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.

2011-01-01

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 to 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 hrs. 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 ingestion

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.

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

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

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

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

International Nuclear Information System (INIS)

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

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

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.

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

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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

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.

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.

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.

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

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.

Haematological changes and wound healing effects of sildenafil ...

African Journals Online (AJOL)

Group G were normal rats without wound treated with sildenafil citrate as in Group A. Blood samples were taken before (day 0) and after the administration of the sildenafil citrate on day 7, 14 and 21. The results of the study showed significant decreased in red blood cells count from 6.28 ± 0.46 × 106 to 2.81 ± 0.46 × 106 in ...

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.

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

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.

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.

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.

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.

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

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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.

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

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

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

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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.

Increased collagen maturity with sildenafil citrate: experimental high risk colonic anastomosis model.

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Cakir, Tebessum; Ozer, Ilter; Bostanci, Erdal Birol; Keklik, Tulay Timucin; Ercin, Ugur; Bilgihan, Ayse; Akoglu, Musa

2015-01-01

Inadequate healing and high anastomosis leak rates at rectal anastomosis may be due to lack of supportive serosal layer and technical difficulty of low anterior resections. Positive effects of sildenafil on wound healing were observed. The aim of this study was to simulate rectal anastomosis as a technical insufficient anastomosis and investigate the effects of sildenafil on anastomosis healing. Colonic anastomoses were carried out in 64 rats and randomized into four groups, CA-S, complete anastomoses without sildenafil (10 mg/kg for 5 days); CA+S, complete anastomoses with sildenafil; IA-S, incomplete anastomoses without sildenafil; IA+S, incomplete anastomoses with sildenafil. Half of the rats in every group were sacrificed on post-operative day (POD) 3, half of them sacrificed on POD 7. Tissues from the anastomoses were used for functional, histochemical, biochemical investigations. Sildenafil treatment resulted in increased bursting pressures in IA+S on POD 7 (p=0.010). Collagen maturity was higher in IA+S on POD 3 and POD 7, CA+S on POD 7 (p=0.010; p=0.010; p<0.007). Collagen content was higher in IA+S on POD 7 (p<0.001). Glutathione, hydroxyproline levels were similar. Malondialdehyde levels were lower in IA+S on POD 3 (p<0.001). Epithelization score was higher in IA+S on POD 7 (p=0.007). Inflammation score was higher in CA-S group on POD 3 and POD 7 (p<0.001; p<0.001). Neutrophil score was lower in CA+S on POD 3 (p=0.005). An increase in collagen content, maturity, and epithelization, a decrease in neutrophil infiltration, oxidative stress and better mechanical strength were observed with the administration of sildenafil. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

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

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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.

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

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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.

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.

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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.

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

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Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

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

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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.

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

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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.

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study

International Nuclear Information System (INIS)

Incrocci, Luca; Koper, Peter C.M.; Hop, Wim C.J.; Slob, A. Koos

2001-01-01

Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer

Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt.

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Sanphui, Palash; Tothadi, Srinu; Ganguly, Somnath; Desiraju, Gautam R

2013-12-02

Sildenafil is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Because of poor aqueous solubility of the drug, the citrate salt, with improved solubility and pharmacokinetics, has been marketed. However, the citrate salt requires an hour to reach its peak plasma concentration. Thus, to improve solubility and bioavailability characteristics, cocrystals and salts of the drug have been prepared by treating aliphatic dicarboxylic acids with sildenafil; the N-methylated piperazine of the drug molecule interacts with the carboxyl group of the acid to form a heterosynthon. Salts are formed with oxalic and fumaric acid; salt monoanions are formed with succinic and glutaric acid. Sildenafil forms cocrystals with longer chain dicarboxylic acids such as adipic, pimelic, suberic, and sebacic acids. Auxiliary stabilization via C-H···O interactions is also present in these cocrystals and salts. Solubility experiments of sildenafil cocrystal/salts were carried out in 0.1N HCl aqueous medium and compared with the solubility of the citrate salt. The glutarate salt and pimelic acid cocrystal dissolve faster than the citrate salt in a two hour dissolution experiment. The glutarate salt exhibits improved solubility (3.2-fold) compared to the citrate salt in water. Solubilities of the binary salts follow an inverse correlation with their melting points, while the solubilities of the cocrystals follow solubilities of the coformer. Pharmacokinetic studies on rats showed that the glutarate salt exhibits doubled plasma AUC values in a single dose within an hour compared to the citrate salt. The high solubility of glutaric acid, in part originating from the strained conformation of the molecule and its high permeability, may be the reason for higher plasma levels of the drug.

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

Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

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Mulhall JP

2013-11-01

Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

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

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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.

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

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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

Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat-related post-traumatic stress disorder: a double-blind, randomized and placebo-controlled study.

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Safarinejad, Mohammad Reza; Kolahi, Ali Asgar; Ghaedi, Gholamhossein

2009-08-01

To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat-related post-traumatic stress disorder (PTSD). In all, 266 combat-exposed war veterans with ED (aged 37-59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician-Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. Patients with comorbid conditions (diabetes mellitus, hypercholesterolaemia, hypertension, Peyronie's disease) and smokers of more than five cigarettes daily were excluded. The patients were randomly divided into a group of 133 who received 100 mg of on-demand sildenafil 0.75-2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use > or =16 doses or attempts at home. The efficacy of the treatments was assessed every four attempts during treatment, and at the end of the study, using responses to the 15-question International Index of Erectile Function (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, patients' event logs of sexual activity, and a Global Assessment Question about erections. Sildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures (P = 0.08). A normal EF domain score (> or =26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively (P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo (P = 0.08). The incidences of treatment

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.

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Fawzi, Amr; Kamel, Mostafa; Salem, Emad; Desoky, Esam; Omran, Mohamed; Elgalaly, Hazem; Sakr, Ahmed; Maarouf, Aref; Khalil, Salem

2017-03-01

To assess the additive effect of sildenafil citrate to tamsulosin in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) in men with or without erectile dysfunction (ED). In all, 150 men with untreated LUTS/BPH with or without ED were randomised to receive sildenafil 25 mg once daily (OD) or placebo OD (night time) combined with tamsulosin 0.4 mg OD (day time) for 6 months. Changes from pre-treatment scores in International Prostate Symptom Score (IPSS), IPSS-quality of life (QoL) score, maximum urinary flow rate ( Q max ), and the five-item version of the International Index of Erectile Function questionnaire (IIEF-5) were assessed at 3 and 6 months. Safety profiles were assessed by physical examination and monitoring clinical adverse events. Group A comprised of men who received tamsulosin and sildenafil (75 men), whilst those in Group B received tamsulosin and placebo (75). The IPSS was significantly improved in Group A compared to Group B, at -29.3% vs -13.7% ( P  = 0.039) at 3 months and -37% vs -19.6% ( P  = 0.043) at 6 months after treatment. Q max significantly improved in both groups compared with before treatment ( P  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.

Ocular safety of Viagra, (sildenafil citrate).

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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

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

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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.

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

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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

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

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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

The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

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López-Tello, Jorge; Arias-Álvarez, María; Jiménez-Martínez, Maria-Ángeles; Barbero-Fernández, Alicia; García-García, Rosa María; Rodríguez, María; Lorenzo, Pedro L; Torres-Rovira, Laura; Astiz, Susana; González-Bulnes, Antonio; Rebollar, Pilar G

2017-06-01

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

Oral sildenafil and inhaled iloprost in the treatment of pulmonary hypertension of the newborn.

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Kahveci, Hasan; Yilmaz, Osman; Avsar, Ummu Zeynep; Ciftel, Murat; Kilic, Omer; Laloglu, Fuat; Ozturk, Kezban

2014-12-01

This study was performed to examine the effectiveness and safety of oral sildenafil and inhaled iloprost in term newborns with persistent pulmonary hypertension of the newborn (PPHN). Oral sildenafil and inhaled iloprost were administered to 27 and 20 neonates, respectively, for treatment of persistent pulmonary hypertension. All patients were term infants at 37 gestational weeks or older. In the sildenafil group, 14 patients had meconium aspiration syndrome, 8 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, 1 had transient tachypnea, and 1 had idiopathic PPHN. In the iloprost group, 9 patients had meconium aspiration syndrome, 7 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, and 1 had transient tachypnea. Sildenafil citrate was administered via an oral feeding tube. Iloprost was administered endotracheally to patients on mechanical ventilation using a jet nebulizer. Iloprost appeared to be more effective than sildenafil in the treatment of PPHN with regard to time to adequate clinical response, ventilatory parameters, duration of drug administration, duration of mechanical ventilation, duration of return to normal values of respiratory failure indices, use of MgSO4 as a second vasodilator and requirement for support with inotropic agents. We observed no side effects on blood pressure or homeostasis in any of the patients in the iloprost group. Systemic hypotension was significantly elevated in the sildenafil group. Four and three infants died of PPHN in the sildenafil and iloprost groups, respectively. Pulmonary systolic arterial pressure decreased to normal levels in the remaining 40 patients, and they were discharged from hospital. We suggested that inhaled iloprost may be a safe and effective treatment choice in newborn infants with persistent pulmonary hypertension. In cases where treatment with inhaled iloprost, ECMO or INO is not possible, oral sildenafil can be an

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

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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.

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

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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

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

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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.

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

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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.

A Case of Recurrent Transient Monocular Visual Loss after Receiving Sildenafil

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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.

Sorption and Transport of Sildenafil in Natural Soils

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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

Sildenafil-associated hepatoxicity: a review of the literature.

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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.

A randomised, double-blind, placebo-controlled trial of nightly sildenafil citrate to preserve erectile function after radiation treatment for prostate cancer

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Ilic, Dragan; Hindson, Ben; Duchesne, Gillian; Millar, Jeremy L.

2013-01-01

Erectile dysfunction (ED) is a common adverse event associated with treatment for prostate cancer. This study aimed to identify whether early, regular use of sildenafil after radiation treatment for prostate cancer is effective at reducing the rate of ED at 2 years. A randomised controlled trial with 27 men planned for radiation treatment for localised prostate cancer recruited from a single radiotherapy centre in Australia. Men were randomised to receive daily sildenafil, or a placebo tablet, for 6 months. The primary end-point was erectile function, as measured by the International Index of Erectile Function (IIEF) score, at 2-year follow-up. The abridged IIEF-5 survey was also used during the treatment period, and could be derived from the full IIEF at other time-points. Two-sided Student's t-tests and Mann–Whitney U-tests were used for the analysis of continuous outcomes, with Fisher's exact test for dichotomous outcomes. No difference was seen at 2 years in the primary end-point, and IIEF scores did not differ significantly between groups during the study. Men in the sildenafil group exhibited significantly better IIEF-5 scores at 4 weeks (P=0.02) and 6 months (P=0.02). There was no difference in erectile function scores between the two groups throughout the treatment period. No significant difference in adverse events was identified between the two groups. There was no evidence from this trial that sildenafil provides long-term erectile function for patients while on medication. Regular use of sildenafil may improve short-term sexual function for patients while on medication. Larger trials are required to examine the effectiveness of implementing sildenafil for prostate cancer patients undergoing radiation treatment.

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

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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.

Emotional changes in men treated with sildenafil citrate for erectile dysfunction: a double-blind, placebo-controlled clinical trial.

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Moncada, Ignacio; Martínez-Jabaloyas, José M; Rodriguez-Vela, Luis; Gutiérrez, Pedro R; Giuliano, Francois; Koskimaki, Juha; Farmer, Ian S; Renedo, Virginia Pascual; Schnetzler, Gabriel

2009-12-01

Erectile dysfunction (ED) has been associated with several comorbidities and can cause significant loss of quality of life and self-esteem. In men with ED, to use the validated Self-Esteem and Relationship (SEAR) questionnaire to evaluate changes in self-esteem associated with sildenafil treatment of ED and to assess changes dependent on concomitant comorbid conditions. This was a 14-week, international, randomized, parallel-group, double-blind, flexible-dose (25, 50, or 100 mg), placebo-controlled study of sildenafil in men aged >or=18 years with a clinical diagnosis of ED (score Erectile Function (IIEF) domain scores and in the intercourse success rate, and the response to the global efficacy assessment and to the global satisfaction assessment. A total of 841 patients were included in the intent-to-treat efficacy analysis (559 sildenafil, 282 placebo). Patients randomized to sildenafil had significantly greater change scores from baseline to the end of treatment on all components of the SEAR and all domains of the IIEF (P Erectile Function domain score (r = 0.6338, P emotional benefits of sildenafil in the treatment of ED were confirmed, overall and in men with comorbid hypertension, hyperlipidemia, benign prostatic hypertrophy, and/or depression. Using both the IIEF and the SEAR questionnaires provides a more complete assessment of ED.

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

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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.

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

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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.

Sildenafil Stimulates Aqueous Humor Turnover in Rabbits

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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

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

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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.

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

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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.

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

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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

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

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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

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

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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

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

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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.

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

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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

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

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Nurnberg, H George; Hensley, Paula L; Gelenberg, Alan J; Fava, Maurizio; Lauriello, John; Paine, Susan

2003-01-01

Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (Psatisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Use of sildenafil citrate in a cat with Eisenmenger’s syndrome and an atrial septal defect

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Ke Shuan Chow

2015-04-01

Full Text Available A 2-year-old male neutered Siamese cat presenting with weakness and dyspnoea was diagnosed with an atrial septal defect and pulmonary hypertension, which resulted in right-to-left shunting (Eisenmenger’s syndrome. The cat was treated with sildenafil (0.25–0.6 mg/kg for 10 months. There were no apparent treatment-related adverse effects. Improvement in clinical signs was noted, although increasing doses of sildenafil were required. After 10 months the cat significantly deteriorated and was euthanased.

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

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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

Gastro Hepatic Protective Effects of Sildenafil in γ-Irradiated Rats

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Tawfik, S.S.; Salama, S.F.

2013-01-01

Sildenafil is a potent specific inhibitor of phosphodiesterase-5 (PDE-5), which ultimately increases intracellular cyclic guanosine monophosphate (cGMP) . Sildenafil commercially named Viagra; was studied for its gastro hepatic protective activity through acute exposure of rats to γ-rays. The experimental groups of rats were: Sildenafil [1 mg/ kg, intra venous (i.v.), in 0.2 ml saline] / day for 5 days and then exposed to 6 Gy γ-rays after 1 h of the last injection (sildenafil+ γ-rays group). Controls received saline as a vehicle/ for 5 day; sildenafil group received drug alone for 5 days, and γ-rays group received saline (without drug) for 5 days and exposed to 6 Gy γ-rays after 1 h of the last injection. All groups were decapitated on the 6th day. Gamma rays increased the level of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO) but, lowered the levels of nitric oxide (NO) and reduced glutathione (GSH) as well as lowering the activities of superoxide dismutase (SOD) and catalase (CAT) in both stomach and hepatic tissues. Sildenafil administrated before γ-rays significantly reduced the level of MDA and the activity of MPO while elevating levels of NO and GSH plus activities of SOD and CAT in both stomach and hepatic tissues compared to control and sildenafil groups. Conclusion: The data reveals that sildenafil pre-treatment has a protective effect against γ-rays-induced gastro hepatic dysfunction and supports the possible use of sildenafil as a protective agent in γ-irradiated rats

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.

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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.

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

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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

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

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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.

Preparation, characterization and in vitro evaluation of a polyvinyl alcohol/sodium alginate based orodispersible film containing sildenafil citrate.

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Shi, Li-Li; Xu, Wei-Juan; Cao, Qing-Ri; Yang, Mingshi; Cui, Jing-Hao

2014-05-01

In this work, we developed a sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)/sodium alginate (ALG-Na) based orodispersible film (ODF) using a solvent casting method. Formulation factors such as the type and amount of plasticizers and disintegrants were optimized on the basis of characteristics of blank ODF, including the disintegration time, elastic modulus (EM) and percentage of elongation (E%). SC-loaded ODF with a loading capacity up to 25 mg in an area of 6 cm2 was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The surface morphology of ODF was visualized under a scanning electron microscope (SEM). The physicochemical properties of ODF were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of PVA, polyethylene glycol 400 (PEG 400) and ALG-Na (20:5:2, w/w) had a remarkably short disintegration time of about 20 s. However, the loading of drug extended the disintegration time (100 s) of ODF, while it still maintained satisfactory mechanical properties. SC was homogenously dispersed throughout the films and the crystalline form of drug changed, with strong hydrogen bonding between the drug and carriers. The PVA/ALG-Na based ODF containing SC prepared by the simple solvent casting method might be an alternative to conventional SC tablets for the treatment of male erectile dysfunction.

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

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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.

The blue pill (sildenafil and its descendants: an overview

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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.

Sildenafil dilates ophthalmic artery in type 2 diabetic patients

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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.

Formulation and in vitro characterization of novel sildenafil citrate-loaded polyvinyl alcohol-polyethylene glycol graft copolymer-based orally dissolving films.

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Xu, Li-Li; Shi, Li-Li; Cao, Qing-Ri; Xu, Wei-Juan; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2014-10-01

This work was aimed to develop novel sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer (Kollicoat(®) IR)-based orally dissolving films (ODFs) using a solvent casting method. Formulation factors such as plasticizers and disintegrants were optimized on the basis of characteristics of blank ODFs. The SC-loaded ODF with a loading capacity up to 6.25mg in an area of 6 cm(2) was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The physicochemical properties of drug-loaded ODF were also investigated using the scanning electron microscope (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of Kollicoat(®) IR, sodium alginate (ALG-Na) and glycerol (10:2:1.5, w/w) had a remarkably short disintegration time of about 20s. The SC-loaded ODF showed a delayed disintegration time (about 25s), but exhibited improved mechanical properties when compared to the blank ODF. SC was homogeneously dispersed throughout the ODF and the crystalline form of drug had been partly changed, existing strong hydrogen bonding between the drug and carriers. The Kollicoat(®) IR/ALG-Na based ODFs containing SC might be an alternative to conventional tablet for the treatment of male erectile dysfunction. Copyright © 2014 Elsevier B.V. All rights reserved.

Sildenafil in the management of neonates with PPHN: A rural ...

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0.43 - 6.8/1 000 live births and carries a high risk of mortality .... pressure and number of ventilation days lower in the sildenafil group. ... premature baby treated with sildenafil ... Sudden decreases in or loss of hearing following ... birth weight.

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

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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 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.

Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate (Viagra).

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Montorsi, Francesco; Padma-Nathan, Harin; Glina, Sidney

2006-09-01

We aimed to determine whether erectile function (EF) and assessments of erection hardness correlate positively with measures of psychosocial outcomes (ie, emotional well-being, sexual satisfaction, and satisfaction with erectile dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra; Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and 4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of these trials were randomized, double-blind, and placebo-controlled (n = 27) and were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour before anticipated sexual activity but not more often than once daily. EF was assessed with use of the EF domain of the International Index of Erectile Function (IIEF) and with assessments of erection hardness (Erection Hardness Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for penetration]). Change (baseline to end point) in emotional well-being in men treated for ED was assessed with the Self-Esteem and Relationship (SEAR) questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem subscale and Overall Relationship subscale) and the Sexual Relationship domain. End point treatment satisfaction (overall, speed of onset, and duration of action) was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). The IIEF was used to assess change and end point sexual satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13, satisfaction with sex life, and Q14, satisfaction with sexual relationship). In men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain, IIEF Q2) and the percentage of erections graded completely hard and fully rigid (EHGS grade 4) correlated positively with scores for

Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

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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

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

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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.

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

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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.

A multicenter, double-blind, placebo-controlled study of sildenafil citrate in Canadian men with erectile dysfunction and untreated symptoms of depression, in the absence of major depressive disorder.

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Kennedy, Sidney H; Dugré, Hélène; Defoy, Isabelle

2011-05-01

Depression and erectile dysfunction (ED) often co-occur. Phosphodiesterase type 5 inhibitors are effective in men with ED and untreated depression, or ED secondary to antidepressants. This study evaluated sildenafil treatment in Canadian men with clinically diagnosed ED (Sexual Health Inventory for Men score ≤ 21) and mild-to-moderate untreated depressive symptoms [Beck Depression Inventory II (BDI-II) score 14-28], but excluding major depressive disorder. Pretreatment screening using the Sexual Health Inventory for Men and BDI-II showed that men with ED were more likely to have depression than men without ED, and ED severity was a predictor of depression (P=0.0226). Two hundred and two men were randomized to 6 weeks of double-blind treatment with placebo (n=98) or sildenafil (n=104), initial dose of 50 mg, adjustable to 25 or 100 mg. The men were evaluated on all domains of the International Index of Erectile Function and the Sex Effects Questionnaire, Global Efficacy Questions, and Event-log data. Compared with placebo, patients treated with sildenafil had significantly greater changes from baseline in BDI-II scores (P<0.001). All International Index of Erectile Function domains and the Sex Effects Questionnaire components were also significantly improved in sildenafil group (P<0.01). The most common adverse events included headache, dyspepsia, vasodilatation, and respiratory tract infections and were generally mild in intensity. 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Changes in Retinal and Choroidal Vascular Blood Flow after Oral Sildenafil: An Optical Coherence Tomography Angiography Study

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David Berrones

2017-01-01

Full Text Available Purpose. To describe changes in the retina and choroidal flow by optical coherence tomography angiography (OCT-A after a single dose of oral sildenafil. Method. A case-control study. Patients in the study group received 50 mg of oral sildenafil. Patients in the control group received a sham pill. Retinal and choroidal images were obtained at baseline (before pill ingestion and 1 hour after ingestion. Central macular and choroidal thickness, choroidal and outer retina flow, and the retinal and choroidal vascular density were compared using a Mann-Whitney U test. Results. Twenty eyes were enrolled into the study group and 10 eyes in the control group. There was a significant difference in central choroidal thickness and outer retina blood flow between groups after 1 hour of sildenafil ingestion (p<0.01. There were no differences in central macular thickness, choroidal flow, and retinal vascular density among groups. Conclusions. A single dose of oral sildenafil increases choroidal thickness, probably due to sildenafil-induced vasodilation.

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

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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.

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

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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.

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

International Nuclear Information System (INIS)

Delolo, Fabio Godoy; Rodrigues, Claudia; Silva, Monize Martins da; Batista, Alzir Azevedo; Dinelli, Luis Rogerio; Delling, Felix Nicolai; Zukerman-Schpector, Julio

2014-01-01

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 3 (dppb)(H 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 -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 -1 H 2 SO 4 (pH 1.0) and 0.1 mol L -1 CH 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 -5 to 4.99 × 10 -4 mol L -1 ). (author)

Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction

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Andersen, Mads J; Ersbøll, Mads; Axelsson, Anna

2013-01-01

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......, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged...

