenario. This article explores the connotations constructed and confirmed by the Brazilian media press about this drug. Two Brazilian newspapers belonging to the same publisher but aimed at different publics were analyzed from April 1998 to April 1999, period that corresponds to the beginning – and apex – of the debate on the Viagra in the country. The discussion focuses on the symbolism and discursive strategies utilized by the newspapers when presenting this medication to the general public. This article also draws the attention to an appeal to traditional logics of gender, despite a contemporary scenario of issues concerning the relationships among the sexes and the sexuality.

  4. Arthropod venom citrate inhibits phospholipase A2.

    Science.gov (United States)

    Fenton, A W; West, P R; Odell, G V; Hudiburg, S M; Ownby, C L; Mills, J N; Scroggins, B T; Shannon, S B

    1995-06-01

    Citrate has been identified as a major component of honey bee (Apis mellifera) venom by gas liquid chromatography-mass spectrometry. A citrate concentration of 9% was found for dried bee venom by a coupled enzyme assay, aconitase-isocitric dehydrogenase. A liquid honey bee venom would contain 140 mM citrate concentration (if the solids content were 30%). Bee venom phospholipase was inhibited at a 43% level with a citrate concentration of 20 mM and calcium ion at 3 mM with the enzyme assay. Citrate was also found in the venoms of bumble bee, Bombus fervidus, 7%; yellow jacket, Vespula maculifrons, 4%; scorpion, Centruroides sculpturatus, 8%; tarantula, Grammastola cala, 8% and brown recluse spider venom gland extract, Loxoceles reclusa, 1.5% based on dried venom solids. Citrate may serve as an endogenous inhibitor of divalent metal ion-dependent enzymes in arthropod venoms as described by Francis et al. (1992, Toxicon 30, 1239-1246). Many arthropod venoms contain calcium-dependent phospholipases. A direct effect of citrate as a venom component may be possible. The presence of citrate in venoms must be considered in research on receptors, ion channels and divalent ion-dependent toxins.

  5. Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2014-01-01

    Category: Pain Mechanisms and Sensory Neuroscience Keywords: Tinnitus, Blast, Traumatic brain injury, Sildenafil ( Viagra , Revatio), Hyperacusis...optimize therapeutic effects. Key words: Tinnitus, Blast, Traumatic brain injury, Sildenafil ( Viagra , Revatio), Hyperacusis, Rat 1 2 3...HearRes 147:282-292. Khan AS, Sheikh Z, Khan S, Dwivedi R, Benjamin E (2011) Viagra deafness--sensorineural hearing loss and phosphodiesterase-5

  6. Patient preference and satisfaction in erectile dysfunction therapy: a comparison of the three phosphodiesterase-5 inhibitors sildenafil, vardenafil and tadalafil

    Directory of Open Access Journals (Sweden)

    Amr Abdel Raheem

    2009-04-01

    Full Text Available Amr Abdel Raheem1, Philip Kell21St. Peter’s Andrology Department, The Institute of Urology, London, and Cairo University, Egypt; 2St. Peter’s Andrology Department, The Institute of Urology, London, UKAbstract: Erectile dysfunction (ED is a problem that may affect up to 52% of men between the ages of 40 and 70. It can be distressing because of its negative effect on self-esteem, quality of life, and interpersonal relationships. Oral phosphodiesterase-5 inhibitors (PDE5 inhibitors are now the first choice of treatment in ED. The availability of three (sildenafil citrate, tadalafil, and vardenafil well tolerated and effective oral PDE5 inhibitors gives treatment options for men with ED. Although the mechanism of action is the same for the three drugs, they differ in their pharmacokinetics. Several preference studies were conducted between the three PDE5 inhibitors but they were not free from bias. Because of the lack of overwhelming reliable data showing that one PDE5 inhibitor is superior to another, current opinion is that the individual patient should have the opportunity to test all three drugs and then select the one that best suits him and his partner.Keywords: erectile dysfunction, PDE5 inhibitors, patient preference

  7. Resposta pressórica de pacientes com miocardiopatia chagásica ante o uso do sildenafil Pressure response in chagasic cardiomyopathy patients after using sildenafil

    Directory of Open Access Journals (Sweden)

    Rodrigo Abensur Athanazio

    2007-03-01

    Full Text Available OBJETIVO: Verificar o efeito do sildenafil na pressão arterial (PA e freqüência cardíaca (FC de indivíduos portadores de miocardiopata chagásica (MCC e de disfunção ventricular sistólica grave (FEOBJECTIVE: To accurately verify the effect of Sildenafil on blood pressure (BP and heart rate (HR in individuals with Chagasic myocardiopathy (CMC and severe systolic ventricular dysfunction (EF<40% submitted to physical activity. METHODS: Twelve men with ejection fractions <40% and CMC confirmed by a serological test were assessed. The six-minute walk test (6MWT was performed before and after administration of 50 mg of Sildenafil, with a 30 minute interval. Heart rate (HR, systolic blood pressure (SBP and diastolic blood pressure were taken and compared before and after each 6MWT. For statistical analysis purposes, the study was divided into four stages: before the 6MWT and administration of Sildenafil (S1; after the 6MWT but before the administration of Sildenafil (S2; after the administration of Sildenafil but before the 6MWT (S3; and after the administration of Sildenafil and the 6MWT (S4. RESULTS: Participant ages ranged from 47 to 68 years (57.6 ± 6.4. SBP and DBP after the 6MWT and the administration of Sildenafil (S4 were lower than before taking the drug (S2: 134.2 ± 15.1 versus 125.5 ± 14.0 and 88.4 ± 12.4 versus 83.0 ± 10.8, respectively. None of the patients reported any symptoms during the 6MWT. There were no differences in the distances walked during the 6MWT before or after taking Sildenafil (487.5±15.22 versus 505.3±18.45 meters, respectively-p=0.056, or in HR (before Sildenafil 75.5 ± 8.79 and 96.8 ± 10.36 bpm and after 77.1 ± 9.81 and 96.1 ± 12.97 bpm. CONCLUSION: Based on these results, it can be concluded that both prediction equations significantly overestimated HRmax measured during maximal GXT in Brazilian elderly women, a finding that may have important implications when prescribing exercise intensity for this

  8. Sildenafil Improves Erectile Function in Men with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Niloufar Samiei

    2015-06-01

    Full Text Available Background: Patients with Chronic Heart Failure (CHF have been shown to have enhanced risk of Erectile Dysfunction (ED due to low cardiac output, endothelial dysfunction, medications, co-morbid conditions, and psychogenic factors. Objectives: The present study aimed to evaluate the effects of sildenafil on erectile function of patients with stable CHF using the abridged 5-item version of the International Index of Erectile Function (IIEF-5. Patients and Methods: Using convenience sampling, 222 sexually-active adult males with NYHA class I-III stable CHF were included in this cross-sectional study. All the patients filled out the IIEF-5 questionnaire, in which they were required to score the five domains of male sexual function, including erectile function, orgasm function, sexual desire, intercourse satisfaction, and overall satisfaction. All the analyses were performed using the SPSS statistical software (v. 19 and P < 0.05 was considered as statistically significant. Results: In our sample, the patients’ mean age was 47.14 ± 11.86 years, their mean left ventricular ejection fraction was 20% (15% - 25%, and the prevalence of ED was 70.3%. In addition, severe, moderate, mild to moderate, and mild ED were seen in 57%, 17%, 7%, and 19% of the patients with ED, respectively. ED was significantly more prevalent in the patients with ischemic heart failure compared to those with idiopathic dilated cardiomyopathy (84.68% vs. 55.85%, P < 0.001. Moreover, the prevalence of ED was significantly lower in the patients taking sildenafil compared to the other group (42.85% vs. 82.89%, P < 0.001. Conclusions: Sildenafil appears to provide satisfactory results toward improving sexual function in patients with CHF.

  9. Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome.

    Science.gov (United States)

    Miwa, Kenji; Matsubara, Takashi; Uno, Yoshihide; Yasuda, Toshihiko; Sakata, Kenji; Tsuda, Toyonobu; Kanaya, Honin

    2007-05-01

    Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.

  10. Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gautam V Ramani

    2010-05-01

    Full Text Available Gautam V Ramani, Myung H ParkUniversity of Maryland, Baltimore, MD, USAAbstract: Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH. The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. Keywords: sildenafil, pulmonary arterial hypertension, phosphodiesterase type 5 inhibitor

  11. 21 CFR 522.800 - Droperidol and fentanyl citrate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

  12. Anaphylaxis related to fentanyl citrate

    Directory of Open Access Journals (Sweden)

    Gaurav Singh Tomar

    2012-01-01

    Full Text Available Anaphylaxis is a fulminant, unexpected, immunoglobulin E-mediated allergic reaction that can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl citrate, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was in one of the patient. An adverse drug reaction is a noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Reactions are classified into two major subtypes: type A, which are dose dependent and predictable; and type B, which are not dose dependent and unpredictable. Unpredictable reactions include immune (allergic or no immune drug hypersensitivity reactions and are related to genetic susceptibilities or undefined mechanisms (formally called idiosyncratic and intolerance reactions. A drug allergy is always associated with an immune mechanism for which evidence of drug-specific antibodies or activated T lymphocytes can be shown. In the last few years, many novel drugs have entered clinical practice (i.e., biologic agents generating novel patterns of drug hypersensitivity reactions. As old drugs continue to be used, new clinical and biologic techniques enable improvement in the diagnosis of these reactions.

  13. Treatment of norovirus particles with citrate.

    Science.gov (United States)

    Koromyslova, Anna D; White, Peter A; Hansman, Grant S

    2015-11-01

    Human norovirus is a dominant cause of acute gastroenteritis around the world. Several norovirus disinfectants label citric acid as an active ingredient. In this study, we showed that norovirus virus-like particles (VLPs) treated with citrate buffer caused the particles to alter their morphology, including increased diameters associated with a new ring-like structure. We also found that epitopes on the protruding (P) domain on these particles were more readily accessible to antibodies after the citrate treatment. These results suggested that citrate had a direct effect on the norovirus particles. Using X-ray crystallography, we showed that the P domain bound citrate from lemon juice and a disinfectant containing citric acid. Importantly, citrate binds at the histo-blood group antigen binding pocket, which are attachment factors for norovirus infections. Taken together, these new findings suggested that it might be possible to treat/reduce norovirus infections with citrate, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Sildenafil after cardiac arrest and infarction; an experimental rat model.

    Science.gov (United States)

    Mennander, Ari A; Vuohelainen, Vilma; Aanismaa, Riikka S; Narkilahti, Susanna; Paavonen, Timo; Tarkka, Matti

    2013-02-01

    Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model. Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology. Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p cardiac arrest and ischemia.

  15. Performance of some supervised and unsupervised multivariate techniques for grouping authentic and unauthentic Viagra and Cialis

    Directory of Open Access Journals (Sweden)

    Michel J. Anzanello

    2014-09-01

    Full Text Available A typical application of multivariate techniques in forensic analysis consists of discriminating between authentic and unauthentic samples of seized drugs, in addition to finding similar properties in the unauthentic samples. In this paper, the performance of several methods belonging to two different classes of multivariate techniques–supervised and unsupervised techniques–were compared. The supervised techniques (ST are the k-Nearest Neighbor (KNN, Support Vector Machine (SVM, Probabilistic Neural Networks (PNN and Linear Discriminant Analysis (LDA; the unsupervised techniques are the k-Means CA and the Fuzzy C-Means (FCM. The methods are applied to Infrared Spectroscopy by Fourier Transform (FTIR from authentic and unauthentic Cialis and Viagra. The FTIR data are also transformed by Principal Components Analysis (PCA and kernel functions aimed at improving the grouping performance. ST proved to be a more reasonable choice when the analysis is conducted on the original data, while the UT led to better results when applied to transformed data.

  16. Erection problems

    Science.gov (United States)

    ... options. Pills you take by mouth, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). They work only ... the muscle. ED pills you take by mouth (Viagra, Levitra, or Cialis) can have side effects. These ...

  17. Hidden Risks of Erectile Dysfunction "Treatments" Sold Online

    Science.gov (United States)

    ... several such "dietary supplements" (see sidebar for list). Viagra Ingredient Found Working with other FDA components, the ... similar substances. Six of the 17 products contained sildenafil (the active ingredient in Viagra) or a substance ...

  18. "Off-Label" Drug Use

    Science.gov (United States)

    ... Inderal), high blood pressure, heart disease Stage fright Sildenafil (Viagra), erectile dysfunction To enhance sexual performance in people ... Should kids take statin drugs? Should women take Viagra? Should you take antidepressants for hot flashes? Statins ...

  19. Sexual Dysfunction in Women

    Science.gov (United States)

    ... for you.You may have heard that taking sildenafil (Viagra) or the male hormone testosterone can help women ... not been many studies on the effects of Viagra or testosterone on women, so doctors do not ...

  20. Combined sildenafil with vacuum erection device therapy in the management of diabetic men with erectile dysfunction after failure of first-line sildenafil monotherapy.

    Science.gov (United States)

    Sun, Lu; Peng, Fang-Li; Yu, Zhi-Ling; Liu, Cai-Ling; Chen, Jun

    2014-12-01

    To evaluate the efficacy and safety of combination therapy of sildenafil plus vacuum erection devices in men with type 2 diabetes mellitus with moderate to severe erectile dysfunction who are dissatisfied with the results of using sildenafil alone. The study included 66 diabetes mellitus patients presenting erectile dysfunction for at least 6 months and dissatisfied with the use of 100 mg sildenafil monotherapy. The patients were randomized in two groups. Those in group A (n = 33) were instructed to use a vacuum erection device only, whereas those in group B (n = 33) were treated with combination therapy, including sildenafil 100 mg and a vacuum erection device. Erectile function was evaluated subjectively using the International Index of Erectile Function, Sexual Encounter Profile questionnaire questions 2 and 3 at visit 1 (baseline; study entry), visit 2 (4 weeks after baseline), and visit 3 (12 weeks after baseline; study end). There were no significant differences in average patient age, duration of diabetes, duration of erectile dysfunction, baseline International Index of Erectile Function scores, hypertension, blood testosterone, smoking and alcohol consumption between two groups. Mean International Index of Erectile Function scores were significantly higher for group B at the 1-month (14.86 ± 2.17 vs 12.41 ± 2.63; P erectile function, and it is well tolerated by diabetes mellitus patients not responding to first-line sildenafil alone. © 2014 The Japanese Urological Association.

  1. Automated flow system for sildenafil enrichment using surfactant coated solid-phase with fluorescence detection.

    Science.gov (United States)

    Wang, Chien Chun; Sombra, Lorena; Fernández, Liliana

    2012-08-30

    In this work, Amberlite XAD-1180 resin is used for on-line surfactant-mediated pre-concentration of sildenafil as a prior step for its fluorescent detection. In order to activate the column for sildenafil pre-concentration, the cationic surfactant (hexadecyltrimethylammoniunm bromide, HTAB) is adsorbed onto the resin. In these conditions, sildenafil is retained by HTAB-resin and then it is eluted with ethanol and analyzed by spectrofluorimetry. Drug-surfactant association produces a considerable fluorescence enhancement, increasing considerably the sensitivity of detection. Therefore, sildenafil can be pre-concentrated and quantitatively determined, with a detection limit of 0.2 ng mL(-1). The proposed method was successfully applied to the analysis of bulk drug, human urine, tablets, and local herbal medicine. Validation processes were performed by recovering studies and statistical analysis with satisfactory results. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial

    National Research Council Canada - National Science Library

    Blanco, Isabel; Santos, Salud; Gea, Joaqím; Güell, Rosa; Torres, Ferran; Gimeno-Santos, Elena; Rodriguez, Diego A; Vilaró, Jordi; Gómez, Begona; Roca, Josep; Barberà, Joan Albert

    2013-01-01

    ... rehabilitation in patients with COPD and increased pulmonary arterial pressure (PAP). In this double-blind, randomised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months...

  3. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S

    2004-01-01

    whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from......Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

  4. Regional citrate anticoagulation for pediatric CRRT using integrated citrate software and physiological sodium concentration solutions.

    Science.gov (United States)

    Liet, Jean-Michel; Allain-Launay, Emma; Gaillard-LeRoux, Bénédicte; Barrière, François; Chenouard, Alexis; Dejode, Jean-Marc; Joram, Nicolas

    2014-09-01

    In continuous renal replacement therapy (CRRT), regional citrate anticoagulation offers an attractive alternative to heparinization, especially for children with a high bleeding risk. We report on a new management approach to CRRT using integrated citrate software and physiological sodium concentration solutions. Convective filtration was performed with pre-filter citrate anticoagulation using an 18 mmol/L citrate solution and a post-filter replacement fluid. The citrate flow rate was automatically adjusted to the blood flow rate by means of integrated citrate software. Similarly, calcium was automatically infused into children to maintain their blood calcium levels within normal range. Eleven CRRT sessions were performed (330 h) in seven critically ill children aged 3-15 years (extreme values 15-66 kg). Disease categories included sepsis with multiorgan dysfunction (n = 2) and hemolytic uremic syndrome (n = 5). Median effluent dose was 2.1 (extreme values 1.7-3.3) L/h/1.73 m2. No session had to be stopped because of metabolic complications. Calcium levels, both in the circuits and in the circulating blood of the children, remained stable and secure. Regional citrate anticoagulation can be used in children with a body weight of >15 kg using integrated citrate software and commercially available solutions with physiological sodium concentrations in a safe, effective and convenient procedure.

  5. Citrate Uptake in Exchange with Intermediates in the Citrate Metabolic Pathway in Lactococcus lactis IL1403

    NARCIS (Netherlands)

    Pudlik, Agata M.; Lolkema, Juke S.

    Carbohydrate/citrate cometabolism in Lactococcus lactis results in the formation of the flavor compound acetoin. Resting cells of strain IL1403(pFL3) rapidly consumed citrate while producing acetoin when substoichiometric concentrations of glucose or L-lactate were present. A proton motive force was

  6. Rerouting Citrate Metabolism in Lactococcus lactis to Citrate-Driven Transamination

    NARCIS (Netherlands)

    Pudlik, Agata M.; Lolkema, Juke S.

    Oxaloacetate is an intermediate of the citrate fermentation pathway that accumulates in the cytoplasm of Lactococcus lactis ILCitM(pFL3) at a high concentration due to the inactivation of oxaloacetate decarboxylase. An excess of toxic oxaloacetate is excreted into the medium in exchange for citrate

  7. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  8. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

    Science.gov (United States)

    Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

    2017-07-04

    Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start

  9. Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction: the Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction (SIDAMI) trial

    DEFF Research Database (Denmark)

    Andersen, Mads Jønsson; Ersboll, M; Axelsson, Anders

    2013-01-01

    BACKGROUND: Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients...... with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9...... but was unchanged in the placebo group. CONCLUSIONS: Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies....

  10. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Kiso, Hironori [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ohba, Takayoshi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University Graduate School of Medicine (Japan); Ono, Kyoichi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Watanabe, Hiroyuki, E-mail: hirow@doc.med.akita-u.ac.jp [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ito, Hiroshi [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan)

    2013-07-05

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.

  11. Why a combined intracavernosal injection with trimix and oral sildenafil is reliable therapy in the ultrasonographic evaluation of erectile dysfunction

    National Research Council Canada - National Science Library

    Park, Jong Kwan; Park, Jung Sun; Jeon, Sang Bong; Cui, Wan Shou; Kim, Sung Zoo; Kang, Kyung Koo; Lee, Sung Won

    2008-01-01

    ... correlating with haemodynamic changes in the cavernosal arteries after an intracavernosal injection (ICI) with vasoactive agents with or without oral sildenafil in men with erectile dysfunction...

  12. Index to FAA Office of Aerospace Medicine Reports: 1961 Through 2006

    Science.gov (United States)

    2007-01-01

    RJ, Johnson RD, Blank CL: A novel method for the determination of sildenafil ( Viagra ®) and its metabolite in postmortem specimens using LC/MS/MS and...Sildenafil ( Viagra ®) and Its metabolite (UK-103,320) in six aviation fatalities. 06-4 Goldman SM, Manning C, Pfleiderer E: Static sector...during angular acceleration, 73-17 ...selegiline metabolites, 97-14 …sildenafil ( Viagra ), method for detecting in postmortem samples, 00-20, 06-3

  13. Sildenafil treatment in a nonsevere hypertensive murine model lowers blood pressure without reducing fetal growth.

    Science.gov (United States)

    Roberts, Robyn P; Refuerzo, Jerrie S; Ferrari, Francesca; Ontiveros, Alejandra E; Tamayo, Esther H; Sibai, Baha M; Blackwell, Sean C; Longo, Monica

    2016-09-01

    Treatment of nonsevere hypertension during pregnancy is controversial. Sildenafil is a phosphodiesterase inhibitor that potentiates nitric oxide by promoting vasodilation. Nitric oxide plays a vital role in mediating the vascular adaptations during pregnancy. The objective of the study was to determine whether treatment with sildenafil during pregnancy would lower maternal systolic blood pressure without adversely affecting fetal growth. Females with nonsevere hypertension (endothelial nitric oxide synthase(+/-)) were cross-bred with normotensive wild-type males. At gestational day 1, pregnant dams were randomized to either sildenafil (0.4 mg/mL per day, comparable dose used in human pregnancy) or water for 3 weeks. Four groups were then generated: wild type (n = 7), wild type-sildenafil (n = 11), endothelial nitric oxide synthase(+/-) (n = 8), and endothelial nitric oxide synthase(+/-)sildenafil (n = 7). On gestational day 18, systolic blood pressure was measured. Dams were killed, fetal and placental weights were obtained, and carotid arteries were dissected to measure in vitro vascular reactivity with a wire-myography system. Responses to phenylephrine, L-NG-nitroarginine methyl ester, acetylcholine, and sodium nitroprusside were studied. Mean systolic blood pressure was elevated in the endothelial nitric oxide synthase(+/-) dams compared with wild-type controls (P = .03). Treatment with sildenafil decreased systolic blood pressure in the endothelial nitric oxide synthase(+/-)-treated dams compared with nontreated endothelial nitric oxide synthase(+/-) dams (P = .03). No differences were seen in the wild-type dams with or without sildenafil (P = .47). Fetuses from endothelial nitric oxide synthase(+/-) dams were smaller compared with wild-type controls (P vascular contraction induced by phenylephrine was blunted in endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with nontreated endothelial nitric oxide synthase(+/-) dams (P

  14. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis.

    Science.gov (United States)

    Gong, Binbin; Ma, Ming; Xie, Wenjie; Yang, Xiaorong; Huang, Yongming; Sun, Ting; Luo, Yanping; Huang, Jiao

    2017-10-01

    Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED. We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0. A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil. Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.

  15. Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology.

    Science.gov (United States)

    Morchi, Gira S; Ivy, D Dunbar; Duster, Mark C; Claussen, Lori; Chan, Kak-Chen; Kay, Joseph

    2009-04-01

    OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. DESIGN: A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t-tests were used for statistical analyses. PATIENTS: Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m(2) prior to starting sildenafil. RESULTS: Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre-treatment vs. 91.0 ± 5.5% post-treatment, P = .017). In the four out of five patients who have had follow-up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre-treatment vs. 13.8 ± 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular resistance pre- and post-sildenafil treatment (3.5 ± 1.0 Wood units × m(2) pre-treatment vs. 2.0 ± 0.4 Wood units × m(2) post-treatment, P = .031). CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.

  16. Neuroprotective effects of sildenafil in experimental spinal cord injury in rabbits

    Directory of Open Access Journals (Sweden)

    Hasan Kara

    2015-01-01

    Full Text Available Neuroprotective agents such as methylprednisolone and sildenafil may limit damage after spinal cord injury. We evaluated the effects of methylprednisolone and sildenafil on biochemical and histologic changes after spinal cord injury in a rabbit model. Female New Zealand rabbits (32 rabbits were allocated to 4 equal groups: laminectomy only (sham control or laminectomy and spinal trauma with no other treatment (trauma control or treatment with either methylprednisolone or sildenafil. Gelsolin and caspase-3 levels in cerebrospinal fluid and plasma were determined, and spinal cord histology was evaluated at 24 hours after trauma. There were no differences in mean cerebrospinal fluid or plasma levels of caspase-3 between the groups or within the groups from 0 to 24 hours after injury. From 0 to 24 hours after trauma, mean cerebrospinal fluid gelsolin levels significantly increased in the sildenafil group and decreased in the sham control and the trauma control groups. Mean plasma gelsolin level was significantly higher at 8 and 24 hours after trauma in the sildenafil than other groups. Histologic examination indicated that general structural integrity was better in the methylprednisolone in comparison with the trauma control group. General structural integrity, leptomeninges, white and grey matter hematomas, and necrosis were significantly improved in the sildenafil compared with the trauma control group. Caspase-3 levels in the cerebrospinal fluid and blood were not increased but gelsolin levels were decreased after spinal cord injury in trauma control rabbits. Sildenafil caused an increase in gelsolin levels and may be more effective than methylprednisolone at decreasing secondary damage to the spinal cord. 

  17. Effects of sildenafil and/or muscle derived stem cells on myocardial infarction

    Directory of Open Access Journals (Sweden)

    Wang Judy SC

    2012-08-01

    Full Text Available Abstract Background Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. Methods MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1 untreated; 2 oral sildenafil 3 mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3 saline; 4 rat MDSC (106 cells; 5 as #4, with sildenafil as in #2. Before surgery, and at 1 and 4 weeks, the left ventricle ejection fraction (LVEF was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. Results As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Conclusions Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5.

  18. Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre.

    Science.gov (United States)

    Douwes, Johannes M; Roofthooft, Marcus T R; Van Loon, Rosa L E; Ploegstra, Mark-Jan; Bartelds, Beatrijs; Hillege, Hans L; Berger, Rolf M F

    2014-02-01

    In paediatric pulmonary arterial hypertension (PAH), the effectiveness of add-on combination PAH-therapy has not yet been systematically studied. The purpose of this study was to determine the effect of sildenafil add-on therapy in paediatric PAH patients treated with bosentan. In this observational study within a national paediatric patient cohort, follow-up data of 24 consecutive paediatric PAH patients initially treated with bosentan monotherapy and prospectively followed at the Dutch national referral centre for paediatric PAH in 2007-2013, were reviewed. Patients received add-on sildenafil therapy in case of clinical worsening. Fifteen children received add-on sildenafil therapy; nine remained on bosentan monotherapy. Patient characteristics, 6-minute walk distance (6MWD), WHO functional class (WHO-FC), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP), and haemodynamic measurements at bosentan start were similar in both patient groups. In children with clinical worsening, sildenafil add-on therapy improved 6MWD at 5, 10, 15 and 21 months of follow-up, improved WHO-FC at 10, 15 and 21 months and stabilised NT-proBNP. Patients who received add-on sildenafil therapy had more advanced disease progression during bosentan monotherapy. Despite that, they had better or, at least, no worse survival compared to patients who remained on bosentan monotherapy. In children with PAH, sildenafil add-on therapy indicated by clinical deterioration on bosentan monotherapy, was associated with a significant improvement of WHO-functional class and 6MWD. Despite clinical deterioration on bosentan monotherapy, patients receiving sildenafil add-on therapy, had either better or, at least, no worse survival than patients remaining on bosentan monotherapy.

  19. Physicochemical action of potassium-magnesium citrate in nephrolithiasis

    Science.gov (United States)

    Pak, C. Y.; Koenig, K.; Khan, R.; Haynes, S.; Padalino, P.

    1992-01-01

    Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

  20. 21 CFR 582.5195 - Calcium citrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

  1. Redox Regulation of Arabidopsis Mitochondrial Citrate Synthase

    National Research Council Canada - National Science Library

    Elisabeth Schmidtmann Ann-Christine Konig Anne Orwat Dario Leister Markus Hartl Iris Finkemeier

    2014-01-01

    Citrate synthase has a key role in the tricarboxylic (TCA) cycle of mitochondria of all organisms, as it cata- lyzes the first committed step which is the fusion of a carbon-carbon bond between oxaloacetate and acetyl CoA...

  2. 21 CFR 73.2110 - Bismuth citrate.

    Science.gov (United States)

    2010-04-01

    ..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on...

  3. Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

    Directory of Open Access Journals (Sweden)

    El-Naa MM

    2016-11-01

    Full Text Available Mona Mohamed El-Naa,1 Mohamed Othman,2,3 Sheren Younes4,5 1Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA, 6 October City, Egypt; 2Preparatory Year College, University of Hail, Hail, Kingdom of Saudi Arabia; 3Faculty of Biotechnology, October University for Modern Science and Arts (MSA, 6 October City, Egypt; 4Pathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt; 5College of Medicine, Princess Nora Bint Abdulrahman University, Riyadh, Kingdom of Saudi ArabiaAbstract: Sildenafil is the first phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. However, recent studies have been suggesting an antitumor effect of sildenafil. The current study assessed the aforementioned activity of sildenafil in vivo and in vitro in solid-tumor-bearing mice and in a human cell line MCF-7, respectively. Moreover, we investigated the impact of sildenafil on cisplatin antitumor activity. The solid tumor was induced by inoculation of Ehrlich ascites carcinoma cells in female mice. The tumor-bearing mice were assigned randomly to control (saline, sildenafil (sildenafil 5 mg/kg/d, PO daily for 15 days, cisplatin (cisplatin 7.5 mg/kg, IP once on the 12th day of Ehrlich ascites carcinoma inoculation, and combination therapy (cisplatin and sildenafil groups. The tumor volume was measured at the end of the treatment period along with the following parameters: angiogenin, vascular endothelial growth factor, tumor necrosis factor-α, Ki-67, caspase-3, DNA-flow cytometry analysis, and histopathological examination. The study results showed that sildenafil has significantly decreased the tumor volume by 30.4%, angiogenin and tumor necrosis factor-α contents, as well as vascular endothelial growth factor expression. Additionally, caspase-3 level significantly increased with sildenafil treatment, whereas Ki-67 expression failed to show any significant changes. Furthermore, the cell cycle

  4. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  5. Sildenafil for pulmonary hypertension due to left-toright shunt after corrective procedure

    Directory of Open Access Journals (Sweden)

    Dyahris Kuntartiwi

    2015-09-01

    Full Text Available Background Pulmonary arterial hypertension (PAH is a common complication seen in those with a left-to-right shunt congenital heart defect (CHD. Corrective procedures by surgery or catheterization are the therapies of choice for reversible PAH. Since morbidity and mortality due to PAH after correction is high, sildenafil has been used as a selective vasodilator of the pulmonary artery, in order to decrease pulmonary arterial pressure. Objectives To evaluate the effect of sildenafil on pulmonary arterial pressure and clinical outcomes after left-to-right shunt CHD corrective procedures. Methods Left-to-right shunt patients aged < 18 years scheduled for corrective treatment were randomized in a double-blind fashion, to receive either oral sildenafil or placebo, given on days 3 to 30 after the corrective procedure. Clinical and pulmonary arterial pressures were evaluated by echocardiography before, 3 days after, and 30 days after the corrective procedure. Results From July 2013 to June 2014, 36 patients were included in the study: 17 in the placebo and 19 in the sildenafil groups. There were no differences in pulmonary arterial pressure or in clinical outcomes after corrective procedure between the two groups. There were no adverse events during the treatment. Conclusion Sildenafil has little effect on decreasing pulmonary arterial pressure, as most of our subjects seem to have hyperkinetic PAH. As such, pulmonary arterial pressure returns to normal soon after corrective procedures.