Correlations between increased erection hardness and improvements in emotional well-being and satisfaction outcomes in men treated with sildenafil citrate for erectile dysfunction.

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King, R; Juenemann, K-P; Levinson, I P; Stecher, V J; Creanga, D L

2007-01-01

To explore relationships between erection hardness and other outcomes in men with erectile dysfunction (ED). Pooled analyses were conducted on 27 randomized, double-blind, placebo-controlled trials and six open-label trials from the worldwide sildenafil database. Outcomes included erection hardness graded subjectively, hardness and sexual satisfaction questions from the International Index of Erectile Function, general and sexually-specific emotional well-being from the self-esteem and relationship questionnaire, and the erectile dysfunction inventory of treatment satisfaction. Hardness outcomes improved (with a possible dose-response relationship for the achievement of fully hard and rigid erections) and correlated positively with the other outcomes. Sildenafil 100 mg produced optimal erection hardness (fully hard and rigid erections) in a substantial proportion of men with ED. Because optimal erection hardness correlated positively with some emotional well-being and satisfaction outcomes, sildenafil 100 mg may be the most appropriate dosage for treatment of ED for most men.

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

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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

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

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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 [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)

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

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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.

Sildenafil delays the intestinal transit of a liquid meal in awake rats

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J.R.V Graça

2008-01-01

Full Text Available Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44 were treated (0.2 mL, iv with sildenafil (4 mg/kg or vehicle (0.01 N HCl. Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP was monitored in a separate group of rats (N = 14. Data (medians within interquartile ranges were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6 vs 2.9 (2.7-3.1; 3.8 (3.4-4.0 vs 2.9 (2.5-3.1, and 4.3 (3.9-4.5 vs 3.4 (3.2-3.7, respectively; P < 0.05. MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05 within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

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

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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

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

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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.

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.

Sildenafil increases cerebrovascular reactivity: a transcranial Doppler study.

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Diomedi, M; Sallustio, F; Rizzato, B; Ferrante, F; Leone, G; Spera, E; Scarfini, M; Bernardi, G

2005-09-27

The authors performed a double-blind, placebo-controlled study in 28 patients to evaluate the effects of sildenafil on cerebral hemodynamics. A significant improvement of cerebrovascular reactivity, without any modification of other variables, was recorded 1 hour after the administration of 50 mg sildenafil. Further investigations are needed to evaluate whether cerebrovascular reactivity improvement could contribute to triggering sildenafil-induced migraine.

Effect of sildenafil citrate on the male sexual experience assessed with the Sexual Experience Questionnaire: a multicenter, double-blind, placebo-controlled trial with open-label extension.

Science.gov (United States)

Jones, LeRoy A; Klimberg, Ira W; McMurray, James G; Padula, Rebecca; Tseng, Li-Jung; Stecher, Vera J

2008-08-01

The Sexual Experience Questionnaire (SEX-Q) enables quick and easy assessment of functional, emotional, and satisfaction-related aspects of the sexual experience in men with erectile dysfunction (ED). To assess correlations between improvement on the SEX-Q and outcomes on other validated questionnaires. METHODS. Men with ED (score Questionnaire (QEQ), Self-Esteem and Relationship (SEAR) Questionnaire, Erection Hardness Score (EHS), successful intercourse attempts (SIAs), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and global efficacy questions (GEQs). Compared with the placebo group (N = 105), the sildenafil group (N = 104) at DBPC end of treatment (EOT) had significantly more improvement (P SIAs and EHS 3 (hard enough for penetration but not completely hard) or EHS 4 (completely hard) erections (odds ratio [OR], 2.52 and 3.46, respectively), EHS 4 erections four times as often (OR, 6.41), more men satisfied with treatment (EDITS; OR, 2.6), approximately twice as many men with improved erections (GEQ1; OR, 5.8) and ability to have sexual intercourse (GEQ2; OR, 5.4), and GEQ3 scores that indicated better sex (P 60% (and approximately half were > or =80%) of the maximum positive result. SEX-Q change scores correlate with several other functional, emotional, and satisfaction-related outcomes in men treated with sildenafil for ED, allowing a simple and focused evaluation of the sexual experience.

Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

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Stephanie Leigh Siehr

2015-03-01

Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

Characterisation of citrate and iron citrate uptake by cultured rat hepatocytes

International Nuclear Information System (INIS)

Graham, R.M.; Morgan, E.H.; Baker, E.

1998-01-01

Background/Aims: the endogenous low molecular weight iron chelator, citrate, is considered to be an important contributor to iron transport and the liver the main site of uptake of iron citrate in subjects suffering from diseases of iron overload. Moreover, the citrate-metabolising enzyme, aconitase, is implicated in the regulation of cellular iron metabolism. This study was undertaken to determine the role of citrate and ferric citrate in the uptake of iron by rat hepatocytes. Methods: Cultured rat hepatocytes were incubated (37 deg. C, 15 min) with 100 μM [ 14 C]-citrate in the presence or absence of 1.0 μM 55 Fe. Membrane-bound and intracellular radiolabel were separated by incubation with the general protease, Pronase. Results: Our results suggest that ferric citrate uptake is mediated by a specific citrate binding site which exhibits a higher affinity for citrate in the presence of iron than in its absence. Citrate was internalised by hepatocytes, with at least 70% being oxidised to CO 2 within 15 min. Citrate uptake was pH-dependent, did not require the presence of sodium and increased with increasing iron concentration. Metabolic energy, anion channels, the Na + , K + -ATPase and vesicle acidification do not appear to play a role in uptake of ferric citrate, but functional sulphydryl groups may be involved. Conclusions: The data suggest either that ferric citrate complexes with higher molar ratios of iron to citrate relative to the incubation medium are bound preferentially to the membrane, or that once citrate has delivered its iron to the membrane, the complex dissociates and the components are internalised separately. (au)

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

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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.

The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study.

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Gökakın, Ali Kağan; Atabey, Mustafa; Deveci, Koksal; Sancakdar, Enver; Tuzcu, Mehmet; Duger, Cevdet; Topcu, Omer

2014-09-01

Severe burn induces systemic inflammation and reactive oxygen species leading to lipid peroxidation which may play role in remote organs injury. Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil reduces oxidative stress and inflammation in distant organs. The aim of the present study was to evaluate the effects of different dosages of sildenafil in remote organs injury. A total of thirty-two rats were randomly divided into four equal groups. The groups were designated as follows: Sham, Control, 10, and T20 mg/kg sildenafil treatment groups. Levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), VEGF receptor (Flt-1), activities of glutathione peroxidase (Gpx), levels of total antioxidative capacity (TAC), and total oxidant status (TOS) were measured in both tissues and serum, and a semi-quantitative scoring system was used for the evaluation of histopathological findings. Sildenafil increased levels of Gpx, and Flt-1, and decreased MDA and VEGF levels in tissues. Sildenafil also increased serum levels of TAC and Flt-1 and decreased TOS, OSI, and VEGF. Sildenafil decreased inflammation scores in remote organs in histopathological evaluation. It has protective effects in severe burn-related remote organ injuries by decreasing oxidative stress and inflammation.

A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

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Washington, Chad W; Derdeyn, Colin P; Dhar, Rajat; Arias, Eric J; Chicoine, Michael R; Cross, DeWitte T; Dacey, Ralph G; Han, Byung Hee; Moran, Christopher J; Rich, Keith M; Vellimana, Ananth K; Zipfel, Gregory J

2016-02-01

Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

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Ivan Novitzky

2016-01-01

Full Text Available To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7 received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16, total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19 were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h bevacizumab injected mice (n=7 they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16 they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03 and sildenafil-treated (p=0.003 groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.

Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

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Denilson C. Albuquerque

2005-08-01

Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

Clinical deterioration after sildenafil cessation in patients with pulmonary hypertension

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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

Cerebral haemodynamic response or excitability is not affected by sildenafil

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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......) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP...... amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication...

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

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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

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

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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

The protective effects of sildenafil in acute lung injury in a rat model of severe scald burn: A biochemical and histopathological study.

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Gokakin, Ali Kagan; Deveci, Koksal; Kurt, Atilla; Karakus, Boran Cihat; Duger, Cevdet; Tuzcu, Mehmet; Topcu, Omer

2013-09-01

Severe burn induces biochemical mediators such as reactive oxygen species that leads to lipid peroxidation which may have a key role in formation of acute lung injury (ALI). Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil preserves alveolar growth, angiogenesis, reduces inflammation and airway reactivity. The purpose of the present study was to evaluate the effects of different dosages of sildenafil in ALI due to severe scald burn in rats. Twenty-four rats were subjected to 30% total body surface area severe scald injury and were randomly divided into three equal groups as follow: control, 10 and 20mg/kg sildenafil groups. Levels of malondialdehyde (MDA), activities of glutathione peroxidase (Gpx), catalase (Cat), total oxidative stress (TOS), and total antioxidative capacity (TAC) were measured in both tissues and serums. Oxidative stress index (OSI) was calculated. A semi-quantitative scoring system was used for the evaluation of histopatological findings. Sildenafil increased Gpx, Cat, TAC and decreased MDA, TOS and OSI. Sildenafil decreased inflammation scores in lungs. Our results reveal that sildenafil is protective against scald burn related ALI by decreasing oxidative stress and inflammation and the dosage of 10mg/kg could be apparently better than 20mg/kg. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.

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Shanmugam, Srinivasan; Kim, Young-Hun; Park, Jeong-Hee; Im, Ho Taek; Sohn, Young Taek; Kim, Kyeong Soo; Kim, Yong-Il; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon; Woo, Jong Soo

2014-06-01

The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.

Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism.

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Song, Qichun; Ni, Jianlong; Jiang, Hongyuan; Shi, Zhibin

2017-10-01

The aim of the study were to evaluate the effect of sildenafil against avascular necrosis of femoral head (ANFH) in a rabbit model, and to study the role of protein kinase G (PKG) pathway and vascular endothelial growth factor (VEGF) in ANFH. Three weeks after inducing ANFH with methylprednisolone injection, 45 female adult New Zealand white rabbits were divided into three groups and treated as follows: group SI received daily intraperitoneal sildenafil with a dose of 10 mg/kg per day; group SD received daily sildenafil identically to group SI plus auricular vein injection DT3 (a specific PKG inhibitor); group NS received only normal saline. The blood perfusion function in the femoral head was measured by perfusion MRI and ink artery infusion. Bilateral femora heads were examined histopathologically for the presence of osteonecrosis; VEGF of tissue was examined by Western blot analysis; cGMP level and PKG activity were also measured. The incidence of ANFH in SI group was significantly lower than that observed in NS and SD groups (p < 0.05). VEGF in SI group was increased compared to NS group. cGMP level and PKG activity were also significantly different between NS and SI group (p < 0.05). However, these effects of sildenafil in SD group were all markedly inhibited by the administration of DT3 compared to SI group. Sildenafil appear to increase the perfusion of femoral head by up-regulating VEGF through PKG pathway. The increased perfusion of femoral head could prevent ANFH. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

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

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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.

Sildenafil normalizes bowel transit in preclinical models of constipation.

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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.

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

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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

Neuroimaging Cerebrovascular Function and Diffuse Axonal Injury after Traumatic Brain Injury and Response to Sildenafil Treatment

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2016-04-05

n=4, FPI+sildenafil n=3). No significant main effect of either injury or treatment was observed (data not shown). Water Maze Animals in all groups...spent in prior quadrant on trial one of test day revealed no significant main effect of either injury or treatment . 41 Figure 15. Water ...injury with sildenafil treatment (each pɘ.0001). Error bars represent SEM. 50 Analysis of mean diffusivity in grey matter ROIs

Cerebral haemodynamic response or excitability is not affected by sildenafil

DEFF Research Database (Denmark)

Kruuse, Christina; 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...... amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication...

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

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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.

Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate-resistant polycystic ovarian syndrome patients.

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Bjelica, Artur; Trninić-Pjević, Aleksandra; Mladenović-Segedi, Ljiljana; Cetković, Nenad; Petrović, Djordje

2016-01-01

Polycystic ovary syndrome is the most common endocrinopathy in women of reproductive-age. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI). The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ± 1.7 mm) compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ± 1.3 mm). The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%), while in the clomiphene citrate group it was (9.6%). This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

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Lei Wang

Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

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

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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.

Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate - resistant polycystic ovarian syndrome patients

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Bjelica Artur

2016-01-01

Full Text Available Introduction. Polycystic ovary syndrome is the most common endocrinopathy in women of reproductiveage. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. Objective. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. Methods. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI. Results. The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ± 1.7 mm compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ± 1.3 mm. The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%, while in the clomiphene citrate group it was (9.6%. Conclusion. This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants

NARCIS (Netherlands)

S. Samiee-Zafarghandy; J.N. van den Anker (John); M. Laughon (Matthew); R.H. Clark; P.B. Smith; C.P. Hornik

2016-01-01

textabstractObjective: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. Study Design: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care

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

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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.

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

Science.gov (United States)

Alnemri, AbdulRahman M

2017-01-01

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.

Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling.

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Das, Anindita; Xi, Lei; Kukreja, Rakesh C

2005-04-01

We investigated the effect of sildenafil in protection against necrosis or apoptosis in cardiomyocytes. Adult mouse ventricular myocytes were treated with sildenafil (1 or 10 microM) for 1 h before 40 min of simulated ischemia (SI). Necrosis was determined by trypan blue exclusion and lactate dehydrogenase release following SI alone or plus 1 or 18 h of reoxygenation (RO). Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and mitochondrial membrane potential measured using a fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1). Sildenafil reduced necrosis as indicated by decrease in trypan blue-positive myocytes and leakage of lactate dehydrogenase compared with untreated cells after either SI or SI-RO. The number of terminal deoxynucleotidyl transferase-mediated nick end labeling-positive myocytes or loss of JC-1 fluorescence following SI and 18 h of RO was attenuated in the sildenafil-treated group with concomitant inhibition of caspase 3 activity. An early increase in Bcl-2 to Bax ratio with sildenafil treatment was also observed in myocytes after SI-RO. The increase of Bcl-2 expression by sildenafil was inhibited by nitric-oxide synthase (NOS) inhibitor, L-nitro-amino-methyl-ester. The drug also enhanced mRNA and protein content of inducible NOS (iNOS) and endothelial NOS (eNOS) in the myocytes. Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes. The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes. Reverse transcription-PCR, Western blots, and immunohistochemical assay confirmed the expression of phosphodiesterase-5 in mouse cardiomyocytes. These data provide strong evidence for a direct protective effect of sildenafil against necrosis and apoptosis through NO signaling pathway. The results may have possible

Should the patient with coronary artery disease use sildenafil?

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Cheitlin, Melvin D

2003-01-01

Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in life will be markedly improved by their ability to engage in sexual activity.

Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

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Mohamed A. Morsy

2014-01-01

Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

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

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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

Effect of Mucuna pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozotocin-induced diabetic rat.

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Suresh, Sekar; Prakash, Seppan

2011-07-01

Erectile dysfunction is one of the major secondary complications of diabetes. Mucuna pruriens (M. pruriens), a leguminous plant identified for its antidiabetic, aphrodisiac, and fertility enhancing properties, has been the choice of Indian traditional medicine. The objective of the present study was to analyze the efficacy of M. pruriens on free radicals-mediated penile tissue alterations in hyperglycemic male rats. Methods.  Male albino rats were divided as group I (sham) control, group II (STZ) diabetes-induced (streptozotocin 60 mg/kg of body weight [bw] in 0.1 M citrate buffer), group III (STZ + MP) diabetic rats administered with 200 mg/kg bw of ethanolic extract of M. pruriens seed, group IV (STZ + SIL) diabetic rats administered with 5 mg/kg bw of sildenafil citrate, group V (sham + MP) administered with 200 mg/kg bw of extract alone, and group VI (sham + SIL) administered with 5 mg/kg bw of sildenafil citrate. The M. pruriens and sildenafil citrate were given (gavage) once daily for a period of 60 days. At the end of 60 days, the animals were sacrificed and subjected to analysis of reactive oxygen species levels, enzymic and nonenzymic antioxidant levels, levels of NOx, histological, and histomorphometrical study of penile tissue. Remedial use of M. pruriens seed extract on diabetes-induced erectile tissue damage. Significantly high levels of oxidative stress and low levels of antioxidants in the penile tissue seem to contribute to the increased collagen deposition and fibrosis of erectile tissue in STZ rats. Relatively, there was increased damage in STZ + SIL group. Supplementation of M. pruriens in STZ + MP group has revealed the potency to overcome oxidative stress, and good preservation of penile histoarchitecture.  The ethanolic extract of M. pruriens seed significantly recovered or protected erectile tissue from the oxidative stress-induced degeneration by its antioxidant potentials. These findings propound to serve mankind by the treatment of

Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

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Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

2015-01-01

The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

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

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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

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

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...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

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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.

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

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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

Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients.

Science.gov (United States)

Kniotek, Monika; Boguska, Agnieszka

2017-01-01

Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system.

A new magnetic nanodiamond/graphene oxide hybrid (Fe3O4@ND@GO) material for pre-concentration and sensitive determination of sildenafil in alleged herbal aphrodisiacs by HPLC-DAD system.

Science.gov (United States)

Yilmaz, Erkan; Ulusoy, Halil İbrahim; Demir, Özge; Soylak, Mustafa

2018-05-01

A sensitive analytical methodology was investigated to concentrate and determine of sildenafil citrate (SLC) present at trace level in herbal supplementary products. The proposed method is based on simple and sensitive pre-concentration of SLC by using magnetic solid phase extraction with new developed magnetic nanodiamond/graphene oxide hybrid (Fe 3 O 4 @ND@GO) material as a sorbent. Experimental variables affecting the extraction efficiency of SLC like; pH, sample volume, eluent type and volume, extraction time and amount of adsorbent were studied and optimized in detail. Determination of sildenafil citrate after magnetic solid phase extraction (MSPE) was carried out by HPLC-DAD system. The morphology, composition, and properties of the synthesized hybrid material was characterized by Fourier transform infrared spectrometry (FT-IR), Raman spectrometry (Raman), X-ray diffraction spectrometry (XRD), scanning electron microscopy (SEM), mapping photographs, zeta potential analyzer, and BET surface area analysis. Under optimized conditions, linear range was ranged from 5.00 to 250.00 ng mL -1 with R 2 of 0.9952. The limit of detection (LOD) was 1.49 ng mL -1 and the recoveries at two spiked levels were ranged from 94.0 to 104.1% with the relative standard deviation (RSD) < 7.1% (n = 5). The enhancement factor (EF) was 86.9. The results show that the combination MSPE with HPLC-DAD is a suitable and sensitive method for the determination of SLC in real samples. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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NAM

onset, painless, visual loss following the use of sildenafil citrate 100mg twice weekly, prescribed for his ... vascular and visceral smooth muscle effects the use of sildenafil has ... Laboratory investigations revealed normal fasting blood glucose ...

Effectiveness of ranitidine bismuth citrate and proton pump inhibitor ...

African Journals Online (AJOL)

Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey. ... Results: When we look at the eradication rates of the treatment groups, only two groups (ranitidine bismuth citrate and rabeprazole groups) had eradication rates greater than 80%, both at intention to ...

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

International Nuclear Information System (INIS)

Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

2013-01-01

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

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

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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.

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

and UK-114,542, and a PDE1 inhibitor UK-90,234 on cGMP hydrolysis were investigated in human and guinea pig cerebral arteries. The vasoactive responses of the compounds were evaluated in guinea pig basilar arteries in vitro, with concomitant measurements of cAMP and cGMP. PDE5 was found in human middle...... cerebral arteries. Sildenafil and UK-114,542 inhibited cGMP hydrolysis concentration-dependently in both species. In guinea pig arteries, sildenafil induced an endothelium-dependent vasodilatation only at concentrations above 10 nM, which was augmented by sodium nitroprusside and attenuated by reduction...... of cGMP, but was cGMP independent at high concentrations. UK-114,542 was more and UK-90,234 was less potent than sildenafil. In conclusion, PDE5 is present in human and guinea pig cerebral arteries, and is inhibited by sildenafil at micromolar levels. Sildenafil in vitro is a poor dilator of guinea pig...

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.

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

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...... 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...... 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...

Comparison of tamsulosin vs tamsulosin/sildenafil effectiveness in the treatment of erectile dysfunction in patients affected by type III chronic prostatitis.

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Cantoro, Ubaldo; Catanzariti, Francesco; Lacetera, Vito; Quaresima, Luigi; Muzzonigro, Giovanni; Polito, Massimo

2013-09-26

We evaluated the effectiveness of tamsulosin monotherapy versus tamsulosin plus sildenafil combination therapy on erectile dysfunction (ED) in young patients with type III chronic prostatitis and ED by using symptom score scales. 44 male patients were divided into 2 groups: the first group (20 patients) was treated with tamsulosin 0,4 mg monotherapy and the second one 24 patients) was treated with tamsulosin 0,4 mg plus sildenafil 50 mg combination therapy. “International Prostate Symptom Score, “National Institute of Health Chronic Prostatitis Symptom Index" (NIH-CPSI) and “International Index of Erectile Function" (IIEF-5) were investigated in each group of patients, and scores calculated during the first medical examination. Both groups were treated with tamsulosin once daily for 60 days, while sildenafil 50 mg was given on demand (at least 2 times per week) for 60 days. During the second medical examination IPSS, NIH-CPSI and IIEF-5 scores were analyzed once more. Afterwards, the alterations of scores among medical examinations in each group and between both groups were statistically compared. The age average of the 44 cases included was 32.04 3.15 years. Both groups present a statistically significant decrease, between the first and the second medical examination, in IPSS, NIH-CPSI scores and statistically significant increase in IIEF-5 score. In addition, there is no statistically significant difference, in all scores, between mono and combination therapy. tamsulosin monotherapy, as well as a combination therapy (tamsulosin plus sildenafil) has an improving effect on symptoms and on ED in patients with type III prostatitis. In the near future alpha-blockers monotherapy could be used in the treatment of chronic prostatitis and ED cases instead of phosphodiesterase type 5 (PDE-5) inhibitors combination therapy.

Sildenafil protects neuronal cells from mitochondrial toxicity induced by β-amyloid peptide via ATP-sensitive K+ channels.

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Son, Yonghae; Kim, Koanhoi; Cho, Hyok-Rae

2018-06-02

To understand the molecular mechanisms underlying the beneficial effects of sildenafil in animal models of neurological disorders, we investigated the effects of sildenafil on the mitochondrial toxicity induced by β-amyloid (Aβ) peptide. Treatment of HT-22 hippocampal neuronal cells with Aβ 25∼35 results in increased mitochondrial Ca 2+ load, which is subsequently suppressed by sildenafil as well as by diazoxide, a selective opener of the ATP-sensitive K + channels (K ATP ). However, the suppressive effects of sildenafil and diazoxide are significantly attenuated by 5-hydroxydecanoic acid (5-HD), a K ATP inhibitor. The increased mitochondrial Ca 2+ overload is accompanied by decrease in the intracellular ATP concentration, increase in intracellular ROS generation, occurrence of mitochondrial permeability transition, and activation of caspase-9 and cell death. Exposure to sildenafil inhibited the mitochondria-associated changes and cell death induced by Aβ. However, the inhibitory effects of sildenafil are abolished or weakened in the presence of 5-HD, suggesting that opening of the mitochondrial K ATP is required for sildenafil to exert these effects. Taken together, these results indicate that at the mitochondrial levels, sildenafil plays a protective role towards neuronal cell in an environment rich in Aβ, and exerts its effects via the mitochondrial K ATP channels-dependent mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

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......), 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...... properties of the prepared powders. CONCLUSION: 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)....

Cerebral venous thrombosis associated with sildenafil intake

International Nuclear Information System (INIS)

Miranda Hernández, José Luis; Fernández Cué, Leda; Garzón Cutiño, Lisbel; Gómez Viera, Nelson; Pérez Esquivel, Lianet

2016-01-01

A 59 year-old male patient with a history of hypertension and regular consumption of sildenafil entered the service because of acute stroke and headache seizure. Physical examination detected left hemiplegia. By skull nuclear gadolinium magnetic resonance, an expansive lesion is observed which caught heterogeneously contrast. Possible diagnosis of high-grade brain glioma was raised. Right frontoparietal craniotomy was performed and a tumor lesion was not visualized. After ruling out the presence of high-grade glioma, the diagnosis of hemorrhagic venous infarction was assessed. CT angiography and clotting was made to rule out prothrombotic states to justify this disease entity. Special hematology studies were within normal values. The case was concluded as a venous sinus thrombosis associated with the use of sildenafil. (author)

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

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

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....... 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......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

Science.gov (United States)

Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

2018-01-01

Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

Sildenafil Improves Erectile Function in Men with Chronic Heart Failure

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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.

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

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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.

Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension.

Science.gov (United States)

Mainguy, Vincent; Malenfant, Simon; Neyron, Anne-Sophie; Bonnet, Sébastien; Maltais, François; Saey, Didier; Provencher, Steeve

2013-08-01

Exercise tolerance in pulmonary arterial hypertension (PAH) is most commonly assessed by the 6-min walk test (6MWT). Whether endurance exercise tests are more responsive than the 6MWT remains unknown. 20 stable PAH patients (mean±sd age 53±15 years and mean pulmonary arterial pressure 44±16 mmHg) already on PAH monotherapy completed the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) before and after the addition of sildenafil citrate 20 mg three times daily or placebo for 28 days in a randomised double-blind crossover setting. Pre- or post-placebo tests were used to assess repeatability of each exercise test, whereas pre- or post-sildenafil citrate tests were used to assess their responsiveness. Sildenafil citrate led to placebo-corrected changes in exercise capacity of 18±25 m (p = 0.02), 58±235 s (p = 0.58) and 29±77 s (p = 0.09) for the 6MWT, the ESWT and the CET, respectively. The 6MWT was associated with a lower coefficient of variation between repeated measures (3% versus 18% versus 13%), resulting in a higher standardised response mean compared with endurance tests (0.72, 0.25 and 0.38 for the 6MWT, the ESWT and the CET, respectively). The 6MWT had the best ability to capture changes in exercise capacity when sildenafil citrate was combined with patients' baseline monotherapy, supporting its use as an outcome measure in PAH.

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

Science.gov (United States)

Sharifi, Seyed Hossein Hosseini; Mokarrar, Mohsen Heidari; Khaledi, Flora; Yamini-Sharif, Reyhaneh; Lashay, Alireza; Soltani, Mohammad Hossein

2014-01-01

To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4 mg plus sildenafil 50mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient's ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

Science.gov (United States)

Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

2009-05-01

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

Iron(III) citrate speciation in aqueous solution.

Science.gov (United States)

Silva, Andre M N; Kong, XiaoLe; Parkin, Mark C; Cammack, Richard; Hider, Robert C

2009-10-28

Citrate is an iron chelator and it has been shown to be the major iron ligand in the xylem sap of plants. Furthermore, citrate has been demonstrated to be an important ligand for the non-transferrin bound iron (NTBI) pool occurring in the plasma of individuals suffering from iron-overload. However, ferric citrate chemistry is complicated and a definitive description of its aqueous speciation at neutral pH remains elusive. X-Ray crystallography data indicates that the alcohol function of citrate (Cit4-) is involved in Fe(III) coordination and that deprotonation of this functional group occurs upon complex formation. The inability to include this deprotonation in the affinity constant calculations has been a major source of divergence between various reports of iron(III)-citrate affinity constants. However the recent determination of the alcoholic pKa of citric acid (H4Cit) renders the reassessment of the ferric citrate system possible. The aqueous speciation of ferric citrate has been investigated by mass spectrometry and EPR spectroscopy. It was observed that the most relevant species are a monoiron dicitrate species and dinuclear and trinuclear oligomeric complexes, the relative concentration of which depends on the solution pH value and the iron : citric acid molar ratio. Spectrophotometric titration was utilized for affinity constant determination and the formation constant for the biologically relevant [Fe(Cit)2]5- is reported for the first time.

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

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

Science.gov (United States)

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite

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 liv...... type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG....

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

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

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

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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.

A nanohybrid system for taste masking of sildenafil

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Lee JH

2012-03-01

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.Keywords: montmorillonite, nanohybrids, polyvinylacetal diethylaminoacetate, sildenafil citrate, taste masking

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

OpenAIRE

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 ...

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

DEFF Research Database (Denmark)

Clemmesen, J.O.; Giraldi, A.; Ott, P.

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 liv...... type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG Udgivelsesdato: 2008/10/28...

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

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Seyed Hossein Hosseini Sharifi

2014-06-01

Full Text Available Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR with tamsulosin alone in patients with benign prostate hyperplasia (BPH. Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92. Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively. Fifteen patients in group A (success rate: 70% and nineteen patients in group B (success rate: 62.7% had failed trial without catheter (TWOC at 7th day following AUR (p value = 0.3. No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively. Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.

Science.gov (United States)

Lindberg, Ulrich; Witting, Nanna; Jørgensen, Stine Lundgaard; Vissing, John; Rostrup, Egill; Larsson, Henrik Bo Wiberg; Kruuse, Christina

2017-01-01

Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in muscles. This causes functional ischemia and contributes to muscle wasting. Similar functional ischemia may be present in brains of patients with BMD, who often have mild cognitive impairment, and nNOS may be important for the regulation of the microvascular circulation in the brain. We hypothesized that treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates nitric oxide responses, would augment both the blood oxygen level-dependent (BOLD) response and cerebral blood flow (CBF) in patients with BMD. Seventeen patients (mean ± SD age 38.5 ± 10.8 years) with BMD were included in this randomized, double-blind, placebo-controlled, crossover trial. Twelve patients completed the entire study. Effects of sildenafil were assessed by 3 T magnetic resonance (MR) scanning, evoked potentials, somatosensory task-induced BOLD functional MR imaging, regional and global perfusion, and angiography before and after 4 weeks of sildenafil, 20 mg (Revatio in gelatine capsules, oral, 3 times daily), or placebo treatment. Sildenafil increased the event-related sensory and visual BOLD response compared with placebo (p < 0.01). However, sildenafil did not alter CBF, measured by MR phase contrast mapping, or the arterial diameter of the middle cerebral artery, measured by MR angiography. We conclude that nNOS may play a role in event-related neurovascular responses. Further studies in patients with BMD may help clarify the roles of dystrophin and nNOS in neurovascular coupling in general, and in patients with BMD in particular.

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

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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.

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.

Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy

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Sameh Mohamed Abouzeid

2016-01-01

Full Text Available Contrast-induced nephropathy (CIN is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalini- zation medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR, 60 mL/min/1.73 m2or less] who underwent elective or emergency coronary angiography (CAG with/without percutaneous coronary intervention (PCI at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was −0.60 ± 1.58 versus −0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39. Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of

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

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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

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

International Nuclear Information System (INIS)

Ding Meijuan; Wu Xiaoli; Yuan Lihua; Wang Shu; Li Yun; Wang Ruoyu; Wen Tingting; Du Shuhu; Zhou, Xuemin

2011-01-01

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 3 O 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 μg g -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.

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

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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.

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

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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

Prevalence and associated factors to tadalafil consumption in colombian college students during first semester of 2013

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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.

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

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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.

Metformin-letrozole in comparison with Metformin-clomiphene citrate in clomiphene-resistance PCOS patients undergoing IUI

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Mohammad Hossein Fallahzadeh

2011-01-01

Full Text Available Background: Polycystic ovary syndrome (PCOS is associated with approximately 75% of women who suffer from infertility due to anovulation. Additionally, around 20– 25% of anovulatory women with PCOS do not respond at all to clomiphene citrate and are considered to be “clomiphene– resistant”. Aromatase inhibitors have been suggested as an alternative treatment to clomiphene as the discrepancy between ovulation and pregnancy rates with clomiphene citrate has been attributed to its anti-estrogenic action and estrogen receptor depletion. Objective: The aim of this study is to compare results of Metformin-letrozole with Metformin-clomiphene citrate in clomiphene resistance PCOS patients undergoing IUI.Materials and Methods: In this single blind randomized trial, ovarian cycles were studied in 100 clomiphene- resistant patients with PCOS. The inclusion criteria were patients who received 150mg clomiphene citrate daily for 3 cycles and failed to become pregnant. The patients were matched for their age, body mass index (BMI, and infertility period. They were randomly allocated to a metformin-letrozole group (n=50 and a metformin-clomiphene citrate group (n=50. Chemical and clinical pregnancies were assessed after IUI. Abortion rates were determined in both groups. Results: Regarding pregnancy rate, there was no significant difference between the two groups. One miscarriage (2% occurred in the metformin-clomiphene citrate group, whereas none was seen in the metformin-letrozole group. Conclusion: There is no significant difference in pregnancy rate between clomiphene citrate and letrozole groups although it has been 2% in the former and 5% in the latter.

Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant

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Luis Almenar Bonet

2014-08-01

Full Text Available The objective of the present work is to describe the experience with intravenous (IV sildenafil in heart transplant (HT patients with reactive pulmonary hypertension (PH who developed right ventricular dysfunction (RVD in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide. All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.

Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant.

Science.gov (United States)

Bonet, Luis Almenar; Guillén, Rosario Vicente; Lázaro, Ignacio Sánchez; de la Fuente, Carmen; Osseyran, Faisa; Dolz, Luis Martínez; Hernández, Mónica Montero; Sanz, Manuel Portolés; Otero, Miguel Rivera; Sanz, Antonio Salvador

2014-01-01

The objective of the present work is to describe the experience with intravenous (IV) sildenafil in heart transplant (HT) patients with reactive pulmonary hypertension (PH) who developed right ventricular dysfunction (RVD) in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP) was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide). All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.

Evaluation of Pharmacokinetic and Pharmacodynamic Drug–Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild‐to‐Moderate Hypertension

Science.gov (United States)

Langenickel, TH; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, MF; Sunkara, G; Rajman, I

2017-01-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open‐label, three‐period, single sequence study, patients with mild‐to‐moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and Cmax of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (–5/–4/–4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. PMID:28599060

Calcium citrate: a new biomaterial that can enhance bone formation in situ

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WANG Li-ming

2012-11-01

Full Text Available 【Abstract】 Objective: To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2 on bone regeneration in a bone defect rabbit model. Methods: Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2 group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respec-tively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg combined with rhBMP-2 (2 mg or rhBMP-2 alone were im-planted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis. Results: Histomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%±1.26% vs 48.21%±2.37% at 2 weeks; 43.40%±1.65% vs 57.32%±1.47% at 4 weeks, and 51.32%±7.80% vs 66.74%±4.05% at 6 weeks (P<0.05 for all. At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group. Conclusion: From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly en-hances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions. Key words: Bone morphogenetic protein-2; Biocompatible materials; Calcium citrate; Gelatin

Citrate and renal calculi: an update

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Pak, C. Y.

1994-01-01

Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

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

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...

The efficacy and safety of on-demand Elonza; a generic product of sildenafil in Thai men with erectile dysfunction.

Science.gov (United States)

Wijitsettakul, Udomsak; Pempongkosol, Sompol

2013-06-01

To evaluate the efficacy and safety of Elonza (generic product of sildenafil) 100 mg, a phosphodiesterase type 5 (PDE5) inhibitor, in Thai men with erectile dysfunction (ED). This prospective, Cohort study was conducted for eight weeks. Two hundred ten male patients, older than 20 years of age with ED were enrolled to receive generic product of sildenafil 100 mg taken as needed. Efficacy is evaluated through the International Index of Erectile Function (IIEF) scores for the five separate response domains, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction domain. After sildenafil administration, erectile function domain scores were significantly increased from baseline, 5.02 (p product of sildenafil, was an effective and well-tolerated treatment for ED in Thai men.

Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.

Science.gov (United States)

Hsiao, H-L; Langenickel, T H; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, M F; Sunkara, G; Rajman, I

2018-03-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, three-period, single sequence study, patients with mild-to-moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and C max of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (-5/-4/-4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

Directory of Open Access Journals (Sweden)

Silvia Elaine Ferreira-Melo

2011-01-01

Full Text Available OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME. METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part by the inhibition of phosphodiesterase-5.

Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.

Science.gov (United States)

Musicki, Biljana; Champion, Hunter C; Becker, Robyn E; Liu, Tongyun; Kramer, Melissa F; Burnett, Arthur L

2005-07-01

Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats "primes" the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis.

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

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.

Sildenafil, a selective phosphodiesterase type 5 inhibitor, enhances memory reconsolidation of an inhibitory avoidance task in mice.

Science.gov (United States)

Boccia, M M; Blake, M G; Krawczyk, M C; Baratti, C M

2011-07-07

Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation. Copyright © 2011 Elsevier B.V. All rights reserved.

Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.

Science.gov (United States)

Orejana, Lourdes; Barros-Miñones, Lucía; Jordan, Joaquin; Cedazo-Minguez, Angel; Tordera, Rosa M; Aguirre, Norberto; Puerta, Elena

2015-06-01

The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. © The Author 2014. Published by Oxford University Press on behalf of

STABILITY OF SYNTHESIZED SILVER NANOPARTICLES IN CITRATE AND MIXED GELATIN/CITRATE SOLUTION

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Jana Kavuličová

2018-04-01

Full Text Available The study focuses on an investigation of the influence of both citrate and mixed gelatin/citrate as a reductant and stabilizer on the colloidal stability of silver nanoparticles (AgNPssynthesized by a chemical reduction of Ag+ ions after a short - (7th day - and long - (118th day - term storage. Formed AgNPs were characterized by a UV–vis Spectroscopy, Transmission Electron Microscope (TEM, Dynamic light scattering (DLS and Zeta-potential (ZP. The obtained results revealed that a short-term stability of the synthesized AgNPs was greatly influenced by a citrate stabilizer with the absence of gelatin. Smaller-sized AgNPs (average particle diameter of 3 nm, roughly spherical in a shape, were obtained with a narrow size distribution. The very negative value of the Zeta-potential confirmed a strong stability of the citrate capped AgNPs. However, a surface coating of the AgNPs by a gelatin/citrate stabilizer was found to be a dominant contributor in improving a long-term stability of the AgNPs (average particle diameter of 26 nm. The use of gelatin in mixed stabilizer solution provided the AgNPs with higher monodispersity and a controllable size after both the short and long-term storage.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

Science.gov (United States)

Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

2017-11-15

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

THERMODYNAMIC PARAMETERS OF SOLUTIONS OF ...

African Journals Online (AJOL)

2014-06-30

Jun 30, 2014 ... Physical Chemistry Laboratory, Department of Chemistry, ... The solubility of Sildenafil citrate in some organic solvents; hexane, ... dichloroethane were analytical grade reagents, which were purified by fractional distillation.

Safety and long-term efficacy of transition from sildenafil to tadalafil due to side effects in patients with pulmonary arterial hypertension.

Science.gov (United States)

Lichtblau, Mona; Harzheim, Dominik; Ehlken, Nicola; Marra, Alberto; Pinado, Fabiola Pena; Grünig, Ekkehard; Egenlauf, Benjamin

2015-02-01

Two phosphodiesterase-type 5 (PDE-5) inhibitors, sildenafil and tadalafil, are approved for treatment of pulmonary arterial hypertension (PAH). It has not yet been observed if transition from sildenafil to tadalafil is beneficial in patients suffering from adverse reactions. Aim of this study was to analyze safety and long-term effects in PAH patients whose treatment was transitioned from sildenafil to tadalafil due to intolerable side-effects. A retrospective analysis of PAH-patients who were stable on sildenafil for >3 months and transitioned to tadalafil due to adverse events was performed. Data collected included demographics, PAH-etiology, WHO-functional class, 6 min walking distance (6MWD), echocardiography, lung function tests, and NTproBNP pre-transition and 3, 6, and 12 months post-transition. Included were 13 PAH patients (8 females mean age 64 ± 10 years) who had been on sildenafil for a mean of 12 ± 8.4 months. In six patients (46.1 %) a switch to tadalafil was feasible and resulted in tolerable side effects and a stable clinical course with improvement of symptoms, 6MWD, stable echocardiographic findings, and NTproBNP-levels during a follow-up of 11 ± 3 months. In 5 out of 13 patients (38.5 %) adverse events occurred under tadalafil as well and therapy with PDE-5 inhibitors was discontinued. In two patients (15.4 %) sildenafil-treatment could be successfully restarted after an intermittent switch to tadalafil. The observations of this study indicate that a transition of sildenafil to tadalafil in case of intolerable side effects is a reasonable therapy option in about 50 % of the patients. These results should be verified by a larger prospective study.

Study on the Antimicrobial Properties of Citrate-Based Biodegradable Polymers

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Lee-Chun eSu

2014-07-01

Full Text Available 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 controllable chemical, mechanical, and biological characteristics. In this study, various citric acid derived biodegradable polymers were synthesized and investigated for their physicochemical and antimicrobial properties. Results indicate that citric acid derived polymers reduced bacterial proliferation to different degrees based on their chemical composition. Among the studied polymers, poly(octamethylene citrate (POC showed approximately 70-80% suppression to microbe proliferation, owing to its relatively higher ratio of citric acid contents. Crosslinked urethane-doped polyester elastomers (CUPEs and biodegradable photoluminescent polymers (BPLPs also exhibited significant bacteria reduction of ~20% and ~50% for Staphylococcus aureus and Escherichia coli, respectively. Thus, the intrinsic antibacterial properties in citrate-based polymers enable them to inhibit bacteria growth without incorporation of antibiotics, silver nanoparticles, and other traditional bacteria-killing agents suggesting that they are unique beneficial materials for wound dressing, tissue engineering, and other potential medical applications where antimicrobial property is desired.

Correlation of improved erectile function and rate of successful intercourse with improved emotional well-being assessed with the Self-Esteem And Relationship questionnaire in men treated with sildenafil for erectile dysfunction and stratified by age.

Science.gov (United States)

Steidle, Christopher P; Stecher, Vera J; Pace, Cindy; Tseng, Li-Jung

2006-05-01

The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED. To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age ( 65 years). This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100 mg) administered for 10 weeks to 382 men with ED (mean +/- SD age, 55 +/- 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States. Analysis (by intent-to-treat, n = 368) of the change from baseline to the week-10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation. For the overall population, there was mean +/- SD improvement (p Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (p 65 years, and six were positive in men aged erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.

21 CFR 582.6195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.6195 Section 582.6195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance is generally...

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...... of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms....

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... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

21 CFR 582.1195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.1195 Section 582.1195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance is...

Scintiscanning of lung cancer with 67Ga-citrate

International Nuclear Information System (INIS)

Abe, Mitsunobu; Ohyama, Shiro; Ohtsuka, Hassau; Hoshina, Toshifumi; Takanashi, Shuko

1982-01-01

The clinical value of scintigram with 67 Ga-citrate in 58 patients with primary lung cancer was investigated and discussed. The results are as follows: 1) Positive 67 Ga-scintigram was obtained in 83% of patients with primary lung cancer. The histologically confirmed positive ratios were 74% in adenocarcinoma, 94% in squamous cell carcinoma, 80% in small cell carcinoma and 100% in large cell carcinoma. 2) The positive ratios according to T category of TNM classification was 0% (0/1) in T1, 83% (20/24) in T2 and 85% (28/33) in T3. 3) According to rules for classification of lung cancer (TNM UICC 1978,) T2 cases were divided into two groups. a) In patients with hilar involvements on chest X-ray, positive accumulation to the hilar region was 88% (7/8). b) In patients without the evidence of hilar involvements on chest X-ray, the positive accumulation to the hilar region was 81% (13/16). 4) All cases extending to the mediastinum showed abnormal 67 Ga-citrate accumulation regardless of histological type. 67 Ga-citrate scanning is useful in evaluating the extent of lung cancer, especially with hilar and mediastinal involvements. Therefore 67 Ga-citrate scanning seems to be very useful for planning the radiotherapy for lung cancer. (author)

Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy.