  6. Erectile Dysfunction (ED)

    Science.gov (United States)

    ... may recommend a medicine to help with it. Sildenafil (brand name: Viagra), tadalfil (brand name: Cialis), and vardenafil (brand name: ... 1 hour before he plans to have sex. Sildenafil works for 4-8 hours; vardenafil works for ...

  7. Erectile Dysfunction

    Science.gov (United States)

    ... rigid. Medications The oral medications for erectile dysfunction, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), relax the muscles ... to begin working; the erection helping effects of sildenafil and vardenafil last for about 8 hours and ...

  8. Antidepressants: Which Cause the Fewest Sexual Side Effects?

    Science.gov (United States)

    ... a medication to improve sexual function, such as sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra, Staxyn). These medications ... treat sexual problems in men. Limited research suggests sildenafil may improve sexual problems caused by antidepressants in ...

  9. Orgasmic Disorder

    Science.gov (United States)

    ... stopped having orgasms when they started taking SSRIs, sildenafil may help them have orgasms again. Spotlight on ... Select Brand Names bupropion WELLBUTRIN, ZYBAN testosterone DELATESTRYL sildenafil VIAGRA Sexual Dysfunction in Women Overview of Sexual ...

  10. Reduction and aggregation of silver ions in aqueous citrate solutions.

    Science.gov (United States)

    Chadha, Ridhima; Maiti, Nandita; Kapoor, Sudhir

    2014-05-01

    Radiolytic reduction of Ag(+) ions and the subsequent formation of Ag clusters were studied in aqueous citrate solutions. Pulse-radiolysis studies show that the presence of citrate in the solution affects the early processes, via complexation of Ag(+) ions with the carboxyl moieties of the citrate. The ratio of citrate to Ag(+) determines the kinetic consequences of the reduction and agglomeration processes. The complexation reduces somewhat the rate of reduction by hydrated electrons. However, when all the ions are complexed to the citrate, the surface plasmon absorption band becomes broader, albeit small, but nevertheless it provides extreme stability to the formed nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Citrate anticoagulation for CRRT in children: comparison with heparin.

    Science.gov (United States)

    Fernández, Sara Nicole; Santiago, Maria José; López-Herce, Jesús; García, Miriam; Del Castillo, Jimena; Alcaraz, Andrés José; Bellón, Jose María

    2014-01-01

    Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P = 0.028). 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I) of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

  12. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

    Directory of Open Access Journals (Sweden)

    Sara Nicole Fernández

    2014-01-01

    Full Text Available Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P=0.028. 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

  13. Isolation and structural elucidation of a new sildenafil analogue from a functional coffee.

    Science.gov (United States)

    Li, Lin; Low, Min-Yong; Ge, Xiaowei; Bloodworth, Bosco C; Koh, Hwee-Ling

    2013-05-01

    A sildenafil analogue was detected in a functional coffee sample labelled to have male sexual performance enhancement effects. This analogue was isolated and purified by flash chromatography and preparative high-performance liquid chromatography. Its structure was elucidated using high-resolution mass spectrometry; electrospray ionization-tandem mass spectrometry; and nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and infrared spectroscopy. Compared with sildenafil, instead of an N-methylpiperazinyl moiety, ring opening of the piperazine ring with the loss of a carbon atom resulted in a substituted benzenesulfonamide. The chemical name of this analogue is N-[2-(dimethylamino)ethyl]-4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide. It is named descarbonsildenafil because it has one less carbon atom when compared with sildenafil.

  14. Black lung persistent pulmonary hypertension of the newborn. Saudi experience with sildenafil and nitric oxide

    Directory of Open Access Journals (Sweden)

    AbdulRahman M. Alnemri

    2017-01-01

    Full Text Available Objectives: To determine the clinical presentation, risk factors, diagnosis, and treatment outcome of Saudi infants with black lung persistent pulmonary hypertension of the newborn (PPHN. Methods: This is a retrospective review of all neonates with PPHN presented to the Armed Force Hospital Southern Region, Kingdom of Saudi Arabia from January 2012 to December 2014. Results: Ten term and near term infants presented with PPHN were included. Maternal diabetes and Down syndrome were the most common identified risk factors for PPHN in the study group. Nine infants were treated with oral sildenafil and did not require mechanical ventilation. Only one infant required mechanical ventilation and inhaled nitric oxide in addition to oral sildenafil. Conclusion: Most of the patients in this cohort with PPHN had risk factors, they did not require mechanical ventilation and responded well to oral sildenafil.

  15. Pulmonary hypertension in end-stage pulmonary sarcoidosis: therapeutic effect of sildenafil?

    DEFF Research Database (Denmark)

    Milman, N.; Burton, C.M.; Iversen, M.

    2008-01-01

    BACKGROUND: The objectives of this study were to assess the frequency and severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in patients with recalcitrant pulmonary sarcoidosis. METHODS: This investigation was a single-center, retrospective study of all patients (n = 25......) with end-stage pulmonary sarcoidosis referred for lung transplantation. Hemodynamic measurements were evaluated by right-side cardiac catheterization in 24 of 25 patients. Sildenafil treatment for patients with sarcoidosis-associated PH was introduced in April 2004. RESULTS: The study group of 24 patients...... (16 men, 8 women) had a median age of 45 (range 35 to 58) years, and duration of sarcoidosis of 11 (range 2 to 38) years. Mean pulmonary arterial pressure (MPAP) was median 36 (range 18 to 73) mm Hg. PH (MPAP >25 mm Hg) was present in 19 of 24 patients (79%). Sildenafil was administered to 12 of 13...

  16. Rosuvastatin, Sildenafil and Their Combination in Monocrotaline-Induced Pulmonary Hypertension in Rat

    Directory of Open Access Journals (Sweden)

    Jasińska-Stroschein Magdalena

    2014-09-01

    Full Text Available There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given for 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development.

  17. Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Yin Zheng

    Full Text Available Regional citrate anticoagulation (RCA is gaining popularity in continous renal replacement therapy (CRRT for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH with RCA.Critically ill patients with AKI (n = 12 and healthy volunteers (n = 12 were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients' CVVH sessions with citrate anticoagulation.Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624. Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively. The predicted citrate curve showed excellent fit to the measurements.Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation.ClinicalTrials.gov Identifier NCT00948558.

  18. Effect of sildenafil in renal ischemia/reperfusion injury in rats Efeito do sildenafil na lesão renal por isquemia/reperfusão em ratos

    Directory of Open Access Journals (Sweden)

    Paulo José de Medeiros

    2010-12-01

    Full Text Available PURPOSE: To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R, by scintigraphy and histopathological evaluation in rats. METHODS: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12 received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12. Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. RESULTS: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (pOBJETIVO: Estudar o efeito do sildenafil, administrado previamente à isquemia/reperfusão (I/R renal, em avaliações cintilográficas e histopatológicas em ratos. MÉTODOS: Vinte e quatro ratos Wistar foram aleatoriamente distribuídos em dois grupos. Os animais receberam 0,1 ml IV de 99mTecnécio-Etilenodicisteína, foram submetidos à cintilografia renal inicial e em seguida submetidos a isquemia no rim esquerdo, com oclusão da artéria renal, durante 60 minutos, com posterior reperfusão. O grupo sildenafil (n=12 recebeu previamente 1mg/kg de sildenafil em suspensão 60 minutos antes da isquemia. Solução salina 0,9% foi administrada no grupo controle (n=12. Metade dos animais de cada grupo foi avaliada após 24 horas e a outra metade após sete dias de reperfusão, com nova cintilografia renal. Após eutanásia, os

  19. Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia.

    Science.gov (United States)

    Constantinescu, Ioana M; Bolfa, Pompei; Constantinescu, Dan; Mironiuc, Aurel I; Gherman, Claudia D

    2017-01-01

    Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.

  20. Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension.

    Science.gov (United States)

    Morris, Claudia R; Kim, Hae-Young; Wood, John; Porter, John B; Klings, Elizabeth S; Trachtenberg, Felicia L; Sweeters, Nancy; Olivieri, Nancy F; Kwiatkowski, Janet L; Virzi, Lisa; Singer, Sylvia T; Taher, Ali; Neufeld, Ellis J; Thompson, Alexis A; Sachdev, Vandana; Larkin, Sandra; Suh, Jung H; Kuypers, Frans A; Vichinsky, Elliott P

    2013-09-01

    Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There are limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We, therefore, designed a 12-week, open-label, phase 1/2, pilot-scale, proof-of-principle trial of sildenafil therapy in 10 patients with β-thalassemia and at increased risk of pulmonary hypertension based on an elevated tricuspid regurgitant jet velocity >2.5 m/s on Doppler-echocardiography. Variables compared at baseline and after 12 weeks of sildenafil treatment included Doppler-echocardiographic parameters, 6-minute walked distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function, and laboratory parameters. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3% (3.0±0.7 versus 2.6±0.5 m/s, P=0.04), improved left ventricular end systolic/diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in 6-minute walked distance was noted. Sildenafil was well tolerated, although minor expected adverse events were commonly reported. The total dose of sildenafil (mg) was strongly correlated with percent change in nitric oxide metabolite concentration in the plasma (ρ=0.80, P=0.01). There were also significant increases in plasma and erythrocyte arginine concentrations. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk of pulmonary hypertension; however, it was not demonstrated to improve the distance walked in 6 minutes. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in patients with β-thalassemia. (clinicaltrials.gov identifier: NCT00872170).

  1. Development and validation of alternative methods by non-aqueous acid-base titration and derivative ultraviolet spectrophotometry for quantification of sildenafil in raw material and tablets

    Directory of Open Access Journals (Sweden)

    Taízia Dutra Silva

    2017-04-01

    Full Text Available Sildenafil citrate (SILC is a potent phosphodiesterase-5 inhibitor used for erectile dysfunction and pulmonary hypertension. This study shows two simple, fast and alternative analytical methods for SILC determination by non-aqueous titration and by derivative ultraviolet spectrophotometry (DUS in active pharmaceutical ingredient and/or dosage forms. The quantitation method of SILC active pharmaceutical ingredient by non-aqueous acid-base titration was developed using methanol as solvent and 0.1 mol/L of perchloric acid in acetic acid as titrant. The endpoint was potentiometrically detected. The non-aqueous titration method shows satisfactory repeatability and intermediate precision (RSD 0.70-1.09%. The neutralization reaction occurred in the stoichiometric ratio 1:1 in methanol. The determination of SILC active pharmaceutical ingredient or dosage forms by DUS was developed in the linear range from 10 to 40 µg/mL, in 0.01 mol/L HCl, using the first order zero-peak method at λ 256 nm. The DUS method shows selectivity toward tablets excipients, appropriate linearity (R2 0.9996, trueness (recovery range 98.86-99.30%, repeatability and intermediate precision in three concentration levels (RSD 1.17-1.28%; 1.29-1.71%, respectively. Therefore, the methods developed are excellent alternatives to sophisticated instrumental methods and can be easily applied in any pharmaceutical laboratory routine due to simple and fast executions.

  2. Sildenafil no tratamento da hipertensão pulmonar após cirurgia cardíaca Sildenafil for pulmonary hypertension treatment after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Maria Regina Bentlin

    2005-04-01

    Full Text Available OBJETIVO: Relatar o uso do Sildenafil no tratamento da hipertensão pulmonar em recém-nascido após cirurgia cardíaca. DESCRIÇÃO: Recém-nascido de termo, feminino, com diagnóstico de dupla via de saída de ventrículo direito, hipoplasia de pulmonar e comunicação interventricular subaórtica, foi submetido à cirurgia de Blalock na primeira semana de vida. No pós-operatório, evoluiu com hipertensão pulmonar e hipoxemia persistente, não-responsiva ao óxido nítrico, porém com melhora da oxigenação após infusão endovenosa contínua de prostaglandina E1. Depois de várias tentativas malsucedidas de retirada da prostaglandina E1, optou-se pela introdução do Sildenafil via oral. Houve queda da resistência vascular pulmonar, com conseqüente melhora na oxigenação e, 48 horas após, foi possível suspender a infusão de prostaglandina E1. COMENTÁRIOS: O Sildenafil pode ser alternativa terapêutica na hipertensão pulmonar, especialmente quando não houver resposta à terapia convencional.OBJECTIVE: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. DESCRIPTION: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. COMMENTS: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy.

  3. Survival with sildenafil and inhaled iloprost in a cohort with pulmonary hypertension: An observational study

    NARCIS (Netherlands)

    H. Gall (Henning); N. Sommer (Natascha); K. Milger (Katrin); M.J. Richter (Manuel); R. Voswinckel (Robert); D. Bandorski (Dirk); W. Seeger (Werner); F. Grimminger (Friedrich); H.A. Ghofrani

    2016-01-01

    textabstractBackground: Combination therapy is frequently used to treat patients with pulmonary hypertension but few studies have compared treatment regimens. This study examined the long-term effect of different combination regimens of inhaled iloprost and oral sildenafil on survival and disease

  4. Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube

    NARCIS (Netherlands)

    Ahsman, Maurice J.; Witjes, Bregje C.; Wildschut, Enno D.; Sluiter, Ilona; Vulto, Arnold G.; Tibboel, Dick; Mathot, Ron A.

    2010-01-01

    To describe the pharmacokinetics and exposure of oral sildenafil (SIL) in neonates (2-5 kg) with pulmonary hypertension (PH). We included 11 neonates (body weight 2-5 kg, postnatal age 2-121 days) who received SIL and extracorporeal membrane oxygenation (ECMO) treatment for PH. SIL capsules were

  5. Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre

    NARCIS (Netherlands)

    Douwes, Johannes M.; Roofthooft, Marcus T. R.; Van Loon, Rosa L. E.; Ploegstra, Mark-Jan; Bartelds, Beatrijs; Hillege, Hans L.; Berger, Rudolphus

    2014-01-01

    Objective In paediatric pulmonary arterial hypertension (PAH), the effectiveness of add-on combination PAH-therapy has not yet been systematically studied. The purpose of this study was to determine the effect of sildenafil add-on therapy in paediatric PAH patients treated with bosentan. Methods In

  6. Influence of sildenafil on blood oxygen saturation of the obstructed bladder

    NARCIS (Netherlands)

    J.R. Scheepe (Jeroen); A. Amelink (Arjen); K.P. Wolffenbuttel (Katja); D.J. Kok (Dirk)

    2014-01-01

    textabstractBackground: Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction. Methods. Thirty-two

  7. Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation

    DEFF Research Database (Denmark)

    Eskesen, Kristian; Olsen, Niels Thue; Dimaano, Veronica L

    2015-01-01

    BACKGROUND: Currently there is no reliable medical treatment for aortic regurgitation (AR). METHODS: Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks...

  8. Functional characterization and Me2+ ion specificity of a Ca2+-citrate transporter from Enterococcus faecalis

    NARCIS (Netherlands)

    Blancato, Victor S.; Magni, Christian; Lolkema, Juke S.

    2006-01-01

    Secondary transporters of the bacterial CitMHS family transport citrate in complex with a metal ion. Different members of the family are specific for the metal ion in the complex and have been shown to transport Mg2+-citrate, Ca2+-citrate or Fe3+-citrate. The Fe3+-citrate transporter of

  9. Aspergillus niger Secretes Citrate to Increase Iron Bioavailability

    Science.gov (United States)

    Odoni, Dorett I.; van Gaal, Merlijn P.; Schonewille, Tom; Tamayo-Ramos, Juan A.; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria; Schaap, Peter J.

    2017-01-01

    Aspergillus niger has an innate ability to secrete various organic acids, including citrate. The conditions required for A. niger citrate overproduction are well described, but the physiological reasons underlying extracellular citrate accumulation are not yet fully understood. One of the less understood culture conditions is the requirement of growth-limiting iron concentrations. While this has been attributed to iron-dependent citrate metabolizing enzymes, this straightforward relationship does not always hold true. Here, we show that an increase in citrate secretion under iron limited conditions is a physiological response consistent with a role of citrate as A. niger iron siderophore. We found that A. niger citrate secretion increases with decreasing amounts of iron added to the culture medium and, in contrast to previous findings, this response is independent of the nitrogen source. Differential transcriptomics analyses of the two A. niger mutants NW305 (gluconate non-producer) and NW186 (gluconate and oxalate non-producer) revealed up-regulation of the citrate biosynthesis gene citA under iron limited conditions compared to iron replete conditions. In addition, we show that A. niger can utilize Fe(III) citrate as iron source. Finally, we discuss our findings in the general context of the pH-dependency of A. niger organic acid production, offering an explanation, besides competition, for why A. niger organic acid production is a sequential process influenced by the external pH of the culture medium. PMID:28824560

  10. Sildenafil in the Treatment of SSRI-Induced Sexual Dysfunction: A Pilot Study

    Science.gov (United States)

    Damis, Marina; Patel, Yatin; Simpson, George M.

    1999-01-01

    Background: Sexual dysfunction is a well-documented side effect of selective serotonin reuptake inhibitors (SSRIs). Commonly reported side effects include erectile impotence, anorgasmia, ejaculatory delay, pain, loss of sensation, and decreased pleasure. Early reports of the reversal of sexual dysfunction after using sildenafil in male and female patients receiving various types and dosages of SSRIs are promising and prompted this study. Our aim was to evaluate the effects of oral sildenafil on reported secondary sexual dysfunction in patients concurrently treated with SSRIs. Method: Fourteen male patients who developed sexual dysfunction while receiving SSRIs were screened using the Arizona Sexual Experience (ASEX) scale. An electrocardiogram was obtained at the beginning and at the end of the study. Each patient was prescribed sildenafil tablets to be taken twice a week, 25–100 mg, prior to sexual activity and told to record the findings in a running diary which he was to keep during his treatment period. The patients were seen weekly and evaluated by clinical interview and ASEX scale. Patients were treated for a total of 8 weeks. Results: All but 1 of the 14 patients experienced an improvement of sexual dysfunction, with 9 patients at the first dose of 25 mg and 4 at higher doses (3 at 50 mg and 1 at 75 mg). One patient required 100 mg to obtain minimal response. Discussion: Sildenafil was shown to be helpful in the treatment of SSRI-induced sexual dysfunction. Three patients continued to experience ongoing positive effects after discontinuation of sildenafil; the other 10 patients relapsed. PMID:15014670

  11. [Features of subjects purchasing Sildenafil at community pharmacies in Concepción, Chile].

    Science.gov (United States)

    Mennickent, Sigrid; Zurita, Libna; Vega, Mario; Villegas, Guiljardy

    2005-06-01

    Erectile dysfunction is a public health problem. Millions of men worldwide experience this condition, affecting their quality of life. Sildenafil, a phosphodiesterase type 5 inhibitor, is the treatment of choice for erectile dysfunction. To study the characteristics of Sildenafil use among costumers of community pharmacies in Concepcion Chile. A structured interview about Sildenafil use was applied to subjects purchasing the drug in community pharmacies and that consented to participate. One hundred thirty eight males were studied. Forty six percent of patients were fifty years old or older. Most (47.1%) used Sildenafil for one year or more and 60.5% had no adverse events. Among those experiencing side effects, headache was experienced by 38.9%, flushing by 16.6% and gastrointestinal effects by 16.7%. Ninety percent of patients had a good evaluation of the drug in terms of benefits and tolerance. Thirty two percent of the subjects, had diseases associated to erectile dysfunction. Among these, 45% had diabetes mellitus, 29.5% had hypertension, and 18.2% had prostatic diseases. In 54% of cases, the drug was prescribed by a physician. Twenty two percent of patients experienced changes in the effect of the drug when it was simultaneously used with other drugs or meals. Thirty four percent of patients used other drugs. Among these, 43.3% were using antihypertensives, and 26.7% were using antidiabetic drugs. Considering the elevated age and the number of associated disease of patients using Sildenafil, the use of the drug under medical prescription must be emphasized to avoid untoward effects.

  12. [Evaluation of self-esteem in males with erectile dysfunction treated with viagra. Analysis of a Spanish patients group selected from a multicenter, international study].

    Science.gov (United States)

    Martínez-Jabaloyas, J M; Moncada, I; Rodríguez-Vela, L; Gutiérrez, P R; Chaves, J

    2010-09-01

    Erectile dysfunction (ED) leads to psychological disturbances, especially anxiety and loss of self-esteem. We try to understand the emotional changes, based on self-esteem and relationships in a group of Spanish men with ED after sildenafil treatment, with the use of the the SEAR questionnaire (Self-Esteem And Relationship). The patients recruited in Spain, where selected from an international, multicenter, randomized, parallel-group, double-blind, placebo-controlled, sildenafil study designed to assess self-esteem and relationships in men with ED. We compared the changes in the different domains of the SEAR questionnaire (Self-steem, sexual activity, self-confidence and general relationships) that was administered before and after treatment; the different domains of the IIEF was evaluated as well. We also calculated the correlation between changes in self-esteem domain of the SEAR questionnaire. The statistical study was based on an analysis of covariance of change in scores and a correlation analysis. The Spanish group of researchers included 119 patients. The erectile function domain score showed significantly greater improvement for the group of sildenafil. The difference in change in total mean score of the SEAR after treatment was 16.9 (95% CI 8.9, 24.8) for sildenafil over placebo (p=0.0001), with a significantly higher score improvement in all the domains of the SEAR for Sildenafil. There was a significant correlation between the changes in the domain of self-esteem of the SEAR and the IIEF erectile function domain for both treatment groups. Emotional improvement was confirmed in patients treated with sildenafil based on improved self-esteem, self-confidence and relationships. Changes in the IIEF erectile function domain correlate with the SEAR self-esteem domain.

  13. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Fu Morgan

    2010-09-01

    Full Text Available Abstract Background We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM. Methods Adult Lewis rats (n = 8 per group were divided into group 1 (normal control, group 2 (saline-treated DCM rats, group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally, and group 5 (DCM rats with combined ADMSC-sildenafil. Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. Results The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p Conclusion Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.

  14. Prevalencia y factores asociados al consumo de citrato de sildenafil en estudiantes universitarios colombianos, durante el primer semestre de 2013

    National Research Council Canada - National Science Library

    Javier Martínez-Torres; Ingrid Katherine Duarte-Corredor; Gaby Johanna García-Vásquez; Gissely Dimarhy Jáuregui-Rodríguez

    2015-01-01

    ... a la disminución de enfermedades de transmisión sexual y embarazos no deseados. Determinar la prevalencia del consumo de Citrato de Sildenafil y sus factores asociados en estudiantes universitarios, durante el primer semestre de 2013...

  15. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  16. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  17. Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis.

    Science.gov (United States)

    Musicki, Biljana; Bivalacqua, Trinity J; Champion, Hunter C; Burnett, Arthur L

    2014-02-01

    Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Continuous treatment with sildenafil reversed (P penis. Sildenafil treatment of WT mice did not affect any of these parameters. Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. © 2013 International Society for Sexual Medicine.

  18. A novel method for the determination of sildenafil (Viagra(R)) and its metabolite (UK-103,320) in postmortem specimens using LC/MS/MS and LC/MS/MS/MS : final report.

    Science.gov (United States)

    2000-05-01

    During the investigation of aviation accidents, postmortem samples from victims are submitted to the FAAs Civil Aeromedical Institute for drug analysis. Because new drugs are continually being released to the market, it is our laboratorys respo...

  19. Lithium citrate as treatment of Canavan disease.

    Science.gov (United States)

    Solsona, María Dolores Edo; Fernández, Laura Lorente; Boquet, Emilio Monte; Andrés, José Luís Poveda

    2012-01-01

    Canavan disease is a rare autosomal recessive leukodystrophy characterized by abnormal accumulation of N-acetyl aspartate (NAA) in brain white matter. Currently, there is no cure for this disease, and management of patients consists mainly of treating symptoms. We describe a 3-month-old girl who was hospitalized for poor head control and decreased muscle tone. A battery of laboratory and genetic (homozygous mutation p.C218X) analysis revealed the presence of Canavan disease. Lithium citrate was initiated at a dosage of 45 mg/kg per day after diagnosis. Periodic controls of thyroid and liver function, and lithium levels in blood showed that this drug was sure and well tolerated. After 1 year of treatment, NAA levels decreased by approximately 20% in the brain region, urinary NAA levels showed a reduction of 80%, and patient improved alertness and visual tracking but continued with no heat support, axial hypotonia, and spastic diplegia. In our patient, the results obtained after drug administration are important with respect to the decrease in NAA and more discreet in clinical improvement. However, given the absence of adverse effects and limited treatment options, lithium citrate may be a good alternative to stop the progression of the disease and improve the quality of life of patients.

  20. Synthesis of core-shell magnetic molecularly imprinted polymers and detection of sildenafil and vardenafil in herbal dietary supplements

    Energy Technology Data Exchange (ETDEWEB)

    Ding Meijuan, E-mail: dmj0817@yahoo.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Wu Xiaoli, E-mail: wuxiaoli2233@yahoo.com.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Yuan Lihua, E-mail: transient_lily@yahoo.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Wang Shu, E-mail: jsntwsh@163.com [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Li Yun, E-mail: lyxfyy@yahoo.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Wang Ruoyu, E-mail: wangyameng1989@yahoo.com.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Wen Tingting, E-mail: pk2008wtt@163.com [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Du Shuhu, E-mail: shuhudu@njmu.edu.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China); Zhou, Xuemin, E-mail: xueminzhou001_001@yahoo.cn [School of Pharmacy, Nanjing Medical University, Nanjing 210029 (China)

    2011-07-15

    An analytical procedure for selective extraction of sildenafil and vardenafil in herbal dietary supplements (HDSs) has been set up by using the magnetic molecularly imprinted polymers (MMIPs) as the extraction and clean-up materials, followed by high performance liquid chromatography-ultraviolet (HPLC-UV). The MMIPs were prepared by a surface molecular imprinting technique, using Fe{sub 3}O{sub 4} magnetite as a magnetically susceptible component, sildenafil as template molecule, 2-(trifluoromethyl) acrylic acid (TFMAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as polymeric matrix components. The MMIPs were characterized by transmission electron microscope (TEM), Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM), respectively. The heterogeneity of the MMIPs was modeled with the Freundlich isotherm equation. The resulting MMIPs had high recognition ability and fast binding kinetics for sildenafil. The MMIPs were used as dispersive solid-phase extraction (DSPE) materials to selectively extract sildenafil and vardenafil from HDSs, the contents of sildenafil and vardenafil were found to be 8.05 and 3.86 {mu}g g{sup -1}, respectively, and the average recoveries in spiked HDSs were 70.91-91.75% with a relative standard deviation (R.S.D.) below 7%. The MMIPs were successfully used to selectively enrich and determine sildenafil and vardenafil from HDSs.

  1. Formulation and process considerations for the design of sildenafil-loaded polymeric microparticles by vibrational spray-drying.

    Science.gov (United States)

    Beck-Broichsitter, Moritz; Bohr, Adam; Aragão-Santiago, Leticia; Klingl, Andreas; Kissel, Thomas

    2017-09-01

    The current study reports the preparation and characterization of sildenafil-loaded poly(lactide-co-glycolide) (PLGA)-based microparticles (MPs) by means of vibrational spray-drying. Emphasis was placed on relevant formulation and process parameters with influence on the properties of obtained powders. Materials and methods, results and discussion: The solid state solubility of sildenafil in spray-dried PLGA-MPs amounted to 17 wt.%. Thus, a drug loading below and above the determined solubility limit resulted in solid solutions and phase separation (i.e. solid dispersions), respectively. Furthermore, interactions between sildenafil and the PLGA matrix were observed for the spray-dried MPs. Optimization of spray-drying conditions allowed for a fabrication of defined MPs (size range of ∼4-8 μm) displaying a high sildenafil encapsulation efficiency (>90%) and sustained sildenafil release (from ∼4 to >12 h). The individual drug release rates from the spray-dried formulations were mainly a function of the drug loading, applied polymer and MP size. Finally, a scale-up of the preparation process did not result in a relevant change of the physicochemical and in vitro drug release properties of the prepared powders. Identification of relevant formulation and spray-drying parameters enabled the fabrication of tailored sildenafil-loaded PLGA-based MPs, which meet the needs of the individual application (e.g. controlled drug delivery to the lungs).