Science.gov (United States)

Percival, Justin M; Whitehead, Nicholas P; Adams, Marvin E; Adamo, Candace M; Beavo, Joseph A; Froehner, Stanley C

2012-09-01

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy caused by mutations in the dystrophin gene. Loss of dystrophin initiates a progressive decline in skeletal muscle integrity and contractile capacity which weakens respiratory muscles including the diaphragm, culminating in respiratory failure, the leading cause of morbidity and mortality in DMD patients. At present, corticosteroid treatment is the primary pharmacological intervention in DMD, but has limited efficacy and adverse side effects. Thus, there is an urgent need for new safe, cost-effective, and rapidly implementable treatments that slow disease progression. One promising new approach is the amplification of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signalling pathways with phosphodiesterase 5 (PDE5) inhibitors. PDE5 inhibitors serve to amplify NO signalling that is attenuated in many neuromuscular diseases including DMD. We report here that a 14-week treatment of the mdx mouse model of DMD with the PDE5 inhibitor sildenafil (Viagra(®), Revatio(®)) significantly reduced mdx diaphragm muscle weakness without impacting fatigue resistance. In addition to enhancing respiratory muscle contractility, sildenafil also promoted normal extracellular matrix organization. PDE5 inhibition slowed the establishment of mdx diaphragm fibrosis and reduced matrix metalloproteinase-13 (MMP-13) expression. Sildenafil also normalized the expression of the pro-fibrotic (and pro-inflammatory) cytokine tumour necrosis factor α (TNFα). Sildenafil-treated mdx diaphragms accumulated significantly less Evans Blue tracer dye than untreated controls, which is also indicative of improved diaphragm muscle health. We conclude that sildenafil-mediated PDE5 inhibition significantly reduces diaphragm respiratory muscle dysfunction and pathology in the mdx mouse model of Duchenne muscular dystrophy. This study provides new insights into the therapeutic utility of targeting defects in NO

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets.

Science.gov (United States)

Silvera, F E; Blasina, M F; Vaamonde, L; Tellechea, S; Godoy, C; Zabala, S; Mañana, G; Martell, M; Olivera, W

2011-08-01

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Directory of Open Access Journals (Sweden)

F.E. Silvera

2011-08-01

Full Text Available Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica aged 12 to 72 h (1660 ± 192 g received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT. Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

The ability of the general male public to assess their suitability to take 50-mg sildenafil: an assessment of the comprehension of patient information materials via internet survey.

Science.gov (United States)

Symonds, Tara; Coyne, Karin S; Margolis, Mary Kay; Schnetzler, Gabriel

2011-07-01

Erectile dysfunction (ED) is the most common male sexual dysfunction and has a negative impact on masculinity and self-esteem. Phosphodiesterase type 5 inhibitors, including sildenafil, are the first-line treatment option for ED. Providing appropriate information regarding suitability for using sildenafil is important. The purpose of this study was to assess whether a broad spectrum of men could appropriately evaluate their suitability for 50-mg sildenafil after reviewing patient information materials. Patient information (Pack) on appropriate use of 50-mg sildenafil and patient information leaflet (PIL), a Web survey including demographics, self-assessed suitability for sildenafil use, and suitability screener. A randomly selected, population-representative Web-based panel of males in the UK was recruited for this study. Eligible men answered a brief sociodemographic questionnaire and then were presented with the Pack. If a participant desired additional information, he could also review the PIL. The participants then rated the Pack and PIL (if reviewed), self-assessed their suitability for sildenafil use, and completed a previously validated screener for suitability. A total of 1,275 men aged 40 and above were included in these analyses; the mean age was 57.8 ± 9.9 years. A total of 1,054 men reported ED; 517 men (40.5%) deemed themselves suitable for sildenafil; 504 men (39.6%) deemed themselves unsuitable; and 254 (19.9%) were unsure. The concordance rate between screener-assessed suitability and self-assessed suitability was 70.9% (95% confidence interval [CI] = 68.1-73.7%). When accounting for men who would not take sildenafil even though they were suitable or would seek additional information from a healthcare professional prior to using sildenafil, the concordance rate was 84.2% (95% CI = 82.2-86.2%). The results of this study suggest that men in the general population are capable of using written sildenafil patient education materials to accurately assess

21 CFR 184.1625 - Potassium citrate.

Science.gov (United States)

2010-04-01

... acid with potassium hydroxide or potassium carbonate. It occurs as transparent crystals or a white... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS...

An excess of topical calcium and magnesium reverses the therapeutic effect of citrate on the development of corneal ulcers after alkali injury.

Science.gov (United States)

Haddox, J L; Pfister, R R; Slaughter, S E

1996-03-01

Our purpose was to determine whether chelation of Ca2+ and Mg2+ is the mechanism by which sodium citrate inhibits corneal ulceration in the alkali-injured rabbit eye. The right eyes of 60 albino rabbits (2-2.5 kg) were alkali-injured by filling a 12-mm-diameter plastic well placed on the corneal surface with 0.4 ml of 1 N NaOH. After 35 s the alkali was aspirated, and the well was rinsed with physiological saline. Animals were randomly distributed to three treatment groups of equal size. Two drops of the following topical medications were administered on the hour (14 times per day) for 35 days: physiological saline, 10% citrate in saline, and 346 mM Ca2+, 346 mM Mg2+, and 10% citrate in saline. During the experiment, significantly fewer ulcerations occurred in the citrate-treated eyes (five of 20, 25%) than in the saline-treated eyes (13 of 20, 65%) or in the calcium-magnesium-citrate-treated eyes (15 of 20, 75%). When ulcerations did develop in the citrate group, they occurred significantly later and were less severe than those in the saline and calcium-magnesium-citrate groups. There was a significant increase in the number of eyes with signs of band keratopathy and translucent areas in the calcium-magnesium-citrate group when compared with the other two groups. As in previous studies, sodium citrate significantly inhibited the development of corneal ulcers after alkali injury. The annullment of the favorable effect of citrate on ulceration in the alkali-injured eye by the addition of calcium and magnesium shows that the mechanism of action of citrate is the chelation of these divalent cations.

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...

Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?

Science.gov (United States)

Bagis, Selda; Karabiber, Mehmet; As, Ismet; Tamer, Lülüfer; Erdogan, Canan; Atalay, Ayçe

2013-01-01

The aims of this study were to investigate the relationship between magnesium levels and fibromyalgia symptoms and to determine the effect of magnesium citrate treatment on these symptoms. Sixty premenopausal women diagnosed with fibromyalgia according to the ACR criteria and 20 healthy women whose age and weight matched the premenopausal women were evaluated. Pain intensity, pain threshold, the number of tender points, the tender point index, the fibromyalgia impact questionnaire (FIQ), the Beck depression and Beck anxiety scores and patient symptoms were evaluated in all the women. Serum and erythrocyte magnesium levels were also measured. The patients were divided into three groups. The magnesium citrate (300 mg/day) was given to the first group (n = 20), amitriptyline (10 mg/day) was given to the second group (n = 20), and magnesium citrate (300 mg/day) + amitriptyline (10 mg/day) treatment was given to the third group (n = 20). All parameters were reevaluated after the 8 weeks of treatment. The serum and erythrocyte magnesium levels were significantly lower in patients with fibromyalgia than in the controls. Also there was a negative correlation between the magnesium levels and fibromyalgia symptoms. The number of tender points, tender point index, FIQ and Beck depression scores decreased significantly with the magnesium citrate treatment. The combined amitriptyline + magnesium citrate treatment proved effective on all parameters except numbness. Low magnesium levels in the erythrocyte might be an etiologic factor on fibromyalgia symptoms. The magnesium citrate treatment was only effective tender points and the intensity of fibromyalgia. However, it was effective on all parameters when used in combination with amitriptyline.

Incompatibility of Contrast Medium and Trisodium Citrate

International Nuclear Information System (INIS)

Delcour, Christian; Bruninx, Guy

2013-01-01

To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

21 CFR 184.1195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium citrate. 184.1195 Section 184.1195 Food and... Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O, CAS Reg. No. 813-0994-095) is the calcium salt of citric acid. It is prepared by neutralizing citric acid with...

Effect of sildenafil on erectile dysfunction in spinal Cord injured ...

African Journals Online (AJOL)

Effect of sildenafil on erectile dysfunction in spinal Cord injured patients. ... Trauma was the etiology in 87.5% of the cases (44% were road accidents). 12/16 patients were paraplegics (10 above ... in SCI patients. This approach is compatible with the efforts to improve the quality of life and rehabilitation of these patients.

Analysis of illicit dietary supplements sold in the Italian market: identification of a sildenafil thioderivative as adulterant using UPLC-TOF/MS and GC/MS.

Science.gov (United States)

Damiano, Fabio; Silva, Claudia; Gregori, Adolfo; Vacondio, Federica; Mor, Marco; Menozzi, Mattia; Di Giorgio, Domenico

2014-05-01

Identification of pharmaceutical active ingredients sildenafil and tadalafil and the characterization of a dimethylated thio-derivative of sildenafil, called thioaildenafil or thiodimethylsildenafil, in illicit dietary supplements were described. A multi-residual ultra-performance liquid chromatography-time of flight mass spectrometry (UPLC-TOF/MS) method was developed to screen for the presence of the phosphodiesterase-5 (PDE-5) inhibitors sildenafil, tadalafil, and vardenafil and their analogues thioaildenafil and thiohomosildenafil in powders and pharmaceutical dosage forms. The study was developed in connection with an operation supervised by the Italian Medicines Agency (A.I.F.A.), aimed to monitor dietary supplements in the Italian market. In two of the eleven specimens under investigation, high-resolution mass spectrometry (HR-MS) allowed the identification of the PDE-5 inhibitors sildenafil and tadalafil, while another specimen proved to contain a unapproved dimethylated thioderivative of sildenafil, thioaildenafil or thiodimethylsildenafil, identified for the first time in Italy as adulterant in food supplements. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

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.

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis.

Science.gov (United States)

Jalal, Diana; McFadden, Molly; Dwyer, Jamie P; Umanath, Kausik; Aguilar, Erwin; Yagil, Yoram; Greco, Barbara; Sika, Mohammed; Lewis, Julia B; Greene, Tom; Goral, Simin

2017-04-01

Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence. © 2016 International Society for Hemodialysis.

Effect of calcium citrate on bone integration in a rabbit femur defect model.

Science.gov (United States)

Zhang, Wei; Wang, Wei; Chen, Qing-Yu; Lin, Zhong-Qin; Cheng, Shao-Wen; Kou, Dong-Quan; Ying, Xiao-Zhou; Shen, Yue; Cheng, Xiao-Jie; Nie, Peng-Fei; Li, Xiu-Cui; Rompis, Ferdinand An; Huang, Hang; Zhang, Hua; Mu, Zhong-Lin; Peng, Lei

2012-04-01

To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Sildenafil in the management of neonates with PPHN: A rural ...

African Journals Online (AJOL)

cytochrome P450 enzyme system, has an elimination half-life ... Sildenafil appears to be beneficial in the treatment of PPHN and its use can be considered in the management of selected cases .... 5 mg/ml, and dilute with 4 parts water before administration .... Kumar S. Indian doctor in protest after using Viagra to save 'blue.

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.

Inducible transport of citrate in Lactobacillus rhamnosus ATCC 7469.

Science.gov (United States)

de Figueroa, R M; Benito de Cárdenas, I L; Sesma, F; Alvarez, F; de Ruiz Holgado, A P; Oliver, G

1996-10-01

Lactobacillus rhamnosus ATCC 7469 exhibited diauxie when grown in a medium containing both glucose and citrate as energy source. Glucose was used as the primary energy source during the glucose-citrate diauxie. Uptake of citrate was carried out by an inducible citrate transport system. The induction of citrate uptake system was repressed in the presence of glucose. This repression was reversible and mediated by cAMP.

Structural and Thermodynamic Analysis of the First Mononuclear Aqueous Aluminum Citrate Complex Using DFT Calculations.

Science.gov (United States)

de Noronha, Antonio Luiz Oliveira; Guimarães, Luciana; Duarte, Hélio Anderson

2007-05-01

Structural and thermodynamic properties of the mononuclear Al/citrate complexes have been theoretically investigated aiming to understand the coordination mechanism at an atomic level. GGA-DFT/PCM calculations have been performed for the different conformations and tautomers arising from the Al(3+) and citric acid (H3L) interaction in aqueous solution. The Gibbs reaction energies were estimated based on the reaction of the trigonal planar Al(OH)3 and H3L to form different Al-citrate complexes. The estimated Gibbs free reaction energies for the [AlL], [AlHL](+), and [Al(OH)L](-) species are in good agreement with the experimental values. In these species, the Al(3+) center is coordinated by two carboxylic and the tertiary hydroxyl groups of the citrate. Conversely to what has been proposed based on the experiments, the present theoretical calculations indicate that the citric acid hydroxyl group remains protonated upon the coordination of Al(3+). In fact, our model turns out to be more consistent with the relative pKa values of citrate protonation groups and with the hydrolysis constant of the H2O bound to Al(3+) leading to better agreement with the available experimental data.

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

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

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...

Sildenafil no tratamento da hipertensão arterial pulmonar idiopática em crianças e adolescentes Sildenafil in the management of idiopathic pulmonary arterial hypertension in children and adolescents

Directory of Open Access Journals (Sweden)

Edmundo Clarindo Oliveira

2005-10-01

Full Text Available OBJETIVO: Este artigo tem por objetivo relatar a experiência com o uso do sildenafil oral no tratamento de pacientes com hipertensão arterial pulmonar idiopática grave em classe funcional III e IV, sem resposta à terapia convencional e às provas de reatividade pulmonar. MÉTODO: Trata-se de estudo prospectivo, tipo de série de casos em que seis pacientes com diagnóstico de hipertensão arterial pulmonar idiopática foram tratados com sildenafil oral, com doses de 2 a 8 mg/kg/dia, divididas em quatro a seis vezes. Os pacientes foram submetidos a exame clínico, eletrocardiograma, ecocardiograma, tomografia do tórax, cintilografia de perfusão e ventilação pulmonar, estudos da coagulação, pesquisa de esquistossomose, doença do colágeno e de síndrome de imunodeficiência adquirida para afastar causas secundárias de hipertensão pulmonar. Todos os pacientes foram submetidos a cateterismo cardíaco para a realização das provas de reatividade pulmonar com óxido nítrico, O2 a 100% e nifedipina oral e ao teste de caminhada de 6 minutos nos pacientes em condições de realizá-lo. RESULTADOS: Todos eles apresentaram boa resposta, traduzida por melhora de, pelo menos, uma classe funcional, aumento da saturação sistêmica. Cinco pacientes apresentaram diminuição da relação da pressão sistólica pulmonar/pressão sistólica sistêmica e aumento da distância percorrida no teste de caminhada nos que a realizaram. Não foram observados efeitos colaterais em um tempo de seguimento de 4 a 36 meses. Um paciente apresentou morte súbita após a suspensão do medicamento. CONCLUSÕES: Os resultados sugerem que o sildenafil possa ser uma droga promissora no tratamento dos pacientes com hipertensão pulmonar idiopática, os quais devem ser conscientizados do risco da suspensão da medicação sem orientação médica.OBJECTIVE: This study aims to provide data on the use of oral sildenafil in patients in New York Heart Association

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...

Efficacy of extended clomifene citrate regimen in comparison with gonadotropins in clomifene citrate-resistant women with polycystic ovary syndrome

OpenAIRE

Mahmoud Fathy Hassan

2014-01-01

Background: Gonadotropins are successful treatment for women with clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that extended CC treatment may be an alternative to gonadotropins in the management of CC-resistant women with PCOS. Methods: A randomized controlled trial comprised 200 women with CC-resistant PCOS were allocated to two equal treatment groups. Patients in the CC group were given 100 mg of CC daily starting fr...

On the nature of citrate-derived surface species on Ag nanoparticles: Insights from X-ray photoelectron spectroscopy

Science.gov (United States)

Mikhlin, Yuri L.; Vorobyev, Sergey A.; Saikova, Svetlana V.; Vishnyakova, Elena A.; Romanchenko, Alexander S.; Zharkov, Sergey M.; Larichev, Yurii V.

2018-01-01

Citrate is an important stabilizing, reducing, and complexing reagent in the wet chemical synthesis of nanoparticles of silver and other metals, however, the exact nature of adsorbates, and its mechanism of action are still uncertain. Here, we applied X-ray photoelectron spectroscopy, soft X-ray absorption near-edge spectroscopy, and other techniques in order to determine the surface composition and to specify the citrate-related species at Ag nanoparticles immobilized from the dense hydrosol prepared using room-temperature reduction of aqueous Ag+ ions with ferrous ions and citrate as stabilizer (Carey Lea method). It was found that, contrary to the common view, the species adsorbed on the Ag nanoparticles are, in large part, products of citrate decomposition comprising an alcohol group and one or two carboxylate bound to the surface Ag, and minor unbound carboxylate group; these may also be mixtures of citrate with lower molecular weight anions. No ketone groups were specified, and very minor surface Ag(I) and Fe (mainly, ferric oxyhydroxides) species were detected. Moreover, the adsorbates were different at AgNPs having various size and shape. The relation between the capping and the particle growth, colloidal stability of the high-concentration sol and properties of AgNPs is briefly considered.

Biotransformation of uranium and transition metal citrate complexes by clostridia

International Nuclear Information System (INIS)

Francis, A.J.; Joshi-Tope, G.A.; Dodge, C.J.; Gillow, J.B.

2002-01-01

Clostridium sphenoides, which uses citric acid as its sole carbon source, metabolized equimolar Fe(III)-citrate with the degradation of citric acid and the reduction of Fe(III) to Fe(II), but not the U(VI)-citrate complex. However, in the presence of excess citric acid or added glucose it was reduced to U(IV)-citrate. In contrast, Clostridium sp., which ferments glucose but not citrate, reduced Fe(III)-citrate to Fe(II)-citrate and U(VI)-citrate to U(IV)-citrate only when supplied with glucose. These results show that complexed uranium is readily accessible as an electron acceptor despite the bacterium's inability to metabolize the organic ligand complexed to the actinide. These results also show that the metabolism of the metal-citrate complex depends upon the type of complex formed between the metal and citric acid. Fe(III) forms a bidentate complex with citric acid and was metabolized, whereas U forms a binuclear complex with citric acid and was recalcitrant. (author)

Citrate-coated silver nanoparticles interactions with effluent organic matter: influence of capping agent and solution conditions

KAUST Repository

Gutierrez, Leonardo

2015-07-31

Fate and transport studies of silver nanoparticles (AgNPs) discharged from urban wastewaters containing effluent organic matter (EfOM) into natural waters represent a key knowledge gap. In this study, EfOM interfacial interactions with AgNPs and their aggregation kinetics were investigated by atomic force microscopy (AFM) and time-resolved dynamic light scattering (TR-DLS), respectively. Two well-characterized EfOM isolates, i.e., wastewater humic (WW humic) and wastewater colloids (WW colloids, a complex mixture of polysaccharides-proteins-lipids), and a River humic isolate of different characteristics were selected. Citrate-coated AgNPs were selected as representative capped-AgNPs. Citrate-coated AgNPs showed a considerable stability in Na+ solutions. However, Ca2+ ions induced aggregation by cation bridging between carboxyl groups on citrate. Although the presence of River humic increased the stability of citrate-coated AgNPs in Na+ solutions due to electrosteric effects, they aggregated in WW humic-containing solutions, indicating the importance of humics characteristics during interactions. Ca2+ ions increased citrate-coated AgNPs aggregation rates in both humic solutions, suggesting cation bridging between carboxyl groups on their structures as a dominant interacting mechanism. Aggregation of citrate-coated AgNPs in WW colloids solutions was significantly faster than those in both humic solutions. Control experiments in urea solution indicated hydrogen bonding as the main interacting mechanism. During AFM experiments, citrate-coated AgNPs showed higher adhesion to WW humic than to River humic, evidencing a consistency between TR-DLS and AFM results. Ca2+ ions increased citrate-coated AgNPs adhesion to both humic isolates. Interestingly, strong WW colloids interactions with citrate caused AFM probe contamination (nanoparticles adsorption) even at low Na+ concentrations, indicating the impact of hydrogen bonding on adhesion. These results suggest the importance

Gallium-67 citrate localization in disseminated sporotrichosis

International Nuclear Information System (INIS)

Moreno, A.J.; Brazier, J.M.; Baker, F.J.; Fox, B.J.; Pittman, D.L.

1985-01-01

A 25-year-old woman demonstrated Ga-67 citrate accumulation within a facial cutaneous lesion and two subcutaneous nodules within the right lower extremity. Cultures of the facial lesion and one of the subcutaneous nodules grew Sporothrix schenckii. Ga-67 citrate uptake has not been reported previously with this fungal infection. Ga-67 citrate scintigraphy was helpful in defining the extent of the disease, following its course, and determining the response to therapy

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

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...... the antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, a downstream effector for cGMP, and whether this may target known pathways in antidepressant action. Purpose We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br.......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...

The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

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Lilies Anggarwati Astuti

2016-06-01

Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

Gold Standard Tests

Science.gov (United States)

2001-06-01

a slow release caffeine . NATO - RTA - Electroencephal Clin Neurophysiol 1997;103:554- AMP Meeting, 29 Sep-3Oct 1997, Rotterdam. 62. 22. Pieron H...I1 yellow Miscellaneous Strychnine + Cannabis indica + Tobacco LI, LII + (amblyopia) Sildenafil citrate + LI, III blue, blue- flashing lights

Morphology of embryonic liver under the influence of silver and gold citrates on a background of lead intoxication

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Harets V.I.

2016-05-01

Full Text Available Morphological state of embryonic liver under the influence of silver and gold citrates on a background of lead intoxication was studied. We found that values of the hepatofetal index in the groups Pb+Ag and Pb+Au had significant differences as compared to the group exposed to lead intoxication, but did not differ significantly from the control group and made up 0,086±0,001 and 0,083±0,001, respectively. Value of the relative area of blood vessels in groups Pb+Ag and Pb+Au was 13.08±0.53% and 16.83±0.53%, respectively, which had no significant difference as compared to control group, but differed from the value of lead intoxication group. Under the influence of silver citrate on a background of lead intoxication the relative area of hematopoietic cells was 52,5±0,95%; this indicates to modification action of silver on haematopoiesis. Thus, injection of silver and gold citrates prevents negative effect of lead on morphometric parameters of embryonic liver, relative area of blood vessels and hematopoietic cells. Experiment results showed protective effect of silver and gold citrates on a background of lead intoxication during hepatogenesis.

Chloride content of solutions used for regional citrate anticoagulation might be responsible for blunting correction of metabolic acidosis during continuous veno-venous hemofiltration.