  2. Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Barbara Rinaldi

    Full Text Available Moderate exercise training improves energetic metabolism, tissue perfusion and induces cardiac and skeletal muscle remodeling. Sildenafil, a potent phosphodiesterase-5 inhibitor used to treat erectile dysfunction, reduces infarct size and increases tissue oxygenation in experimental models of cardiovascular disease. We have evaluated the effects of prolonged moderate exercise training and a repeat administration of sildenafil on the rat gastrocnemius and cardiac muscles. Animals were divided into two groups: sedentary and trained. Each group was subdivided into animals treated with vehicle or with two doses of sildenafil (10 or 15 mg/kg/day during the last week of training. Physical exercise did not induce cardiac hypertrophy, whereas it increased mRNA levels of the PGC-1α, HIF-1α and VEGF genes, which are involved in mitochondrial biogenesis and angiogenesis, and reduced mRNA levels of FoxO3a, MuRF-1 and Atrogin-1. Sildenafil dose-dependently promoted both angiogenesis, as shown by increased capillary density, and muscle atrophy, as shown by muscle fibre size. These effects were more pronounced in trained animals. Our data confirm the beneficial effects of a moderate and prolonged training on cardiovascular and skeletal systems and document the positive and negative effects of sildenafil on these tissues at doses higher than those used in clinical practice. This report may impact on the use of sildenafil as a substance able to influence sports performance.

  3. Herb-Drug Interaction of Epimedium sagittatum (Sieb. et Zucc. Maxim Extract on the Pharmacokinetics of Sildenafil in Rats

    Directory of Open Access Journals (Sweden)

    Chi-Hung Lin

    2013-06-01

    Full Text Available Epimedium sagittatum (Sieb. et Zucc. Maxim is one of the herbs used to treat erectile dysfunction in Traditional Chinese Medicine. Sildenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction in Western Medicine. This study evaluates the herbal-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil in rats by ultra-performance liquid chromatography. The rat plasma was sampled from each anesthetized rat after pretreatment with 3-days Epimedium sagittatum extract (1/2 g/kg/day and intravenous injection with sildenafil (10/30 mg/kg. The pharmacokinetic data demonstrate that the area under the concentration-time curve (AUC of sildenafil (10 mg/kg was significantly decreased in groups that received a high dose of Epimedium sagittatum extract. In conclusion, the study demonstrates that there was significant herb-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil at low and high daily doses, suggesting co-administration use of Epimedium sagittatum extract and sildenafil in clinical practice should be prevented due to possible herb-drug interactions.

  4. Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis.

    Science.gov (United States)

    Arrabal-Polo, Miguel Angel; Arrabal-Martin, Miguel; Arias-Santiago, Salvador; Garrido-Gomez, Juan; Poyatos-Andujar, Antonio; Zuluaga-Gomez, Armando

    2013-04-01

    Different studies have shown the importance of citrate in the formation of calcium stones. It has further been shown that the states of metabolic acidosis result in an increase in bone resorption and lower urinary citrate levels. Increasing the intake of citrate in these patients can reduce the lithogenic risk and improve bone mineral density (BMD), contributing to control of both diseases. The study shows the importance of citrate in patients with calcium stones and BMD loss. The deficit in citrate excretion is associated with a decrease in bone mineralization and increased β-crosslaps. A calcium : citrate ratio >0.25 in patients with calcium stones and loss of mineral density may predict severe lithogenic activity. To analyse the importance of urinary citrate and the urinary calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis compared with a control group of patients without lithiasis. A cross-sectional study of 115 patients in eastern Andalusia, Spain was conducted. The patients were divided into two groups: Group A: 56 patients aged 25-60 years without calcium renal lithiasis; Group B: 59 patients aged 25-60 years, presenting with calcium renal lithiasis and severe lithogenesis. The citrate levels and the calcium : citrate ratio in the patients' urine and the relationship of these two factors to lithiasic activity were analysed and compared. In Group B, 32.2% of the patients presented with hypocitraturia, compared with 14.3% of the patients in Group A (P = 0.02). The urinary citrate levels were lower in Group B than in Group A (P = 0.001) and the calcium : citrate ratio was higher in Group B than in Group A (P = 0.005). The results suggest that a patient urinary calcium : citrate ratio > 0.25 indicates severe lithogenesis (with a sensitivity of 89% and a specificity of 57%). After linear regression analysis, we found that the urinary citrate level is an independent factor associated with the changes in bone densitometry T

  5. [sup 99m]Tc-Citrate versus [sup 67]Ga-citrate for the scintigraphic visualization of inflammatory lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ercan, M.T.; Aras, T.; Unlenen, E.; Unsal, I.S.; Hascelik, Z. (Hacettepe Univ., Ankara (Turkey)); Unlu, M. (Gazi Univ., Ankara (Turkey). Dept. of Nuclear Medicine)

    1993-10-01

    Citric acid was labeled with [sup 99m]Tc with an efficiency of > 99%. The biodistribution of [sup 99m]Tc-citrate was studied in mice with turpentine-induced abscesses in comparison to [sup 67]Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 [+-] 1.92 (3 h) for [sup 99m]Tc-citrate and 4.76 [+-] 2.04 (4 h) for [sup 67]Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of [sup 99m]Tc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 [+-] 1.29 (3 h) and 6.47 [+-] 3.71 (24 h) for [sup 99m]Tc- and [sup 67]Ga-citrate, respectively. The blood clearance curve of [sup 99m]Tc-citrate in rabbits was biexponential with a fast and a slow component, compared to mono-exponential clearance of [sup 67]Ga-citrate. In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 [+-] 0.81 and 4.95 [+-] 2.56 for [sup 99m]Tc-citrate and [sup 99m]Tc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that [sup 99m]Tc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to [sup 67]Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion. (Author).

  6. 21 CFR 522.300 - Carfentanil citrate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carfentanil citrate injection. 522.300 Section 522....300 Carfentanil citrate injection. (a) Specifications. Each milliliter of sterile aqueous solution..., shoulder, back, or hindquarter. Avoid intrathoracic, intra-abdominal, or subcutaneous injection. To reverse...

  7. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622 Diethylcarbamazine citrate oral dosage forms. ...

  8. Pre-process desilication of wheat straw with citrate

    DEFF Research Database (Denmark)

    Le, Duy Michael; Sorensen, Hanne R.; Meyer, Anne S.

    2017-01-01

    Effects of treatment time, citrate concentration, temperature, and pH on Si extraction from wheat straw prior to hydrothermal pretreatment were investigated for maximising Si removal and biomass recovery before biomass refining. With citrate, an almost linear negative correlation between Si conte...

  9. Structural basis for norovirus inhibition and fucose mimicry by citrate.

    Science.gov (United States)

    Hansman, Grant S; Shahzad-Ul-Hussan, Syed; McLellan, Jason S; Chuang, Gwo-Yu; Georgiev, Ivelin; Shimoike, Takashi; Katayama, Kazuhiko; Bewley, Carole A; Kwong, Peter D

    2012-01-01

    Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses. Crystals of citrate in complex with the protruding domain from norovirus GII.10 Vietnam026 diffracted to 1.4 Å and showed a single citrate bound at the site of HBGA interaction. The citrate interaction was coordinated with a set of capsid interactions almost identical to that involved in recognizing the terminal HBGA fucose, the saccharide which forms the primary conserved interaction between HBGAs and GII noroviruses. Citrate and a water molecule formed a ring-like structure that mimicked the pyranoside ring of fucose. STD NMR showed the protruding domain to have weak affinity for citrate (460 μM). This affinity, however, was similar to the affinities of the protruding domain for fucose (460 μM) and H type 2 trisaccharide (390 μM), an HBGA shown previously to be specifically recognized by human noroviruses. Importantly, competition STD NMR showed that citrate could compete with HBGA for norovirus binding. Together, the results suggest that citrate and other glycomimetics have the potential to block human noroviruses from binding to HBGAs.

  10. Structural Basis for Norovirus Inhibition and Fucose Mimicry by Citrate

    Energy Technology Data Exchange (ETDEWEB)

    Hansman, Grant S.; Shahzad-ul-Hussan, Syed; McLellan, Jason S.; Chuang, Gwo-Yu; Georgiev, Ivelin; Shimoike, Takashi; Katayama, Kazuhiko; Bewley, Carole A.; Kwong, Peter D. (NIAID)

    2012-01-20

    Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses. Crystals of citrate in complex with the protruding domain from norovirus GII.10 Vietnam026 diffracted to 1.4 {angstrom} and showed a single citrate bound at the site of HBGA interaction. The citrate interaction was coordinated with a set of capsid interactions almost identical to that involved in recognizing the terminal HBGA fucose, the saccharide which forms the primary conserved interaction between HBGAs and GII noroviruses. Citrate and a water molecule formed a ring-like structure that mimicked the pyranoside ring of fucose. STD NMR showed the protruding domain to have weak affinity for citrate (460 {mu}M). This affinity, however, was similar to the affinities of the protruding domain for fucose (460 {mu}M) and H type 2 trisaccharide (390 {mu}M), an HBGA shown previously to be specifically recognized by human noroviruses. Importantly, competition STD NMR showed that citrate could compete with HBGA for norovirus binding. Together, the results suggest that citrate and other glycomimetics have the potential to block human noroviruses from binding to HBGAs.

  11. Citrate increases glass transition temperature of vitrified sucrose preparations

    NARCIS (Netherlands)

    Kets, E.P.W.; Lipelaar, P.J.; Hoekstra, F.A.; Vromans, H.

    2004-01-01

    The aim of this study was to investigate the effect of sodium citrate on the properties of dried amorphous sucrose glasses. Addition of sodium citrate to a sucrose solution followed by freeze-drying or convective drying resulted in a glass transition temperature (T-g) that was higher than the

  12. Association between clomiphene citrate and central retinal vein ...

    African Journals Online (AJOL)

    Central retinal vein occlusion (CRVO) is a common retinal vascular disorder associated with cardiovascular disorders and other related risk factors. A case of CRVO secondary to clomiphene citrate has been reported. We present a case that also illustrates the association between clomiphene citrate and CRVO, and hope ...

  13. Uniport of Anionic Citrate and Proton Consumption in Citrate Metabolism Generates a Proton Motive Force in Leuconostoc oenos

    NARCIS (Netherlands)

    RAMOS, A; POOLMAN, B; SANTOS, H; LOLKEMA, JS; KONINGS, WN

    The mechanism and energetics of citrate transport in Leuconostoc oenos were investigated. Resting cells of L. oenos generate both a membrane potential (Delta Psi) and a pH gradient (Delta pH) upon addition of citrate. After a lag time, the internal alkalinization is followed by a continuous

  14. Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

    DEFF Research Database (Denmark)

    Clemmesen, Jens-Otto; Giraldi, Annamaria; Ott, Peter

    2008-01-01

    AIM: To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver...... disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown. METHODS: Ten patients with biopsy proven cirrhosis (five females/five males, mean age 54 +/- 8 years) and an HVPG above 12 mmHg were studied after informed...... consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick's principle, with correction for non-steady state...

  15. Circadian urinary citrate excretion in a rat model of exercise.

    Science.gov (United States)

    Nuñez, Paula; Diaz, Irene; Perillan, Carmen; Arguelles, Juan; Diaz, Elena

    2017-01-15

    Circadian rhythms are the approximate 24h biological cycles that function to prepare an organism for daily environmental changes. Circadian rhythms unquestionably play critical roles in metabolic homeostasis and the exercise has emerged as a strong non-photic time cue or zeitgeber in animal models and humans. Numerous studies about the effects of exercise on the citrate synthase activity have been published. Citrate is used to assess energy production or expenditure because it is a substrate of the Krebs Cycle, a cycle for oxidative energy production. We tested the existence of a rhythmic urinary citrate excretion in a rat model that is made to exercise at six different points during the day. The data obtained by the enzyme assays were fitted to a mathematical model (Fourier series), showing for the first time, the existence of a distinct ultradian rhythm in the urinary citrate excretion. The aerobic exercise led to the increase in the period length of the ultradian rhythm and raised the acrophase value of the urinary citrate excretion. Therefore, the urinary citrate excretion pattern changed after exercise, showing a clear circadian rhythm fitted to the mathematical model. The citrate urine samples could provide accurate data for ranking an individual's metabolic status. Using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective to prevent cardiometabolic disease development. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Sildenafil Effect on Nitric Oxide Secretion by Normal Human Endometrial Epithelial Cells Cultured In vitro

    Directory of Open Access Journals (Sweden)

    Farzaneh Chobsaz

    2011-01-01

    Full Text Available Background: Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specificphosphodiesterase type 5. It increases intracellular nitric oxide (NO production in some cells.There are reports on its positive effect on uterine circulation, endometrial thickness, and infertilityimprovement. Endometrial epithelial cells (EEC play an important role in embryo attachment andimplantation. The present work investigates the effect of sildenafil on human EEC and their NOsecretion in vitro.Materials and Methods: In this experimental in vitro study, endometrial biopsies (n=10 werewashed in a phosphate buffered solution (PBS and digested with collagenase I (2 mg/ml in DMEM/F12 medium at 37°C for 90 minutes. Epithelial glands were collected by sequential filtrationthrough nylon meshes (70 and 40 μm pores, respectively. Epithelial glands were then treated withtrypsin to obtain individual cells. The cells were counted and divided into four groups: control and1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; themedia were changed every 3 days, and their supernatants were collected for the NO assay. NO wasmeasured by standard Greiss methods. Data were analyzed by one way ANOVA.Results: There was no significant difference between groups in cell count and NO secretion, but thelevel of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cellcount. EEC morphology changed into long spindle cells in the case groups.Conclusion: Sildenafil (1, 10, and 20 μM showed a mild proliferative effect on human EECnumbers, but no significant change was seen in NO production.

  17. Safety and efficacy of sildenafil in Brazilian men with erectile dysfunction secondary to spinal cord injury

    Directory of Open Access Journals (Sweden)

    Carlos Eurico Dornelles Cairoli

    2008-03-01

    Full Text Available Objective: To evaluate the effect of sildenafil in Brazilian patientswith erectile dysfunction secondary to spinal cord injury. Methods:Participants were examined at the time of enrollment and two andsix weeks later. Baseline and follow-up data on sexual functionwere collected. After the second week, the initial dose of sildenafil(50 mg could be adjusted according to efficacy and tolerability.Efficacy was assessed primarily through the scores on questions 3and 4 of the International Index of Erectile Dysfunction. Secondaryanalyses included questions and domains of the index, globalefficacy evaluation, percentage of success in sexual intercourseattempts, answers to the Quality of Life and Erectile FunctionQuestionnaire, and partner’s satisfaction. Results: Ninety-onepatients were evaluated as to efficacy and 94 as to safety. Medianage of patients was 33 years, and median time between spinal cordinjury and study enrollment was three years. Sildenafil produceda significant increase in the mean scores of questions 3 and 4(p < 0.001 in both comparisons, as well as in other questionsand in all domains of the International Index of Erectile Dysfunction.Improved erections were reported by 89% of patients, and theproportion of successful sexual intercourse attempts went from6 to 74% (p < 0.001. Mean scores on the Quality of Life andErectile Dysfunction Questionnaire increased from 60 to 74%(p < 0.001. Ninety percent of 42 women reported being moderatelysatisfied to very satisfied with their partners’ treatment. The mostcommon adverse events were headache (16%, flushing (11% andnasal congestion (10%. Conclusions: Sildenafil proved to be safeand effective in treating Brazilian men with erectile dysfunctionsecondary to traumatic spinal injury.

  18. Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt-Sensitive Rat.

    Science.gov (United States)

    Gillis, Ellen E; Mooney, Jennifer N; Garrett, Michael R; Granger, Joey P; Sasser, Jennifer M

    2016-03-01

    Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. There is currently no effective treatment, but sildenafil, a phosphodiesterase-5 inhibitor, has been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. We hypothesized that sildenafil would improve the maternal syndrome and fetal outcomes in the Dahl S rat model of superimposed preeclampsia. Dahl S rats were mated, and half received sildenafil (50 mg/kg per day, via food) from day 10 through day 20 of pregnancy. The untreated Dahl S rats had a significant rise in blood pressure and a 2-fold increase in urinary protein excretion from baseline to late pregnancy; however, sildenafil-treated Dahl S rats exhibited ≈40 mm Hg drops in blood pressure with no rise in protein excretion. Sildenafil also increased creatinine clearance and reduced nephrinuria and glomerulomegaly. Sildenafil treatment reduced the uterine artery resistance index during late pregnancy in the Dahl S rat and improved fetal outcomes (survival, weight, and litter size). In addition, 19% of all pups were resorbed in untreated rats, with no incidence of resorptions observed in the treated group. Furthermore, tumor necrosis factor-α, endothelin-1, and oxidative stress, which are characteristically increased in women with preeclampsia and in experimental models of the disease, were reduced in treated rats. These data suggest that sildenafil improves the maternal syndrome of preeclampsia and blood flow to the fetoplacental unit, providing preclinical evidence to support the hypothesis that phosphodiesterase type 5 inhibition may be an important therapeutic target for the treatment of preeclampsia. © 2016 American Heart Association, Inc.

  19. Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress.

    Science.gov (United States)

    Sikandaner, Hu Erxidan; Park, So Young; Kim, Min Jung; Park, Shi Nae; Yang, Dong Won

    2017-02-15

    Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level. Sildenafil (15mg/kg) was orally administered 30min before noise exposure for 14days. Behavioral assessments were performed using novel object recognition (NOR) test and radial arm maze (RAM) test. Higher levels of memory dysfunction and oxidative stress were observed in noise alone-induced mice compared to control group. Interestingly, sildenafil administration increased memory performance, decreased oxidative stress, and increased neuroprotection in the hippocampus region of noise alone-induced mice likely through affecting memory related pathways such as cGMP/PKG/CREB and p25/CDK5, and induction of free radical scavengers such as SOD1, SOD2, SOD3, Prdx5, and catalase in the brain of stressed mice. Copyright © 2016. Published by Elsevier B.V.

  20. Identification of sildenafil, tadalafil and vardenafil by gas chromatography-mass spectrometry on short capillary column.

    Science.gov (United States)

    Man, Che Nin; Nor, Noorjuliana Md; Lajis, Razak; Harn, Gam Lay

    2009-11-20

    Sildenafil and its analogues (tadalafil and vardenafil) are phosphodiesterase type 5 inhibitors used in the treatment of male erectile dysfunction. Some dietary supplements, herbal preparations and food products which claim to enhance male sexual function have been found to be adulterated with these drugs. In this study, a gas chromatograph-mass spectrometer (GC-MS) assay was developed for identification of the drugs. In addition to good and short chromatographic separation that can be achieved within 6 min by using a short 10 m capillary column, no prior sample clean-up before GC-MS analysis was required, thus making this assay a cost saving and rapid method. Furthermore, the assay is specific as the identification of sildenafil, tadalafil and vardenafil were done by detection of molecular ions; m/z 474, 389 and 488, [corrected] respectively, and several other characteristic ions resulted from the mass fragmentation of individual molecules. Using our currently developed assay, sildenafil and its analogues were successfully identified in food and herbal matrices.

  1. Sildenafil limits monocrotaline-induced pulmonary hypertension in rats through suppression of pulmonary vascular remodeling.

    Science.gov (United States)

    Yen, Chia-Hung; Leu, Steve; Lin, Yu-Chun; Kao, Ying-Hsien; Chang, Li-Teh; Chua, Sarah; Fu, Morgan; Wu, Chiung-Jen; Sun, Cheuk-Kwan; Yip, Hon-Kan

    2010-06-01

    We hypothesize that sildenafil attenuates pulmonary hypertension through suppressing pulmonary vascular remodeling. Thirty male adult Sprague-Dawley rats were randomized to receive saline injection (Group 1), subcutaneous monocrotaline (MCT) (60 mg/kg) (Group 2), and MCT plus oral sildenafil (30 g/kg per day) (Group 3) 5 days after MCT administration. By Day 35, Western blot showed lower connexin43 and membranous protein kinase C epsilon expressions but higher oxidative stress in right ventricle in Group 2 compared with the other groups. Additionally, pulmonary Smad1/5 was lowest, whereas connexin43 and Smad3 were highest in Group 2. Pulmonary mRNA expressions of tumor necrosis factor-alpha, caspase-3, plasminogen activator inhibitor-1, and transforming growth factor-beta were higher, whereas bone morphogenetic protein Type II receptor, Bcl-2, and endothelial nitric oxide synthase were lower in Group 2 than in the other groups. Similarly, mRNA expressions of tumor necrosis factor-alpha, caspase-3, and beta-myosin heavy chain were increased, whereas Bcl-2, endothelial nitric oxide synthase, and alpha-myosin heavy chain expressions in right ventricle were reduced in Group 2 compared with the other groups. Number of lung arterioles was lowest, whereas number of arterioles with muscularization of the medial layer was highest in Group 2. Right ventricle systolic pressure and weight were elevated in Group 2 compared with the other groups. In conclusion, sildenafil effectively alleviates MCT-induced pulmonary hypertension through suppressing pulmonary vascular remodeling.

  2. PbSO4 Leaching in Citric Acid/Sodium Citrate Solution and Subsequent Yielding Lead Citrate via Controlled Crystallization

    Directory of Open Access Journals (Sweden)

    Dongsheng He

    2017-06-01

    Full Text Available Lead citrate is a key precursor for the green recycling of spent lead acid battery paste in a citric acid/sodium citrate (CA/SC solution. In this study, the main paste component, PbSO4, was leached and crystallized to yield lead citrate. Results showed that the leaching of PbSO4 in citric acid/sodium citrate solution was remarkably enhanced by an increase in temperature from 35 °C to 95 °C and an increase in sodium citrate (SC concentration from 50 to 650 g/L. In comparison, increasing the citric acid/sodium citrate molar ratio inhibited this leaching. Controlled crystallization through cooling the solution or adjusting the pH of the solution can effectively produce lead citrate crystals. The X-ray diffraction patterns of four products obtained in a comparison test were all consistent with Pb3(C6H5O72. However, the scanning electron microscopy analysis suggested that the morphology was distinct from rods to sheets, which were mainly affected by the temperature variation.

  3. Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies.

    Science.gov (United States)

    Brink, C B; Clapton, J D; Eagar, B E; Harvey, B H

    2008-01-01

    The phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals, and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma cells. We also show that fluoxetine (20 mg/kg/day x 7 days), as well as a combination of sildenafil (10 mg/kg/day x 7 days) plus the antimuscarinic atropine (1 mg/kg/day x 7 days) demonstrates significant, comparable antidepressant-like effects in the rat forced swim test (FST) and also reduces cortical beta-adrenergic receptor (beta-AR) density, while sildenafil or atropine alone did not. Importantly, sildenafil did not modify fluoxetine's response. Sildenafil thus demonstrates antidepressant-like effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in the neurobiology of depression.

  4. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

    Science.gov (United States)

    Karp, Heini J; Ketola, Maarit E; Lamberg-Allardt, Christel J E

    2009-11-01

    Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

  5. The Effects of Trimetazidine and Sildenafil on Bilateral Cavernosal Nerve Injury Induced Oxidative Damage and Cavernosal Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Dogan Atilgan

    2014-01-01

    Full Text Available Aim. The aim of this study was to compare the effects of sildenafil and trimetazidine on bilateral cavernosal nerve injury-induced oxidative damage and fibrotic changes in cavernosal tissue in rat model. Material and Methods. A total of 32 male Sprague-Dawley rats were randomly divided into 4 groups; each group consist 8 rats (control, BCI, BCI + TMZ, and BCI + sildenafil groups. Tissue superoxide dismutase (SOD, malondialdehyde (MDA, and protein carbonyl (PC levels were determined biochemically and distribution of cavernosal fibrosis density among groups was performed histopathologically. Results. Tissue SOD levels in BCI group were significantly lower than the control group (P<0.05. Tissue MDA and PC levels in BCI group were significantly higher than the control group (P<0.05. TMZ and sildenafil administration significantly increased tissue SOD levels (P<0.05 and reduced tissue MDA and PC levels (P<0.05. Histologically, the degree of cavernosal fibrosis and collagen density was higher in BCI group in comparison to control, TMZ-treated, and sildenafil-treated groups. Conclusion. BCI caused oxidative damage and increased cavernosal fibrosis in rat penis. TMZ and sildenafil treatment decreased oxidative damage and reduced the degree of fibrosis in penile tissue due to BCI.

  6. Effect of long-term administration of sildenafil on lipid profile and organ functions in hyperlipidemic rats.

    Science.gov (United States)

    El-Mahmoudy, Abubakr M; Shousha, Saad M; Abdel-Maksoud, Hussein; Abouzaid, Omayma

    2013-06-01

    The aim of the present study was to elucidate the possible biochemical alterations in lipid metabolic profile and organ function profiles that may result from continuous treatment with the drug, sildenafil in normal and hyperlipidemic rats. Blood samples were taken for biochemical analysis on days 30, 45 and 60 of the experiment. Sildenafil (5.625 mg/kg) significantly decreased the serum lipid parameters including total lipid, triacylglycerols, cholesterol, HDL-C, LDL-C, VLDL-C concentrations of rats fed on fat-enriched diet. However, it increased their values in serum of negative control rats. In addition, administration of sildenafil to normal rats caused insignificant changes in serum liver enzymes ALT and AST concentrations all over the period of the experiment; as well as serum urea and creatinine; yet, it significantly decreased their serum concentrations in animals fed on fat-enriched diet compared to the +ve untreated ones, upon its administration starting from the 30th day of the experiment.However, concurrent administration of sildenafil with highfat diet (group-iv) failed to guard against the rise in such liver and kidney function biomarkers. These data suggest that sildenafil may act as a mixed blessing drug; therefore it must be used carefully and under physician supervision to get its therapeutic benefits and guard against its adverse effects.

  7. Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Berger Ariel

    2012-12-01

    Full Text Available Abstract Background Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH impacts patterns of healthcare utilization and costs. Methods Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8 who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the “index date,” and claims data were compiled for all study subjects for 6 months prior to their index date (“pretreatment” and 6 months thereafter (“follow-up”; patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. Results A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD age was 52 (10 years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p  Conclusions The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

  8. Simplified Citrate Anticoagulation for CRRT Without Calcium Replacement.

    Science.gov (United States)

    Broman, Marcus; Klarin, Bengt; Sandin, Karin; Carlsson, Ola; Wieslander, Anders; Sternby, Jan; Godaly, Gabriela

    2015-01-01

    Since 2012, citrate anticoagulation is the recommended anticoagulation strategy for continuous renal replacement therapy (CRRT). The main drawback using citrate as anticoagulant compared with heparin is the need for calcium replacement and the rigorous control of calcium levels. This study investigated the possibility to achieve anticoagulation while eliminating the need for calcium replacement. This was successfully achieved by including citrate and calcium in all CRRT solutions. Thereby the total calcium concentration was kept constant throughout the extracorporeal circuit, whereas the ionized calcium was kept at low levels enough to avoid clotting. Being a completely new concept, only five patients with acute renal failure were included in a short, prospective, intensely supervised nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters were stable and remained within physiologic levels. Ionized calcium levels declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized calcium levels were CRRT.

  9. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    National Research Council Canada - National Science Library

    Fatemeh Fattahi; Abolfazl Aslani

    2013-01-01

    Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods...

  10. Counterfeits and imitations of Viagra and Cialis tablets: trends and risks to public health - A survey of the analyses carried out at the Dutch National Institute for Public Health and the Environment in the time period 2000 - 2004

    NARCIS (Netherlands)

    Blok-Tip L; Vogelpoel H; Vredenbregt MJ; Barends DM; de Kaste D; KCF

    2005-01-01

    De Nederlandse markt is de afgelopen jaren overspoeld met vervalsingen van Viagra. en Cialis. Beide producten worden gebruikt voor de behandeling van erectiestoornissen. Dit rapport gaat over een trendanalyse van deze vervalsingen over de jaren 2000 - 2004. Ook de risico's van deze

  11. Counterfeits and imitations of Viagra and Cialis tablets: trends and risks to public health - A survey of the analyses carried out at the Dutch National Institute for Public Health and the Environment in the time period 2000 - 2004

    NARCIS (Netherlands)

    Blok-Tip L; Vogelpoel H; Vredenbregt MJ; Barends DM; Kaste D de; KCF

    2005-01-01

    During the last years de Dutch market has been flooded with falsifications of Viagra. and Cialis.. Both products are used for the treatment of erectile dysfunction. This report is about the trend of these falsifications during the years 2000 - 2004. The risks of these products to public health are

  12. Prevalence and associated factors to tadalafil consumption in colombian college students during first semester of 2013

    Directory of Open Access Journals (Sweden)

    Javier Martínez-Torres

    2015-07-01

    Full Text Available The knowledge of sexual practices in young adults is required to run preventive actions aimed at the reduction of transmitted sexual diseases and unwanted pregnancies. To determine the prevalence Sildenafil Citrate consumption and its associated factors in College Students, during the first half-year of 2013. A crosssectional, descriptive study was conducted between April and June of 2013, the sample size was 340, and all of them are male college students, aged 18 to 26 years; all information were collected using a structured survey. The prevalence of Viagra or Sildenafil Citrate was 7,56% (CI95% 4,6%-10,6%; the main predisposing factors for its use is to suffer of Male Erectile Dysfunction (OR 14.72, CI95% 5.29 to 40.96, when it was adjusted by a multivariate model this association increases about 50% (OR 21.67, CI95% 6.27 to 74.89 and curiosity about this drug (OR 4 21 CI95% 1.63 to 11.3 is the second one. Although Sildenafil Citrate consumption has low prevalence; it is mainly related with men who have suffered erectile dysfunction and curiosity to experience its effects.