Science.gov (United States)

Jacobs, Rita; Honore, Patrick M; Diltoer, Marc; Spapen, Herbert D

2016-08-26

Citrate, the currently preferred anticoagulant for continuous veno-venous hemofiltration (CVVH), may influence acid-base equilibrium. The effect of 2 different citrate solutions on acid-base status was assessed according to the Stewart-Figge approach in two consecutive cohorts of critically ill adult patients. The first group received Prismocitrate 10/2 (PC10/2; 10 mmol citrate/L). The next group was treated with Prismocitrate 18/0 (PC18; 18 mmol citrate/L). Both groups received bicarbonate-buffered fluids in post-dilution. At similar citrate flow, the metabolic acidosis present at baseline in both groups was significantly attenuated in PC18 patients but persisted in PC10/2 patients after 24 h of treatment (median pH 7,42 vs 7,28; p = 0.0001). Acidosis in the PC10/2 group was associated with a decreased strong ion difference and an increased strong ion gap (respectively 43 vs. 51 mmol/L and 17 vs. 12 mmol/L, PC10/2 vs. PC18; both p = 0.001). Chloride flow was higher in PC10/2 than in PC18 subjects (25.9 vs 14.3 mmol/L blood; p < 0.05). Correction of acidosis was blunted in patients who received 10 mmol citrate/L as regional anticoagulation during CVVH. This could be explained by differences in chloride flow between the applied citrate solutions inducing hyperchloremic acidosis.

A study on 99Tcm-citrate and 99Tcm (V)-DMSA imaging in the diagnosis of acute purulent osteoarthritis

International Nuclear Information System (INIS)

Wu Zhaozhong; Lin Wei; Wu Hengfu; Wu Changwei; Yuan Gewen; Fan Ziwen; Wu Boyi

2003-01-01

Objective: To assess the clinical diagnostic value of 99 Tc m -citrate and 99 Tc m (1/2ae)-dimercaptosuccinic acid (DMSA) imaging in the acute purulent osteoarthritis. Methods: Seventeen patients with confirmed acute purulent osteoarthritis and nineteen patients with non-purulent osteoarthritis were studied. In all patients, 99 Tc m -methylene diphosphonic acid (MDP), 99 Tc m -citrate and 99 Tc m (1/2ae)-DMSA imaging were sequentially performed and the images were analyzed semiquantitatively. Results: In the acute purulent osteoarthritis group, there were positive bonetactic accumulations at certain areas on the three kinds of imaging. In the non-purulent osteoarthritis group, 99 Tc m -MDP and 99 Tc m (1/2ae)-DMSA imaging showed clear bonetactic accumulation, but 99 Tc m -citrate imaging showed only light bonetactic accumulation in addition to the accumulations in soft tissue at certain areas. Lesion to nonlesion ratio (L/N=2.300±0.094) of acute purulent osteoarthritis was greater than that in non-purulent osteoarthritis group (1.298±0.054, P 99 Tc m -citrate imaging, and there was no significant difference between two groups on 99 Tc m (1/2ae)-DMSA imaging (L/N ratio of acute purulent osteoarthritis group was 3.495±0.180, and L/N ratio of non-purulent osteoarthritis group was 3.091±0.091, P>0.05). Conclusions: To diagnose the bone inflammation, 99 Tc m -citrate imaging coalesced with 99 Tc m -MDP or 99 Tc m (1/2ae)-DMSA imaging can help to evaluate the pathologic and physiologic progresses in bone inflammatory areas, at the same time , the information by 99 Tc m -citrate imaging is telling the actual inflammation areas, and that by 99 Tc m (1/2ae)-DMSA and 99 Tc m -MDP imaging is about the response to the increase of bone metabolism

Determination of sildenafil mixed into herbal honey mixture by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry

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Neira Mustabasic

2017-01-01

Full Text Available There has been a number of reports of natural products contaminated with illegal adulterants that threaten consumer health because of their adverse pharmacological effects worldwide. In this study, a multi-residual ultra-performance liquid chromatography method with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS was applied for the identification of sildenafil added into a herbal honey mixture used as an immune system booster. Electrospray ionization (ESI source was applied and operated in the positive ion mode. The mobile phase consisted of 0.1% formic acid aqueous solution/acetonitrile (70:30, v/v using the isocratic gradient elution system at a detection wavelength of 290 nm. The compound of sildenafil added into traditional herbal mixed honey was identified according to the spectrum, chromatographic behavior, and mass spectral data were identified by comparison with the reference substance. The method is selective, sensitive and can be used to detect the sildenafil illegally added into traditional herbal medicinal preparations.

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

The Effects of Sodium Bicarbonate and Sodium Citrate on Blood pH, HCO3-, Lactate Metabolism and Time to Exhaustion

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Soetanto Hartono

2017-02-01

Full Text Available The purpose of this study was to compare the effects of sodium bicarbonate and sodium citrate in increasing lactate concentration, blood pH, HCO3-, and time to exhaustion. Increased time to exhaustion is an advantage since the athletes can do more anaerobic work. Exhaustion could be delayed by increasing HCO3- to catch H+ produced by lactate metabolism to form H2O and CO2. The design of this research was randomized pretest posttest control group design. Thirty badminton student players were randomly selected and randomly assigned to three groups. The first group (the control group was given placebo, NaCl .9 g/dl, the second group was given sodium bicarbonate 300 mg/kg in 500 ml aqua, and the third group was given sodium citrate 300 mg/kg in 500 ml aqua. Blood pH and bicarbonate ion (HCO3- were measured through Opti Medical Blood gas Analyzer. Lactate was measured by Cobas Roche lactate Analyzer. Data was analyzed using Manova with .05 significant level. Blood pH of the groups taking sodium bicarbonate and sodium citrate were higher significantly against control group (p.05. Sodium bicarbonate is better than sodium citrate, although both were better than control (p<.05. Sodium bicarbonate is better than sodium citrate in increasing blood pH and time to exhaustion. The disadvantage of using sodium bicarbonate is that it can cause gastrointestinal problem and headache, so it is not advisable to be used by athletes who have the symptoms.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

Science.gov (United States)

Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

2015-01-01

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.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

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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.

Colon transit scintigraphy by 67 Ga citrate for idiopathic constitution

International Nuclear Information System (INIS)

Neshandar Asll, I.; Ehsani, M.J.; Javadi, H.

2005-01-01

Background/objective: segmental colonic transit studies are important in patients with severe constipation. This study is the first Iranian preliminary survey of colonic transit scintigraphy using 67 Ga -citrate as a new method in constipated patients with normal radiographic and colonoscopic evaluations. Patients and methods: thirteen patients with idiopathic constipation underwent colon transit scintigraphy. After oral administration of 6-7 MBq Ga-citrates, serial abdominal images were taken up to 72 hours. Pattern classification wa s performed visually according to the distribution of radioactivity, Scintigraphic parameters such as geometric mean center of seq mental retention of tracer, as well as mean ac activity profiles and colonic tracer half-clearance time were calculated Results: Three patterns of colonic transit scintigraphy were recognized. Nine patients had the normal pattern, i.e. excellent propagation of ac activity. Three patients had the colonic inertia pattern with marked retention of activity in the transverse colon and splenic flexure at 48 hours, One patient had significant retention of activity in the recto sigmoid at 72 hours, defined as functional recto sigmoid obstruction . No significant difference was seen in GMC24h between the normal pattern and colonic inertia (P4.053), but GMC48h and GMC72h markedly differed between the two groups (P50.0 16 and 0.025 respectively). 'The mean half clearance time of the two groups was di different (P4.017). Our results are well compatible with scintigraphic diagnostic criteria in different patterns of colonic transit defined by other studies with different radiotracer. Conclusion: oral 67 Ga -citrate colon transit scintigraphy is a feasible method to evaluate idiopathic constipation and seems to be a suitable surrogate for radio-opaque markers. Keywords: oral 67 Ga -citrate, colonic transit study, idiopathic constipation, scintigraphy

Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism

Science.gov (United States)

Rodriguez, Katherine M.; Pastuszak, Alexander W.; Lipshultz, Larry I.

2016-01-01

Introduction Hypogonadism is a growing concern in an aging male population. Historically treated using exogenous testosterone, concerns about possible adverse effects of testosterone have led physicians to seek alternative treatment approaches. Areas Covered Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist that is FDA-approved for the treatment of ovarian dysfunction in women. Clomiphene citrate has also been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility. Here we review the literature examining the efficacy and safety of enclomiphene citrate in the setting of androgen deficiency. Expert Opinion Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option. PMID:27337642

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.

THERMODYNAMIC PARAMETERS OF SOLUTIONS OF ...

African Journals Online (AJOL)

2014-06-30

Jun 30, 2014 ... ABSTRACT. 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.

Synthesis and characterization of the Rhodium (II) citrate complex

International Nuclear Information System (INIS)

Najjar, R.; Santos, F.S. dos; Seidel, W.

1987-01-01

The preparation and characterization of the rhodium (II) citrate is described. Rhodium citrate was prepared by reacting citric acid trihydrated (3,4 g, 16 mmols) with anhydrous rhodium acetate (0,44 g, 1 mmol). Th electronic instruments, thermogravimetric curve and spectrum of rhodium (II) citrate are analysed. (M.J.C.) [pt

The impact of citrate introduction at UK syringe exchange programmes: a retrospective cohort study in Cheshire and Merseyside, UK

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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.

Clomiphene citrate-induced visual hallucinations: a case report

OpenAIRE

Venkatesh, Ramesh; Gujral, Gaganjeet Singh; Gurav, Prachi; Tibrewal, Shailja; Mathur, Umang

2017-01-01

Background Polycystic ovary syndrome is a common cause of chronic anovulation and infertility in otherwise healthy fertile couples. Clomiphene citrate is used as a first-line ovulation induction therapy in patients with polycystic ovary syndrome. Clomiphene citrate can cause both systemic and ocular side effects. We report a rare side effect of illusory palinopsias in a patient with polycystic ovary syndrome treated with ovulation induction therapy with clomiphene citrate, and emphasize the n...

Preparation of lead titanate zirconate from metal citrates

International Nuclear Information System (INIS)

Bastos, C.M.R.

1994-01-01

Lead titanate zirconate (PZT) preparation from its metal constituent citrates have been investigated. Metal citrates were obtained by forced precipitation using a dehydration alcohol mixture. Salt solutions of lead nitrate and octahydrated zirconyl chloride, and titanium tetrachloride were treated separately with citric acid and ammonium hydroxide. Zirconium, titanium and lead oxides resulted from thermal decomposition of corresponding citrates at 500 0 C, 450 0 C and 250 0 C, respectively. Lead titanate (PT) and lead zirconate (P Z) were obtained by calcining at 450 0 C and 500 0 C, respectively, after adequate heating of citrates mechanically mixed in ethyl ether. PZT samples were obtained with different starting stoichiometry. Rhombohedral PZT-1 53/47 sample was prepared from co precipitating zirconyl ammonium and ammonium lead citrates in presence of ethanolic titanium oxide dispersion, and calcinating at 800 0 C. Rhombohedral PZT-q 52/48 sample was obtained from heating at 500 0 C for 2 hours a mixture of metal citrates coprecipitated by dehydration mixture of acetone-ethanol-formic acid (2:1:0,06). Tetragonal PZT-m stoichiometry 53/47 sample were obtained by calcining at after 600 0 C for 2 hours after heating a mechanically mixed metal citrates. PT phase arose at 400 0 C. PZT-m powders obtained in a range of 400 0 C-800 0 C were isostatically pressed, and sintered at 1100 0 C and 1200 0 C in saturated Pb O atmosphere. Rhombohedral sintered PZT was obtained with 7,78 g.cm -3 at 1200 0 C. (author). 123 refs, 53 figs, 32 tabs

Differentiation of malignant and degenerative benign bone disease using 99mTc-citrate scintigraphy

International Nuclear Information System (INIS)

Guo Rui; Jin Jianhua; Li Sijin; Li Xianfeng; Zhang Xiaojuan; Ren Yuan

2008-01-01

Objective: To differentiate malignant and degenerative benign bone disease using 99m Tc- citrate scintigraphy. Methods: Thirty-nine patients (92 lesions) with confirmed malignant bone disease or degenerative benign bone disease were studied, for which the results of 99m Te-methylene diphosphonate( 99m Tc- MDP) scintigraphy were positive. 99m Tc-citrate scintigraphy was performed within a time interval of 2-7 days after 99m Tc-MDP scintigraphy. Visual analysis and semiquantitative analysis were applied. Each lesion was scored as malignant or benign, which was independently verified, using conventional techniques (histopathology, X-ray, CT, MRI and clinical follow up). Results: In visual analysis of 99m Tc-citrate imaging, most malignant lesions (35/48, 72.92%) clearly showed high radioactivity accumulation, while most benign lesions (39/44, 88.64%) had not obviously visible uptake of 99m Tc-citrate. In semiquantitative analysis of 99m Tc- citrate image, malignant lesions demonstrated a higher lesion-to-background radioisotope uptake ratio (RUR) than that of benign degenerative lesions (1.47 ± 0.42 vs. 1.09 ± 0.38, t=2.887, P 99m Tc-MDP in the two groups is of the same (1.96 ± 0.25 vs. 1.87 ± 0.21, t=1.178, P>0.20). Conclusion: 99m Tc- citrate scintigraphy is a promising method to differentiate malignant from benign degenerative lesions seen as areas of increased activity on 99m Tc-MDP bone scintigraphy. (authors)

Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study

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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.

Citrate and succinate uptake by potato mitochondria

International Nuclear Information System (INIS)

Jung, D.W.; Laties, G.G.

1979-01-01

Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate. Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar. Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels

A randomized prospective triaI comparing oral sodium phosphate with magnesium citrate in preparing of patients for double contrast barium enema

International Nuclear Information System (INIS)

Lee, Eun Joo; Lee, Sung Woo; Lee, Hyeon Kyeong; Yang, Chang Hun; Kim, Soon; Oh, Yoen Hee; Kim, Seung Hyeon

2004-01-01

The purpose of this study was to compare two bowel preparation agents, sodium phosphate solution with magnesium citrate solution. A total of 94 subjects that underwent a double-contrast barium enema were included in this study. Bowel preparation before performing the barium study was done by using a sodium phosphate solution in 47 subjects and by using a magnesium citrate solution in the other 47 subjects. We evaluated the presence or absence of side effects when using these bowel preparation agents. Two radiologist who were blinded to the type of bowel preparation evaluated the quality of bowel preparation at the colonic segments (ascending, descending, and sigmoid colon) on the radiographs obtained by double-contrast barium enema, with regard to stool cleansing, water retention, barium coating and bubble formation. The side effects, such as abdominal clamping pain, nausea, hunger pain and chill occurred more frequently in the sodium phosphate group than in the magnesium citrate group (p< 0.001). Stool retention was more frequently found in the magnesium citrate group (p< 0.001). However, no statistical difference was noted on the status of water retention and barium coating between two groups. Gas bubble formation was more commonly seen in the sodium phosphate group (p< 0.001). The sodium phosphate solution appeared to be more effective in cleansing the right colon (p=0.001). Sodium phosphate solution appears to be more effective for colonic cleansing, with a lower incidence of side effects, than when using magnesium citrate solution

A test of the citrate method of PMI estimation from skeletal remains.

Science.gov (United States)

Wilson, Sarah J; Christensen, Angi M

2017-01-01

Citrate content in bone has been shown to be associated with the postmortem interval (PMI), with citrate decreasing after death as a function of time. Here we test this method using porcine ribs for the period of 1-165days after death, and also assess citrate content and variation from samples placed into two different postmortem environments (terrestrial and aquatic). Higher citrate variation, lower citrate recovery, and a weaker association with time were found in this study as compared to others. Citrate content, however, was found to decrease with increasing PMI, and the method was found to be easy and inexpensive to apply. No significant differences were found in citrate loss between terrestrial and aquatic environments. Although more research is needed, citrate content appears to be a promising new approach in estimating PMI from skeletal remains. Published by Elsevier B.V.

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

Science.gov (United States)

Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

2015-05-01

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

Structural, spectroscopic and Thermal Studies of Potassium Di-hydrogen Citrate Crystal

Directory of Open Access Journals (Sweden)

N.D. Pandya

2017-04-01

Full Text Available Potassium dihydrogen citrate (KDC finds wide applications in food products. Pure potassium dihydrogen citrate crystal was grown by slow solvent evaporation technique at room temperature. Grown crystal exhibited needle like morphology. The powder XRD shows triclinic structure symmetry with lattice parameters a=11.820 Å, b=14.970 Å, c=9.442 Å with angles α = 91.60°, β = 93.35°, γ = 110°. The presence of various functional groups of grown crystal was confirmed by using FT-IR spectroscopy. The thermogram indicates the thermal stability of the sample up to 100oC and then decomposes slowly into oxide stage through two stages. The results are discussed here.

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.

Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

Science.gov (United States)

CAVASSIM, Rodrigo; LEITE, Fábio Renato Manzolli; ZANDIM, Daniela Leal; DANTAS, Andrea Abi Rached; RACHED, Ricardo Samih Georges Abi; SAMPAIO, José Eduardo Cezar

2012-01-01

Objective The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. Material and Methods A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group). After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. Results Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. Conclusion Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning. PMID:22858707

Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

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Rodrigo Cavassim

2012-06-01

Full Text Available OBJECTIVES: The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. MATERIAL AND METHODS: A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group. After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. RESULTS: Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. CONCLUSION: Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning.

Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.

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Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-10-01

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli and can utilize various NADH-reoxidizing routes (e.g., citrate, glycerol, and oxygen) according to environmental conditions. In this study, we investigated the ability of L. panis PM1 to produce succinate, acetate, and lactate via citrate utilization. Possible pathways, as well as regulation, for citrate metabolism were examined on the basis of the genome sequence data and metabolic profiles of L. panis PM1. The presence of citrate led to the up-regulation, at the transcriptional level, of the genes encoding for citrate lyase, malate dehydrogenase, and malic enzyme of the citrate pathways by 10- to 120-fold. The transcriptional regulator of the dha operon coding for glycerol dehydratase of L. panis PM1 repressed the expression of the citrate lyase gene (10-fold). Metabolite analyses indicated that the transcriptional enhancement by citrate stimulated succinate yield. Citrate metabolism contributed to energy production by providing a major alternate pathway for NAD(+) regeneration and allowed acetyl phosphate to yield acetate/ATP instead of ethanol/NAD(+). Additionally, a branching pathway from oxaloacetate to pyruvate increased the pool of lactate, which was then used to produce ATP during stationary phase. However, the redirection of NADH-to-citrate utilization resulted in stress caused by end-products (i.e., succinate and acetate). This stress reduced succinate production by up to 50 % but did not cause significant changes at transcriptional level. Overall, citrate utilization was beneficial for the growth of L. panis PM1 by providing a NAD(+) regeneration route and producing extra ATP.

Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?

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Moll, E; Korevaar, J C; Bossuyt, P M M; van der Veen, F

2008-08-01

An RCT among newly diagnosed, therapy naive women with polycystic ovary syndrome (PCOS) showed no significant differences in ovulation rate, ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate. We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates. Subgroup analysis based on clinical and biochemical parameters of 111 women randomized to clomifene citrate plus metformin compared with 114 women randomized to clomifene citrate plus placebo. The data for age, BMI, waist-hip ratio (WHR) and plasma testosterone were available in all women, 2 h glucose in 80% of women and homeostatic model assessment for assessing insulin sensitivity (HOMA) in 50% of women. Of the women who were allocated to the metformin group, 44 women (40%) reached an ongoing pregnancy. In the placebo group, 52 women (46%) reached an ongoing pregnancy. There was a significantly different chance of an ongoing pregnancy for metformin versus placebo between subgroups based on age and WHR (P = 0.014). There was a positive effect of metformin versus placebo on pregnancy rate in older women (>or=28 years) with a high WHR, a negative effect of metformin versus placebo in young women (Metformin may be an effective addition to clomifene citrate in infertile women with PCOS, especially in older and viscerally obese patients.

Evaluation of oral abdominal contrast agent containing ferric ammonium citrate

International Nuclear Information System (INIS)

Shiga, Toshiko; Kawamura, Yasutaka; Iwasaki, Toshiko

1991-01-01

We evaluated the effectiveness of oral MRI contrast agent containing ferric ammonium citrate. Twenty patients were arbitrarily divided into 2 groups according to the given dose of 100 and 200 mg Fe of oral MRI contrast agent. MRI was performed before and immediately after ingesting 300 ml solution of oral MRI contrast agent using a 1.5 T superconducting system (GE: Signa). Each dose of 100 and 200 mg Fe of oral MRI contrast agent produced sufficient enhancement of gastrointestinal tract, enough to make clear the pancreatic contour and porta hepatis. There was no significant change in blood and urine analysis observed after taking oral MRI contrast agent. The use of ferric ammonium citrate as an oral MRI contrast agent seems to add valuable information in performing upper abdominal MRI imaging. (author)

FERRIC CITRATE: AN IRON-BASED ORAL PHOSPHATE BINDER

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T. Christopher Bond

2012-06-01

Based on actual physician behavior in response to ferritin and TSAT increases and ferric citrate clinical trial results, and assuming equivalent pricing to other PBs, there would be cost savings with ferric citrate use through reduced ESA and iron use.

Preparation of electrocatalysts by reduction of precursors with sodium citrate

OpenAIRE

Briskeby, Stein Trygve; Tsypkin, Mikhail; Tunold, Reidar; Sunde, Svein

2014-01-01

In this work synthesis of Pt/C catalysts by reduction of H2PtCl6 with sodium citrate has been investigated. The strong pH-dependence of citrate as a reducing and stabilizing agent has been explored, and an optimum pH range for production of well dispersed catalysts is proposed. To achieve stabilizing and reducing conditions, the presence of both citrate anions and protonated citrates are required. This is achieved in an intermediate pH range between pKa2 and pKa3 (4.76 and 6.4) of citric acid...

Metformin-clomiphene citrate vs. clomiphene citrate alone: Polycystic ovarian syndrome

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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.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

Science.gov (United States)

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] 24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

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

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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

New approaches to the synthesis of sildenafil analogues and their enzyme inhibitory activity

Czech Academy of Sciences Publication Activity Database

Mojzych, M.; Karczmarzyk, Z.; Wysocki, W.; Ceruso, M.; Supuran, C.T.; Kryštof, Vladimír; Urbanczyk-Lipkowska, Z.; Kalicki, P.

2015-01-01

Roč. 23, č. 7 (2015), s. 1421-1429 ISSN 0968-0896 R&D Projects: GA ČR GAP305/12/0783 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional support: RVO:61389030 Keywords : Sildenafil analogues * Pyrazolo[4,3-e][1,2,4] triazine * Sulfonamides Subject RIV: CE - Biochemistry Impact factor: 2.923, year: 2015

Citrate content of bone for time since death estimation: results from burials with different physical characteristics and known PMI.