  13. Genomic diversity of citrate fermentation in Klebsiella pneumoniae

    Directory of Open Access Journals (Sweden)

    Liu Yen-Ming

    2009-08-01

    Full Text Available Abstract Background It has long been recognized that Klebsiella pneumoniae can grow anaerobically on citrate. Genes responsible for citrate fermentation of K. pneumoniae were known to be located in a 13-kb gene cluster on the chromosome. By whole genome comparison of the available K. pneumoniae sequences (MGH 78578, 342, and NTUH-K2044, however, we discovered that the fermentation gene cluster was present in MGH 78578 and 342, but absent in NTUH-K2044. In the present study, the previously unknown genome diversity of citrate fermentation among K. pneumoniae clinical isolates was investigated. Results Using a genomic microarray containing probe sequences from multiple K. pneumoniae strains, we investigated genetic diversity among K. pneumoniae clinical isolates and found that a genomic region containing the citrate fermentation genes was not universally present in all strains. We confirmed by PCR analysis that the gene cluster was detectable in about half of the strains tested. To demonstrate the metabolic function of the genomic region, anaerobic growth of K. pneumoniae in artificial urine medium (AUM was examined for ten strains with different clinical histories and genomic backgrounds, and the citrate fermentation potential was found correlated with the genomic region. PCR detection of the genomic region yielded high positive rates among a variety of clinical isolates collected from urine, blood, wound infection, and pneumonia. Conserved genetic organizations in the vicinity of the citrate fermentation gene clusters among K. pneumoniae, Salmonella enterica, and Escherichia coli suggest that the13-kb genomic region were not independently acquired. Conclusion Not all, but nearly half of the K. pneumoniae clinical isolates carry the genes responsible for anaerobic growth on citrate. Genomic variation of citrate fermentation genes in K. pneumoniae may contribute to metabolic diversity and adaptation to variable nutrient conditions in different

  14. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    OpenAIRE

    Fatemeh Fattahi; Abolfazl Aslani

    2013-01-01

    Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tabl...

  15. Coconut milk - citrate as extender for West African dwarf buck ...

    African Journals Online (AJOL)

    motility of 52.6% was highly significant (p = 0.018) at 2 hours post-extension in preserving motility of extended buck semen un-refrigerated compared to both D3 (40% coconut milk and 60% citrate buffer) and D4 (50% coconut milk and 50% citrate buffer). D2 also maintained mean sperm cell motility of 45% and was highly ...

  16. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

    NARCIS (Netherlands)

    Moll, Etelka; Bossuyt, Patrick M. M.; Korevaar, Johanna C.; Lambalk, Cornelis B.; van der Veen, Fulco

    2006-01-01

    OBJECTIVE: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. DESIGN: Randomised clinical trial. SETTING: Multicentre trial in 20 Dutch hospitals. PARTICIPANTS: 228 women with polycystic ovary

  17. Aroma compounds generation in citrate metabolism of Enterococcus faecium: Genetic characterization of type I citrate gene cluster.

    Science.gov (United States)

    Martino, Gabriela P; Quintana, Ingrid M; Espariz, Martín; Blancato, Victor S; Magni, Christian

    2016-02-02

    Enterococcus is one of the most controversial genera belonging to Lactic Acid Bacteria. Research involving this microorganism reflects its dual behavior as regards its safety. Although it has also been associated to nosocomial infections, natural occurrence of Enterococcus faecium in food contributes to the final quality of cheese. This bacterium is capable of fermenting citrate, which is metabolized to pyruvate and finally derives in the production of the aroma compounds diacetyl, acetoin and 2,3 butanediol. Citrate metabolism was studied in E. faecium but no data about genes related to these pathways have been described. A bioinformatic approach allowed us to differentiate cit(-) (no citrate metabolism genes) from cit(+) strains in E. faecium. Furthermore, we could classify them according to genes encoding for the transcriptional regulator, the oxaloacetate decarboxylase and the citrate transporter. Thus we defined type I organization having CitI regulator (DeoR family), CitM cytoplasmic soluble oxaloacetate decarboxylase (Malic Enzyme family) and CitP citrate transporter (2-hydroxy-carboxylate transporter family) and type II organization with CitO regulator (GntR family), OAD membrane oxaloacetate decarboxylase complex (Na(+)-transport decarboxylase enzyme family) and CitH citrate transporter (CitMHS family). We isolated and identified 17 E. faecium strains from regional cheeses. PCR analyses allowed us to classify them as cit(-) or cit(+). Within the latter classification we could differentiate type I but no type II organization. Remarkably, we came upon E. faecium GM75 strain which carries the insertion sequence IS256, involved in adaptative and evolution processes of bacteria related to Staphylococcus and Enterococcus genera. In this work we describe the differential behavior in citrate transport, metabolism and aroma generation of three strains and we present results that link citrate metabolism and genetic organizations in E. faecium for the first time

  18. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film.

    Science.gov (United States)

    Cocci, Andrea; Capece, Marco; Cito, Gianmartin; Russo, Giorgio Ivan; Falcone, Marco; Timpano, Massimiliano; Rizzo, Michele; Della Camera, Pier Andrea; Morselli, Simone; Campi, Riccardo; Sessa, Francesco; Cacciamani, Giovanni; Minervini, Andrea; Gacci, Mauro; Mirone, Vincenzo; Morelli, Girolamo; Mondaini, Nicola; Polloni, Gaia; Serni, Sergio; Natali, Alessandro

    2017-12-01

    A new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT). To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT. From May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks. The International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11-16), or mild (IIEF-15 score = 17-25). All patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = -0.19; P study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the "additional" side effects of the ODF formulation compared with FCT are reported. The new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy. Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of

  19. Citrate-release-mediated aluminum resistance is coupled to the inducible expression of mitochondrial citrate synthase gene in Paraserianthes falcataria.

    Science.gov (United States)

    Osawa, Hiroki; Kojima, Katsumi

    2006-05-01

    Aluminum (Al) resistance in some leguminous plants is achieved by enhanced citrate release from roots. Enhancement requires several hours for complete activation and is postulated to involve Al-responsive genes or components. We examined the mechanism of Al-induced citrate release by studying the relationship between citrate release and expression of the mitochondrial citrate synthase (mCS) gene in three leguminous trees. Root elongation in Leucaena leucocephala (Lam.) de Wit was arrested within 24 h by 30 microM Al, whereas root elongation in Paraserianthes falcataria (L.) Neilson and Acacia mangium Willd. was inhibited mangium maintained enhanced release and accumulation of citrate for at least 28 days in response to Al treatment. Aluminum increased the accumulation of mCS transcripts in P. falcataria roots, but not in L. leucocephala roots, and thus up-regulation decreased following removal of Al. Lanthanum did not alter the expression level of mCS. Aluminum increased mCS activity concomitantly with enhanced mCS gene expression in P. falcataria, whereas it did not affect mCS activity in L. leucocephala. Aluminum content in root apices of P. falcataria was increased by cycloheximide, supporting the idea that de novo synthesis of proteins is a prerequisite for Al resistance. Our findings suggest that Al-inducible expression of mCS coupled with enhanced citrate release mediates Al resistance in P. falcataria.

  20. The effects of sildenafil and n-acetylcysteine on ischemia and reperfusion injury in gastrocnemius muscle and femoral artery endothelium.

    Science.gov (United States)

    Aksu, Volkan; Yüksel, Volkan; Chousein, Serchat; Taştekin, Ebru; İşcan, Şahin; Sağiroğlu, Gönül; Canbaz, Suat; Sunar, Hasan

    2015-02-01

    We aimed to examine the effects of sildenafil and n-acetylcystein on ischemia/reperfusion injury in femoral artery endothelium and gastrocnemius muscle. 32 rats of Sprague-Dawley breed were randomly divided into four groups (n=8). Median laparotomy was performed, then a 120-minute ischemia was created by microvascular clamping of infrarenal aorta, followed by the release of clamping. In sildenafil group, 1 mg/kg of sildenafil infusion and in the n-acetylcystein group, 100 mg/kg of n-acetylcystein infusion was administered after release of clamps. Blood samples and tissue samples of femoral artery and gastrocnemius muscle were extracted for a histopathological evaluation. Serum levels of malondialdehyde in ischemia/reperfusion group (6.16±0.79) were higher compared to the control group (4.69±0.33), whereas a significant decrease was detected in sildenafil (5.17±0.50) and n-acetylcystein (4.96±0.49) groups. Femoral artery tissue sections of the control group, mean tumor necrosis factor alpha and hypoxy-induced factor-1 alpha immunoreactivity were found to be negative. In the ischemia/reperfusion group, mean tumor necrosis factor α immunoreactivity was intense and mean hypoxy-induced factor-1 alpha immunoreactivity was 51-75%. In the ischemia/reperfusion+Sildenafil and ischemia/reperfusion+NAS groups, mean tumor necrosis factor α immunoreactivity was slight and mean hypoxy-induced factor-1 alpha immunoreactivity was 26-50%. In conclusion, sildenafil and n-acetylcystein may reduce femoral artery endothelium and gastrocnemius muscle injury following lower extremity ischemia/reperfusion. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Why a combined intracavernosal injection with trimix and oral sildenafil is reliable therapy in the ultrasonographic evaluation of erectile dysfunction.

    Science.gov (United States)

    Park, Jong Kwan; Park, Jung Sun; Jeon, Sang Bong; Cui, Wan Shou; Kim, Sung Zoo; Kang, Kyung Koo; Lee, Sung Won

    2008-09-01

    To evaluate prospectively and compare the clinical response and the change in nucleotides correlating with haemodynamic changes in the cavernosal arteries after an intracavernosal injection (ICI) with vasoactive agents with or without oral sildenafil in men with erectile dysfunction (ED). In all, 80 patients with ED were prospectively evaluated by clinical assessments, measuring nucleotides in blood plasma and haemodynamics in cavernosal arteries. All patients had colour Doppler ultrasonography (CDU) twice with an interval of 5 h. First, each patient had CDU after ICI with trimix (0.25 mL) or prostaglandin E1 (PGE1, 5 microg), and the second CDU was after ICI trimix given 1 h after oral placebo (group I), sildenafil 25 mg (group II) or 100 mg (group III) and after ICI with PGE1 at 1 h after oral placebo (group IV) or 100 mg sildenafil (group V). Levels of cGMP and cAMP in peripheral venous and penile cavernosal blood plasma were measured at 15 min after ICI. The mean peak systolic velocity (PSV) at 5, 10, 15 min, and resistive index at 10 min in the second CDU after ICI with trimix, were significantly increased in group III. The mean (sem) levels of cavernosal cGMP were significantly increased in group III and V, from 1130.1 (313.5) to 2056.7 (580.4) and 1017.0 (214.2) to 1905.2 (915.0) fmol/mL, respectively. cAMP was significantly increased in group V, from 9533.1 (2068.4) to 12150 (3684.2) fmol/mL. The haemodynamic changes and cGMP and cAMP production in the cavernosum were improved by trimix plus sildenafil more than with than PGE1 plus sildenafil or one ICI with trimix or PGE1. The results suggest that ICI with trimix and sildenafil is the best combination for a pharmacological erection test.

  2. Formulation and process considerations for the design of sildenafil-loaded polymeric microparticles by vibrational spray-drying

    DEFF Research Database (Denmark)

    Beck-Broichsitter, Moritz; Bohr, Adam; Aragão-Santiago, Leticia

    2017-01-01

    CONTEXT AND OBJECTIVE: The current study reports the preparation and characterization of sildenafil-loaded poly(lactide-co-glycolide) (PLGA)-based microparticles (MPs) by means of vibrational spray-drying. Emphasis was placed on relevant formulation and process parameters with influence on the pr......CONTEXT AND OBJECTIVE: The current study reports the preparation and characterization of sildenafil-loaded poly(lactide-co-glycolide) (PLGA)-based microparticles (MPs) by means of vibrational spray-drying. Emphasis was placed on relevant formulation and process parameters with influence...

  3. Appraisal of sildenafil binding on the structure and promiscuous esterase activity of native and histidine-modified forms of carbonic anhydrase II.

    Science.gov (United States)

    Mahdiuni, Hamid; Bijari, Nooshin; Varzandian, Masoud; Ghadami, Seyyed Abolghasem; Khazaei, Mozafar; Nikbakht, Mohammad Reza; Khodarahmi, Reza

    2013-01-01

    Sildenafil was investigated for its interaction with the native and modified human carbonic anhydrase II (hCA II). Modification of exposed histidine side chains with diethyl pyrocarbonate decreased esterase activity of the enzyme. The treatment of both native and modified CA with sildenafil revealed slight and moderate enzyme activation profiles, respectively. In addition, in the present study the effects of sildenafil on the structural properties of native and modified hCA II were investigated employing different computer simulation and spectroscopic techniques such as UV-vis, circular dichroism (CD), fluorescence spectroscopy and molecular dynamics. Fluorescence measurements showed that the sildenafil acts as a quencher of the native and modified enzyme fluorescence. Stern-Volmer analyses revealed the existence of one binding site on the native/modified enzyme for sildenafil. The thermodynamic parameters, enthalpy change (∆H) and entropy change (∆S) of drug binding were not also similar, which indicate that different interactions are responsible in CA-drug interaction. Calculation of the protein surface hydrophobicity (PSH), using 1,8-Anilinonaphtalene Sulfonate (ANS), indicated the increment of PSH of native and modified hCA II in the presence of sildenafil. Overall, sildenafil-CA interaction probably induces protein conformational changes and completes reorganization of both hydrogen bond networks within the active site cavity and hydration positions on the protein surface. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment.

    Science.gov (United States)

    Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye

    2010-04-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.

  5. Oral sildenafil as a rescue therapy in presumed acute pulmonary hypertensive crisis.

    Science.gov (United States)

    Maxted, Andrew Peter; Hill, Abigail; Davies, Patrick

    2013-02-01

    A 23-week-old baby, born at 26(+2) weeks, presented to the hospital with critical respiratory failure, which was impossible to stabilize. She had unstable oxygen saturations between 35% and 95%. A presumptive diagnosis of bronchopulmonary dysplasia with associated pulmonary hypertensive crisis was made. In the absence of inhaled nitric oxide, 2 oral doses of 1 mg/kg sildenafil were given, with a dramatic improvement 30 to 45 minutes later. Her oxygenation index fell from 43 to 14. She made a full recovery and was discharged from the hospital 2 weeks later.

  6. Application of Triethyl Citrate to Filters in Virginia Type Cigarettes*

    Directory of Open Access Journals (Sweden)

    Jin Yong

    2015-01-01

    Full Text Available Triethyl citrate (TEC was applied in the preparation of cigarette filter rods by two approaches. One was to utilize TEC as a plasticizer sprayed onto the surface of cellulose acetate (CA fibers. The other was to apply TEC as an additive coated onto the cellulosic paper of acetate-paper dual filters. Three types of cigarette filter rods, namely, triethyl citrate-cellulose acetate (TEC-CA filter rods, triethyl citrate-cellulose acetate-paper (TEC-CA-paper dual filter rods and cellulose acetate-paper-triethyl citrate (CA-paper-TEC dual filter rods, were manufactured. In order to promote the curing of CA rods, high-frequency radiation was introduced into the procedure of filter manufacture. Then Virginia type cigarettes, combined with the three kinds of prepared filter rods were manufactured and the removal efficiency of phenols from the cigarette mainstream smoke was investigated. The results revealed that no matter where the triethyl citrate was applied as plasticizer or coating additive, the content of phenol, o-, m-and p-cresol in cigarette mainstream smoke could be greatly reduced. The optimal removal efficiency for phenol was 50% compared with the control. [Beitr. Tabakforsch. Int. 26 (2014 176-182

  7. Inpatient citrate-based hemodialysis in pediatric patients.

    Science.gov (United States)

    Fajardo, Cecile; Sanchez, Cheryl P; Cutler, Drew; Sahney, Shobha; Sheth, Rita

    2016-10-01

    Citrate-based dialysate is an effective method of hemodialysis (HD) anticoagulation in adults. The objective of this study was to evaluate this therapy as an alternative to heparin anticoagulation in pediatric patients in the inpatient setting requiring HD. We performed a prospective, non-randomized study of citrate-based dialysate HD treatments (N = 119) over a 9-month period in 18 pediatric patients (age range 0-18 years) admitted to hospital. Primary outcome measures were thrombosis incidence rates that resulted in circuit loss, catheter loss or early dialysis termination. Secondary outcome measures were hypocalcemia incidence and heparin use. Data analysis was performed using descriptive and comparative statistics. There was a thrombosis incidence rate of 2.5 % circuit loss, 2.5 % catheter loss and 5.9 % early dialysis termination due to the thrombosis risk. In 64 % of treatments a circuit clot developed but with no circuit loss, and mild asymptomatic hypocalcemia deveoped in 58 % of the monitored HD sessions . No patient required additional heparin during the citrate-based HD treatments, but 11.1 % were subsequently converted to heparin anticoagulation. Our study showed a low percentage of thrombotic episodes resulting in catheter or circuit loss. Hypocalcemia was common but remained mild and asymptomatic. Citrate-based dialysate was well tolerated by our patients. We therefore conclude that citrate-based dialysate is a safe alternative to heparin-based hemodialysis anticoagulation.

  8. Sildenafil obviates ischemia-reperfusion injury-induced acute kidney injury through peroxisome proliferator-activated receptor γ agonism in rats.

    Science.gov (United States)

    Mohey, Vinita; Singh, Manjinder; Puri, Nikkita; Kaur, Tajpreet; Pathak, Devendra; Singh, Amrit Pal

    2016-03-01

    Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor γ (PPAR-γ) in sildenafil-mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to ischemia-reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-γ receptor antagonist, was given before sildenafil administration followed by IRI. The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-γ agonism in the sildenafil-mediated renoprotective effect. It is concluded that sildenafil protects against ischemia-reperfusion-induced AKI through PPAR-γ agonism in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Enhanced citrate production through gene insertion in Aspergillus niger

    DEFF Research Database (Denmark)

    Jongh, Wian de; Nielsen, Jens

    2007-01-01

    The effect of inserting genes involved in the reductive branch of the tricarboxylic acid (TCA) cycle on citrate production by Aspergillus niger was evaluated. Several different genes were inserted individually and in combination, i.e. malate dehydrogenase (mdh2) from Saccharomyces cerevisiae, two...... truncated, cytosolic targeted, fumarases (Fum1s and FumRs) from S. cerevisiae and Rhizopus oryzae, respectively, and the cytosolic soluble fumarate reductase (Frds1) from S. cerevisiae. Overexpression of these genes in their native strain backgrounds has been reported to lead to alterations...... in the intracellular cytosolic dicarboxylate concentrations. It was found that all the transformant strains had enhanced yield and productivities of citrate compared with the wild-type strain. The transformants also had the ability to produce citrate in trace-manganese-contaminated medium, where the wild type...

  10. Efficacies of Papaverine and Sildenafil in the Treatment of Erectile Dysfunction in Early-Stage Paraplegic Men

    Science.gov (United States)

    Yildiz, Necmettin; Gokkaya, Nilufer Kutay Ordu; Koseoglu, Fusun; Gokkaya, Serkan; Comert, Didem

    2011-01-01

    The aim of the study was to determine which vasoactive agent was more efficacious for erectile dysfunction (ED), intracavernosal papaverine or oral sildenafil, in paraplegic men within the first year after injury by using a penile color Doppler ultrasound as a quantitative imaging method and to determine the association between responses to these…

  11. Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

    Directory of Open Access Journals (Sweden)

    Leah A. Garcia

    2014-09-01

    Full Text Available Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG. Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1 β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1, and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH oxidase, Myeloperoxidase (MPO, inducible nitric oxide synthase (iNOS, TNF receptor superfamily member 5 (CD40 that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.

  12. Sildenafil and tadalafil in simulated chlorination conditions: Ecotoxicity of drugs and their derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Temussi, Fabio; DellaGreca, Marina; Pistillo, Paola; Previtera, Lucio; Zarrelli, Armando [UdR Napoli 4 INCA, Dipartimento di Scienze Chimiche, Complesso Universitario di Monte Sant' Angelo, Università Federico II, Via Cintia, I-80126 Napoli (Italy); Criscuolo, Emma; Lavorgna, Margherita; Russo, Chiara [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Isidori, Marina, E-mail: marina.isidori@unina2.it [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy)

    2013-10-01

    Chlorination experiments on two drugs (sildenafil and tadalafil) were performed mimicking the conditions of a typical wastewater treatment process. The main transformation products were isolated by chromatographic techniques (Thin Layer Chromatography (TLC), Column Chromatography (CC), High Performance Liquid Chromatography (HPLC)) and fully characterized employing Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) analyses. The environmental effects of the parent compounds and transformation products were evaluated using an overall toxicity approach that considered aquatic acute and chronic toxicity on Brachionus calyciflorus and Ceriodaphnia dubia as well as mutagenesis and genotoxicity on bacterial strains. The results revealed that both parent drugs did not show high acute and chronic toxicity for the organisms utilized in the bioassays while, chronic exposure to chlorine derivatives caused inhibition of growth population on rotifers and crustaceans. A mutagenic potential was found for all the compounds investigated. - Highlights: • Simulated disinfection process of pharmaceuticals was performed. • Toxicity and genotoxicity of sildenafil, tadalafil and their derivatives were evaluated. • Chlorine derivatives caused chronic toxicity on rotifers and crustaceans. • A mutagenic potential was found for all the compounds investigated.

  13. CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population.

    Science.gov (United States)

    Wonnacott, Rob; Josephs, Brandi; Jamieson, Jill

    2016-01-01

    Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate-reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT.

  14. Physical profiling and IR spectroscopy: simple and effective methods to discriminate between genuine and counterfeit samples of Viagra® and Cialis®.

    Science.gov (United States)

    Custers, Deborah; Vandemoortele, Suzanne; Bothy, Jean-Luc; De Beer, Jacques O; Courselle, Patricia; Apers, Sandra; Deconinck, Eric

    2016-01-01

    Counterfeit medicines are a global threat to public health. High amounts enter the European market, enforcing the need for simple techniques to help customs detect these pharmaceuticals. This study focused on physical profiling and IR spectroscopy to obtain a prime discrimination between genuine and illegal Viagra® and Cialis® medicines. Five post-tableting characteristics were explored: colour, mass, long length, short length, and thickness. Hypothesis testing showed that most illegal samples (between 60 and 100%) significantly differ from the genuine medicines, in particular for mass and long length. Classification and Regression Trees (CART) analysis resulted in a good discrimination between genuine and illegal medicines (98.93% correct classification rate for Viagra®, 99.42% for Cialis®). Moreover, CART confirmed the observation that mass and long length are the key physical characteristics which determine the observed discrimination. IR analysis was performed on tablets without blister and on tablets in intact blister. These data were analyzed using Soft Independent Modelling of Class Analogy (SIMCA) and Partial Least Squares - Discriminant Analysis (PLS-DA). Supervised techniques needed to be applied since Principal Component Analysis (PCA) was not able to generate the desired discrimination. Our study shows that a perfect discrimination between genuine and illegal medicines can be made by both SIMCA and PLS-DA without removing the tablets from the blister. This approach has the advantage of keeping the blister intact. Our study demonstrates that these user friendly techniques are reliable methods to aid customs to obtain a prime distinction between genuine and illegal samples on the spot. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study

    Directory of Open Access Journals (Sweden)

    Radhouane Bousselmi

    2015-01-01

    Full Text Available A prospective, observational, feasibility study was carried out on four patients with end-stage renal failure undergoing bicarbonate hemodialysis to study the feasibility of an on-line hemodiafiltration technique using a citrate dialysate with pre-dilutional infusion of citrate as a technique for regional citrate anticoagulation. All patients had contraindication to systemic heparin anticoagulation. The dialysis technique consisted of an on-line hemodiafiltration with a citrate dialysate without calcium using a Fresenius 4008S dialysis machine and Fresenius Polysulfone F60 dialyzers. The infusion solution was procured directly from the dialysate and was infused into the arterial line. To avoid the risk of hypocalcemia, calcium gluconate was infused to the venous return line. The study was carried out in two stages. During the first stage, the citrate infusion rate was 80 mL/min and the calcium infusion rate was 9 mmol/h. At the second stage, the rates were 100 mL/min and 11 mmol/h, respectively. The primary endpoint of this study was the incidence of thrombosis in the extracorporeal blood circuit and/or the dialyzer. A total of 78 sessions were conducted. All the sessions were well tolerated clinically and there were no major incidents in any of the four patients. At the first stage of the study, there were five incidences of small clots in the venous blood chamber, an incidence of extracorporeal blood circuit thrombosis of 12.5%. At the second stage of the study, no cases of extracorporeal blood circuit or dialyzer thrombosis were noted. Hemodiafiltration with on-line citrate dialysate infusion to the arterial line is safe and allows an effective regional anticoagulation of the extracorporeal blood circuit without the need for systemic anticoagulation.

  16. Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

    Science.gov (United States)

    Constantinescu, Mihaela Ioana; Constantinescu, Dan Petru; Andercou, Aurel; Mironiuc, Ion Aurel

    2013-01-01

    Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH

  17. Citrate anticoagulation for CRRT: don?t always trust the postfilter iCa results!

    OpenAIRE

    Oudemans-van Straaten, Heleen M.; Ostermann, Marlies

    2015-01-01

    Citrate has been recommended as the first-line anticoagulant for continuous renal replacement therapy (CRRT) in critically ill patients. Compared with heparin, citrate anticoagulation is safer and more efficacious. Citrate inhibits the coagulation cascade by lowering the ionized calcium (iCa) concentration in the filter. Monitoring of systemic iCa concentrations is inherent to the protocol, and monitoring of postfilter iCa is recommended to adjust citrate flow and optimize anticoagulation. Wh...

  18. Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury

    National Research Council Canada - National Science Library

    Xu, Y; Xin, H; Wu, Y; Guan, R; Lei, H; Fu, X; Xin, Z; Yang, Y

    2017-01-01

    .... The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague...

  19. Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats

    Directory of Open Access Journals (Sweden)

    Sumanta Kumar Goswami, PhD

    2016-06-01

    Conclusion: Phloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity.

  20. 75 FR 34360 - Listing of Color Additives Exempt From Certification; Bismuth Citrate; Confirmation of Effective...

    Science.gov (United States)

    2010-06-17

    ... Certification; Bismuth Citrate; Confirmation of Effective Date AGENCY: Food and Drug Administration, HHS... level of bismuth citrate as a color additive in cosmetics intended for coloring hair on the scalp. DATES... increasing the permitted use level of bismuth citrate as a color additive in cosmetics intended for coloring...

  1. 75 FR 14491 - Listing of Color Additives Exempt From Certification; Bismuth Citrate

    Science.gov (United States)

    2010-03-26

    ... Certification; Bismuth Citrate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food... level of bismuth citrate as a color additive in cosmetics intended for coloring hair on the scalp. This.... 73.2110 Bismuth citrate (21 CFR 73.2110) by increasing the maximum permitted use level of bismuth...

  2. Enzyme Basis for pH Regulation of Citrate and Pyruvate Metabolism by Leuconostoc oenos

    NARCIS (Netherlands)

    Ramos, Ana; Lolkema, Juke S.; Konings, Wilhelmus; Santos, Helena

    Citrate and pyruvate metabolism by nongrowing cells of Leuconostoc oenos was investigated. 13C nuclear magnetic resonance (NMR) spectroscopy was used to elucidate the pathway of citrate breakdown and to probe citrate or pyruvate utilization, noninvasively, in living cell suspensions. The utilization

  3. 77 FR 24461 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Science.gov (United States)

    2012-04-24

    ..., which are intermediate products in the production of citric acid, sodium citrate, and potassium citrate... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... the preliminary results of the administrative review of the antidumping duty order on citric acid and...

  4. Ca2+-Citrate Uptake and Metabolism in Lactobacillus casei ATCC 334

    NARCIS (Netherlands)

    Mortera, Pablo; Pudlik, Agata; Magni, Christian; Alarcon, Sergio; Lolkema, Juke S.

    The putative citrate metabolic pathway in Lactobacillus casei ATCC 334 consists of the transporter CitH, a proton symporter of the citrate-divalent metal ion family of transporters CitMHS, citrate lyase, and the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Resting cells of

  5. 78 FR 34338 - Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of Antidumping Duty...

    Science.gov (United States)

    2013-06-07

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of... administrative review of the antidumping duty order on citric acid and certain citrate salts (citric acid) from... is citric acid and certain citrate salts. The product is currently classified in the Harmonized...

  6. 78 FR 64914 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Science.gov (United States)

    2013-10-30

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... of the antidumping duty order on citric acid and certain citrate salts from Canada.\\1\\ The review... period of review (POR) is May 1, 2011, through April 30, 2012. \\1\\ See Citric Acid and Certain Citrate...

  7. Ovarian capsular drilling in the treatment of clomiphene citrate ...

    African Journals Online (AJOL)

    Background: Laparoscopic Ovarian Drilling (LOD) is an effective and a well evaluated surgical Treatment of Clomiphene Citrate resistant Polycystic ovarian syndrome. Transvaginal hydrolaparoscopy (TVHL) is a relatively new simple method of exploring the pelvis and has recently been introduced as a transvaginal ...

  8. The Effect of Polymer Molecular Weight on Citrate Crosslinked ...

    African Journals Online (AJOL)

    Erah

    The Effect of Polymer Molecular Weight on Citrate. Crosslinked Chitosan Films for Site-Specific Delivery of a Non-Polar Drug. Soheyla Honary*, Behnam Hoseinzadeh and Payman. Shalchian. Mazandaran University of Medical Sciences, School of Pharmacy, Pharmaceutical Sciences Research Center, Sari,. Iran. Abstract.

  9. Acute effect of citrate bath on postdialysis alkalaemia

    Directory of Open Access Journals (Sweden)

    Patricia De Sequera Ortiz

    2015-03-01

    Conclusion: Dialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease.

  10. 21 CFR 520.1803 - Piperazine citrate capsules.

    Science.gov (United States)

    2010-04-01

    ... animal has finished eating the dosed food, the remainder of the food may be given. Dogs and cats may be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine citrate capsules. 520.1803 Section 520.1803 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  11. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate tablets. 520.622a Section 520.622a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... mouth. For the treatment of ascarid infections, repeat in 10 to 20 days to remove immature worms that...

  12. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... should be given in 10 to 20 days to remove immature worms which may enter the intestine from the lungs...

  13. The Effect of Polymer Molecular Weight on Citrate Crosslinked ...

    African Journals Online (AJOL)

    Methods: Films prepared with different molecular weights of chitosan and incorporating indomethacin as a non-polar model drug were obtained by a casting/solvent evaporation method. The chitosan films were crosslinked by dipping in varying concentrations of sodium citrate solution and for different crosslinking times.

  14. Mayenite Synthesized Using the Citrate Sol-Gel Method

    Energy Technology Data Exchange (ETDEWEB)

    Ude, Sabina N [ORNL; Rawn, Claudia J [ORNL; Meisner, Roberta A [University of Tennessee (UTK) and Oak Ridge National Laboratory (ORNL); Kirkham, Melanie J [ORNL; Jones, Gregory L. [University of Tennessee, Knoxville (UTK); Payzant, E Andrew [ORNL

    2014-01-01

    A citrate sol-gel method has been used to synthesize mayenite (Ca12Al14O33). X-ray powder diffraction data show that the samples synthesized using the citrate sol-gel method contained CaAl2O4 and CaCO3 along with mayenite when fired ex-situ in air at 800 C but were single phase when fired at 900 C and above. Using high temperature x-ray diffraction, data collected in-situ in air at temperatures of 600 C and below showed only amorphous content; however, data collected at higher temperatures indicated the first phase to crystallize is CaCO3. High temperature x-ray diffraction data collected in 4% H2/96% N2 does not show the presence of CaCO3, and Ca12Al14O33 starts to form around 850 C. In comparison, x-ray powder diffraction data collected ex-situ on samples synthesized using traditional solid-state synthesis shows that single phase was not reached until samples were fired at 1350 C. DTA/TGA data collected either in a nitrogen environment or air on samples synthesized using the citrate gel method suggest the complete decomposition of metastable phases and the formation of mayenite at 900 C, although the phase evolution is very different depending on the environment. Brunauer-Emmett-Teller (BET) measurements showed a slightly higher surface area of 7.4 0.1 m2/g in the citrate gel synthesized samples compared to solid-state synthesized sample with a surface area of 1.61 0.02 m2/g. SEM images show a larger particle size for samples synthesized using the solid-state method compared to those synthesized using the citrate gel method.

  15. Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.

    Science.gov (United States)

    Damy, Thibaud; Hobkirk, James; Walters, Mandy; Ciobanu, Andrea; Rigby, Alan S; Kallvikbacka-Bennett, Anna; Guellich, Aziz; Dubois-Randé, Jean-Luc; Hittinger, Luc; Clark, Andrew L; Cleland, John G F

    2015-09-01

    Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P exercise was not substantially reduced by sildenafil. Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

  16. A role for ATP-citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion.

    Science.gov (United States)

    Guay, Claudiane; Madiraju, S R Murthy; Aumais, Alexandre; Joly, Erik; Prentki, Marc

    2007-12-07

    In pancreatic beta-cells, metabolic coupling factors generated during glucose metabolism and pyruvate cycling through anaplerosis/cataplerosis processes contribute to the regulation of insulin secretion. Pyruvate/citrate cycling across the mitochondrial membrane leads to the production of malonyl-CoA and NADPH, two candidate coupling factors. To examine the implication of pyruvate/citrate cycling in glucose-induced insulin secretion (GIIS), different steps of the cycle were inhibited in INS 832/13 cells by pharmacological inhibitors and/or RNA interference (RNAi) technology: mitochondrial citrate export, ATP-citrate lyase (ACL), and cytosolic malic enzyme (ME1). The inhibitors of the di- and tri-carboxylate carriers, n-butylmalonate and 1,2,3-benzenetricarboxylate, respectively, reduced GIIS, indicating the importance of transmitochondrial transport of tri- and dicarboxylates in the action of glucose. To directly test the role of ACL and ME1 in GIIS, small hairpin RNA (shRNA) were used to selectively decrease ACL or ME1 expression in transfected INS 832/13 cells. shRNA-ACL reduced ACL protein levels by 67%, and this was accompanied by a reduction in GIIS. The amplification/K(ATP)-independent pathway of GIIS was affected by RNAi knockdown of ACL. The ACL inhibitor radicicol also curtailed GIIS. shRNA-ME1 reduced ME1 activity by 62% and decreased GIIS. RNAi suppression of either ACL or ME1 did not affect glucose oxidation. However, because ACL is required for malonyl-CoA formation, inhibition of ACL expression by shRNA-ACL decreased glucose incorporation into palmitate and increased fatty acid oxidation in INS 832/13 cells. Taken together, the results underscore the importance of pyruvate/citrate cycling in pancreatic beta-cell metabolic signaling and the regulation of GIIS.

  17. Bosentan and sildenafil: successful treatment in a sclerodermic patient with refractory ulcers

    Directory of Open Access Journals (Sweden)

    E. Catarsi

    2013-05-01

    Full Text Available Systemic sclerosis is an inflammatory disease of the connective tissue characterized by vasculopathy and accumulation of collagen and other components of the connective matrix, affecting the skin and internal organs. The appearance of skin ulcers as a result of vascular damage is very common in the history of the disease. Skin ulcers, painful and slow healing due to atrophy and local ischemia, get worse the quality of life of patients. Often, the use of conventional therapies (such as calcium channel blockers and prostanoids does not cause the complete healing of the lesions. We report the case of a patient in whom therapeutic association between endothelin antagonist (bosentan and phosphodiesterase-V inhibitor (sildenafil resulted in complete healing of old ulcers both to upper and lower limbs and allowed the interruption of intravenous therapies.

  18. Acute effect of citrate bath on postdialysis alkalaemia.

    Science.gov (United States)

    Ortiz, Patricia De Sequera; Ramón, Marta Albalate; Pérez-García, Rafael; Prats, Elena Corchete; Cobo, Patricia Arribas; Arroyo, Roberto Alcázar; Díaz, Maira Ortega; Carretero, Marta Puerta

    2015-01-01

    The correction of metabolic acidosis caused by renal failure is achieved by adding bicarbonate during dialysis. In order to avoid the precipitation of calcium carbonate and magnesium carbonate that takes place in the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid, usually acetate, which is not free of side effects. Thus, citrate appears as an advantageous alternative to acetate, despite the fact that its acute effects are not accurately known. To assess the acute effect of a dialysis fluid containing citrate instead of acetate on acid-base balance and calcium-phosphorus metabolism parameters. A prospective crossover study was conducted with twenty-four patients (15 male subjects and 9 female subjects). All patients underwent dialysis with AK-200-Ultra-S monitor with SoftPac® dialysis fluid, made with 3 mmol/L of acetate and SelectBag Citrate®, with 1 mmol/L of citrate and free of acetate. The following were measured before and after dialysis: venous blood gas monitoring, calcium (Ca), ionic calcium (Cai), phosphorus (P) and parathyroid hormone (PTH). Differences (p<0.05) were found when using the citrate bath (C) compared to acetate (A) in the postdialysis values of: pH, C: 7.43 (0.04) vs. A: 7.47 (0.05); bicarbonate, C: 24.7 (2.7) vs. A: 27.3 (2.1) mmol/L; base excess (BEecf), C: 0.4 (3.1) vs. A: 3.7 (2.4) mmol/L; corrected calcium (Cac), C: 9.8 (0.8) vs. A: 10.1 (0.7) mg/dL; and Cai, C: 1.16 (0.05) vs. A: 1.27 (0.06) mmol/L. No differences were found in either of the parameters measured before dialysis. Dialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease. Copyright © 2015. Published by Elsevier España, S.L.U.

  19. Metformin-clomiphene citrate vs. clomiphene citrate alone: Polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Aqueela Ayaz

    2013-01-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is the commonest endocrinopathy in women that is associated with reproductive and metabolic disorders. Objectives: We compared the ovulation and conception rates after the treatment with clomiphene citrate (CC alone and in combination with metformin in infertile patients presented with polycystic ovarian syndrome (PCOS. Materials and Methods: This randomized controlled trial of independent cases and controls was conducted at the Department of Obstetrics and Gynecology, Hera General Hospital, Makkah, Saudi Arabia from February 01 to December 31, 2008. The 42 subjects diagnosed as PCOS were divided into group A and B (21 subjects in each for management with CC + metformin and CC alone, respectively. Group A received 500 mg three times a day of metformin continuously from the first cycle for 6 months or till pregnancy was confirmed. In both groups CC was started at a dose of 50 mg from day-2 till day-6 of the menstrual cycle. The dose of CC was increased to 100 mg in second and 150 mg in third cycle, and then remained 150 mg for the remaining three cycles. With ovulation the dose of CC was unaltered in both groups. Data were analyzed using Statistical Package for the Social Sciences (SPSS version 16. Results: More than 50% females in both groups were had body mass index > 25. Group A achieved high rate of regular cycles, ovulation success, and conception than group B (71.4% vs. 38.1%; P = 0.03, (76.2% vs. 38.1%; P = 0.021, and (66.6% vs. 28.6%; P = 0.01, respectively. Conclusion: Management with metformin + CC increased the ovulation and conception rates.

  20. Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching.

    Science.gov (United States)

    Chamorro, Virginia; Morales-Cano, Daniel; Milara, Javier; Barreira, Bianca; Moreno, Laura; Callejo, María; Mondejar-Parreño, Gema; Esquivel-Ruiz, Sergio; Cortijo, Julio; Cogolludo, Ángel; Barberá, Joan A; Perez-Vizcaino, Francisco

    2018-01-01

    Current treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized. Contraction was recorded in pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized to record PA pressure. Ventilation and perfusion were analyzed by micro-CT-SPECT images in rats with pulmonary fibrosis induced by bleomycin. The PDE5 inhibitor sildenafil and the sGC stimulator riociguat similarly inhibited HPV in vitro and in vivo. Riociguat was more effective as vasodilator in isolated rat and human PA than sildenafil. Riociguat was ≈3-fold more potent under hypoxic conditions and it markedly inhibited HPV in vivo at a dose that barely affected the thromboxane A2 (TXA2) mimetic U46619-induced pressor responses. Pulmonary fibrosis was associated with V'/Q' uncoupling and riociguat did not affect the V'/Q' ratio. PDE5 inhibitors and sGC stimulators show a different vasodilator profile. Riociguat was highly effective and potentiated by hypoxia in rat and human PA. In vivo, riociguat preferentially inhibited hypoxic than non-hypoxic vasoconstriction. However, it did not worsen V'/Q' coupling in a rat model of pulmonary fibrosis.

  1. 77 FR 56188 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Notice of Rescission...

    Science.gov (United States)

    2012-09-12

    ... citrate tetrahydrate, which are intermediate products in the production of citric acid, sodium citrate... International Trade Administration Citric Acid and Certain Citrate Salts from the People's Republic of China... of the countervailing duty (CVD) order on citric acid and certain citrate salts from the People's...

  2. Ca2+-Citrate Uptake and Metabolism in Lactobacillus casei ATCC 334

    Science.gov (United States)

    Mortera, Pablo; Pudlik, Agata; Magni, Christian; Alarcón, Sergio

    2013-01-01

    The putative citrate metabolic pathway in Lactobacillus casei ATCC 334 consists of the transporter CitH, a proton symporter of the citrate-divalent metal ion family of transporters CitMHS, citrate lyase, and the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Resting cells of Lactobacillus casei ATCC 334 metabolized citrate in complex with Ca2+ and not as free citrate or the Mg2+-citrate complex, thereby identifying Ca2+-citrate as the substrate of the transporter CitH. The pathway was induced in the presence of Ca2+ and citrate during growth and repressed by the presence of glucose and of galactose, most likely by a carbon catabolite repression mechanism. The end products of Ca2+-citrate metabolism by resting cells of Lb. casei were pyruvate, acetate, and acetoin, demonstrating the activity of the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Following pyruvate, the pathway splits into two branches. One branch is the classical citrate fermentation pathway producing acetoin by α-acetolactate synthase and α-acetolactate decarboxylase. The other branch yields acetate, for which the route is still obscure. Ca2+-citrate metabolism in a modified MRS medium lacking a carbohydrate did not significantly affect the growth characteristics, and generation of metabolic energy in the form of proton motive force (PMF) was not observed in resting cells. In contrast, carbohydrate/Ca2+-citrate cometabolism resulted in a higher biomass yield in batch culture. However, also with these cells, no generation of PMF was associated with Ca2+-citrate metabolism. It is concluded that citrate metabolism in Lb. casei is beneficial when it counteracts acidification by carbohydrate metabolism in later growth stages. PMID:23709502

  3. Aparição do Viagra na cena pública brasileira: discursos sobre corpo, gênero e sexualidade na mídia The emergence of Viagra in the Brazilian public scenario: discourses on body, gender and sexuality in the media

    Directory of Open Access Journals (Sweden)

    Mauro Brigeiro

    2009-04-01

    Full Text Available Este trabalho propõe uma reflexão antropológica sobre os discursos e imagens do corpo e da sexualidade na sociedade brasileira com base em um fenômeno social particular: o surgimento do Viagra na esfera pública nacional. Explora as conotações construídas e/ou ratificadas pela mídia impressa em torno deste medicamento, a partir da análise de conteúdo de reportagens publicadas em dois jornais de grande circulação, pertencentes à mesma organização empresarial e dirigidos a públicos distintos. O material analisado data de abril de 1998 a abril de 1999, período correspondente ao início - e ápice - do debate sobre o medicamento no país. O artigo trata dos simbolismos e das estratégias discursivas utilizadas pelos jornais na apresentação do remédio para o público geral e chama a atenção para um apelo a lógicas tradicionais de gênero, a despeito de um cenário contemporâneo de questionamentos acerca das relações entre os sexos e da sexualidade.This work proposes an anthropological reflection on the images and discourses of the body and the sexuality in the Brazilian society, focusing on a particular social phenomenon: the emergence of the Viagra in the national public scenario. This article explores the connotations constructed and confirmed by the Brazilian media press about this drug. Two Brazilian newspapers belonging to the same publisher but aimed at different publics were analyzed from April 1998 to April 1999, period that corresponds to the beginning - and apex - of the debate on the Viagra in the country. The discussion focuses on the symbolism and discursive strategies utilized by the newspapers when presenting this medication to the general public. This article also draws the attention to an appeal to traditional logics of gender, despite a contemporary scenario of issues concerning the relationships among the sexes and the sexuality.

  4. Antidepressant-like properties of sildenafil in a genetic rat model of depression: Role of cholinergic cGMP-interactions

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Brink, Christiaan; Brand, Linda

    2008-01-01

    any antidepressant-like effect when administered alone. In the current study, we investigated these findings in a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats. In addition, we evaluated the dose-dependency and onset of action for sildenafil + atropine, as well....... Conclusions: Using a genetic animal model of depression, we have confirmed the antidepressant-like property of sildenafil following “unmasking” by concomitant block of muscarinic receptors. These findings hint at a novel interaction between the cGMP and cholinergic systems in depression, and suggest...... was scored during five minutes swim in the FST. In addition, locomotor activity was evaluated in the Open Field Test 2 hours prior to the FST. Results: Fluoxetine and imipramine separately decreased immobility in FSL rats, comparable to that of FRL control rats, after 14 but not after 7 days. Likewise, when...

  5. Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Ye, M; Robinson, H; Fransis, S; Ke, H

    2007-01-01

    Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction. However, the molecular basis for these differences is puzzling because two drugs have similar chemical structures. Reported here is a crystal structure of the fully active and nonmutated PDE5A1 catalytic domain in complex with vardenafil. The structure shows that the conformation of the H-loop in the PDE5A1-vardenafil complex is different from those of any known structures of the unliganded PDE5 and its complexes with the inhibitors. In addition, the molecular configuration of vardenafil differs from that of sildenafil when bound to PDE5. It is noteworthy that the binding of vardenafil causes loss of the divalent metal ions that have been observed in all the previously published PDE structures. The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs.

  6. Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Verdenafil and Sildenafil

    Energy Technology Data Exchange (ETDEWEB)

    Wang,H.; Ye, M.; Robinson, H.; Francis, S.; Ke, H.

    2008-01-01

    Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction. However, the molecular basis for these differences is puzzling because two drugs have similar chemical structures. Reported here is a crystal structure of the fully active and nonmutated PDE5A1 catalytic domain in complex with vardenafil. The structure shows that the conformation of the H-loop in the PDE5A1-vardenafil complex is different from those of any known structures of the unliganded PDE5 and its complexes with the inhibitors. In addition, the molecular configuration of vardenafil differs from that of sildenafil when bound to PDE5. It is noteworthy that the binding of vardenafil causes loss of the divalent metal ions that have been observed in all the previously published PDE structures. The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs.

  7. Interaction of horse-spleen ferritin with aluminium citrate.

    Science.gov (United States)

    Cochran, M; Chawtur, V

    1988-11-01

    Horse-spleen ferritin was found to bind Al systematically following gel filtration in buffered Al citrate 30 microM, and up to molar ratio 98 when incubated at 37 degrees C with Al citrate, buffered to pH 7.4. Pre-incubation with 3 concentrations of neutral sodium phosphate (0.1, 1.0, 10.0 mM) had no significant effect on binding. Apotransferrin interaction with the Al-ferritin complex to release Fe but not Al. Protein-digestion and EDTA washing procedures showed that the Al was firmly bound to the ferritin, probably to the core. Since ferritin species from different organs are relatively alike, we suggest that in the gut ferritin may scavenge Al followed by its re-excretion into the lumen with the mucosal cells, thus protecting against absorption of the metal.

  8. Renal Localization of {sup 67}Ga Citrate in Noninfectious Nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu [Chungnam University College of Medicine, Deajeon (Korea, Republic of)

    1992-07-15

    {sup 67}Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of {sup 67}Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal {sup 67}Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of {sup 67}Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher {sup 67}Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal {sup 67}Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal {sup 67}Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, {sup 67}Ga citrate scan is useful in predicting renal involvement.

  9. Acute effect of citrate bath on postdialysis alkalaemia

    OpenAIRE

    De Sequera Ortiz, Patricia; Albalate Ramón, Marta; Pérez-García, Rafael; Corchete Prats, Elena; Arribas Cobo, Patricia; Alcázar Arroyo, Roberto; Ortega Díaz, Maira; Puerta Carretero, Marta

    2015-01-01

    Introduction: The correction of metabolic acidosis caused by renal failure is achieved by adding bicarbonate during dialysis. In order to avoid the precipitation of calcium carbonate and magnesium carbonate that takes place in the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid, usually acetate, which is not free of side effects. Thus, citrate appears as an advantageous alternative to acetate, despite the fact that its acute effects are not accurately known. Obj...

  10. Does intravenous sildenafil clinically ameliorate pulmonary hypertension during perioperative management of congenital heart diseases in children? - A prospective randomized study

    Directory of Open Access Journals (Sweden)

    Vipul Krishen Sharma

    2015-01-01

    Full Text Available Background: Pulmonary hypertension (PHT, if present, can be a significant cause of increased morbidity and mortality in children undergoing surgery for congenital heart diseases (CHD. Various techniques and drugs have been used perioperatively to alleviate the effects of PHT. Intravenous (IV sildenafil is one of them and not many studies validate its clinical use. Aims and Objectives: To compare perioperative PaO 2 - FiO 2 ratio peak filling rate (PFR, systolic pulmonary artery pressure (PAP - systolic aortic pressure (AoP ratio, extubation time, and Intensive Care Unit (ICU stay between two groups of children when one of them is administered IV sildenafil perioperatively during surgery for CHDs. Materials and Methods: Patients with ventricular septal defects and proven PHT, <14 years of age, all American Society of Anesthesiologists physical status III, undergoing cardiac surgery, were enrolled into two groups - Group S (IV sildenafil and Group C (control - over a period of 14 months, starting from October 2013. Independent t-test and Mann-Whitney U-test were used to compare the various parameters between two groups. Results: PFR was higher throughout, perioperatively, in Group S. PAP/AoP was 0.3 and 0.4 in Group S and Group C, respectively. In Group S, mean group extubation time was 7 ± 7.34 h, whereas in Group C it was 22.1 ± 10.6. Postoperative ICU stay in Group S and Group C were 42.3 ± 8.8 h and 64.4 ± 15.9 h, respectively. Conclusion: IV sildenafil, when used perioperatively, in children with CHD having PHT undergoing corrective surgery, improves not only PaO 2 - FiO 2 ratio and PAP - AoP ratio but also reduces extubation time and postoperative ICU stay.

  11. Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections.

    Science.gov (United States)

    Nandipati, K; Raina, R; Agarwal, A; Zippe, C D

    2006-01-01

    Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy (RP). In this study, we evaluated the role of intracavernosal alprostadil (PGE1) combined with sildenafil in stimulating early recovery of spontaneous erections following RP. In this prospective study, we included 22 patients who underwent bilateral nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 microg (1-8) and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are followed up at regular intervals (3, 6, 9 and 12 months) with abridged version of the International Index for Erectile Function-5 questionnaire. Patient compliance, return of sexual activity and return of natural erection, adverse effects and reasons for discontinuation were recorded. Penile doppler studies were performed during followup visits to assess the vascular status. After a mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of spontaneous partial erections. Of the 18 PGE1 users, six continued 4 microg PGE1, four increased the dose to 8 microg, six decreased the dose to 2 microg and two patients further reduced the dose to 1 microg. Of four low-dose Trimix users, three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21 were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%) with combination therapy (injections (PGE1) and sildenafil). Penile doppler studies revealed arterial insufficiency in 77% (17/22) patients and venous insufficiency in one patient. Early intracavernosal injections following RP facilitated early sexual intercourse, patient satisfaction and potentially earlier return of natural erections. Early combination therapy with sildenafil allowed a lower dose of intracavernous injections, minimizing the penile discomfort.

  12. Sildenafil improves erectile hardness in Chinese men with erectile dysfunction: a real-life study analyzed on age stratification.

    Science.gov (United States)

    Zhang, Kai; Xu, Ben; Liu, Defeng; Wang, Xiaofeng; Zhu, Jichuan; Deng, Chunhua; Jin, Jie; Jiang, Hui

    2014-04-01

    To evaluate the clinical efficacy of sildenafil for the improvement of penile erection hardness in erectile dysfunction (ED) patients and to determine the relationship between this improvement in erection hardness and social and psychological functioning. From 2007 to 2008, a total of 4507 men diagnosed with ED were enrolled from 46 centers in China; 4039 of these patients were treated with sildenafil and asked to complete the Erectile Function domain of the International Index of Erectile Function, Erection Hardness Score, and Quality of Erection Questionnaire. The patients were divided into 5 groups on the basis of their age (group A: 20-30 years; group B: 31-40 years; group C: 41-50 years; group D: 51-60 years; and group E: >60 years). A total of 3837 (95.0%) patients completed the entire study. After sildenafil treatment, the vast majority (96.3%) of the men were able to achieve grade 3-4 erection hardness. Patients with a better baseline erection hardness were more able to achieve grade 4 hardness after treatment (P <.001). Comparisons of the Erection Hardness Score improvement before and after treatment between the age-categorized groups also showed that the erection hardness improvement was much greater in men older than 50 years. Sildenafil can help the vast majority of Chinese ED patients achieve grade 3-4 erection hardness. Grade 4 hardness can improve the patients' sexual life to a greater extent than grade 3 hardness. A marked improvement in erection hardness can be achieved in patients older than 50 years. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  13. A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment.

    Science.gov (United States)

    Branigan, Emmett F; Estes, M Antoinette

    2003-06-01

    The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant. Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 (oral contraceptive/clomiphene citrate), which received continuous oral contraceptives followed by clomiphene citrate, or to group 2 (control) received no treatment in the cycle before clomiphene citrate treatment. On day 3, 17 beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and androgens were assayed before and after treatment. Follicle growth, ovulation, and pregnancy were evaluated. The Student t test and analysis of variance were used for statistical significance. The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies. Significantly lower levels of 17 beta-estradiol, luteinizing hormone, and androgen levels were seen in the oral contraceptive/clomiphene citrate group, with no significant changes in group 2. Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate. The decreases in ovarian androgens, luteinizing hormone, and 17 beta-estradiol may be responsible for the improved response.

  14. Transport of citrate catalyzed by the sodium-dependent citrate carrier of Klebsiella pneumoniae is obligatorily coupled to the transport of two sodium ions

    NARCIS (Netherlands)

    Lolkema, Juke S.; Enequist, Hans; Rest, Michel E. van der

    1994-01-01

    Aerobically grown Escherichia coli GM48 harboring plasmid pKScitS that codes for the sodium-dependent citrate carrier from Klebsiella pneumoniae (CitS) allows initial-rate measurements of citrate uptake in whole cells. The cation stoichiometry and selectivity of CitS was studied using this

  15. Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt(-/-) Mouse Model of Preeclampsia/Fetal Growth Restriction.

    Science.gov (United States)

    Stanley, Joanna L; Sulek, Karolina; Andersson, Irene J; Davidge, Sandra T; Kenny, Louise C; Sibley, Colin P; Mandal, Rupasri; Wishart, David S; Broadhurst, David I; Baker, Philip N

    2015-12-15

    Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT(-/-)) and endothelial nitric oxide synthase (Nos3(-/-)) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT(-/-) mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3(-/-), COMT(-/-) and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3(-/-) and C57BL/6J mice (p treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT(-/-) mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action.

  16. Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

    Science.gov (United States)

    Asplin, John R.; Frick, Kevin K.; Granja, Ignacio; Culbertson, Christopher D.; Ng, Adeline; Grynpas, Marc D.; Bushinsky, David A.

    2015-01-01

    Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

  17. The LC/MS Quantitation of Vardenafil (Levitra) in Postmortem Biological Specimens

    Science.gov (United States)

    2006-01-01

    inhibition. Int J Impot Res. 16 Suppl 1: S11-4 (2004). 10. TOXI-NEWS. Sildenafil ( viagra ). TOXI-LAB, Irvine, CA,. 18: 1 (1999). 11. Borrillo, D.J...Dangers of Viagra use in pilots. Federal Air Surg Med Bull. 98-3:1 (1998). 12. Bischoff, E. Vardenafil preclinical trial data: Po- tency

  18. Histological evaluation of the rat dental pulp after indirect capping with sildenafil or L-NAME incorporated into a bioadhesive thermoresponsive system

    Directory of Open Access Journals (Sweden)

    Rogério Rodrigues Cupertino

    2016-06-01

    Full Text Available We evaluated the histological dental pulp state in vivo after indirect pulp capping using sildenafil or LG-nitro-L-arginine (L-NAME, incorporated into a new bioadhesive thermoresponsive system (BTS. Male Wistar rats were subjected to an upper and lower first molar class I cavity preparation followed by indirect pulp capping with sildenafil or L-NAME. Calcium hydroxide (CaOH2 was used as a control. The teeth and surrounding bone were properly dissected and processed for Nissl’s staining. Pulp state was evaluated considering the morphological aspects of the inflammatory response, type of inflammatory infiltrate, organization of the odontoblast layer, blood vessel condition, and presence of abscesses or necrosis. The results were expressed as average of observations. The most intense inflammatory response was observed 3 days after the cavity preparation. No identified changes were detected in the dental pulp response of the molars treated with L-NAME compared with those treated with CaOH2. A dual effect was observed in the teeth treated with sildenafil. While low sildenafil concentration (0.015% w w-1 promoted effects comparable to CaOH2, at a higher concentration (0.15% w w-1, sildenafil caused a severe inflammatory response and pulp necrosis. This pioneering suggest that NO pathway activity may be a determinant in the process of dental pulp healing.

  19. Citrate uptake into tonoplast vesicles from acid lime (Citrus aurantifolia) juice cells.

    Science.gov (United States)

    Brune, A; Gonzalez, P; Goren, R; Zehavi, U; Echeverria, E

    1998-12-01

    Citrate transport into the vacuoles of acid lime juice cells was investigated using isolated tonoplast vesicles. ATP stimulated citrate uptake in the presence or in the absence of a Delta mu H+. Energization of the vesicles only by an artificial K+ gradient (establishing an inside-positive Delta psi) also resulted in citrate uptake as was the case of a Delta pH dominated Delta mu H+. Addition of inhibitors to endomembrane ATPases showed no direct correlation between the inhibition to the tonoplast bound H+/ATPase and citrate uptake. The data indicated that, although some citrate uptake can be accounted for by Delta psi and by a direct primary active transport mechanism involving ATP, under in vivo conditions of vacuolar pH of 2.0, citrate uptake is driven by Delta pH.

  20. El sildenafil mejora la capacidad de ejercicio en pacientes con insuficiencia cardíaca crónica

    Directory of Open Access Journals (Sweden)

    Clemente H. Magallanes

    2010-01-01

    Full Text Available AntecedentesLos agentes inhibidores de la fosfodiesterasa 5, como el sildenafil, son vasodilatadores moderados ampliamente utilizados para el tratamiento de la disfunción eréctil. En la actualidad, la evidencia disponible establece su potencial aplicación en otras patologías, como la hipertensión pulmonar, la disfunción endotelial y la insuficiencia cardíaca crónica. ObjetivoEl presente estudio fue diseñado para comprobar si la administración de sildenafil en pacientes con insuficiencia cardíaca crónica en clase funcional II-III mejora la capacidad de ejercicio en comparación con placebo.Material y métodosSe seleccionaron en forma aleatoria 70 pacientes portadores de insuficiencia cardíaca crónica de cualquier etiología, excepto valvulares, todos con tratamiento óptimo. Para su inclusión en el estudio, los pacientes debían tener un diámetro diastólico ventricular izquierdo > 55 mm, una fracción de eyección 90 mm Hg. Se excluyeron los que se encontraban anémicos, aquellos con indicación de cirugía por cualquiercausa o los que por diversos motivos no pudieran realizar una caminata de seis minutos. Luego de una caminata de seis minutos fueron aleatorizados para recibir 50 mg de sildenafil o placebo, conformándose dos grupos, placebo y sildenafil, ambos con 35 participantes. Luego de 1 hora de la ingestión de las drogas se realizó una nueva caminata de seis minutos. Antes y después de cada caminata se controlaron las siguientes variables: presión arterial sistólica, diastólica y frecuencia cardíaca; se registraron también los metros caminados en cada prueba.ResultadosCaracterísticas generales, grupo placebo versus grupo sildenafil: hombres: 74% vs 88%, etiología isquémico-necrótica: 71% vs 77%, clase funcional II: 37% vs 34%, clase funcional III: 63% vs 66%, edad: 68 ± 10 vs 68 ± 12 años, fracción de eyección: 26,5% ± 7,8% vs 26,5% ± 6,5%, diámetro diastólico ventricular izquierdo: 65 ± 6 vs 66 ± 9

  1. Ferric Citrate Hydrate as a Phosphate Binder and Risk of Aluminum Toxicity

    OpenAIRE

    Ajay Gupta

    2014-01-01

    Ferric citrate hydrate was recently approved in Japan as an oral phosphate binder to be taken with food for the control of hyperphosphatemia in patients with chronic kidney disease (CKD). The daily therapeutic dose is about 3 to 6 g, which comprises about 2 to 4 g of citrate. Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion. In healthy animals d...