Science.gov (United States)

Kanz, Fabian; Reiter, Christian; Risser, Daniele U

2014-05-01

A recently introduced method to determine the postmortem interval (PMI) based on quantification of the citrate content in bone was applied on the temporal bones and femora of 20 individuals buried in wooden coffins (WO) and body bags (BB), respectively. Concerning known vs. calculated PMI, a significant difference between the temporal and the femur bone samples of the same individuals was observed in the BB group (p = 0.012). In contrast, differences were insignificant for the WO group (p = 0.400). Moreover, similar levels of underestimation of PMIs resulted from the analysis of the femora for both burial groups (p = 0.247). Also, there was consistently less citrate preserved in the flat temporal bones as compared to the femora, indicating that the cortical layer of the long bones should be preferentially employed for citrate-based PMI estimations. The results call for additional research on subsurface-buried and surface-deposited remains to enhance the accuracy of the published PMI equation. © 2014 American Academy of Forensic Sciences.

Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal male rats.

Science.gov (United States)

Suresh, Sekar; Prithiviraj, Elumalai; Prakash, Seppan

2009-04-21

According to Indian Systems of Medicine, Mucuna pruriens Linn., belonging to the leguminous family (Papilionaceae), were used for treating male sexual disorders since ancient times. In this study, the effects of ethanolic extracts of the Mucuna pruriens Linn. seed on general mating behaviour, libido and potency of normal male Wister albino rats were investigated and also compared with the standard reference drug, Sildenafil citrate. Animals were divided into one control group (Group I--received saline) and four experimental groups (Groups II-V). Experimental groups were divided on the basis of the dosage of extract to the animals as follows: 150 mg/kg body weight (Group I), 200mg/kg body weight (Group II) and 250 mg/kg body weight (Group IV) while Group V received Sildenafil citrate (5mg/kg body weight). Animals were fed PO with saline or extract or standard drug once in a day for 45 days. To analyse the mating behaviour, female rats with oestrus phase were used. The extract administered PO significantly increased the mounting frequency, intromission frequency and ejaculation latency, and decreased the mounting latency, intromission latency, post-ejaculatory interval and inter-intromission interval. The potency test significantly increased erections, quick flips, long flips and total reflex. Therefore, the results indicated that the ethanolic extracts of Mucuna pruriens Linn. seed produced a significant and sustained increase in the sexual activity of normal male rats at a particular dose (200mg/kg). When compared to control, all the drug-treated groups have shown drug-induced effects for a few parameters. However in Group II, there was an obvious enhancement in all parameters, without affecting the normal behaviour. When compared with the standard drug, the net effect of extract is even less than that in Group II. Therefore, the resulting aphrodisiac activity of the extract lends support to the claim that it has traditionally been used for the treatment of sexual

Whole-body retention studies of /sup 167/Tm--citrate. Estimation of radiation dose to humans from /sup 167/Tm--citrate

Energy Technology Data Exchange (ETDEWEB)

Hiraki, T; Ando, A [Kanazawa Univ. (Japan). School of Paramedicine; Mori, H; Ando, I; Sakamoto, K

1978-02-01

For the purpose of calculating absorbed dose to humans from /sup 167/Tm-citrate, the whole-body retention studies using 5 rats were carried out. Up to 40 days following intravenous injection of /sup 167/Tm-citrate, the whole-body counts were monitored with an animal counter. The whole-body retention curve was obtained with three exponential components. Namely, the 26% of the injected /sup 167/Tm-citrate had a biological half-time of 3.4 hours, 12.5% had a biological half-time of 99 hours and 61.5% had a biological half-time of 106 days. These results indicate, that three components consist of the rapid clearance from the kidneys, the retention in the liver and other soft tissues with relatively long half-time and the retention in the bones with long half-time. Based on these biological data and the MIRD Committee method, the average dose estimates to the bone and whole-body from intravenous administration of 1 mCi /sup 167/Tm-citrate were 7.08 rads and 1.28 rads, respectively.

STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis

NARCIS (Netherlands)

Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N.

2014-01-01

In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these

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.

Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.

Science.gov (United States)

Majd, Homa; King, Martin S; Smith, Anthony C; Kunji, Edmund R S

2018-01-01

Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes. Copyright © 2017. Published by Elsevier B.V.

The use of sildenafil in the treatment of persistent pulmonary hypertension of the newborn: a review of the literature.

Science.gov (United States)

Iacovidou, Nicoletta; Syggelou, Aggeliki; Fanos, Vassilios; Xanthos, Theodoros

2012-01-01

Persistent pulmonary hypertension of the newborn (PPHN) is a serious and potentially fatal condition, characterized by hypoxemia due to increased pulmonary vascular resistance (PVR) with resultant shunting of pulmonary blood to the systemic circulation. Inhaled nitric oxide (iNO) has been considered a revolutionary treatment of PPHN. Data show that the use of iNO has reduced the need of ECMO in neonates with severe PPHN, while in moderate PPHN, iNO administration has been associated with a significant decrease in ventilatory support and prevented progression to severe PPHN. Not all neonates respond to iNO therapy though, and phosphodiesterase (PDE) inhibitors with their potent vasodilator properties have evolved as an alternative therapy or as an adjunct to the treatment of PPHN with iNO. There are ten families of PDE isoenzymes. PDE 5 is particularly prevalent in vascular smooth muscle (VSM) and PDE 5 inhibitors, such as sildenafil, have been used in clinical practice. This review provides a comprehensive account of existing data in the literature, from animal and clinical studies, on the use of sildenafil for the treatment of PPHN. Sildenafil may also have a role as a single mode of therapy, since in resource-limited settings the cost of iNO is a serious concern.

The Effectiveness of Clomiphene Citrate and Letrozole for Ovulation Induction Related to Endometrial Thickness and Number of Dominant Follicle

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Budi Wiweko

2016-09-01

Full Text Available The aim of the study is to know the effectiveness of clomiphene citrate and letrozole for ovulationrelated to endometrial thickness and number of dominant follicle. Study design was cross sectional basedon medical records of women who underwent ovulation induction from January 2011-May 2015. A numberof 143 anovulation women were divided into clomiphene citrate 50mg, clomiphene citrate 100 mg, letrozole2.5mg and letrozole 5mg. Each group received the agent daily on 3rd-7th day of menstrual cycle. On 12thday of menstrual cycle, the transvaginal ultrasound was performed to measure endometrial thickness anddominant follicle number. From all subjects, 45 subjects (31.5% were in 50mg clomiphene citrate groups, 29subjects (20.3% in 100mg clomiphene citrate group, 23 subjects (16.1% in 2,5mg letrozole group, and 46subjects (32.2% in 5mg letrozole group. Subjects who received letrozole had thicker endometrium comparedto clomiphene citrate (p<0.05. Different doses were not associated with endometrial thickness betweensubjects who received either letrozole or clomiphene citrate. In addition, subjects receiving letrozole hadhigher proportion of having trilaminar endometrium morphology. We did not observe the difference in totalnumber of dominant follicle between groups. It is concluded that letrozole is more effective than clomiphenecitrate in terms of endometrial thickness but not for number of dominant follicles. Keywords: clomiphene citrate, letrozole, ovulation induction, endometrial thickness, dominant follicle   Efektivitas Induksi Ovulasi Klomifen Sitrat dan Letrozol dalam Hal KetebalanEndometrium dan Jumlah Folikel Dominan Abstrak Studi ini bertujuan untuk menilai efektivitas induksi ovulasi klomifen sitrat dan letrozol dalam halketebalan endometrium dan jumlah folikel dominan pada perempuan yang tidak berovulasi. Desain studiadalah potong lintang menggunakan rekam medik pasien yang menjalani induksi ovulasi pada bulan Januari2011-Mei 2015

Citrate-Induced Nanocubes: A Re-Examination of the Role of Citrate as a Shape-Directing Capping Agent for Ag-Based Nanostructures.

Science.gov (United States)

Hajfathalian, Maryam; Gilroy, Kyle D; Hughes, Robert A; Neretina, Svetlana

2016-07-01

Seed-mediated syntheses utilizing facet-selective surface passivation provide the necessary chemical controls to direct noble metal nanostructure formation to a predetermined geometry. The foremost protocol for the synthesis of (111)-faceted Ag octahedra involves the reduction of metal ions onto pre-existing seeds in the presence of citrate and ascorbic acid. It is generally accepted that the capping of (111) facets with citrate dictates the shape while ascorbic acid acts solely as the reducing agent. Herein, a citrate-based synthesis is demonstrated in which the presence or absence of ascorbic acid is the shape-determining factor. Reactions are carried out in which Ag(+) ions are reduced onto substrate-immobilized Ag, Au, Pd, and Pt seeds. Syntheses lacking ascorbic acid, in which citrate acts as both the capping and the reducing agent, result in a robust nanocube growth mode able to withstand wide variations in the concentration of reactants, reaction rates, seed material, seed orientation and faceting, pH, and substrate material. If, however, ascorbic acid is included in these syntheses, then the growth mode reverts to one that advances the octahedral geometry. The implication of these results is that citrate, or one of its oxidation products, selectively caps (100) facets, but where this capability is compromised by ascorbic acid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citrate Anticoagulation during Continuous Renal Replacement Therapy.

Science.gov (United States)

Ricci, Davide; Panicali, Laura; Facchini, Maria Grazia; Mancini, Elena

2017-01-01

During extracorporeal dialysis, some anticoagulation strategy is necessary to prevent the coagulation of blood. Heparin has historically been used as an anticoagulant because of its efficacy combined with low cost. However, a variable incidence of hemorrhagic complications (5-30%) has been documented in patients undergoing continuous renal replacement therapy (CRRT) with heparin as an anticoagulant. Citrate has anticoagulation properties secondary to its ability to chelate calcium, which is necessary for the coagulation cascade. Citrate may thus be used in a regional anticoagulation (RCA), limited to the extracorporeal circuit of CRRT, to avoid systemic anticoagulation. Recent meta-analysis confirmed the advantage of RCA over heparin in terms of incidence of bleeding during CRRT. Moreover, an increase in filter lifespan is documented, with a secondary advantage in reaching the prescribed dialysis dose. In our experience, we could confirm this positive effect. In fact, with a progressive increase in the proportion of CRRT with citrate as RCA, we obtained a reduction in the number of filters used for every 72 h of treatment (from 2.4 in 2011 to 1.3 in 2015), and most importantly, a reduction in the difference between the prescribed and delivered dialysis doses (from 22 to 7%). Citrate has an intense effect on the acid-base balance as well, if fully metabolized through the Krebs cycle, due to the production of bicarbonate. Even more severely ill patients, such as those with liver dysfunction, may be treated with RCA without severe complications, because modern machines for CRRT are equipped with simple systems that are able to manage the citrate infusion and control the calcium levels, with minimal risks of metabolic derangements. © 2017 S. Karger AG, Basel.

Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle

NARCIS (Netherlands)

Borgdorff, Marinus A. J.; Bartelds, Beatrijs; Dickinson, Michael G.; Weij, Michel; Zandvoort, Andre; Sillje, Herman H. W.; Steendijk, Paul; de Vroomen, Maartje; Berger, Rolf M. F.; Boersma, B.

Right ventricular (RV) failure due to pressure or volume overload is a major risk factor for early mortality in congenital heart disease and pulmonary hypertension, but currently treatments are lacking. We aimed to demonstrate that the phosphodiesterase 5A inhibitor sildenafil can prevent adverse

Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial

Directory of Open Access Journals (Sweden)

Sedigheh Amooee

2013-01-01

Full Text Available Background: Chromium picolinate could be effective in clomiphen citrate resistant PCOS patients. Objective: To compare the effects of chromium picolinate vs. metformin in clomiphen citrate resistant PCOS patients. Materials and Methods: The present randomized clinical trial was performed on 92 women with clomiphen citrate-resistant PCOS at the clinics which were affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The subjects were randomly assigned to two groups receiving either chromium picolinate (200μg daily or metformin (1500mg daily for 3 months. Anthropometric and hormonal profile were measured and compared both before and after the treatment. Ovulation and pregnancy rate was measured in the two study groups, as well. Results: Chromium picolinate significantly decreased fasting blood sugar (FBS after 3 months of treatment (p=0.042. In the same way, the serum levels of fasting insulin had significantly decreased leading to an increase in insulin sensitivity as measured by QUICKI index (p=0.014. In comparison to the patients who received chromium picolinate, those who received metformin had significantly lower levels of testosterone (p=0.001 and free testosterone (p=0.001 after 3 months of treatment. Nevertheless, no significant difference was found between the two study groups regarding ovulation (p=0.417 and pregnancy rates (p=0.500. Conclusion: Chromium picolinate decreased FBS and insulin levels and, thus, increased insulin sensitivity in clomiphene citrate-resistance PCOS women. These effects were comparable with metformin; however, metformin treatment was associated with decreased hyperandrogenism. Overall, chromium picolinate was better tolerated compared to metformin; nonetheless, the two study groups were not significantly different regarding ovulation and pregnancy rates.

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

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Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

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 ...

Sildenafil reduces polyuria in rats with lithium-induced NDI.

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Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

2012-01-01

Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia.

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Jhagroo, R Allan; Wertheim, Margaret L; Penniston, Kristina L

2016-01-01

The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia. Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared. Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate. Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions. © 2015 The British Pharmacological Society.

Study of Np speciation in citrate medium

Energy Technology Data Exchange (ETDEWEB)

Bonin, L.; Den Auwer, C.; Ansoborlo, E.; Moisy, P. [CEA Valrho - DEN/DRCP/SCPS, Bagnols sur Ceze (France); Cote, G. [ENSP - LECA, UMR 7575, Paris (France)

2007-07-01

In the framework of the French Environmental Nuclear Toxicology program, additional experiments related to the decorporation of actinides are planned. Decorporation is the removal or release from target organs (bones, liver, kidney..), tissues or cells of radioactive material previously incorporated in them, using chelating agents or other administrated pharmaceutical agents. The contradictory data on the neptunium complexation behaviour within blood and its transfer to target organs, as well as the inefficiency of therapeutic treatments, led us to study the complexation of this element with biological constituents. Within this purpose, the in vitro behaviour of Np(IV) and Np(V) in simple media simulating biological fluids was studied. This study was more specifically focused on the behaviour of neptunium with citrate ion, which is an essential component in a number of metalloenzyme active sites. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np(V) with various acido-basic forms of the citrate anion was observed; regarding Np(IV), complexes with Cit{sup 3-} have been observed. From the quantitative study of these equilibria, the values of the absolute constants for the complexation of Np(IV) and Np(V) with citrate were determined. Concerning the stability of neptunium towards oxydo-reduction, it was confirmed that Np(VI) was very quickly reduced to Np(V) by the citrate anions, whereas Np(IV) was stable. In the case of Np(V), it was observed that, depending on the pH and the citrate concentration, Np(V) was unstable and was reduced to Np(IV). The E-pH diagrams, constructed using the stability constants determined in this study, showed that this instability was due to the Np(V) disproportionation. (orig.)

The significance of anthropometric and endocrine parameters in ovulation induction with clomiphene citrate in women with polycystic ovary syndrome.

Science.gov (United States)

Akpinar, Funda; Dilbaz, Berna; Cırık, Derya A; Yilmaz, Saynur; Kiykac, Sadiman; Karahanoglu, Ertugrul; Mollamahmutoglu, Leyla

2016-11-01

To investigate factors associated with the response to ovarian stimulation in patients with polycystic ovary syndrome. Methods: The records of patients with polycystic ovary syndrome and infertility who underwent ovulation induction with clomiphene citrate were reviwed between January 2011 and December 2014 in Etlik Zübeyde Hanim Women's Health Training and Research Hospital Ankara, Turkey. The anthropometric and endocrine factors of patients who were resistant to treatment at a dose of 150 mg/day (n=84) were compared with those who responded with growth of at least one graaffian follicle at a dose of 50 mg/day (n=342). Results: Of the parameters examined, body mass index, luteinizing hormone level, and luteinizing hormone/follicle stimulating hormone ratio were significantly higher in the clomiphene citrate-resistant group compared with the responsive group. Conclusion: Reproductive treatment in patients with polycystic ovary syndrome show different outcomes. Significantly higher body mass index, luteinizing hormone level, and luteinizing hormone/follicle stimulating hormone ratio observed in clomiphene citrate resistant group can be a possible explanation for this impedance.

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

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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.

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

Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia.

Science.gov (United States)

Amarapurkar, Deepak N; Rane, Priya

2004-12-01

Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly used in the management of functional dyspepsia. However, in a recently conducted international, multicentric study, efficacy of 3 different regimens of mosapride was shown to be comparable to placebo. The objective of this phase 4 randomised, double blind, prospective study was to compare the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia among patients attending the gastroenterology outpatient department of a tertiary care hospital. Ganaton 50 mg or mosapride citrate 5 mg three times daily before meals for a period of 2 weeks was administered orally. Thirty functional dyspepsia patients in each group (total = 60) were randomised to receive itopride hydrochloride or mosapride citrate treatment for 2 weeks. In itopride versus mosapride groups, global efficacy as judged by patients was excellent in 17 versus 9 (p itopride versus mosapride group global efficacy as judged by physician was excellent in 24 (80%) versus 15 (50%) and poor in 0 (0%) versus 3 (10%) patients respectively. The global efficacy was rated as excellent to good in significantly (p itopride (93.3%) group as compared to mosapride (63.33 %) group. None of the patients reported any adverse events with itopride treatment. In the mosapride group 5 patients (16.7%) reported adverse events. Two patients (6.7%) were withdrawn from mosapride treatment due to adverse events. The physician rated global tolerability ofitopride versus mosapride treatment as excellent in 23 (76.7%) versus 8 (26.7%) (p itopride hydrochloride) is superior in efficacy and safety over mosapride citrate in the management of functional dyspepsia.

The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial.

Science.gov (United States)

Mehrabian, Ferdous; Eessaei, Fatemeh

2012-03-01

This study aimed to compare two methods of treatment of infertility with gonadotropin with laparoscopic ovarian electrocauterization in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). A number of 104 nulipara patients with polycystic ovary syndrome, who were resistant to clomiphene citrate were randomly assigned to two groups. One group received gonadotropin; after the bleeding withdrawal and from the third day of the cycle, the injection of human menopausal gonadotropin (HMG) was started with 10 mg medroxy progesterone. The patients were followed with serial trans-vaginal sonographies. When the diameter of follicles reached to 18 mm, human chorionic gonadotropin (HCG) was prescribed. The other group was treated with laparoscopic ovarian electrocauterization under general anesthesia. If after 3 cycles, the anovulation was established with progesterone measurement, the clomiphene citrate was prescribed. Gonadotropin was administered, if the lack of ovulation persisted. No significant difference was documented between the two groups in terms of the obesity indexes, duration of infertility, age, sonographic and laboratory findings. In the gonadotropin group, 37 cases (71%) of pregnancy occurred. The rate of pregnancy was the same in the other group consisting of 18 cases treated by electrocautery, 9 cases with cautery + clomiphene, and 10 cases with clomiphene + cautery + gonadotropin. In the group treated with gonadotropin, there were 1 triple and 4 twins pregnancies. In the group treated with ovarian electrocautery, one twin pregnancy was observed. In the group treated with gonadotropin, 2 cases of ovarian hyperstimulation syndrome, 1 case of ectopic pregnancy and 6 cases of miscarriage occurred; the corresponding figure in the ovarian electrocautery group consisted of 5 cases of miscarriage. Our findings suggest that ovarian electrocauterization is an appropriate method with good efficacy and low complication rate for infertility

Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel.

Science.gov (United States)

Kaminetsky, Jed; Werner, Michael; Fontenot, Greg; Wiehle, Ronald D

2013-06-01

Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75-334 × 10(6) /mL range. The gel was ineffective in raising sperm counts above 20 × 10(6) /mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization

Comparison of letrazole and Clomiphene Citrate in Women with Polycystic Ovaries Undergoing Ovarian Stimulation

International Nuclear Information System (INIS)

Sharief, M.; Nafee, N. R.

2015-01-01

Objective: To compare the efficacy of letrazole in the induction of ovulation with clomiphene citrate in patients with polycystic ovary syndrome and primary infertility. Methods: The prospective clinical trial was conducted at Basrah Maternity and Child Hospital, Basrah, Iraq, between January 2012 and April 2013, and comprised women with polycystic ovarian syndrome and primary infertility who were randomised into 2 groups. Group A received 100-200mg clomiphene citrate daily while group 2 received letrazole (2.5-5mg) daily. Both groups were followed by ultrasound until the dominant follicle reached a diameter >18mm, human chorionic gonadotropin10.000 U/L was given and timed intercourse was advised. Results: Of the 75 subjects in the study, 40(53.3 percent) were in group A and 35(46.6 percent) in group B. The mean age in group A was 25.3+2.1 years versus 26.1+1.3 years in group B (p=0.05). The number of mature follicles was significantly lower, but the endometrial thickness and ovulation were significantly higher in group B than in group A (p<0.05 each). There was no significant difference in pregnancy rate between the two groups (p>0.05). Conclusion: Letrazole may have a role as the first-line treatment for unovulatory patients with polycystic ovary syndrome. (author)

Efficacies of Papaverine and Sildenafil in the Treatment of Erectile Dysfunction in Early-Stage Paraplegic Men

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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…

Diffuse abdominal gallium-67 citrate uptake in salmonella infections

International Nuclear Information System (INIS)

Garty, I.; Koren, A.

1987-01-01

Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate

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

Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

Science.gov (United States)

Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

2013-04-01

Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

Gallium-67 Citrate uptake in cryptoccal thyroiditis in a Homosexual male

International Nuclear Information System (INIS)

Machac, J.; Nejatheim, M.; Goldsmith, S.J.

1985-01-01

A case of disseminated cryptococcosis and autopsy proven cryptococcal thyroiditis is described in a homosexual male. Thyroid uptake of Gallium-67 citrate was seen one week prior to positive blood cultures. This finding was the sole indication of thyroid involvement. Focal Gallium uptake may be considered as an indication for biopsy and culture in the initial work up of this group of immunocompromised hosts

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...

Successful Treatment of Suspected Pulmonary Arterial Hypertension in a Mealy Amazon Parrot (Amazona farinose).