  2. Citrate versus heparin anticoagulation in continuous renal replacement therapy in small children.

    Science.gov (United States)

    Raymakers-Janssen, Paulien A M A; Lilien, Marc; van Kessel, Ingrid A; Veldhoen, Esther S; Wösten-van Asperen, Roelie M; van Gestel, Josephus P J

    2017-10-01

    Citrate is preferred over heparin as an anticoagulant in adult continuous renal replacement therapy (CRRT). However, its potential adverse effects and data on use in CRRT in infants and toddlers is limited. We conducted a prospective study on using citrate in CRRT in critically ill small children. Children who underwent CRRT with the smallest filter in our PICU between November 2011 and November 2016 were included. Both heparin and citrate were applied according to a strict protocol. Our primary outcome was circuit survival time. Secondary outcomes were alkalosis, citrate toxicity, and number of red blood cell transfusions. Heparin was used in six patients (121 circuits, total CRRT time 3723 h). Citrate was used in 14 patients (105 circuits, total CRRT time 4530 h). Median circuit survival time with heparin was 21 h (IQR 14.5-27.5) compared to 45.2 h (IQR 37.5-52.8) with citrate (p CRRT regimes. In the heparin group, a median of 6.5 units of red blood cells (IQR 1.5-23.8) were given during CRRT, compared to three in the citrate group (IQR 2.0-5.0, p = 0.12). Use of regional citrate significantly prolongs circuit survival time and thereby should increase CRRT efficiency when compared to heparin. In addition, citrate appears safe for CRRT in critically ill small children.

  3. Citrate synthase purified from Tetrahymena mitochondria is identical with Tetrahymena 14-nm filament protein.

    Science.gov (United States)

    Kojima, H; Chiba, J; Watanabe, Y; Numata, O

    1995-07-01

    A 14-nm filament protein (designated as 49K protein) was purified from a ciliated protozoan, Tetrahymena, using the polymerization and depolymerization procedure. Previous studies in our laboratory showed that its primary structure shared a high sequence identity with citrate synthases known so far and that the 49K protein possessed citrate synthase activity. To ascertain whether or not Tetrahymena's mitochondrial citrate synthase is identical to the 49K protein, citrate synthase was purified from Tetrahymena mitochondria using ammonium sulfate fractionation, Butyl-Toyopearl and SP-Toyopearl column chromatographies, based on monitoring of the enzymatic activity. The molecular weight of the purified citrate synthase was estimated to be 49 kDa, as was that of the 49K protein and the enzyme cross-reacted with an anti-49K protein antiserum. The purified citrate synthase showed much the same optimum pH, optimum KCl concentration, effects of substrate concentrations (acetyl-CoA and oxaloacetate), and inhibitory effect by ATP as those of purified 49K protein. Furthermore, an anti-49K protein monoclonal antibody strongly suppressed the enzymatic activity of the purified citrate synthase. Thus, we suggest that mitochondrial citrate synthase and the 49K protein are identical and that the 49K protein has dual functions in the cytoskeleton in cytoplasm and as a TCA cycle enzyme, citrate synthase, in mitochondria.

  4. Engineering genetically encoded nanosensors for real-time in vivo measurements of citrate concentrations.

    Directory of Open Access Journals (Sweden)

    Jennifer C Ewald

    Full Text Available Citrate is an intermediate in catabolic as well as biosynthetic pathways and is an important regulatory molecule in the control of glycolysis and lipid metabolism. Mass spectrometric and NMR based metabolomics allow measuring citrate concentrations, but only with limited spatial and temporal resolution. Methods are so far lacking to monitor citrate levels in real-time in-vivo. Here, we present a series of genetically encoded citrate sensors based on Förster resonance energy transfer (FRET. We screened databases for citrate-binding proteins and tested three candidates in vitro. The citrate binding domain of the Klebsiella pneumoniae histidine sensor kinase CitA, inserted between the FRET pair Venus/CFP, yielded a sensor highly specific for citrate. We optimized the peptide linkers to achieve maximal FRET change upon citrate binding. By modifying residues in the citrate binding pocket, we were able to construct seven sensors with different affinities spanning a concentration range of three orders of magnitude without losing specificity. In a first in vivo application we show that E. coli maintains the capacity to take up glucose or acetate within seconds even after long-term starvation.

  5. Photochemistry of iron citrates initiated by UV-VIS light

    Science.gov (United States)

    Corral Arroyo, Pablo; Dou, Jing; Alpert, Peter; Krieger, Ulrich; Ammann, Markus

    2017-04-01

    Aerosol aging refers to the multitude of physical and chemical transformation atmospheric particles undergo, which play an important role in the impact of aerosols on climate, air quality and health. Aging processes may be started by chromophores, which act as photocatalysts that induce the oxidation of non-absorbing molecules [1]. Iron (Fe(III)) carboxylate complexes absorb light below about 500 nm, which is followed by ligand to metal charge transfer (LMCT) resulting in the reduction of iron to Fe(II) and oxidation of the carboxylate ligands, a process that represents an important sink of organic acids in the troposphere [2]. Our goal is to investigate how these photochemical processes contribute to the change of chemical and physical properties of the aerosol particles. To achieve this scope, we carry out coated wall flow tube experiments, exposing films with iron citrate to UV light, which will give information about the radical and LVOC production (connecting the CWFT to a Chemiluminescent Detector or PTR-TOF-MS respectively). From extracting and analyzing the films after irradiation with UV light, we obtain a profile of low-volatility products evolving from the photochemistry of iron citrates. By Scanning Transmission X-Ray Microspectroscopy (STXM) we analyze changes in the C K-edge and Fe L-edge in particles loaded with iron citrate upon exposure to light and follow their chemical and structural evolution upon photochemical oxidation in situ to investigate the degradation kinetics under varying environmental conditions. [1] George G., Ammann M., D'Anna B., Donaldson D. J., Nizkorodov S. A., Heterogeneous photochemistry in the Atmosphere, Chem. Rev., 2015, 115 (10), pp 4218-4258 [2] Weller, C., Horn, S., and Herrmann, H.: Photolysis of Fe(III) carboxylate complexes: Fe(II) quantum yields and reaction mechanisms, Photochemistry and Photobiology A: Chemistry, 268, 24-36, 2013.

  6. The role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Wegener, Gregers; Brink, Christiaan

    2010-01-01

    .c.v.) ± atropine (1 mg/kg, i.p.), Rp-8-Br-PET-cGMP or atropine. Antidepressant-like activity was scored in terms of a reduction of immobility (in seconds) relative to vehicle-treated controls. Swimming and climbing behaviours were scored as an indication of serotonergic and noradrenergic mechanisms, respectively....... This was in contrast to sildenafil + atropine which, like imipramine, selectively increased climbing. Infusion of Rp-8-Br-PET-cGMP prevented the 8-Br-cGMP-induced increase in swimming, whereas Rp-8-Br-PET-cGMP also attenuated the increase in climbing induced by sildenafil + atropine. Rp-8-Br-PET-cGMP alone did...... not affect swimming or climbing. Lastly, locomotor activity was unaltered by all treatment conditions. Conclusions These results confirm cholinergic-cGMP-PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces...

  7. Methodology of citrate-based biomaterial development and application

    Science.gov (United States)

    Tran, M. Richard

    Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to

  8. Citrate anticoagulation for continuous renal replacement therapy in small children

    OpenAIRE

    Soltysiak, Jolanta; Warzywoda, Alfred; Kociński, Bartłomiej; Ostalska-Nowicka, Danuta; Benedyk, Anna; Silska-Dittmar, Magdalena; Zachwieja, Jacek

    2013-01-01

    Background Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. Methods This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± ...

  9. Combinatorial delivery of Crizotinib-Palbociclib-Sildenafil using TPGS-PLA micelles for improved cancer treatment.

    Science.gov (United States)

    de Melo-Diogo, Duarte; Gaspar, Vítor M; Costa, Elisabete C; Moreira, André F; Oppolzer, David; Gallardo, Eugénia; Correia, Ilídio J

    2014-11-01

    The co-delivery of multiple chemotherapeutics by micellar delivery systems is a valuable approach to improve cancer treatment since various disease hallmarks can be targeted simultaneously. However, the delivery of multiple drugs requires a nanocarrier structure that can encapsulate various bioactive molecules. In this study, we evaluate the simultaneous encapsulation of a novel triple drug combination in D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactic acid) (TPGS-PLA) amphiphilic micelles for cancer therapy. The drug mixture involves two anti-tumoral drugs, Crizotinib and Palbociclib combined with Sildenafil, a compound that is capable of increasing drug accumulation in the intracellular compartment. Such combination aims to achieve an enhanced cytotoxic effect in cancer cells. Our results demonstrated that TPGS-PLA copolymers self-assembled into stable nanosized micelles (158.3nm) capable of co-encapsulating the three drugs with high loading efficiency. Triple drug loaded TPGS-PLA micelles were internalized in A549 non-small lung cancer cells and exhibited an improved cytotoxic effect in comparison with single (Crizotinib) or dual (Crizotinib-Palbociclib) drug loaded micelles, indicating the therapeutic potential of the triple co-delivery strategy. These findings demonstrate that TPGS-PLA micelles are suitable carriers for multiple drug delivery and also that this particular drug combination may have potential to improve cancer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects

    DEFF Research Database (Denmark)

    Kruuse, Christina; Thomsen, Lars Lykke; Jacobsen, Torsten Bjørn

    2002-01-01

    Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics...... and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler...

  11. Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly (lactide-co-glycolide) microparticles

    DEFF Research Database (Denmark)

    Beck-Broichsitter, Moritz; Stoisiek, Katharina; Bohr, Adam

    2016-01-01

    Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model and the d......Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model...

  12. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    Directory of Open Access Journals (Sweden)

    Fatemeh Fattahi

    2013-02-01

    Full Text Available Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon and (strawberry - raspberry had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

  13. Formulation, characterization and physicochemical evaluation of potassium citrate effervescent tablets.

    Science.gov (United States)

    Aslani, Abolfazl; Fattahi, Fatemeh

    2013-01-01

    The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pHtablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

  14. Impacto do sildenafil sublingual na hipertensão pulmonar de pacientes com insuficiência cardíaca Impacto del sildenafil sublingual en la hipertensión pulmonar de pacientes con insuficiencia cardiaca Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure

    Directory of Open Access Journals (Sweden)

    Aguinaldo Figueiredo de Freitas Jr.

    2009-02-01

    Full Text Available FUNDAMENTO: A hipertensão pulmonar (HP é fator de mau prognóstico no pós-operatório de transplante cardíaco (TC e, desta forma, o estudo do grau de reversibilidade a vasodilatadores é obrigatório durante avaliação pré-operatória. OBJETIVO: Avaliar os efeitos hemodinâmicos pulmonares e sistêmicos do sildenafil como droga vasodilatadora durante o teste de reversibilidade da HP em candidatos a transplante cardíaco. MÉTODOS: Pacientes em fila para TC foram submetidos à medida de variáveis hemodinâmicas sistêmicas e pulmonares antes e após a administração de 100mg dose única e sublingual de sildenafil, durante cateterização cardíaca direita. RESULTADOS: Quatorze pacientes (idade: 47±12 anos, 71,4% homens com insuficiência cardíaca avançada, Fração de Ejeção (FE 25 ± 7%, Classe Funcional (CF- NYHA CF III - 6 e CF IV - 8, foram avaliados neste estudo. A administração aguda de sildenafil mostrou ser eficaz na redução das pressões sistólica (62,4 ± 12,1 vs. 51,5 ± 9,6 mmHg, IC=95%, pFUNDAMENTO: La hipertensión pulmonar (HP se muestra factor de mal pronóstico en el postoperatorio de transplante cardiaco (TC y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluación preoperatoria. OBJETIVO: Evaluar los efectos hemodinámicos pulmonares y sistémicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. MÉTODOS: Pacientes en fila para TC fueron sometidos a la medición de variables hemodinámicas sistémicas y pulmonares, antes y luego de la administración de 100mg en dosificación única y sublingual de Sildenafil, durante cateterización cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 años, el 71,4% varones con insuficiencia cardiaca avanzada, fracción de eyección (FE 25 ± 7%, clase funcional (CF-NYHA CF III - 6 y CF IV - 8. La

  15. Evaluating the efficacy of citrate anticoagulation during CRRT in cardiac patients

    Directory of Open Access Journals (Sweden)

    А. М. Караськов

    2015-10-01

    Full Text Available Systemic anticoagulation during renal replacement therapy in cardiac patients increases the risk of postoperative complications. Citrate anticoagulation is a promising alternative. The objective of our study was to evaluate the efficacy of citrate anticoagulation and its influence on the parameters of hemostasis and complications.

  16. Bioavailability of zinc and phosphorus in calcareous soils as affected by citrate exudation

    NARCIS (Netherlands)

    Duffner, A.; Hoffland, E.; Temminghoff, E.J.M.

    2012-01-01

    Aims Zinc (Zn) and phosphorus (P) deficiency often occurs at the same time and limits crop production in many soils. It has been suggested that citrate root exudation is a response of plants to both deficiencies. We used white lupin (Lupinus albus L.) as a model plant to clarify if citrate exuded by

  17. Citrate versus heparin anticoagulation in continuous renal replacement therapy in small children

    NARCIS (Netherlands)

    Raymakers-Janssen, Paulien A M; Lilien, Marc; van Kessel, Ingrid A.; Veldhoen, Esther S.; Wösten-van Asperen, Roelie M.; van Gestel, Josephus P.J.

    2017-01-01

    Background: Citrate is preferred over heparin as an anticoagulant in adult continuous renal replacement therapy (CRRT). However, its potential adverse effects and data on use in CRRT in infants and toddlers is limited. We conducted a prospective study on using citrate in CRRT in critically ill small

  18. 76 FR 34044 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Science.gov (United States)

    2011-06-10

    ... tricalcium citrate tetrahydrate, which are intermediate products in the production of citric acid, sodium... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... preliminary results of the first administrative review of the antidumping duty order on citric acid and...

  19. 78 FR 34648 - Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing Duty Administrative...

    Science.gov (United States)

    2013-06-10

    ... International Trade Administration Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing... review of the countervailing duty (CVD) order on citric acid and citrate salts from the People's Republic... (202) 482-1503. Scope of the Order The merchandise subject to the order is citric acid and certain...

  20. Effects of citrate on hexavalent chromium reduction by structural Fe(II) in nontronite.

    Science.gov (United States)

    Liu, Xiaolei; Dong, Hailiang; Yang, Xuewei; Kovarik, Libor; Chen, Yu; Zeng, Qiang

    2018-02-05

    Previous studies have shown that organic ligands could influence Cr(VI) reduction by aqueous Fe(2+) and pyrite. In this study, the effects of citrate on Cr(VI) reduction by structural Fe(II) in nontronite (NAu-2) were investigated at pH 6. Our results showed that the presence of citrate decreased the rate but increased the amount of Cr(VI) reduction. The decreased rate was likely due to competitive sorption of citrate and anionic dichromate (Cr2O7(-)) to NAu-2 surface sites, because sorption of dichromate appeared to be the first step for subsequent Cr(VI) reduction. The increased amount of Cr(VI) reduction was likely because citrate served as an additional electron donor to reduce Cr(VI) through ligand-metal electron transfer in the presence of soluble Fe(3+), which was possibly derived from dissolution of reduced NAu-2. Soluble Cr(III)-citrate complex was a possible form of reduced Cr(VI) when citrate was present. Without citrate, nanometer-sized Cr2O3 particles were the product of Cr(VI) reduction. Our study highlights the importance of citrate on Cr(VI) reduction and immobilization when iron-rich smectite is applied to treat Cr(VI) contaminant in organic carbon rich environments. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil

    Science.gov (United States)

    Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Kurucz, Andrea; Kertész, Attila; Takacs, Akos; Posa, Aniko; Kiss, Rita; Szilvassy, Zoltan; Juhasz, Bela

    2017-01-01

    Right-sided heart failure—often caused by elevated pulmonary arterial pressure—is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease. In this present investigation, PAH was induced by a single dose of monocrotaline (MCT) injection in Sprague-Dawley rats, and animals were divided into 4 treatment groups as follows: I. healthy control animals (Control group); II. pulmonary hypertensive rats (PAH group); III. pulmonary hypertensive rats + daily sildenafil treatment (Sildenafil group); and IV. pulmonary hypertensive rats + Wild garlic liophylisate-enriched chow (WGLL group), for 8 weeks. Echocardiographic measurements were obtained on the 0 and 8 weeks with fundamental and Doppler imaging. Isolated working heart method was used to determinate cardiac functions ex vivo after thoracotomy on the 8th week. Histological analyses were carried out on excised lung samples, and Western blot technique was used to determine Phosphodiesterase type 5 enzyme (PDE5) expression in both myocardial and pulmonary tissues. Our data demonstrate that right ventricle function measured by echocardiography was deteriorated in PAH animals compared to controls, which was counteracted by AU treatment. Isolated working heart measurements showed elevated aortic flow in WGLL group compared to PAH animals. Histological analysis revealed dramatic increase in medial wall thickness of pulmonary arteries harvested from PAH animals, but arteries of animals in sildenafil- and WGLL-treated groups showed physiological status

  2. Erectile function, erection hardness and tolerability in men treated with sildenafil 100 mg vs. 50 mg for erectile dysfunction.

    Science.gov (United States)

    Kirby, M; Creanga, D L; Stecher, V J

    2013-10-01

    To compare efficacy and tolerability between 100-mg and 50-mg sildenafil doses in five double-blind, placebo-controlled (DBPC) fixed-dose studies. Doses were compared for the change (baseline to end of 8-12 weeks of DBPC treatment) in score on the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF; from five fixed-dose studies, > 1500 men); the per-patient estimated percentage of occasions that a specified Erection Hardness Score (EHS; from two of the five fixed-dose studies, > 500 men) was achieved, computed from logistic regression; the odds ratio (OR) of achieving EHS3 (hard enough for penetration, but not completely hard) and EHS4 (fully hard and completely rigid); and the adverse event incidence by treatment (from all five fixed-dose studies). For the 100-mg vs. 50-mg dose, IIEF-EF score improvement was consistently greater across the five studies and was statistically significant when data from two studies with similar design were pooled (10.7 ± 0.64 vs. 8.9 ± 0.83, p = 0.0287); and during the first 2 weeks of treatment, the odds of achieving EHS4 erections were almost doubled in one study (OR = 1.77, p = 0.0398). Sildenafil was generally well tolerated at either dose. Men with erectile dysfunction treated with 100-mg compared with 50-mg sildenafil may be more likely to achieve a greater improvement in erectile function and, within the first 2 weeks, completely hard and fully rigid erections, with little or no greater risk to tolerability. © 2013 John Wiley & Sons Ltd.

  3. Interrelationship of sildenafil treatment effects on the physiological and psychosocial aspects of erectile dysfunction of mixed or organic etiology.

    Science.gov (United States)

    Althof, Stanley E; Berner, Michael M; Goldstein, Irwin; Claes, Hubert I M; Cappelleri, Joseph C; Bushmakin, Andrew G; Symonds, Tara; Schnetzler, Gabriel

    2010-09-01

    In a previous paper using mediation modeling, the direct and indirect effects of sildenafil on erection maintenance were demonstrated. In an extension of this previous work, the historical psychosocial paradigm of ED, which focuses on performance anxiety, is tested by using mediation modeling to define the relationship of the physiological aspects (hardness and maintenance) and the associated psychosocial aspects (confidence, sexual relationship satisfaction, and performance anxiety) of ED. Statistical mediation analysis using the following outcomes from a double-blind placebo-controlled trial of fixed-dose sildenafil 100 mg or 50 mg: Erection Hardness Score; the 15-item International Index of Erectile Function (IIEF), including item 4 (frequency of erection maintenance after penetration) and item 5 (difficulty of erection maintenance to intercourse completion); the Self-Esteem And Relationship questionnaire; and the question, "Do you feel anxious about your next attempt at sexual intercourse?" Estimated percentages of direct and indirect effects of sildenafil on psychosocial aspects of ED (95% confidence intervals). The model estimated that erection hardness mediated 43.7% (29.3%, 62.4%) of the effect of treatment onto confidence and 45.9% (32.2%, 61.8%) of the effect of treatment onto sexual relationship satisfaction, and that erection maintenance (using IIEF item 4 as a proxy) mediated 23.0% (10.1%, 39.1%) and 22.4% (10.1%, 36.5%), respectively. Similar results were obtained when IIEF item 5 was used as the proxy for measurement of maintenance. Of all possible paths to performance anxiety, only that from treatment via confidence was statistically significant, mediating an estimated 88.6% (55.5%, 146.2%; item 4 model) or 74.9% (47.0%, 121.0%; item 5 model) of the effect of treatment onto anxiety. The direct path to anxiety from treatment was not statistically significant. In men treated with sildenafil for ED, performance anxiety might be ameliorated by improved

  4. Comparative genomics and transcriptome analysis of Aspergillus niger and metabolic engineering for citrate production

    Science.gov (United States)

    Yin, Xian; Shin, Hyun-dong; Li, Jianghua; Du, Guocheng; Liu, Long; Chen, Jian

    2017-01-01

    Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains—namely, A. niger H915-1 (citrate titer: 157 g L−1), A1 (117 g L−1), and L2 (76 g L−1)—to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis. Furthermore, transcriptome analysis of A. niger H915-1 revealed that the transcription levels of 479 genes changed between the cell growth stage (6 h) and the citrate synthesis stage (12 h, 24 h, 36 h, and 48 h). In the glycolysis pathway, triosephosphate isomerase was up-regulated, whereas pyruvate kinase was down-regulated. Two cytosol ATP-citrate lyases, which take part in the cycle of citrate synthesis, were up-regulated, and may coordinate with the alternative oxidases in the alternative respiratory pathway for energy balance. Finally, deletion of the oxaloacetate acetylhydrolase gene in H915-1 eliminated oxalate formation but neither influence on pH decrease nor difference in citrate production were observed. PMID:28106122

  5. Citrate shows protective effects on cardiovascular and renal function in ischemia-induced acute kidney injury.

    Science.gov (United States)

    Bienholz, Anja; Reis, Jonas; Sanli, Pinar; de Groot, Herbert; Petrat, Frank; Guberina, Hana; Wilde, Benjamin; Witzke, Oliver; Saner, Fuat H; Kribben, Andreas; Weinberg, Joel M; Feldkamp, Thorsten

    2017-04-10

    Ischemia and reperfusion (I/R) is one of the major causes of acute kidney injury (AKI). Citrate reduces hypoxia-induced mitochondrial energetic deficits in isolated proximal tubules. Moreover, citrate anticoagulation is now frequently used in renal replacement therapy. In the present study a rat model of I/R-induced AKI was utilized to examine renal protection by citrate in vivo. AKI was induced by bilateral renal clamping (40 min) followed by reperfusion (3 h). Citrate was infused at three different concentrations (0.3 mmol/kg/h; 0.6 mmol/kg/h and 1.0 mmol/kg/h) continuously for 60 min before and 45 min after ischemia. Plasma calcium concentrations were kept stable by infusion of calcium gluconate. The effect of citrate was evaluated by biomonitoring, blood and plasma parameters, histopathology and tissue ATP content. In comparison to the normoxic control group bilateral renal ischemia led to an increase of creatinine and lactate dehydrogenase activity and a decrease in tissue ATP content and was accompanied by a drop in mean arterial blood pressure. Infusion of 1.0 mmol/kg/h citrate led to lower creatinine and reduced LDH activity compared to the I/R control group and a tendency for higher tissue ATP content. Pre-ischemic infusion of 1.0 mmol/kg/h citrate stabilized blood pressure during ischemia. Citrate has a protective effect during I/R-induced AKI, possibly by limiting the mitochondrial deficit as well as by beneficial cardiovascular effects. This strengthens the rationale of using citrate in continuous renal replacement therapy and encourages consideration of citrate infusion as a therapeutic treatment for AKI in humans.

  6. 76 FR 77206 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Final Results of...

    Science.gov (United States)

    2011-12-12

    ... intermediate products in the production of citric acid, sodium citrate, and potassium citrate. The scope of the... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China...'') has completed its administrative review of the countervailing duty (``CVD'') order on citric acid and...

  7. 77 FR 9891 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Amended Final Results...

    Science.gov (United States)

    2012-02-21

    ... International Trade Administration Citric Acid and Certain Citrate Salts from the People's Republic of China... antidumping duty order on citric acid and certain citrate salts (``citric acid'') from the People's Republic... Act of 1930, as amended (``the Act''). \\1\\ See Citric Acid and Certain Citrate Salts from the People's...

  8. 76 FR 17835 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Science.gov (United States)

    2011-03-31

    ... International Trade Administration A-570-937] Citric Acid and Certain Citrate Salts From the People's Republic... order on citric acid and certain citrate salts (``citric acid'') from the People's Republic of China.... See Citric Acid and Certain Citrate Salts from the People's Republic of China: Notice of Extension of...

  9. Presence of Fe3+ and Zn2+ promoted biotransformation of Cd-citrate complex and removal of metals from solutions.

    Science.gov (United States)

    Qian, Jun-Wei; Tao, Yong; Zhang, Wen-Jie; He, Xiao-Hong; Gao, Ping; Li, Da-Ping

    2013-12-15

    The promotion to Cd-citrate complex biotransformation via addition of Fe(3+) and Zn(2+) was investigated. Single Fe(III)- or Zn-citrate complex was completely degraded by Pseudomonas sp. MBR, Cd-citrate complex was not. In the Cd-citrate media with molar ratio of 1:2 and 1:3, pH increase obtained from the metabolism of excess citrate slightly promoted the biotransformation of Cd-citrate complex, Cd remained in solutions. The presence of Fe(3+) and Zn(2+) resulted in complete biotransformation of Cd-citrate complex in the 1:1:2 Fe:Cd:citrate and Zn:Cd:citrate and 1:1:1:3 Fe:Zn:Cd:citrate media. Alkaline pH obtained from biotransformation of metal-citrate complexes caused almost complete removal of metals (>98%) through precipitation and co-precipitation. Pseudomonas sp. MBR potentially could be used to treat wastewater containing mixed citrate complexes of Fe(III), Zn and Cd. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Browse Title Index

    African Journals Online (AJOL)

    Vol 77, No 2 (2000), Sildenafil (Viagra) in the treatment of male erectile dysfunction in Nairobi, Abstract PDF. GAO Magoha. Vol 83, No 6 (2006):, Sildenafil in management of persistent pulmonary hypertension of the newborn: report of two cases, Abstract PDF. DE Simiyu, C Okello, EG Nyakundi, AH Tawakal. Vol 87, No 6 ...

  11. Effect of Nb on barium titanate prepared from citrate solutions

    Directory of Open Access Journals (Sweden)

    Stojanović Biljana D.

    2002-01-01

    Full Text Available The influence of the addition of dopants on the microstructure development and electrical properties of BaTiO3 doped with 0.2, 0.4, 0.6, 0.8 mol% of Nb and 0.01 mol% of Mn based compounds was studied. Doped barium titanate was prepared using the polymeric precursor method from citrate solutions. The powders calcined at 700°C for 4 hours were analysed by infrared (IR spectroscopy to verify the presence of carbonates, and by X-ray diffraction (XRD for phase formation. The phase composition, microstructure and dielectric properties show a strong dependence on the amount of added niobium.

  12. Use of Blemaren citrate formula in gout patients with nephrolithiasis

    Directory of Open Access Journals (Sweden)

    M S Eliseev

    2008-01-01

    Results. After completion of a course of Blemaren therapy, there was an 8% reduction in the mean serum UA levels, which correlated with an increase in its daily excretion (by an average of 20%. The highest increase in UA excretion was observed in 20 patients with baseline hypoex-cretion (<700 mg/day: from 226,3 (range 201,6-436,8 to 635,0 (range 272,2-705,6 mg/day (p = 0,01. UA excretion substantially unchanged in patients with normal uricosuria (>700 mg/day. Side effects that could cause the agent to be discontinued were absent. Conclusion. The Blemaren citrate formula used in gout patients with nephrolithiasis causes a significant increase in the renal excretion of UA (p = 0,01, normalizes its metabolic parameters, and shows a high safety, without worsening hepatic and renal functions and electrolyte metabolism.

  13. Usefulness of gallium-67 citrate scanning in testicular seminoma

    Energy Technology Data Exchange (ETDEWEB)

    Willan, B.D.; Penney, H.; Castor, W.R.; McGowan, D.G.

    1987-10-01

    An analysis of 77 consecutive patients with a histologic diagnosis of seminoma testis, assessed and treated at the Cross Cancer Institute between 1977 and 1982, is presented. Ga-67 citrate was first used in the assessment of patients with malignant testicular tumors in 1973. Following three years of study that supported the observation of the gallium-avid nature of seminoma, gallium scans became routine in the initial staging assessment and were used also when recurrence was suspected. From 1977 through 1982, 72 patients with biopsy-proven seminoma testis were assessed initially for extent of disease by Ga-67 scanning. Comparison with intravenous pyelography and bipedal lymphography was possible for accuracy of tumor assessment. The scan sensitivity was 83%, and the specificity was 95%. During the same period, gallium was studied in nonseminomatous testicular tumors but the results were disappointing and its use was discontinued. The gallium-avid nature of seminoma testis may be useful in determining the extent of disease.

  14. Self-esteem, confidence and relationship satisfaction in men with erectile dysfunction: a randomized, parallel-group, double-blind, placebo-controlled study of sildenafil in Mexico.

    Science.gov (United States)

    Zonana Farca, E; Francolugo-Vélez, V; Moy-Eransus, C; Orozco Bravo, A; Tseng, L-J; Stecher, V J

    2008-01-01

    Erectile dysfunction (ED) negatively impacts self-esteem and relationship satisfaction. The Self-Esteem and Relationship (SEAR) questionnaire is a validated, ED-specific, patient-reported instrument that specifically addresses self-esteem and relationship issues within the context of ED. Effective ED treatment with sildenafil in a double-blind, placebo-controlled clinical trial conducted in Brazil, Mexico, Australia and Japan showed pooled cross-cultural improvements in self-esteem, confidence and relationship satisfaction. This report focuses on the results from the subgroup of men from nine Mexican centers who participated in the multinational study. A total of 95 men aged >or=18 years with clinically diagnosed ED and currently in a stable relationship were randomized to placebo (n=47) or sildenafil (n=48). The SEAR results for Mexican men showed that sildenafil treatment led to significant improvements in self-esteem, confidence and relationship satisfaction. These data support an earlier study showing that Latin American men taking sildenafil have similar safety and efficacy profiles compared to non-Latin counterparts.

  15. Genome-wide identification of citrus ATP-citrate lyase genes and their transcript analysis in fruits reveals their possible role in citrate utilization.

    Science.gov (United States)

    Hu, Xiao-Mei; Shi, Cai-Yun; Liu, Xiao; Jin, Long-Fei; Liu, Yong-Zhong; Peng, Shu-Ang

    2015-02-01

    ATP-citrate lyase (ACL, EC4.1.3.8) catalyzes citrate to oxaloacetate and acetyl-CoA in the cell cytosol, and has important roles in normal plant growth and in the biosynthesis of some secondary metabolites. We identified three ACL genes, CitACLα1, CitACLα2, and CitACLβ1, in the citrus genome database. Both CitACLα1 and CitACLα2 encode putative ACL α subunits with 82.5 % amino acid identity, whereas CitACLβ1 encodes a putative ACL β subunit. Gene structure analysis showed that CitACLα1 and CitACLα2 had 12 exons and 11 introns, and CitACLβ1 had 16 exons and 15 introns. CitACLα1 and CitACLβ1 were predominantly expressed in flower, and CitACLα2 was predominantly expressed in stem and fibrous roots. As fruits ripen, the transcript levels of CitACLα1, CitACLβ1, and/or CitACLα2 in cultivars 'Niuher' and 'Owari' increased, accompanied by significant decreases in citrate content, while their transcript levels decreased significantly in 'Egan No. 1' and 'Iyokan', although citrate content also decreased. In 'HB pummelo', in which acid content increased as fruit ripened, and in acid-free pummelo, transcript levels of CitACLα2, CitACLβ1, and/or CitACLα1 increased. Moreover, mild drought stress and ABA treatment significantly increased citrate contents in fruits. Transcript levels of the three genes were significantly reduced by mild drought stress, and the transcript level of only CitACLβ1 was significantly reduced by ABA treatment. Taken together, these data indicate that the effects of ACL on citrate use during fruit ripening depends on the cultivar, and the reduction in ACL gene expression may be attributed to citrate increases under mild drought stress or ABA treatment.

  16. Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

    Science.gov (United States)

    Goren, A; Mccoy, J; Kovacevic, M; Situm, M; Lonky, N

    2017-01-01

    Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

  17. Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients.

    Science.gov (United States)

    Mariano, Filippo; Morselli, Maurizio; Bergamo, Daniela; Hollo, Zsuzsanna; Scella, Sandro; Maio, Mariella; Tetta, Ciro; Dellavalle, Ambrogio; Stella, Maurizio; Triolo, Giorgio

    2011-12-01

    Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation. In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

  18. Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility.

    Science.gov (United States)

    Yapca, O E; Delibas, I B; Karaca, I; Kumtepe, Y; Kadanali, S

    2015-01-01

    To evaluate time-limited hydrotubation combined with clomiphene citrate as treatment for unexplained infertility. In this unblinded, randomized controlled trial of patients who had unexplained infertility, 40 patients were treated with time-limited hydrotubation (saline, 20 ml; flushed within 20 to 30 seconds) and clomphene citrate (total, 70 cycles) and 40 patients were treated with clomiphene citrate alone (total, 74 cycles). All women underwent an ovulation induction protocol with clomiphene citrate (100 mg/d orally for five days, from day 3 to day 7 of the cycle). Hydrotubation was performed after detection of the dominant follicle. There were 15 pregnancies in the 80 patients (19%) (total, 144 stimulated cycles; 10% pregnancies per cycle). The frequency of clinical pregnancy per cycle was significantly greater in patients who were treated with hydrotubation and clomiphene citrate (nine pregnancies per cycle [13%]) than those treated with clomiphene citrate alone (two pregnancies per cycle [3%]; odds ratio, 5.3; 95% confidence interval, 1.1 to 25.5; p ≤ 0.05). The frequency of pregnancy per patient (total, clinical, or chemical) was similar for the two treatment groups. The frequency of live birth or abortion per cycle or patient was similar between the two treatment groups. Time-limited hydrotubation and clomiphene citrate may increase the frequency of clinical pregnancy per cycle in women who have unexplained infertility.

  19. The efficacy and safety of sildenafil in patients with pulmonary arterial hypertension associated with the different types of congenital heart disease.

    Science.gov (United States)

    Zeng, Wei-Jie; Lu, Xian-Ling; Xiong, Chang-Ming; Shan, Guang-Liang; Liu, Zhi-Hong; Ni, Xin-Hai; Gu, Qing; Zhao, Zhi-Hui; Li, Jian-Jun; He, Jian-Guo

    2011-08-01

    The difference in underlying pathophysiology in different congenital heart disease (CHD) may have an influence on clinical outcome. It remains unclear whether the effect of sildenafil on pulmonary arterial hypertension (PAH) varies in different types of CHD. The potential effect of sildenafil on pulmonary arterial hypertension related to CHD may be associated with shunt location. In this 12-week, prospective, open label, multicenter trial, 55 patients with CHD were divided into the 3 groups: atrial septal defects group (ASD, n = 15), ventricular septal defects group (VSD, n = 24), and patent ductus arteriosus group (PDA, n = 16). Exercise capacity, hemodynamic parameters, and arterial oxygen saturation were assessed at baseline and after sildenafil therapy (25 mg, 3 times daily). Six-minute walk distance significantly increased from 377.2 ± 68.7 m to 436.0 ± 70.4 m in patients with ASD, from 371.2 ± 66.0 m to 413.7 ± 83.1 m in VSD, and from 384.3 ± 90.2 m to 440.9 ± 71.8 m in PDA (P<0.01, respectively). Moreover, sildenafil also improved the pulmonary vascular resistance and pulmonary blood flow index in the 3 groups, whereas no significant changes in systemic vascular resistance and systemic arterial pressure were observed. However, arterial oxygen saturation was significantly improved in the ASD group only. The incidence of adverse events was similar among the 3 groups. Sildenafil therapy seems to be effective and safe for PAH secondary to ASD, VSD, and PDA, although some clinical and hemodynamic parameters were changed in a different manner among the 3 groups. © 2011 Wiley Periodicals, Inc.

  20. Evaluation of the effect of sildenafil on the microvascular blood flow in patients with systemic sclerosis: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Andrigueti, Fernando V; Ebbing, Pâmela C C; Arismendi, Maria I; Kayser, Cristiane

    2017-01-01

    To evaluate the effect of sildenafil as add-on therapy on the microvascular blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). In this double-blind, placebo-controlled study, 41 patients with RP secondary to SSc were randomly assigned to receive oral sildenafil 100 mg/day (21 patients, mean age 47.2 years) or placebo (20 patients, mean age 41.6 years) for 8 weeks. Patients were evaluated at baseline, 8 weeks after treatment, and 2 weeks after the end of the treatment. The primary outcome measures were the mean changes in finger blood flow (FBF) measured using laser Doppler imaging before and after cold stimulus at 8 weeks of treatment. Secondary endpoints included frequency and duration of RP attacks, Visual Analog Scale (VAS) score for RP severity, Raynaud's condition score, and serum levels of VEGF and endothelial progenitor cells (EPCs). After 8 weeks of treatment, the sildenafil group presented a significantly higher mean percentage change from baseline in FBF before cold stimulus (p=0.026), and in FBF after cold stimulus (p=0.028) compared with the placebo group. There was a significant improvement in the duration of RP and in the percentage change from baseline to week 8 in the RP VAS score in sildenafil compared with placebo. There were no changes in EPCs and VEGF levels after treatment in either group. Sildenafil improved digital blood flow and RP symptoms in SSc patients after 8 weeks of treatment, and might be a good therapeutic option for secondary RP.

  1. Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability.

    Science.gov (United States)

    Semen, Khrystyna; Yelisyeyeva, Olha; Jarocka-Karpowicz, Iwona; Kaminskyy, Danylo; Solovey, Lyubomyr; Skrzydlewska, Elzbieta; Yavorskyi, Ostap

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a rare multifactorial disease with an unfavorable prognosis. Sildenafil therapy can improve functional capacity and pulmonary hemodynamics in PAH patients. Nowadays, it is increasingly recognized that the effects of sildenafil are pleiotropic and may also involve changes of the pro-/antioxidant balance, lipid peroxidation and autonomic control. In present study we aimed to assess the effects of sildenafil on the fatty acids (FAs) status, level of hydroxynonenal (HNE) and heart rate variability (HRV) in PAH patients. Patients with PAH were characterized by an increase in HNE and changes in the FAs composition with elevation of linoleic, oleic, docosahexanoic acids in phospholipids as well as reduced HRV with sympathetic predominance. Sildenafil therapy improved exercise capacity and pulmonary hemodynamics and reduced NT-proBNP level in PAH. Antioxidant and anti-inflammatory effects of sildenafil were noted from the significant lowering of HNE level and reduction of the phopholipid derived oleic, linoleic, docosahexanoic, docosapentanoic FAs. That was also associated with some improvement of HRV on account of the activation of the neurohumoral regulatory component. Incomplete recovery of the functional metabolic disorders in PAH patients may be assumed from the persistent increase in free FAs, reduced HRV with the sympathetic predominance in the spectral structure after treatment comparing to control group. The possibilities to improve PAH treatment efficacy through mild stimulation of free radical reactions and formation of hormetic reaction in the context of improved NO signaling are discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

    Science.gov (United States)

    Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

    2016-01-01

    Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

  3. Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury.

    Science.gov (United States)

    Xu, Y; Xin, H; Wu, Y; Guan, R; Lei, H; Fu, X; Xin, Z; Yang, Y

    2017-05-01

    The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p erectile dysfunction in the future. The underlying mechanisms appears to involve two aspects: (i) icariin promotes differentiation of endogenous stem cells to Schwann cells, which help to repair the damaged neural pathway for erection; (ii) on this basis, sildenafil can further improve penile engorgement through the cyclic guanosine monophosphate-dependent smooth muscle relaxation. © 2017 American Society of Andrology and European Academy of Andrology.

  4. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  5. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study

    Science.gov (United States)

    2012-01-01

    Introduction Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients. Methods We conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run. Results Accumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time). Conclusions Despite substantial accumulation of citrate in serum, CVVHD with regional citrate

  6. [Dissolution of pancreatic calcifications with oral citrates in a woman with chronic idiopathic pancreatitis].

    Science.gov (United States)

    Uscanga, L; Galván Guerra, E; Robles-Díaz, G; Campuzano Fernández, M

    1992-01-01

    Pain control is one of the most important objectives in the medical treatment of patients with chronic calcifying pancreatitis (CCP). It is generally accepted that pain in CCP is secondary to the obstruction of the pancreatic duct by calcifications, protein plugs and stenotic areas. Experimental studies have shown that calculi and protein plugs are soluble in citrates. We report here the case of a young non alcoholic woman with idiopathic CCP who after a pancreatojejunostomy developed again pain and pancreatic calcifications which were dissolved with oral citrates. The case confirms previous observations and illustrates the potential use of citrates in subjects with CCP.

  7. A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

    Directory of Open Access Journals (Sweden)

    Audrey Etienne

    Full Text Available Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity.

  8. A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

    Science.gov (United States)

    Etienne, Audrey; Génard, Michel; Bugaud, Christophe

    2015-01-01

    Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity.

  9. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome.

    Science.gov (United States)

    El-khayat, Waleed; Abdel Moety, Ghada; Al Mohammady, Maged; Hamed, Dalia

    2016-02-01

    To examine the efficacy of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone among women with polycystic ovary syndrome (PCOS) resistant to clomifene citrate. A prospective double-blind randomized controlled trial of women younger than 40 years who had primary/secondary infertility associated with PCOS and had not ovulated in response to clomifene citrate regimens previously was conducted at a center in Cairo, Egypt, between August 1, 2013, and December 31, 2014. Computer-generated random number tables and opaque envelopes were used to assign participants to group A or group B. Participants allocated to group A received 100mg clomifene citrate daily for 5 days from the third day of the menstrual cycle, whereas those in group B received 5mg letrozole daily in the same regimen. All patients received 850 mg metformin and 15 mg pioglitazone for 10 days from the first day of the menstrual cycle. The primary outcome was cumulative ovulation rate. Analyses were by intention to treat. Fifty women were assigned to each group. Ovulation occurred in 108 (92.3%) of 117 cycles in group A and 93 (86.9%) of 107 cycles in Group B (P=0.184). Combined treatment with letrozole, metformin, and pioglitazone was efficacious among women with PCOS resistant to clomifene citrate. ClinicalTrials.gov: NCT01909141. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension.

    Science.gov (United States)

    Vizza, Carmine Dario; Sastry, B K S; Safdar, Zeenat; Harnisch, Lutz; Gao, Xiang; Zhang, Min; Lamba, Manisha; Jing, Zhi-Cheng

    2017-02-23

    In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, functional class, and biomarkers were assessed. The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated. At week 12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and 47 m, respectively). At week 12, changes in hemodynamic parameters were generally small and variable between treatment groups; odds ratios for improvement in functional class were not statistically significantly different. Improvements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg. Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID. ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007).

  11. The impact of citrate introduction at UK syringe exchange programmes: a retrospective cohort study in Cheshire and Merseyside, UK

    Directory of Open Access Journals (Sweden)

    Wareing Michelle

    2007-12-01

    Full Text Available Abstract Background In 2003, it became legal in the UK for syringe exchange programmes (SEPs to provide citrate to injecting drug users to solubilise heroin. Little work has been undertaken on the effect of policy change on SEP function. Here, we examine whether the introduction of citrate in Cheshire and Merseyside SEPs has altered the number of heroin/crack injectors accessing SEPs, the frequency at which heroin/crack injectors visited SEPs and the number of syringes dispensed. Methods Eleven SEPs in Cheshire and Merseyside commenced citrate provision in 2003. SEP-specific data for the six months before and six months after citrate was introduced were extracted from routine monitoring systems relating to heroin and crack injectors. Analyses compared all individuals attending pre and post citrate and matched analyses only those individuals attending in both periods (defined as 'longitudinal attenders'. Non-parametric tests were used throughout. Results Neither new (first seen in either six months period nor established clients visited SEPs more frequently post citrate. New clients collected significantly less syringes per visit post citrate, than pre citrate (14.5,10.0; z = 1.992, P Conclusion The introduction of citrate did not negatively affect SEP attendance. 'Longitudinal attenders' visited SEPs more frequently post citrate, providing staff with greater opportunity for intervention and referral. As the number of syringes they collected each visit remained unchanged the total number of clean syringes made available to this group of injectors increased very slightly between the pre and post citrate periods. However, new clients collected significantly less syringes post citrate than pre citrate, possibly due to staff concerns regarding the amount of citrate (and thus syringes to dispense safely to new clients. These concerns should not be allowed to negatively impact on the number of syringes dispensed.

  12. A discrete neutral transition-metal citrate cubane with an M₄O₄ core; coordinative versatility of the [M(II)₄(citrate)₄]⁸⁻ fragment.

    Science.gov (United States)

    Falvello, Larry R; Forcén-Vázquez, Elena; Palacio, Fernando; Sanz, Sergio; Tomás, Milagros

    2014-07-28

    The neutral cluster [Mn(II)8(citrate)4(H2O)18] is formed by the [M4(citrate)4](8-) fragment, with an Mn4O4 cubane core, which bonds four peripheral aquomanganese units--two [Mn(H2O)4](2+) and two [Mn(H2O)5](2+)--through a total of six metal-ligand bonds, giving a discrete neutral compound. The compound presents a unique coordination mode in which the citrate cubane acts as a chelate to each of the two peripheral [Mn(H2O)4](2+) (tetra-aquo) units. A detailed analysis of the central and peripheral geometries is given in terms of the tetrahedral distortions of key structural features. A reversible dehydration-rehydration process has been observed in a polycrystalline sample of the complex, whose structure lacks pores or channels.

  13. Tamoxifen citrate: a glimmer of hope for silicosis.

    Science.gov (United States)

    Yoldas, Omer; Karaca, Turgut; Bilgin, Bulent Caglar; Yilmaz, Omer Hinc; Simsek, Gulcin Guler; Alici, Ibrahim Onur; Uzdogan, Andaç; Karaca, Nihal; Akin, Tezcan; Yoldas, Suna; Akbiyik, Filiz

    2015-01-01

    Inhalation of crystalline silica nanoparticles causes pulmonary damage resulting in progressive lung fibrosis. Currently, there is no effective treatment for silicosis. Tamoxifen citrate is a selective estrogen receptor modulator, which is one of the adjuvant treatment choices for breast cancer. It is also known with its inhibitory effect on the production of transforming growth factor-beta (TGF-β) and studied for the anti-fibrotic effect in some fibrotic diseases. The aim of the study was to determine the effect of tamoxifen citrate on the prevention of pulmonary fibrosis and the treatment of silicosis. A total of 100 adult female Wistar Albino rats (200-250 g) were used in this study. The rats were divided into five groups including 20 rats in each. Rats were exposed to silica for 84 d in all groups. In group 1, rats were sacrificed on the day 84 without receiving treatment. In group 2, rats received 1 mg/kg tamoxifen (tmx1 + 1), from the first day of the study for the whole 114 d of the study. In group 3, (tmx10 + 10) rats were given 10 mg/kg tamoxifen from the first day of the study for the whole 114 d of the study. In group 4 (tmx1), rats were started 1 mg/kg of tamoxifen on day 84 and were given until day 114. In group 5 (tmx10), rats were fed with 10 mg/kg tamoxifen starting from day 84 to day 114. All rats except group 1 were sacrificed on 114 day of the study. Lung inflammation and fibrosis scores, serum TGF β levels, lung smooth muscle antigen and tissue transforming growth factor β (t-TGF-β) antibody staining levels, and number of silicotic rats were compared between groups. Silicosis was caused successfully in all rats in group 1. There were six silicotic rats in group 3 and it was the lowest number of all groups. Plasma TGF-ß levels and fibrosis score were significantly lower in all groups when compared with the control group. Tamoxifen could have preventive or treating effects in silicosis and found that lung fibrosis score was

  14. Closed circuit recovery of copper, lead and iron from electronic waste with citrate solutions.

    Science.gov (United States)

    Torres, Robinson; Lapidus, Gretchen T

    2017-02-01

    An integral closed circuit hydrometallurgical process is presented for base metal recovery from electronic waste. The leaching medium consists of a sodium citrate solution, from which base metals are retrieved by direct electrowinning, and the barren solution is recycled back to the leaching stage. This leaching-electrowinning cycle was repeated four times. The redox properties of the fresh citrate solution, as well as the leach liquors, were characterized by cyclic voltammetry to determine adequate conditions for metal reduction, as well as to limit citrate degradation. The leaching efficiency of electronic waste, employing the same solution after four complete cycles was 71, 83 and 94% for copper, iron and lead, respectively, compared to the original leach with fresh citrate solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Electrodeposition and characterisation of Ni/Cu nanostructured multilayers from citrate solutions

    CERN Document Server

    Meuleman, W R A

    2002-01-01

    A study of the effect of chemical and electrochemical parameters such as solution composition, pH, and current and potential waveforms on magnetic metal multi-layers plated from citrate electrolytes was carried out. Until now, magnetic multilayers have usually been electrodeposited mainly form sulfamate electrolytes; far less information is available on Cu-Ni multilayers obtained from citrate electrolytes. Since copper is deposited at its diffusion limiting current during multilayer deposition from citrate electrolytes, a rotating disc electrode study was carried out. It was found that the apparent diffusion coefficient changes significantly depending on the citrate ion concentration and pH, indicating the importance of metal speciation. In order to identify the rate controlling species, speciation calculations were carried out in order to model the dependence of the limiting current on the solution composition. The model is based on the assumption that complexes in solution are either labile or inert. A vert...

  16. Atomic force microscopy reveals hydroxyapatite-citrate interfacial structure at the atomic level.

    Science.gov (United States)

    Jiang, Wenge; Pan, Haihua; Cai, Yurong; Tao, Jinhui; Liu, Peng; Xu, Xurong; Tang, Ruikang

    2008-11-04

    An approach to organic-inorganic interfacial structure at the atomic level is a great challenge in the studies of biomineralization. We demonstrate that atomic force microscopy (AFM) is powerful tool to discover the biomineral interface in detail. By using a model system of (100) hydroxyapatite (HAP) face and citrate, it reveals experimentally that only a side carboxylate and a surface calcium ion are involved in the binding effect during the citrate adsorption, which is against the previous understandings by using Langmuir adsorption and computer simulation. Furthermore, the adsorbed citrate molecules can use their free carboxylate and hydroxyl groups to be self-assembled on the HAP surface. AFM examination also finds that the presence of citrate molecules on the HAP crystal faces can enhance the adhesion force of the HAP surface. We suggest that the established AFM method can be used for a precise and direct understanding of biointerfaces at the atomic level.

  17. Effect of temperature on copper, iron and lead leaching from e-waste using citrate solutions.

    Science.gov (United States)

    Torres, Robinson; Segura-Bailón, Brenda; Lapidus, Gretchen T

    2018-01-01

    E-waste is a potential source of large quantities of metals. The ability of citrate solutions to recover base metals from these materials has been demonstrated. In the present study, the effect of the temperature on base metal leaching capacity by the citrate solutions is determined. The material employed consisted of a mechanically prepared, gravity concentrated e-waste, with a metallic content greater than 90%. The leaching conditions were selected based on previous research performed by the authors (0.5 M sodium citrate, pH 4.5 and 20 g per liter e-waste concentrate). Leaching tests were performed at temperatures between 0° and 70 °C. The initial leaching rates for the three metals increased with temperature. However, these tapered off with time for temperatures above 30 °C, which can be associated to citrate destruction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. DnaK protein alleviates toxicity induced by citrate-coated gold nanoparticles in Escherichia coli

    National Research Council Canada - National Science Library

    Makumire, Stanley; Revaprasadu, Neerish; Shonhai, Addmore

    2015-01-01

    ... (called DnaK in prokaryotes) is one of the most prominent molecular chaperones. Since gold nanoparticles exhibit chaperone-like function in vitro, we investigated the effect of citrate-coated gold nanoparticles on the growth of E...

  19. Citrate salts for preventing and treating calcium containing kidney stones in adults.

    Science.gov (United States)

    Phillips, Rebecca; Hanchanale, Vishwanath S; Myatt, Andy; Somani, Bhaskar; Nabi, Ghulam; Biyani, C Shekhar

    2015-10-06

    Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain. The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones. We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months. Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to

  20. Iron transport in Mycobacterium smegmatis: uptake of iron from ferric citrate

    Energy Technology Data Exchange (ETDEWEB)

    Messenger, A.J.M.; Ratledge, C.

    1982-01-01

    In mycobacterial growth medium 40 to 400 ..mu..M citrate was required to solubilize 2 ..mu..M /sup 55/Fe. This solubilized /sup 55/Fe was taken up into both iron-deficient and iron-sufficient washed cell suspensions of Mycobacterium smegmatis and Mycobacterium bovis BCG. Although the /sup 55/Fe was taken up into the cell, the citrate was not. The uptake system with M. smegmatis was not inhibited by electron transport inhibitors, uncouplers of oxidative phosphorylation, or thiol reagents and was saturable with iron at approximately 35 ..mu..M. The system was independent of the iron transport systems already known to exist in M. smegmatis: i.e., the two exochelin routes of assimilation as well as the mycobactin-salicylate system. It was not induced by the presence of 400 ..mu..M citrate in the growth medium, nor did the presence of citrate in the medium affect the production of either exochelin or mycobactin.

  1. Study on the Antimicrobial Properties of Citrate-Based Biodegradable Polymers

    OpenAIRE

    Lee-Chun eSu; Zhiwei eXie; Yi eZhang; Kytai Truong Nguyen; Jian eYang

    2014-01-01

    Citrate-based polymers possess unique advantages for various biomedical applications since citric acid is a natural metabolism product, which is biocompatible and antimicrobial. In polymer synthesis, citric acid also provides multiple functional groups to control the crosslinking of polymers and active binding sites for further conjugation of biomolecules. Our group recently developed a number of citrate-based polymers for various biomedical applications by taking advantage of their controlla...

  2. Citrate anticoagulation for CRRT: don't always trust the postfilter iCa results!

    Science.gov (United States)

    Oudemans-van Straaten, Heleen M; Ostermann, Marlies

    2015-12-04

    Citrate has been recommended as the first-line anticoagulant for continuous renal replacement therapy (CRRT) in critically ill patients. Compared with heparin, citrate anticoagulation is safer and more efficacious. Citrate inhibits the coagulation cascade by lowering the ionized calcium (iCa) concentration in the filter. Monitoring of systemic iCa concentrations is inherent to the protocol, and monitoring of postfilter iCa is recommended to adjust citrate flow and optimize anticoagulation. While systemic iCa targets are in the physiological range, postfilter iCa concentrations are targeted between 0.20 and 0.35 mmol/l. In a previous issue of Critical Care, Schwarzer et al. compared systemic and postfilter iCa measurements of patients receiving citrate-based CRRT between six devices. They highlight the unreliability of iCa concentrations in the postfilter range, because the instruments cannot be validated in the low iCa range. The maximum mean difference between two instruments was as high as 0.33 mmol/l (range 0.21-0.50 mmol/l). The authors call for dialysis companies to revise their protocols. However, the first implication of their study is that the accuracy of blood gas analyzers to measure iCa in the low range needs to improve; and, secondly, clinicians using citrate anticoagulation need to be aware that the postfilter iCa result may be falsely high or low. This is particularly relevant when frequent premature filter clotting is observed despite postfilter iCa results in the seemingly target range. In these situations, citrate flow can be safely increased up to 4 mmol/l blood flow under monitoring of signs of citrate accumulation.

  3. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study

    OpenAIRE

    Wiehle, Ronald; Cunningham, Glenn R; Pitteloud, Nelly; Wike, Jenny; Hsu, Kuang; Fontenot, Gregory K; Rosner, Michele; Dwyer, Andrew; Podolski, Joseph

    2013-01-01

    Objectives To determine the pharmacodynamic profile of serum total testosterone and luteinizing hormone (LH) levels in men with secondary hypogonadism after initial and chronic daily oral doses of enclomiphene citrate vs transdermal testosterone. To determine the effects of daily oral doses of enclomiphene citrate in comparison with transdermal testosterone on other hormones and markers in men with secondary hypogonadism. Patients and Methods This was a randomized, single-blind, two-centre, p...

  4. [Cloning and tissue expression pattern analysis of the human citrate synthase cDNA].

    Science.gov (United States)

    Liu, Q; Yu, L; Han, X F; Fu, Q; Zhang, J X; Tang, H; Zhao, S Y

    2000-09-01

    Tricarboxylic acid (TCA) cycle is an important way to generate ATP, which is widely distributed in the cells of animal, plant or microorganism. It catalyses the catabolism of sugar as well as protein and fat. Citrate synthase plays a key role in regulating TCA cycle and is responsible for catalysing the synthesis of citrate from oxaloacetate and acetyl CoA. Screening of genomic informatics was performed by using pig citrate synthase cDNA as a probe and a contig which is 1636 bp long and has highly homologous to the pig citrate synthase cDNA was obtained from selected ESTs with the ASSEMBLY program. According to the sequence of this contig, a pair of primers was designed and used to amplify cDNA libraries. A 1492 bp cDNA containing an open reading frame encoding 466 amino acids was cloned from human testis and skeletal muscle cDNA libraries. The deduced amino acid sequence of the cDNA showed 95%, 92% and 60.9% identity to pig, chicken and yeast citrate synthase respectively. Because the deduced amino acids sequence contains a highly conserved motif of citrate synthase from three different species, it is believed that this cDNA may be a transcript of human citrate synthase gene. Northern analysis showed that the human citrate synthase was expressed at high level in heart and muscle, at middle level in brain, kidney and pancreas tissues, not detectable in thymus and small intestine tissues, and at low level in other nine tested human tissues.