Science.gov (United States)

Brady, Sean M; Burgdorf-Moisuk, Anne; Silverman, Sarah; Wack, Raymund F

2016-12-01

A 25-year-old, male mealy Amazon parrot (Amazona farinose) with a history of polycythemia, hepatomegaly, and epistaxis was evaluated for progressive lethargy and anorexia. Clinical laboratory testing revealed severe polycythemia (71%), hypophosphatemia (1.6 mg/dL), and mild hypokalemia (2.8 mEq/L). Radiographs showed marked hepatomegaly and loss of air sac space. Despite supportive treatments, the bird's condition deteriorated, and it developed ataxia, was unable to fly, and became oxygen dependent. An echocardiogram, including an air bubble study, revealed a right-to-left atrial shunt and presumed pulmonary arterial hypertension. The bird was started on periodic phlebotomy (5-10 mL/kg q6wk) to reduce packed cell volume and sildenafil citrate (2.5 mg/kg PO q8h) for treatment of suspected pulmonary arterial hypertension. One week later, the patient was weaned off oxygen, and 24 days after initial presentation, the parrot was returned to its outdoor exhibit. Intermittent periods of increased respiratory rate and effort have been reported but have resolved without additional treatments. Epistaxis, once common in this bird, has not been noted since initiating treatment with sildenafil citrate 15 months ago.

Artificial citrate operon and Vitreoscilla hemoglobin gene enhanced mineral phosphate solubilizing ability of Enterobacter hormaechei DHRSS.

Science.gov (United States)

Yadav, Kavita; Kumar, Chanchal; Archana, G; Kumar, G Naresh

2014-10-01

Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment.

Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila Seguimiento de dos años en pacientes con hipertensión arterial pulmonar bajo tratamiento con sildenafil Two-year follow-up of pulmonary arterial hypertension patients treated with sildenafil

Directory of Open Access Journals (Sweden)

Sonia Meiken Franchi

2010-05-01

6 minutos (DC6M y por el grado de disnea al final de la caminata (escala de Borg, siendo también registrada la saturación periférica de oxígeno (SpO26M, oximetría de pulso. RESULTADOS: En los 18 pacientes que completaron dos años de seguimiento, hubo un incremento progresivo y sostenido en la DC6M, tanto en el grupo HAPI (de 239 ± 160 m a 471 ± 66 m, p = 0,0076 como en el grupo HAP-CCg (de 361 ± 144 m a 445 ± 96m, p = 0,0031, con mejora de la disnea al final de la caminata (p BACKGROUND: The long-term effects of drugs developed for the control of pulmonary arterial hypertension (PAH are little known, since multicenter studies usually last 12 to 16 weeks. OBJECTIVE: To evaluate the two-year outcome of PAH patients receiving monotherapy with sildenafil (a phosphodiesterase-5 inhibitor, with regard to their functional capacity. METHODS: Twenty four patients (ages between 8 and 54 years with idiopathic PAH (IPAH, n = 9 or congenital heart disease-associated PAH (CHD-PAH, n = 15 were treated with sildenafil for two years, with daily oral doses ranging from 60 to 225 mg (tid. Physical capacity was assessed by the distance walked in the 6-minute walk test (DW6M and by the degree of dyspnea at the end of the walk (Borg scale; peripheral oxygen saturation was also recorded (SpO(26M, pulse oximetry. RESULTS: In the 18 patients who completed the two-year follow-up, there was a progressive and sustained increase in DW6M, both in the IPAH group (from 239 ± 160 m to 471 ± 66 m, p = 0.0076 and in the CHD-PAH group (from 361 ± 144 m to 445 ± 96m, p = 0.0031, with improvement of dyspnea at the end of the walk (p<0.05 for both groups. No decrease in SpO(26M was observed in the groups; in patients with CHD-PAH, in particular, SpO(26M went from 77 ± 20% to 79 ± 16% (p = 0.5248. Five deaths occurred (three in the IPAH group and one patient was lost to follow-up during the study period. CONCLUSION: In a two-year follow-up, sildenafil proved useful in the control of the

Affinity for a malignant tumor and organs of sup(99m)Tc-citrate complex

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Sanada, S; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K; Nakazawa, N

1976-12-01

In order to investigate the tumor affinity of sup(99m)Tc-citrate complex, it was synthesized in three different ways. By (1) reducing sup(99m)TcO/sub 4//sup -/ with FeCl/sub 3//sup -/ ascorbic acid in 0.15 M sodium citrate, (2) reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution in 0.15 M sodium citrate, and (3) reducing sup(99m)TcO/sub 4//sup -/ with NaBH/sub 4/ in 0.45 sodium citrate. It was presumed from thinlayer chromatography that the sup(99m)Tc-citrate complexes synthesized in three ways were chemically different. These sup(99m)Tc-citrate complexes were injected intravenously into the rats subcutaneously transplanted with Yoshida sarcoma. These rats were sacrificed at one hour and three hours after injection. The radioactivity of the tumor, blood, muscle, liver, kidney, spleen and urine was measured by well-type scintillation counter. The retention values in these organs and the excretion rates in the urine were calculated. sup(99m)Tc-citrate complex synthesized by reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution had very strong affinity for the malignant tumor but the other two sup(99m)Tc-citrate complexes had no affinity to the malignant tumor. Excretion rates (% dose) of sup(99m)Tc-citrate complexes in one hour were from 65% to 75%.

Clomiphene citrate therapy for male infertility.

Science.gov (United States)

Allag, I S; Alexander, N J

1979-11-01

We have summarized 697 reported cases of the use of clomiphene citrate for the improvement of semen quality. Basal levels of gonadotropins are useful criteria for the differential diagnosis of hypo- and hypergonadotropic hypogonadism. Patients with an intact hypothalamic-pituitary-gonadal axis are most likely to respond to clomiphene citrate. Twenty-five mg. per day, administered in a cyclic fashion for a period of six to nine months, caused the greatest improvement. A higher dose (50 mg. per day) may be effective in men who do not respond to 25 mg. During the course of therapy gonadotropin levels and semen samples should be analyzed periodically. This drug is not currently approved for use in men; the incidence of side effects, particularly with long-term treatment, is unknown.

Solid-phase extraction assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet to determine sildenafil and its analogues in dietary supplements.

Science.gov (United States)

Li, Jing; Roh, Si Hun; Shaodong, Jia; Hong, Ji Yeon; Lee, Dong-Kyu; Shin, Byong-Kyu; Park, Jeong Hill; Lee, Jeongmi; Kwon, Sung Won

2017-08-01

A novel analytical method for the simultaneous determination of the concentration of sildenafil and its five analogues in dietary supplements using solid-phase extraction assisted reversed-phase dispersive liquid-liquid microextraction based on solidification of floating organic droplet combined with ion-pairing liquid chromatography with an ultraviolet detector was developed. Parameters that affect extraction efficiency were systematically investigated, including the type of solid-phase extraction cartridge, pH of the extraction environment, and the type and volume of extraction and dispersive solvent. The method linearity was in the range of 5.0-100 ng/mL for sildenafil, homosildenafil, udenafil, benzylsildenafil, and thiosildenafil and 10-100 ng/mL for acetildenafil. The coefficients of determination were ≥0.996 for all regression curves. The sensitivity values expressed as limit of detection were between 2.5 and 7.5 ng/mL. Furthermore, intraday and interday precisions expressed as relative standard deviations were less than 5.7 and 9.9%, respectively. The proposed method was successfully applied to the analysis of sildenafil and its five analogues in complex dietary supplements. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

nanoparticles synthesized by citrate precursor m

African Journals Online (AJOL)

user

(M=Co, Cu) nanoparticles synthesized by citrate precursor method ... The structural characterization was carried out using an X-ray Diffractometer (Rikagu Miniflex, Japan) ..... His current area of interest includes magnetic nanomaterials.

SERS substrates fabricated using ceramic filters for the detection of bacteria: Eliminating the citrate interference

Science.gov (United States)

Mosier-Boss, P. A.; Sorensen, K. C.; George, R. D.; Sims, P. C.; O'braztsova, A.

2017-06-01

It was found that spectra obtained for bacteria on SERS substrates fabricated by filtering citrate-generated Ag nanoparticles (NPs) onto rigid, ceramic filters exhibited peaks due to citrate as well as the bacteria. In many cases the citrate spectrum overwhelmed that of the bacteria. Given the simplicity of the method to prepare these substrates, means of eliminating this citrate interference were explored. It was found that allowing a mixture of bacteria suspension and citrate-generated Ag NPs to incubate prior to filtering onto the ceramic filter eliminated this interference.

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.

Whole-body retention studies of /sup 169/Yb-citrate. Estimation of radiation dose to humans from /sup 169/Yb-citrate

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Mori, H; Ando, I; Hisada, K

1977-09-01

For purpose of the estimation of the radiation dose to humans from /sup 169/Yb-citrate, the whole-body retention studies using five rats were carried out. Following intravenous administration of /sup 169/Yb-citrate, the whole-body activity was monitored for 40 days by the animal counter. The whole-body retention curve consisted of three components: the first with a 3.6 hours effective half-time, the second with an 154 hours effective half-time and the third with a 29.9 days effective half-time. Therefore it was assumed that 32% of the administered /sup 169/Yb-citrate clears from the kidney with a short biologic half-time (3.6 hours), 18% remains in the liver and other soft tissues with a relatively long biologic half-time (194 hours) and 50% remains in the bone with a long biologic half-time (850 days). Based on these biological data and the MIRD Committee method, the average dose to the bone and whole-body were 20.8 rads/mCi and 4.5 rads/mCi respectively.

[Effect of glucose and lactose on the utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469].

Science.gov (United States)

Benito de Cárdenas, I L; Medina, R; Oliver, G

1992-01-01

The utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469 in a complex medium containing glucose, lactose or citrate was investigated, as an approach to the question of the transport of this acid and the possible relationship with the production of flavour compounds (diacetyl and acetoin). This lactobacillus uses citrate as an energy source in the absence of carbohydrates. External pH and growth increases when citrate is added to complex medium. The presence of citrate does not affect glucose uptake. L. casei ATCC 7469 possibly uses a transport system for citrate utilization, and citrate uptake seems to be under glucose or lactose control. Lactose only inhibits the entrance of citrate at high concentration while the utilization of this acid was negatively regulated by low glucose concentration.

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Science.gov (United States)

2011-01-01

Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development. PMID:21443799

Evaluating the efficacy of citrate anticoagulation during CRRT in cardiac patients

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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.

Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate-resistant polycystic ovary disease.

Science.gov (United States)

Seyam, Emaduldin; Hasan, Momen; Khalifa, Eissa M; Ramadan, Ahmad; Hefzy, Enas

2017-11-01

The aim of this work was to investigate the level of the serum level of tumor necrosis factor alpha (TNF-α) as an inflammatory biomarker in lean and obese women with polycystic ovary disease (PCOD), who are resistant to clomiphene citrate (CCR-PCOD). It is a case-controlled study, where 150 (n = 150) PCOD women (study group), who are resistant to clomiphene citrate (CCR-PCOD) had been recruited, in addition to 100 (n = 100) women with PCOD, who are not resistant to clomiphene citrate (NCCR-PCOD) as the first control group, and another 100 women (n = 100) fertile women with normal reproductive health, as the second control group. All the recruited subjects had been divided into subgroups according to the BMI: One obese group with BMI ≥ 27 and the second lean group with BMI PCOD-relevant biochemical and hormonal tests. TNF-α level was found to be higher in all PCOD women, either the study or control PCOD groups, than the fertile control group (49.93 ± 3.39 versus 35.83 ± 2.47 pg/ml, p PCOD women (obese CCR-PCOD), while the lowest has come in the lean PCOD women, who are not resistant to clomiphene citrate (NCCR-PCOD). Free Androgen Index (FAI) and androgenic obesity with higher W/H ratio were clearly going with TNF-α pattern and have come higher in all PCOD compared to the fertile control group. Insulin resistance (IR) shows a positive correlation with BMI regardless off PCOD status and androgen level as well. The level of other basic and PCOD-relevant hormones like FSH, TSH and prolactin have never shown statistically significant differences between all the study and control groups, except LH serum level which has shown a nonsignificant higher level in all PCOD women included either resistant to CC or not. TNF-α serum level has come significantly higher in all women with PCOD, especially in those resistant to CC. Androgenic obesity with higher W/H ratio has shown a positive correlation with TNF-α level, which could consider it

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

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

-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (r...... that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use...

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 ...

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

African Journals Online (AJOL)

Eectile/sexual functions including libido, erection frquency, masturbation ability, pattern of ejaculation, and pattern of erection lost were noted during audiovisual sexual stimulation in 50 insulin dependent diabetes mellitus (IDDM) and in 50 non insulin dependent diabetes mellitus (NIDDM) patients with and without an ...

Effect of two tumors (metastatic and non-metastatic) on tissue distribution of Ga-67 citrate in the rat

International Nuclear Information System (INIS)

Durakovic, A.

1985-01-01

The effect of metastatic and non-metastatic mammary adenocarcinoma on tissue distribution of Ga-67 citrate in Fischer female rats was studied. The homogenate (0.1 ml) of each tumor was injected subcutaneously in separate groups of rats and the animals were studied from day 2-30 after tumor homogenate implantation. All animals were injected with 30 μCi of Ga-67 citrate and sacrificed by halothane anethesia 48 hours later. Tissue samples of blood, lung, heart, liver, spleen, kidney, adrenal, stomach, small and large intestine, ovaries, and lymph nodes (popliteal, lumbar, and mediastinal) were obtained and counted in a gamma well counter. The control group consisted of four animals and tumor bearing groups of seven to eight animals at each time. Ga-67 uptake was increased in the liver (24 days) and in the popliteal lymph nodes on days 7, 10, and 18 in the metastatic tumor group (P<0.05). This probably represents Ga-67 uptake in the metastatic deposits in these organs. No difference was observed in non-metastatic tumor group

Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

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Silva Sérgio Marques da

2003-01-01

Full Text Available Hipertensão pulmonar primária é uma doença rara, progressiva e com alta mortalidade, cujo tratamento baseia-se em medicações de alto custo e pouco disponíveis em nosso meio. O sildenafil é um vasodilatador de fácil administração por via oral, com indicação primária para disfunção erétil e que recentemente tem sido descrito como opção terapêutica para a hipertensão pulmonar primária. Relata-se o caso de uma paciente de 21 anos com diagnóstico de hipertensão pulmonar primária, que apresentou piora abrupta da saturação de oxigênio, com abertura do forame oval e shunt direita-esquerda, evidenciados ao ecocardiograma. Foi introduzido sildenafil na dose de 225mg/dia com melhora progressiva da oxigenação e reversão do shunt após 40 dias. Os autores acreditam que o sildenafil seja uma opção no tratamento da hipertensão pulmonar primária, embora estudos clínicos que comprovem sua segurança e eficácia ainda sejam necessários.

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...

76 FR 19997 - Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn...

Science.gov (United States)

2011-04-11

...] Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that FENTORA (fentanyl citrate) buccal tablet, 300... allow FDA to approve abbreviated new drug applications (ANDAs) for fentanyl citrate buccal tablet, 300...

Nitrate Protects Cucumber Plants Against Fusarium oxysporum by Regulating Citrate Exudation.

Science.gov (United States)

Wang, Min; Sun, Yuming; Gu, Zechen; Wang, Ruirui; Sun, Guomei; Zhu, Chen; Guo, Shiwei; Shen, Qirong

2016-09-01

Fusarium wilt causes severe yield losses in cash crops. Nitrogen plays a critical role in the management of plant disease; however, the regulating mechanism is poorly understood. Using biochemical, physiological, bioinformatic and transcriptome approaches, we analyzed how nitrogen forms regulate the interactions between cucumber plants and Fusarium oxysporum f. sp. cucumerinum (FOC). Nitrate significantly suppressed Fusarium wilt compared with ammonium in both pot and hydroponic experiments. Fewer FOC colonized the roots and stems under nitrate compared with ammonium supply. Cucumber grown with nitrate accumulated less fusaric acid (FA) after FOC infection and exhibited increased tolerance to chemical FA by decreasing FA absorption and transportation in shoots. A lower citrate concentration was observed in nitrate-grown cucumbers, which was associated with lower MATE (multidrug and toxin compound extrusion) family gene and citrate synthase (CS) gene expression, as well as lower CS activity. Citrate enhanced FOC spore germination and infection, and increased disease incidence and the FOC population in ammonium-treated plants. Our study provides evidence that nitrate protects cucumber plants against F. oxysporum by decreasing root citrate exudation and FOC infection. Citrate exudation is essential for regulating disease development of Fusarium wilt in cucumber plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Post-Dilution on Line Haemodiafiltration with Citrate Dialysate: First Clinical Experience in Chronic Dialysis Patients

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Vincenzo Panichi

2013-01-01

Full Text Available Background. Citrate has anticoagulative properties and favorable effects on inflammation, but it has the potential hazards of inducing hypocalcemia. Bicarbonate dialysate (BHD replacing citrate for acetate is now used in chronic haemodialysis but has never been tested in postdilution online haemodiafiltration (OL-HDF. Methods. Thirteen chronic stable dialysis patients were enrolled in a pilot, short-term study. Patients underwent one week (3 dialysis sessions of BHD with 0.8 mmol/L citrate dialysate, followed by one week of postdilution high volume OL-HDF with standard bicarbonate dialysate, and one week of high volume OL-HDF with 0.8 mmol/L citrate dialysate. Results. In citrate OL-HDF pretreatment plasma levels of C-reactive protein and β2-microglobulin were significantly reduced; intra-treatment plasma acetate levels increased in the former technique and decreased in the latter. During both citrate techniques (OL-HDF and HD ionized calcium levels remained stable within the normal range. Conclusions. Should our promising results be confirmed in a long-term study on a wider population, then OL-HDF with citrate dialysate may represent a further step in improving dialysis biocompatibility.

Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continous renal replacement therapy with calcium-free replacement solution

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See Kay

2009-01-01

Full Text Available Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group, received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020. When calcium-containing replacement solution was used, more citrate was required (mean 280ml/h, CI 227.2-332.8 vs. 265ml/h, CI 203.4-326.6, P = 0.069, but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6ml/h, CI 26.8-76.4, P ≤ 0.0001.

Differentiation of malignant and degenerative benign bone disease using Tc-99m Citrate and Tc-99m MDP scintigraphy

International Nuclear Information System (INIS)

Jin, J.; Guo, R.; Li, S.-J.; Ren, Y.; Zhang, C.; Zhang, X.

2007-01-01

Full text: For the evaluation of bone metastases in patients (pts) with cancer, 99mTcMDP bone scintigraphy is an important tool, but some limitations exist. One of these is the differential diagnosis of malignant and degenerative benign bone disease. The aim of this study was to differentiate them using 99mTcCitrate and 99mTcMDP scintigraphy. Methods: 39 pts (92 lesions) with known malignant or degenerative benign bone disease were studied. 23 pts had malignant bone disease (48 lesions, group 1), the other 16 pts had degenerative benign bone disease (44 lesions, group2), for which the results of 99mTcMDP scintigraphy were positive. In both groups, 99mTcCitrate scintigraphy was performed within a time interval of 2-7 days after 99mTcMDP scintigraphy (555∼740MBq. static, 3hr, planar or SPECT i m a g e s w h e n r e q u i r e d ) . The 99mTccitrate/99mTcMDP lesion-to-background radioisotope uptake ratio (RUR) was calculated for each lesion. Conventional techniques (histopathology, X-ray, CT, MRI and clinical follow up) were considered to be proof of the presence of bone metastases and degenerative benign bone disease. Results: Uptake of 99mTcMDP in the two groups is the same (1.96±0.25 vs. 1.87±0.21; t=1.178, P>0.20), while in 99mTcCitrate image, malignant lesions demonstrated a higher uptake of lesion activity than that of benign degenerative lesions (1.47±0.42 vs. 1.09±0.38; t=2.887, P<0.01). The mean 99mTccitrate/99mTcMDP RUR in the malignant group was significantly higher than the mean in the benign group (0.78±0.21 vs. 0.54±0.19; t=3.646, P<0.001). Conclusions: The preliminary results of the study confirm the usefulness and feasibility of 99mTcCitrate scintigraphy for differentiating malignant from benign degenerative lesions seen as areas of increased activity on 99mTcMDP bone scintigraphy. (author)

Electrospray ionization of uranyl-citrate complexes

Science.gov (United States)

Somogyi, Árpád; Pasilis, Sofie P.; Pemberton, Jeanne E.

2007-09-01

Results presented here demonstrate the usefulness of electrospray ionization and gas-phase ion-molecule reactions to predict structural and electronic differences in complex inorganic ions. Electrospray ionization of uranyl citrate solutions generates positively and negatively charged ions that participate in further ion-molecule reactions in 3D ion trap and FT-ICR mass analyzers. Most ions observed are derived from the major solution uranyl-citrate complexes and involve species of {(UO2)2Cit2}2-, (UO2)3Cit2, and {(UO2)3Cit3}3-, where Cit indicates the citrate trianion, C6H5O73-. In a 3D ion trap operated at relatively high pressure, complex adducts containing solvent molecules, alkali and ammonium cations, and nitrate or chloride anions are dominant, and proton/alkali cation (Na+, K+) exchange is observed for up to six exchangeable protons in an excess of alkali cations. Adduct formation in a FT-ICR cell that is operated at lower pressures is less dominant, and direct detection of positive and negative ions of the major solution complexes is possible. Multiply charged ions are also detected, suggesting the presence of uranium in different oxidation states. Changes in uranium oxidation state are detected by He-CID and SORI-CID fragmentation, and certain fragments undergo association reactions in trapping analyzers, forming "exotic" species such as [(UO2)4O3]-, [(UO2)4O4]-, and [(UO2)4O5]-. Ion-molecule reactions with D2O in the FT-ICR cell indicate substantial differences in H/D exchange rate and D2O accommodation for different ion structures and charge states. Most notably, the positively charged ions [H2(UO2)2Cit2(H)]+ and [(UO2)2(Cit)]+ accommodate two and three D2O molecules, respectively, which reflects well the structural differences, i.e., tighter uranyl-citrate coordination in the former ion than in the latter. The corresponding negatively charged ions accommodate zero or two D2O molecules, which can be rationalized using suggested solution phase structures

Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate resistant polycystic ovary disease

OpenAIRE

Seyam, Emaduldin; Hasan, Momen; Khalifa, Eissa M.; Ramadan, Ahmad; Hefzy, Enas

2017-01-01

Objective: The aim of this work was to investigate the level of the serum level of tumor necrosis factor alpha (TNF-α) as an inflammatory biomarker in lean and obese women with polycystic ovary disease (PCOD), who are resistant to clomiphene citrate (CCR-PCOD). Patients and design: It is a case controlled study, where one hundred and fifty (n = 150) PCOD women (study group), who are resistant to clomiphene citrate (CCR-PCOD) had been recruited, in addition to one hundred (n = 100) women wi...