  5. Effects of citrate on hexavalent chromium reduction by structural Fe(II) in nontronite

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaolei; Dong, Hailiang; Yang, Xuewei; Kovarik, Libor; Chen, Yu; Zeng, Qiang

    2018-02-01

    Iron-bearing clay minerals and organic matter are two important components in natural environments that influence hexavalent chromium (Cr(VI)) reduction. Previous studies have shown that organic ligands could influence Cr(VI) reduction by aqueous Fe2+ and pyrite. However, the effects of organic ligands on Cr(VI) reduction by structural Fe(II) in clays are not well understood. In this study, the effects of citrate on Cr(VI) reduction by nontronite (NAu-2) were investigated under near neutral pH condition (pH=6). Our results showed that the presence of citrate decreased the rate but increased the amount of Cr(VI) reduction by structural Fe(II) in NAu-2. The decreased reaction rate was likely due to competitive sorption of citrate and polyanionic dichromate (Cr2O7- ), because sorption of dichromate appeared to be the first step for subsequent Cr(VI) reduction. The increased amount of Cr(VI) reduction in the presence of citrate was likely because citrate provided additional reducing power through ligand-metal electron transfer in the presence of soluble Fe 3+ derived from dissolution of reduced NAu-2. Soluble Cr(III)-citrate complex was the possible form of reduced chromium when citrate was present. In contrast, nanometer-sized Cr2O3 particles were the product of Cr(VI) reduction by reduced NAu-2 without citrate. Our study highlights the importance of organic ligands on Cr(VI) reduction and immobilization when iron-bearing clay minerals are applied to treat Cr(VI) contaminant in organic matter rich environments.

  6. Sildenafil vs. Nitroprussiato de Sódio durante Teste de Reatividade Pulmonar pré-transplante cardíaco Sildenafil vs. sodium before nitroprusside for the pulmonary hypertension reversibility test before cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Aguinaldo Figueiredo Freitas Jr

    2012-09-01

    Full Text Available FUNDAMENTO: A hipertensão pulmonar é associada ao pior prognóstico no pós-transplante cardíaco. O teste de reatividade pulmonar com Nitroprussiato de Sódio (NPS está associado a elevados índices de hipotensão arterial sistêmica, disfunção ventricular do enxerto transplantado e elevadas taxas de desqualificação para o transplante. OBJETIVO: Neste estudo, objetivou-se comparar os efeitos do Sildenafil (SIL e NPS sobre variáveis hemodinâmicas, neuro-hormonais e ecocardiográficas durante teste de reatividade pulmonar. MÉTODOS: Os pacientes foram submetidos, simultaneamente, ao cateterismo cardíaco direito, ao ecocardiograma e à dosagem de BNP e gasometria venosa, antes e após administração de NPS (1 - 2 µg/Kg/min ou SIL (100 mg, dose única. RESULTADOS: Ambos reduziram a hipertensão pulmonar, porém o nitrato promoveu hipotensão sistêmica significativa (Pressão Arterial Média - PAM: 85,2 vs. 69,8 mmHg, p BACKGROUND: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. OBJECTIVE: This study was aimed at comparing the effects of sildenafil (SIL and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. METHODS: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 µg/kg/min or SIL (100 mg, single dose. RESULTS: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001. Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0

  7. Clomiphene citrate treatment for late onset hypogonadism: rise and fall.

    Science.gov (United States)

    Marconi, Marcelo; Souper, Renato; Hartmann, Jonathan; Alvarez, Matías; Fuentes, Ignacio; Guarda, Francisco J

    2016-01-01

    Previous series have demonstrated that Clomiphene Citrate (CC) is an effective treatment to increase Total Testosterone (TT) in Late Onset Hypogonadism (LOH) patients. However, what happens to TT levels after ending CC treatment is still debatable. The objective of this study is to evaluate TT levels 3 months after the discontinuation of CC in patients with LOH who were previously successfully treated with the same drug. Twenty-seven patients with LOH that were successfully treated (achieved TT levels >11nmol/l) with CC 50mgs daily for 50 days were prospectively recruited in our Andrological outpatient clinic. CC was then stopped for 3 months and TT levels were measured at the end of this period. Mean TT level before discontinuation of CC was 22.7±8.1nmol/L (mean±SD). Three months after discontinuation, mean TT level significantly decreased in all pa¬tients, 10.2±3.9nmol/l (p < 0.01). Twenty-one patients (78%) decreased TT levels under 11nmol/L. Six patients (22%) had TT levels that remained within the normal recommended range (≥11nmol/l). No statistical significant differences were observed between both groups. In the short term LOH does not seem to be a reversible condition in most patients after CC treatment. More studies with longer follow-up are needed to evaluate the kinetics of TT in LOH. Copyright® by the International Brazilian Journal of Urology.

  8. Compartmentation of ATP:citrate lyase in plants.

    Science.gov (United States)

    Rangasamy, D; Ratledge, C

    2000-04-01

    Extracts prepared from young leaves of Pea (Pisum sativum), tobacco (Nicotiana tabacum), rape (Brassica napus), and spinach (Spinacia oleracea) all contained ATP:citrate lyase (ACL) activity, which was most active in rape leaflets (130 nmol min(-1) g fresh weight). In rape and spinach, ACL activity was predominantly localized in the plastids (between about 78% and 90% of the total activity), whereas in pea and tobacco, distribution was mainly cytosolic (about 85% and 78%, respectively, of the total). These distributions were calculated from the relative distributions of plastid and cytosol marker enzymes. Cross-reactivity between plant and rat ACL antibody was carried out by immunoblot analysis and, in rape and spinach, showed that a 120-kD protein, presumably indicating homomeric ACL proteins, was present in both cytosolic and plastidic fractions. In pea, two cross-reacting proteins were detected, the major material being in the cytosol fraction. Therefore, ACL occurs both in the cytosol and plastids of higher plants, but the distribution of activity changes according to the species. The plastidic ACL is proposed to function for the supply of acetyl-coenzyme A for lipid biosynthesis de novo, whereas the cytosolic ACL may provide acetyl-coenzyme A for the mevalonate pathway or fatty acid elongation.

  9. Anticaries effect of dentifrices with calcium citrate and sodium trimetaphosphate

    Directory of Open Access Journals (Sweden)

    Alberto Carlos Botazzo Delbem

    2012-02-01

    Full Text Available Because of the growing concerns regarding fluoride ingestion by young children and dental fluorosis, it is necessary to develop new dentifrices. OBJECTIVE: The aim of this study was to evaluate the effect of dentifrices with calcium citrate (Cacit and sodium trimetaphosphate (TMP on enamel demineralization. MATERIAL AND METHODS: Enamel blocks (n=70, previously selected through surface hardness analysis, were submitted to daily treatment with dentifrices diluted in artificial saliva and to a pH-cycling model. The fluoride concentration in dentifrices was 0, 250, 450, 550, 1,000 and 1,100 µg F/g. CrestTM was used as a positive control (1,100 mg F/g. Cacit (0.25% and TMP (0.25% were added to dentifrices with 450 and 1,000 µg F/g. Surface hardness was measured again and integrated loss of subsurface hardness and fluoride concentration in enamel were calculated. Parametric and correlation tests were used to determine difference (p0.05. CONCLUSIONS: Dentifrices with 450 and 1,000 µg F/g, Cacit and TMP were as effective as a gold standard one.

  10. Pseudohypernatremia secondary to trisodium citrate (Citra-LockTM).

    Science.gov (United States)

    Milliere, Janice; Corriveau, Daryl; Parmar, Malvinder S

    2016-01-01

    Hypernatremia is common among hospitalized patients especially in the intensive care units and presents an independent risk factor for mortality. Mild hypernatremia is often asymptomatic but severe hypernatremia causes central nervous system dysfunction with initial non-specific symptoms of encephalopathy that may progress to seizures, coma and death, if left untreated. Severe hypernatremia is a medical emergency and requires emergent medical attention. A haemodialysis patient who arrived for his scheduled haemodialysis treatment had monthly blood work drawn and was reported to have severe hypernatremia with serum sodium concentration of 183 mmol/L. The possibility of technique or laboratory error was considered and systematically evaluated. The serum sodium measurement using another analyser showed similar value of 182 mmolL. A repeat serum sodium level on a sample drawn 2 h later showed normal value of 139-140 mmol/L. A step-wise evaluation of the complete procedure from blood collection to analysis of the sample revealed this to be spuriously elevated serum sodium concentration secondary to contamination of the sample during sample collection with trisodium citrate, a catheter-lock solution, commonly used in dialysis units to maintain patency of dialysis catheters. Spuriously elevated plasma sodium concentration (pseudohypernatremia) of mild degree is common but severe pseudohypernatremia is rare and the possibility of sample contaminations or laboratory error should be considered. Vigilance is required by both the medical and the laboratory staff to resolve such issues in a timely fashion to avoid unintended consequences.

  11. Preparation and Quality Control of 68Ga-Citrate for PET Applications

    Directory of Open Access Journals (Sweden)

    Ayuob Aghanejad

    2015-07-01

    Full Text Available Objective(s: In nuclear medicine studies, gallium-68 (68Ga citrate has been recently known as a suitable infection agent in positron emission tomography (PET. In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. Methods: 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC, chemical purity (assessed by ICP-EOS, radionuclide purity (evaluated by HPGe, and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. Results: 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC, specific activity (4-6 GBq/mM, chemical purity (Sn, FeConclusion: This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country.

  12. Transport of citrate across renal brush border membrane: effects of dietary acid and alkali loading

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, A.D.; Dousa, T.P.; Smith, L.H.

    1985-10-01

    Dietary acid or alkali loading was given to rats by providing 150 mM NH4Cl or 150 mM NaHCO3 in place of drinking water for 6 days; control animals received 150 mM NaCl. After 6 days, the citrate clearance was 0.04 +/- 0.01 ml/min (mean +/- SE) in the acid-loaded group, 0.9 +/- 0.1 ml/min in the control group, and 2.5 +/- 0.2 ml/min in the alkali-loaded group. At the end of the experiment, the rats were killed, and the Na gradient-dependent citrate uptake was measured in brush border membrane (BBM) vesicles prepared from each group. At 0.3 min, the ( UC)citrate uptake was 198 +/- 8 pmol/mg protein (mean +/- SE) in the acid-loaded group, 94 +/- 16 pmol/mg protein in the control group, and 94 +/- 13 pmol/mg protein in the alkali-loaded group. The rate of Na -independent (NaCl in medium replaced by KCl) ( UC)-citrate uptake by BBM vesicles was the same for acid-loaded, control, and alkali-loaded animals. Thus, the increased capacity of the proximal tubular BBM to transport citrate from the tubular lumen into the cell interior may be an important factor that contributes to decreased urinary citrate in the presence of metabolic acidosis induced by chronic dietary acid loading.

  13. Is it safe to prescribe clomiphene citrate without ultrasound monitoring facilities?

    LENUS (Irish Health Repository)

    Coughlan, C

    2010-05-01

    The majority of triplet and higher order multiple pregnancies now result from ovulation induction\\/superovulation rather than in vitro fertilisation. However, clomiphene citrate is still widely prescribed by gynaecologists and general practitioners who do not have access to ultrasound monitoring. The objective of our study was to determine the prevalence of multifollicular development with different doses of clomiphene citrate. A retrospective review of transvaginal ultrasound monitoring of 425 cycles in 182 women receiving clomiphene citrate from January 2002 to December 2003, was studied. Three or more follicles of >or= 14 mm were identified in 58 cycles (14%). Patients received 50 mg of clomiphene citrate in 52 of these 58 cycles and 25 mg in the remaining six. One patient was noted to have developed five follicles and 10 patients developed four follicles. One patient developed six follicles, despite receiving only 25 mg clomiphene citrate daily. It was concluded that a significant number of women (14%) developed three or more follicles, despite receiving low doses of clomiphene citrate.

  14. Preparation and Quality Control of (68)Ga-Citrate for PET Applications.

    Science.gov (United States)

    Aghanejad, Ayuob; Jalilian, Amir Reza; Ardaneh, Khosro; Bolourinovin, Fatemeh; Yousefnia, Hassan; Samani, Ali Bahrami

    2015-01-01

    In nuclear medicine studies, gallium-68 ((8)Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced (68)Ge/(68)Ga generator, a simple technique for the synthesis and quality control of (68)Ga-citrate was introduced; followed by preliminary animal studies. (68)GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. (68)Ga-citrate was prepared from eluted (68)GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. (68)Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fequality control of (68)Ga-citrate, using a commercially available (68)Ge/(68)Ga generator for PET imaging throughout the country.

  15. Spirocyclic character of ixazomib citrate revealed by comprehensive XRD, NMR and DFT study

    Science.gov (United States)

    Skorepova, Eliska; Čerňa, Igor; Vlasáková, Růžena; Zvoníček, Vít; Tkadlecová, Marcela; Dušek, Michal

    2017-11-01

    Ixazomib citrate is a very recently approved anti-cancer drug. Until now, to the best of our knowledge, no one has been able to solve any crystal structures of this compound. In this work, we present the crystal structures of two isostructural solvates of ixazomib citrate. In all currently available literature, the molecule is characterized as containing a single optically active carbon atom and a borate cycle formed when ixazomib is reacted with citric acid to form a stabilized ixazomib citrate that can be administered orally. However, the crystal structures revealed that none of the up-to-date presented structural formulas of ixazomib citrate are fully accurate. In addition to the citrate ring, another 5-membered ring is formed. These two rings are connected by the boron atom, making this compound a spirocyclic borate. By spirocyclization, the boron atom becomes tetrahedral and therefore optically active. In the crystal structures, ixazomib citrate was found to be in forms of two RR and RS stereoisomers. The results are supported by solid-state and solution NMR and DFT quantum mechanical calculations.

  16. Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

    Science.gov (United States)

    Nikolaidis, Lazaros; Memon, Nabeel; O'Murchu, Brian

    2015-02-01

    We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

  17. Sildenafil, nifedipine and acetazolamide do not allow for blood flow through intrapulmonary arteriovenous anastomoses during exercise while breathing 100% oxygen.

    Science.gov (United States)

    Elliott, Jonathan E; Friedman, Jonathan M; Futral, Joel E; Goodman, Randall D; Lovering, Andrew T

    2014-12-01

    Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) is known to increase in healthy humans during exercise while breathing room air, but is prevented or significantly reduced during exercise while breathing 100% O2, potentially due to vasoconstriction of IPAVAs. Thus, pharmacological interventions that target known pathways regulating the cardiopulmonary circulation may be able to prevent the hyperoxia-induced reduction in IPAVA blood flow (Q̇ IPAVA ) during exercise. In nine healthy human subjects, we investigated the effects of sildenafil (100 mg p.o.), nifedipine (20 mg p.o.) and acetazolamide (250 mg p.o. three times a day for 3 days) on Q̇ IPAVA at rest and during cycle ergometer exercise at 50, 100, 150, 200 and 250 W, while breathing room air (normoxia) and 100% O2 (hyperoxia). Transthoracic saline contrast echocardiography and a 0-5 bubble scoring system were used to detect and assess Q̇ IPAVA qualitatively; ultrasound was used to assess the blood flow velocity oftricuspid regurgitation and the left ventricular outflow tract blood flow to calculate pulmonary artery systolic pressure (PASP) and cardiac output, respectively. Without drugs, bubble scores increased significantly to ≥2 at 150 W in normoxia and to ≤2 at 200 W in hyperoxia. Only nifedipine consistently increased cardiac output at rest and during low-intensity exercise in normoxia and hyperoxia. However, there was no detectable effect of any drug on Q̇ IPAVA ; specifically, bubble scores were the same during exercise in either normoxia or hyperoxia. Accordingly, the reduction in Q̇ IPAVA during exercise while breathing 100% O2 is likely not to be due to the independent pharmacological mechanisms of action associated with sildenafil, nifedipine or acetazolamide. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  18. A COMPARISON OF CLOMIPHENE CITRATE AND SEQUENTIAL CLOMIPHENE CITRATE PLUS HUMAN MENOPAUSAL GONADOTROPIN FOR USE IN CONJUNCTION WITH INTRAUTERINE INSEMINATION

    Directory of Open Access Journals (Sweden)

    B. H. Rashidi

    2005-06-01

    Full Text Available There are currently ‎many different protocols in use for controlled ovarian hyperstimulation (COH, but the optimal method has ‎not yet been determined. To compare the outcome of COH using ‎clomiphene citrate (CC versus CC plus human menopausal gonadotropin (hMG in conjunction with intrauterine insemination (IUI, we studied 117 infertile couples‎. IUI with CC was used in 92 cycles ‎(group A and IUI with CC plus hMG was used in 66 cycles (group B. ‎Data analysis demonstrated no significant difference between the two ‎groups with respect to patients’ age, duration and type of infertility, prior COH and endometrial thickness and pattern. Group A had a little ‎longer follicular phase length than group B. ‎Pregnancy rate for group A and B were 6.52% and 12.12%, respectively (P= 0.22. ‎Endometrial pattern and thickness had no impact on pregnancy rate. ‎There were no multiple gestation and obvious hyperstimulation syndrome. ‎For patients undergoing controlled ovarian hyperstimulation with IUI, ‎CC plus hMG protocol yields higher pregnancy rate than one using CC, although this ‎difference was not statistically significant because of limitation of number of ‎cycles.

  19. Transport of citrate-coated silver nanoparticles in unsaturated sand

    Energy Technology Data Exchange (ETDEWEB)

    Kumahor, Samuel K., E-mail: samuel.kumahor@ufz.de [Department of Soil Physics, Helmholtz Centre for Environmental Research–UFZ, Theodor-Lieser-Strasse 4, 06120 Halle-Saale (Germany); Hron, Pavel, E-mail: pavel.hron@iwr.uni-heidelberg.de [Interdisciplinary Center for Scientific Computing, University of Heidelberg, Im Neuenheimer Feld 368, Raum 422, 69120 Heidelberg (Germany); Metreveli, George, E-mail: metreveli@uni-landau.de [Universität Koblenz-Landau, Institute for Environmental Sciences, Group of Environmental and Soil Chemistry, Fortstr. 7, D-76829 Landau (Germany); Schaumann, Gabriele E., E-mail: schaumann@uni-landau.de [Universität Koblenz-Landau, Institute for Environmental Sciences, Group of Environmental and Soil Chemistry, Fortstr. 7, D-76829 Landau (Germany); Vogel, Hans-Jörg, E-mail: hans-joerg.vogel@ufz.de [Department of Soil Physics, Helmholtz Centre for Environmental Research–UFZ, Theodor-Lieser-Strasse 4, 06120 Halle-Saale (Germany); Institute of Soil Science and Plant Nutrition, Martin-Luther-University Halle-Wittenberg, Von-Seckendorff-Platz 3, 06120 Halle-Saale (Germany)

    2015-12-01

    Chemical factors and physical constraints lead to coupled effects during particle transport in unsaturated porous media. Studies on unsaturated transport as typical for soils are currently scarce. In unsaturated porous media, particle mobility is determined by the existence of an air–water interface in addition to a solid–water interface. To this end, we measured breakthrough curves and retention profiles of citrate-coated Ag nanoparticles in unsaturated sand at two pH values (5 and 9) and three different flow rates corresponding to different water contents with 1 mM KNO{sub 3} as background electrolyte. The classical DLVO theory suggests unfavorable deposition conditions at the air–water and solid–water interfaces. The breakthrough curves indicate modification in curve shapes and retardation of nanoparticles compared to inert solute. Retention profiles show sensitivity to flow rate and pH and this ranged from almost no retention for the highest flow rate at pH = 9 to almost complete retention for the lowest flow rate at pH = 5. Modeling of the breakthrough curves, thus, required coupling two parallel processes: a kinetically controlled attachment process far from equilibrium, responsible for the shape modification, and an equilibrium sorption, responsible for particle retardation. The non-equilibrium process and equilibrium sorption are suggested to relate to the solid–water and air–water interfaces, respectively. This is supported by the DLVO model extended for hydrophobic interactions which suggests reversible attachment, characterized by a secondary minimum (depth 3–5 kT) and a repulsive barrier at the air–water interface. In contrast, the solid–water interface is characterized by a significant repulsive barrier and the absence of a secondary minimum suggesting kinetically controlled and non-equilibrium interaction. This study provides new insights into particle transport in unsaturated porous media and offers a model concept representing the

  20. Assembly of citrate gold nanoparticles on hydrophilic monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Vikholm-Lundin, Inger, E-mail: inger.vikholm-lundin@uta.fi [University of Tampere, BioMediTech, Tampere (Finland); Fimlab Laboratories Ltd., Tampere (Finland); Rosqvist, Emil; Ihalainen, Petri [Abo Akademi University, Center for Functional Materials, Laboratory of Physical Chemistry (Finland); Munter, Tony [VTT Technical Research Centre of Finland, Process Chemistry end Environmental Engineering, Tampere (Finland); Honkimaa, Anni [University of Tampere, Department of Virology, School of Medicine, Tampere (Finland); Marjomäki, Varpu [University of Jyväskylä, Department of Biological and Environmental Science, Nanoscience Center, Jyväskylä (Finland); Albers, Willem M. [BioNavis Oy Ltd., Ylöjärvi, Tampere (Finland); Peltonen, Jouko [Abo Akademi University, Center for Functional Materials, Laboratory of Physical Chemistry (Finland)

    2016-08-15

    Highlights: • The self-assembled layers were all hydrophilic with Lipa-pTHMMAA exhibiting close to full wetting. • The polyacrylamide layers smoothen the gold surface to a higher extent than the polyethylene glycol and lipoic acid terminated with an amino group. • SPR resonance curves shift to higher angles and become increasingly damped when large nanoparticles assembled on the surface. • Topographical images confirmed that the highest number of particles were assembled on the polyethylene glycol monolayer. • By increasing the interaction time more particles could be assembled on the surface. - Abstract: Self-assembled monolayers (SAMs) as model surfaces were linked onto planar gold films thorough lipoic acid or disulfide groups. The molecules used were polyethylene glycol (EG-S-S), N-[tris-(hydroxymethyl)methyl]acrylamide polymers with and without lipoic acid (Lipa-pTHMMAA and pTHMMAA) and a lipoic acid triazine derivative (Lipa-MF). All the layers, but Lipa-MF with a primary amino group were hydroxyl terminated. The layers were characterized by contact angle measurements and atomic force microscopy, AFM. Citrate stabilized nanoparticles, AuNPs in water and phosphate buffer were allowed to assemble on the layers for 10 min and the binding was followed in real-time with surface plasmon resonance, SPR. The SPR resonance curves were observed to shift to higher angles and become increasingly damped, while also the peaks strongly broaden when large nanoparticles assembled on the surface. Both the angular shift and the damping of the curve was largest for nanoparticles assembling on the EG-S-S monolayer. High amounts of particles were also assembled on the pTHMMAA layer without the lipoic acid group, but the damping of the curve was considerably lower with a more even distribution of the particles. Topographical images confirmed that the highest number of particles were assembled on the polyethylene glycol monolayer. By increasing the interaction time more

  1. Citrate-Permeable Channels in the Plasma Membrane of Cluster Roots from White Lupin1

    Science.gov (United States)

    Zhang, Wen-Hao; Ryan, Peter R.; Tyerman, Stephen D.

    2004-01-01

    White lupin (Lupinus albus) is well adapted to phosphorus deficiency by developing cluster roots that release large amounts of citrate into the rhizosphere to mobilize the sparingly soluble phosphorus. To determine the mechanism underlying citrate release from cluster roots, we isolated protoplasts from different types of roots of white lupin plants grown in phosphorus-replete (+P) and phosphorus-deficient (−P) conditions and used the patch-clamp technique to measure the whole-cell currents flowing across plasma membrane of these protoplasts. Two main types of anion conductance were observed in protoplasts prepared from cluster root tissue: (1) an inwardly rectifying anion conductance (IRAC) activated by membrane hyperpolarization, and (2) an outwardly rectifying anion conductance (ORAC) that became more activated with membrane depolarization. Although ORAC was an outward rectifier, it did allow substantial inward current (anion efflux) to occur. Both conductances showed citrate permeability, with IRAC being more selective for citrate3− than Cl− (PCit/PCl = 26.3), while ORAC was selective for Cl− over citrate (PCl/PCit = 3.7). Both IRAC and ORAC were sensitive to the anion channel blocker anthracene-9-carboxylic acid. These currents were also detected in protoplasts derived from noncluster roots of −P plants, as well as from normal (noncluster) roots of plants grown with 25 μm phosphorus (+P). No differences were observed in the magnitude or frequency of IRAC and ORAC currents between the cluster roots and noncluster roots of −P plants. However, the IRAC current from +P plants occurred less frequently than in the −P plants. IRAC was unaffected by external phosphate, but ORAC had reduced inward current (anion efflux) when phosphate was present in the external medium. Our data suggest that IRAC is the main pathway for citrate efflux from white lupin roots, but ORAC may also contribute to citrate efflux. PMID:15516510

  2. Localization of the calcium-regulated citrate transport process in proximal tubule cells.

    Science.gov (United States)

    Hering-Smith, Kathleen S; Mao, Weibo; Schiro, Faith R; Coleman-Barnett, Joycelynn; Pajor, Ana M; Hamm, L Lee

    2014-06-01

    Urinary citrate is an important inhibitor of calcium-stone formation. Most of the citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport. The present studies address several fundamental properties of this novel process: the polarity of the transport process, the location of the calcium-sensitivity and whether NaDC1 is present in OK cells. OK cells grown on permeable supports exhibited apical >basolateral citrate transport. Apical transport of both citrate and succinate was sensitive to extracellular calcium whereas basolateral transport was not. Apical calcium, rather than basolateral, was the predominant determinant of changes in transport. Also 2,3-dimethylsuccinate, previously identified as an inhibitor of basolateral dicarboxylate transport, inhibited apical citrate uptake. Although the calcium-sensitive transport process in OK cells is functionally not typical NaDC1, NaDC1 is present in OK cells by Western blot and PCR. By immunolocalization studies, NaDC1 was predominantly located in discrete apical membrane or subapical areas. However, by biotinylation, apical NaDC1 decreases in the apical membrane with lowering calcium. In sum, OK cells express a calcium-sensitive/regulated dicarboxylate process at the apical membrane which responds to variations in apical calcium. Despite the functional differences of this process compared to NaDC1, NaDC1 is present in these cells, but predominantly in subapical vesicles.

  3. Secreted Citrate Serves as Iron Carrier for the Marine Pathogen Photobacterium damselae subsp damselae

    Directory of Open Access Journals (Sweden)

    Miguel Balado

    2017-08-01

    Full Text Available Photobacterium damselae subsp damselae (Pdd is a Vibrionaceae that has a wide pathogenic potential against many marine animals and also against humans. Some strains of this bacterium acquire iron through the siderophore vibrioferrin. However, there are virulent strains that do not produce vibrioferrin, but they still give a strong positive reaction in the CAS test for siderophore production. In an in silico search on the genome sequences of this type of strains we could not find any ORF which could be related to a siderophore system. To identify genes that could encode a siderophore-mediated iron acquisition system we used a mini-Tn10 transposon random mutagenesis approach. From more than 1,400 mutants examined, we could isolate a mutant (BP53 that showed a strong CAS reaction independently of the iron levels of the medium. In this mutant the transposon was inserted into the idh gene, which encodes an isocitrate dehydrogenase that participates in the tricarboxylic acid cycle. The mutant did not show any growth impairment in rich or minimal media, but it accumulated a noticeable amount of citrate (around 7 mM in the culture medium, irrespective of the iron levels. The parental strain accumulated citrate, but in an iron-regulated fashion, being citrate levels 5–6 times higher under iron restricted conditions. In addition, a null mutant deficient in citrate synthase showed an impairment for growth at high concentrations of iron chelators, and showed almost no reaction in the CAS test. Chemical analysis by liquid chromatography of the iron-restricted culture supernatants resulted in a CAS-positive fraction with biological activity as siderophore. HPLC purification of that fraction yielded a pure compound which was identified as citrate from its MS and NMR spectral data. Although the production of another citrate-based compound with siderophore activity cannot be ruled out, our results suggest that Pdd secretes endogenous citrate and use it for

  4. AB037. Role of nocturnal penile erection test on response to daily sildenafil in patients with erectile dysfunction due to pelvic fracture urethral disruption

    OpenAIRE

    Lin, Jian; Peng, Jing; Zhang, Zhichao; Cui, Wanshou; Yuan, Yiming; Gao, Bing; Song, Weidong; Tang, Yan; Xin, Zhongcheng

    2015-01-01

    Objective To evaluate the results of nocturnal penile erection test and response to daily sildenafil in patients with erectile dysfunction (ED) due to pelvic fracture urethral disruption. Methods In the past three years, we included 38 patients with ED due to pelvic fracture urethral disruption. The mean age was 33.1 years (range, 22-49 years). All were evaluated subjectively and objectively by the International Index of Erectile Function-5, nocturnal penile tumescence and rigidity (NPTR) tes...

  5. Sarcoidosis-associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long-term effect of sildenafil

    DEFF Research Database (Denmark)

    Milman, Nils; Svendsen, Claus Bo; Iversen, Martin

    2009-01-01

    Abstract Background: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. Objectives: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil....... Methods: A retrospective chart review of 25 patients with recalcitrant pulmonary sarcoidosis being evaluated for lung transplantation at our centre. Haemodynamics were evaluated by right heart catheterisation in 24 patients of whom 19 had PH. Eight of the 19 patients received vasodilator challenge...

  6. Evaluation of Pharmacokinetic Interactions Between Lesinurad, a New Selective Urate Reabsorption Inhibitor, and CYP Enzyme Substrates Sildenafil, Amlodipine, Tolbutamide, and Repaglinide.

    Science.gov (United States)

    Gillen, Michael; Yang, Chun; Wilson, David; Valdez, Shakti; Lee, Caroline; Kerr, Bradley; Shen, Zancong

    2017-07-01

    Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. In vitro assays indicate that lesinurad is an inducer of CYPs in the order CYP3A > CYP2C8 > CYP2C9 > CYP2C19 > CYP2B6 and an inhibitor of CYP2C8 and CYP2C9. To investigate the drug interaction potential of lesinurad, clinical drug interaction studies were conducted. Open-label studies in volunteers investigated the effect