Controlled swelling and degradation studies of alginate microbeads in dilute natrium-citrate solutions

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Mitrović Dragana D.

2010-01-01

Full Text Available Alginate hydrogels are widely used in biomedicine due to alginate availability, hydrophilic nature, biocompatibility and biodegradability. Alginate microbeads are particularly attractive for applications in pharmacy and regenerative medicine due to high surface to volume ratio, low mass transfer limitations and simple implantation by injection. Aim of this work was to investigate possibilities for controlled degradation of alginate microbeads in cell culture medium (Dulbecco’s modified Eagle’s medium with Na-citrate added in small concentrations (0.05 - 0.5 mM. Alginate microbeads (1.5% w/w, 800 m in diameter were produced by electrostatic droplet extrusion and evaluated over a period of 10 days regarding appearance, kinetics and degree of swelling as well as biomechanical properties determined in a novel bioreactor with mechanical stimulation under in vivo-like conditions in articular cartilage (10% strain, 337.5 m/s compression rate. In the citrate concentration range investigated, microbeads initially swelled reaching an equilibrium value (~150-170% with respect to the initial mass, upon which they appeared stable for a certain period of time (1 to over 7 days followed by bead bursting and degradation. This degradation process indicated that Na+ ions from the solution initially replaced Ca2+ ions bound mainly to COO- groups in polymannuronate sequences inducing electrostatic repulsion of polymer chains and, consequently, swelling of the beads. Citrate ions assisted in this process by forming insoluble calcium citrate. Thus, the specific rate of the bead swelling increased with the increase in citrate concentration approaching a maximal value of ~0.34 d-1. In the last phase, the beads burst into pieces, which slowly continued to degrade by replacement of Ca2+ ions bonded to polyguluronate blocks in the egg-box structure. Compression moduli for packed beds of control, freshly produced microbeads, and microbeads swelled at the equilibrium

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.

Inhibition of citric acid accumulation by manganese ions in Aspergillus niger mutants with reduced citrate control of phosphofructokinase

Energy Technology Data Exchange (ETDEWEB)

Schreferl, G.; Kubicek, C.P.; Roehr, M.

1986-03-01

Mutant strains of Aspergillus niger with reduced citrate control of carbohydrate catabolism (cic mutants) grow faster than the parent strain on media containing 5% (wt/vol) citrate. The mutants tolerated a higher intracellular citrate concentration than the parent strain. One mutant (cic-7/3) contained phosphofructokinase activity significantly less sensitive towards citrate than the enzyme from the parent strain. When this mutant was grown under citrate accumulating conditions, acidogenesis was far less sensitive to inhibition by Mn/sup 2 +/ than in the parent strain. Some of the cic mutants also showed altered citrate inhibition of NADP-specific isocitrate dehydrogenase.

Bio-inspired citrate functionalized apatite coating on rapid prototyped titanium scaffold

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Yu, Peng [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Lu, Fang [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Zhu, Wenjun [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Wang, Di [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhu, Xiaojing [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Tan, Guoxin, E-mail: tanguoxin@126.com [Institute of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006 (China); Wang, Xiaolan [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhang, Yu; Li, Lihua [General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010 (China); Ning, Chengyun, E-mail: imcyning@scut.edu.cn [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China)

2014-09-15

Highlights: • Designed and reproducible porous titanium scaffolds were produced. • Hydrophilic nanoporous film was built on scaffold. • Apatite coating was deposited on scaffold under the modulation of citrate ions. • Citrate ions could affect CO{sub 3}{sup 2−} incorporation in apatite coatings. - Abstract: Scaffold functionalized with appropriate osteogenic coatings can significantly improve implant-bone response. In this study, with designed model and optimized manufacture parameters, reproducible and precise titanium scaffolds were produced. Reconstructed three-dimensional image and sectional structure of the scaffold were examined by micro-computed tomography and relative software. Alkali treatment was carried out on these manufactured porous scaffolds to produce nanoporous hydrophilic film. After 6 days deposition in simulated body fluid (SBF) containing sodium citrate (SC-SBF), plate-like amorphous calcium phosphate (ACP) coating was deposited on scaffold surface. Ultrasonication tests qualitatively indicated an enhanced adhesion force of apatite coatings deposited in SC-SBF compared to that deposited in SBF. And the effect of citrate ions on the CO{sub 3}{sup 2−} incorporation rate in apatite coating was quantitatively examined by bending vibration of CO{sub 3}{sup 2−} at ∼874 cm{sup −1}. Results indicated the highest carbonate content was obtained at the citrate ion concentration of 6 × 10{sup −5} mol/L in SC-SBF. These three-dimensional porous titanium-apatite hybrid scaffolds are expected to find application in bone tissue regeneration.

The effect of citric acid and citrate on protoplasmic droplet of bovine epididymal sperms

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Keivan Abdy

2011-11-01

Full Text Available AbstractFor evaluation of citric acid and citrate effects on bovine epididymal protoplasmic droplets, fifty bovine testes were collected in the October 2007 till June 2008 from Urmia slaughterhouse and transported to the laboratory in a cool container filled with 5 °C ice pack. Caudal epididymis was incised and sperm cells were put into Petri dishes containing hams f10 media with 10% fetal calf serum (FCS, which were kept in 37 °C, CO2 incubator. Then sperm cells were counted and 50-milion per mL concentration was prepared. After this stage, three dilutions of citric acid (0.1, 0.2, 0.3 N and one dilution of citrate (1N, based on normal osmolarity and normal pH were added to a micro tube containing 25 milion per mL sperm. Then one-step eosin-nigrosin staining in 30-60-120-240-360 minutes was performed and slides were evaluated with 1000-x phase contrast microscope and 200 sperm cells per slide were counted. The results revealed significant difference between blank and citric acid 0.3 N. The proportion of protoplasmic droplet in group consisting of 0.3 N acid citric in 120-240-360 minutes, was significantly lower than that of blank (P < 0.05. There was no significant difference between citrate – blank and citric acid 0.1N-blank groups, but after 240 minutes significant difference was observed between blank & citric acid 0.2 N (P < 0.05. In conclusions citric acid based on dilution and time duration can reduce the proportion of bovine epididymal sperm cytoplasmic droplets.

A COMPARISON OF CLOMIPHENE CITRATE AND SEQUENTIAL CLOMIPHENE CITRATE PLUS HUMAN MENOPAUSAL GONADOTROPIN FOR USE IN CONJUNCTION WITH INTRAUTERINE INSEMINATION

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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.

A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

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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.

A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation

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Niamh C. Williams

2018-02-01

Full Text Available Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria via the mitochondrial citrate- carrier. Cytosolic metabolism of citrate to acetyl-coenzyme A (acetyl-CoA is important for both fatty-acid synthesis and protein acetylation, both of which have been linked to macrophage and DC activation. Citrate-derived itaconate has a direct antibacterial effect and also has been shown to act as an anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify citrate as an important metabolite for macrophage and DC effector function.

A light-up fluorescent probe for citrate detection based on bispyridinum amides with aggregation-induced emission feature.

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Liu, Chenchen; Hang, Yandi; Jiang, Tao; Yang, Ji; Zhang, Xiao; Hua, Jianli

2018-02-01

Citrate is an important intermediate in the citric acid cycle, a vital metabolic pathway for animals, plants and bacteria. It is of great significance to detect its levels in human beings because several diseases may cause the abnormal of citrate. In this paper, a new turn-on fluorescent sensor (TPE-Py) using the classic tetraphenylethylene (TPE) as the aggregation-induced emission (AIE) fluorophore and bipyridinium-based amides as the recognition receptor has been synthesized for the detection of citrate. The probe exhibits good selectivity and sensitivity to citrate with a relatively low detection limit (1.0 × 10 -7 M). The enhancement of the fluorescence is relevant with the AIE property based on the complexation of TPE-Py with citrate caused by the hydrogen bonding and electrostatic interactions between the bipyridinium diamides and citrate, which has been proved by 1 H NMR and mass spectra titration, scanning electronic microscope and dynamic light scattering analyses. More importantly, the quantification of citrate in artificial urine may develop TPE-Py fluorometric probe for the citrate detection in real biosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of 67Ga citrate in the diagnosis of lung cancer

International Nuclear Information System (INIS)

Bogdasarov, Yu.B.; Zajtseva, T.I.; Gabuniya, R.I.; Abramov, V.F.

1981-01-01

A study was of the potentialities of 67 Ga citrate in the diagnosis of lung cancer, in differentiation from benign tumors and chronic inflammatory processes of the lungs. A total of 101 lung cancer patients were examined, of them 64 with central, and 37 with peripheral cancer. The results of radionuclide studies were correlated with those of surgery and with morphological findings. It has been established that in central cancer scintigraphy with 67 Ga citrate gives positive results in 87% of cases, and in peripheral cancer in 89%. This method is of great value for the diagnosis of cancer metastases to the mediastinal lymph nodes. No correlation between the intensity of 67 Ga citrate accumulation in lung tumors and their histological structure has been revealed [ru

Determination of radiation loads from examination of the colon by 67Ga citrate

International Nuclear Information System (INIS)

Mihalova, P.; Buncova, M.; Vrba, T.

2011-01-01

This paper deals with the determination of radiation loads from examination of the colon by gallium citrate. The average calculated committed effective dose after administration of 5 MBq of 67 Ga-citrate is 2.05 mSv.

A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

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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.

Follow-up of rheumatic carditis using 67Ga-citrate imaging

International Nuclear Information System (INIS)

Calegaro, J.U.M.; Bae, S.H.; Prado, E.S.; Gomes, E.F.

2002-01-01

Aim: This study reports the follow -up of 25 patients (pts) with rheumatic carditis (9 male, 16 females; 4-29 years, mean 12,12) using 67-gallium citrate. Materials and Methods: the pts were divided in 2 groups: I- first attack (7pts, 2 males, with a mean follow-up of 5,65 years); II- recurrence (18 pts, 7 males, with a mean follow-up of 5,27 years).Images of the thorax and semi quantitative indexes were obtained 72 hours after intravenous injection of 37-74 MBq (1-2 mCi) of 67-gallium citrate, using a LFOV scintillation camera. 67-gallium uptake in the cardiac area was graded as mild, moderate or severe using the tracer uptake in the lung as a reference (normal up to 130%). Results: all pts in group I (2 severe, 2 moderate, and 3 mild carditis) had normal gallium uptake in up to 9 weeks after the institution of cortico therapy, with a better outcome in follow-up.In group II, 8 pts presented moderately active carditis (2 had good and 6 had a poor outcome) and 10 mildly active carditis (7 had good and 3 had poor outcome). The evolution of the disease was better in 8 pts that the reduction of 67- gallium uptake to normal limits occurred in up to 9 weeks, than in 9 pts that the scintigraphy was only normal after 10 weeks of therapy. Conclusion: normal gallium uptake in up to 9 weeks of treatment seems to be a good predictor of evolution in rheumatic carditis first attack or recurrence; in recurrence, reduction of 67-gallium uptake only after 10 weeks or increasing uptake seems to be worse predictors

Citric complexes, neodymium citrate and americium citrate

International Nuclear Information System (INIS)

Bouhlassa, Saidati.

1981-06-01

The behaviour of neodymium and americium has been studied in citric aqueous medium by two methods: solvent extraction of elements at tracer scale as chelates and by potentiometry. So range of pH and concentrations of elements and citric acid never reached before have been explored: 10 -7 -1 M, 10 -10 -3 , Csub(H3 Cit) -1 M, 1 2 O; AmCit, xH 2 O; NdCit 2 Co(NH 3 ) 6 , 8H 2 O; AmCit 2 Co(NH 3 ) 6 , xH 2 O and Nd 3 (OH) 4 (Cit) 4 NH 4 (Co(NH 3 ) 6 ) 2 , 18H 2 O. Their spectroscopic and crystallographic characteristics have been listed and studied. The nephelauxetic effect has been estimated from citric complexes as well as from citrates of these elements. The structure of the complexes in solution has been discussed on the basis of analysis of hypersensitive transition in different complexes [fr

Artificial Citrate Operon Confers Mineral Phosphate Solubilization Ability to Diverse Fluorescent Pseudomonads

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Adhikary, Hemanta; Sanghavi, Paulomi B.; Macwan, Silviya R.; Archana, Gattupalli; Naresh Kumar, G.

2014-01-01

Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1) and citrate transporter (citC) genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP) buffered medium, which was sufficient to release 200–1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration. PMID:25259527

Alkali absorption and citrate excretion in calcium nephrolithiasis

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Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

1993-01-01

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training

DEFF Research Database (Denmark)

Vigelsø, Andreas; Andersen, Nynne B; Dela, Flemming

2014-01-01

Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and chan......Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity...... and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake (V.O2max) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed. The search profile included: citrate...... and CS activity. 70 publications with 97 intervention groups were included. There was a positive (r = 0.45) correlation (P

Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial

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Ragni Guido

2012-12-01

Full Text Available Abstract Background The aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins. Methods Women with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145 or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146. They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle. Results The study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5 and 5% (n=7, respectively (p=0.77. The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed. Conclusions In women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive. Trial registration Trial registered on http://www.clinicaltrials.gov (NCT01389713

STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis.

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Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N

2014-03-11

In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol. The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015.The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment

A prospective comparison of topical feracrylum citrate versus adrenaline as haemostatic agent in hypospadias surgery in children

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Ashok Kumar Laddha

2014-01-01

Full Text Available Background: A comparative study of topical feracrylum citrate versus adrenaline to minimise haemorrhage-related complications in paediatric hypospadiac patients. Patients and Methods: A total of 108 consecutive paediatric hypospadiac patients (48 in the study group and 60 control - random allocation were studied. In the study group, 1% feracrylum citrate solution was used and adrenaline (1:100,000 in controls. Results: Among the study group, average number of blood-soaked gauge pieces were 2.95/patient, correlating with average intraoperative blood loss of 14.74 ml. In controls, average blood-soaked gauge pieces were 4.83/patient corresponding to an average blood loss of 24.13 ml. The average amount of blood loss during surgery in the <5 years was 13.70 ml/patient in the feracrylum group, while the same in the adrenaline group was 23.45 ml. Average duration of surgery was 79 min in the study group, while the same in controls was 94 min/patient. Average number of cauterisations was 0.255/patient in the study group and 0.583/patient among controls. Postoperative haematoma was seen in 8% study group compared with 18% controls. Wound oedema appeared in 4.17% study group and 11.67% controls. Postoperative complications were higher among controls. Conclusions: Feracrylum is more efficient and safer topical haemostatic agent than adrenaline. It reduced the frequency of cauterisation and tissue damage, intraoperative blood loss, and postoperative complications.

Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

International Nuclear Information System (INIS)

Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

1987-01-01

We performed the biodistribution and imaging studies of 111 In and 67 Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of 67 Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111 In and 67 Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of 67 Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of 67 Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67 Ga citrate. The imaging studies performed with 111 In T4NMPYP and 67 Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111 In T4NMPYP. 15 refs., 3 figs., 5 tabs

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

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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.

Comparison of pregnancy rates in PCOS patients undergoing clomiphene citrate and IUI treatment with different leading follicular sizes.

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Seckin, Berna; Pekcan, Meryem Kuru; Bostancı, Esra Isci; Inal, Hasan Ali; Cicek, Mahmut Nedim

2016-04-01

The objective of the study was to compare the pregnancy rates in PCOS patients undergoing clomiphene citrate (CC) and intrauterine insemination (IUI) treatment with different leading follicular sizes. A total of 358 infertile women with PCOS who underwent 563 clomiphene citrate and IUI treatment cycles were included in this prospective study. Treatment cycles were divided into three groups according to leading follicular size on the day of hCG administration: Group I: follicular size 17-18 mm (n = 177), Group II: 19-22 mm (n = 321), and Group III : >22 mm (n = 65). Pregnancy rates were evaluated. Treatment outcomes of the groups were further analyzed related to endometrial thickness measurement on the day of hCG. For this purpose, cycles were placed into three subgroups as follows: endometrial thickness 9 mm. There was no statistically significant difference in clinical pregnancy rate per cycle between the groups (8.5, 10, and 9.2 % for Group I, II, and III, respectively, p = 0.86). In further analyses related to endometrial thickness, no significant difference was also found in pregnancy rate among the groups. This results suggest that pregnancy rate is not related to leading follicle size on the day of hCG administration in PCOS patients treated with CC and IUI. In addition, pregnancy rate in women with different follicular sizes is not influenced by the endometrial thickness.

Citrus PH5-like H+-ATPase genes: identification and transcript analysis to investigate their possible relationship with citrate accumulation in fruits

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Cai-Yun eShi

2015-03-01

Full Text Available PH5 is a petunia gene that encodes a plasma membrane H+-ATPase and determines the vacuolar pH. The citrate content of fruit cell vacuoles influences citrus organoleptic qualities. Although citrus could have PH5-like homologs that are involved in citrate accumulation, the details are still unknown. In this study, extensive data-mining with the PH5 sequence and PCR amplification confirmed that there are at least eight PH5-like genes (CsPH1-8 in the citrus genome. CsPHs have a molecular mass of approximately 100 kDa, and they have high similarity to PhPH5, AtAHA10 or AtAHA2 (from 64.6% to 80.9%. They contain 13-21 exons and 12-20 introns and were evenly distributed into four subgroups of the P3A-subfamily (CsPH1, CsPH2, and CsPH3 in Group I, CsPH4 and CsPH5 in Group II, CsPH6 in Group IV, and CsPH7 and CsPH8 in Group III together with PhPH5. A transcript analysis showed that CsPH1, 3, and 4 were predominantly expressed in mature leaves, whereas CsPH2 and 7 were predominantly expressed in roots, CsPH5 and 6 were predominantly expressed in flowers, and CsPH8 was predominantly expressed in fruit juice sacs. Moreover, the CsPH transcript profiles differed between orange and pummelo, as well as between high-acid and low-acid cultivars. The low-acid orange ‘Honganliu’ exhibits low transcript levels of CsPH3, CsPH4, CsPH5, and CsPH8, whereas the acid-free pummelo has only a low transcript level of CsPH8. In addition, ABA injection increased the citrate content significantly, which was accompanied by the obvious induction of CsPH2, 6, 7, and 8 transcript levels. Taken together, we suggest that CsPH8 seems likely to regulate citrate accumulation in the citrus fruit vacuole.

21 CFR 73.2110 - Bismuth citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Bismuth citrate. 73.2110 Section 73.2110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... paragraph (c)(1), effective April 27, 2010. For the convenience of the user, the revised text is set forth...

Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664 or nitroglycerin

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Sidi Avner

2008-01-01

Full Text Available In patients at risk for sudden ethanol (ETOH intravascular absorption, prompt treatment of pulmonary hypertension (PHTN will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664 and nitroglycerin (NTG during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT, as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP, and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7 normal saline, a 500-μg/kg bolus of UK343-664 ( n = 8, or NTG 1 μg/kg ( n = 8; each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP, and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR. Within 2 minutes after treatment with either drug, CVP, heart rate (HR, and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from

Rôle modeste du citrate comme transporteur d'acétyl-CoA chez l'animal vivant.

Science.gov (United States)

Rous, S

1971-02-09

2,4-(14) C-Citrate incorporated to a far greater extent than 1,5-(14) C-citrate into liver, carcass or adipose tissue fatty acids of living mice. This finding excludes the possibility that the acetyl units emerge from the mitochondria in the form of citrate.

Plasma Membrane Na+-Coupled Citrate Transporter (SLC13A5 and Neonatal Epileptic Encephalopathy

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Yangzom D. Bhutia

2017-02-01

Full Text Available SLC13A5 is a Na+-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na+:citrate3− stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 μM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150–200 μM. Li+ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy. Human SLC13A5 differs from rodent Slc13a5 in two important aspects: the affinity of the human transporter for citrate is ~30-fold less than that of the rodent transporter, thus making human SLC13A5 a low-affinity/high-capacity transporter and the rodent Slc13a5 a high-affinity/low-capacity transporter. In the liver, SLC13A5 is expressed exclusively in the sinusoidal membrane of the hepatocytes, where it plays a role in the uptake of circulating citrate from the sinusoidal blood for metabolic use. In the testis, the transporter is expressed only in spermatozoa, which is also only in the mid piece where mitochondria are located; the likely function of the transporter in spermatozoa is to mediate the uptake of citrate present at high levels in the seminal fluid for subsequent metabolism in the sperm mitochondria to generate biological energy, thereby supporting sperm motility. In the brain, the transporter is expressed mostly in neurons. As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism. Slc13a5-knockout mice have been generated; these mice do not have any overt phenotype but are resistant to experimentally induced metabolic syndrome. Recently however, loss-of-function mutations in human SLC13A5 have been found to cause severe epilepsy

CITRATE 1.0: Phytoplankton continuous trait-distribution model with one-dimensional physical transport applied to the North Pacific

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B. Chen

2018-02-01

Full Text Available Diversity plays critical roles in ecosystem functioning, but it remains challenging to model phytoplankton diversity in order to better understand those roles and reproduce consistently observed diversity patterns in the ocean. In contrast to the typical approach of resolving distinct species or functional groups, we present a ContInuous TRAiT-basEd phytoplankton model (CITRATE that focuses on macroscopic system properties such as total biomass, mean trait values, and trait variance. This phytoplankton component is embedded within a nitrogen–phytoplankton-zooplankton–detritus–iron model that itself is coupled with a simplified one-dimensional ocean model. Size is used as the master trait for phytoplankton. CITRATE also incorporates trait diffusion for sustaining diversity and simple representations of physiological acclimation, i.e., flexible chlorophyll-to-carbon and nitrogen-to-carbon ratios. We have implemented CITRATE at two contrasting stations in the North Pacific where several years of observational data are available. The model is driven by physical forcing including vertical eddy diffusivity imported from three-dimensional general ocean circulation models (GCMs. One common set of model parameters for the two stations is optimized using the Delayed-Rejection Adaptive Metropolis–Hasting Monte Carlo (DRAM algorithm. The model faithfully reproduces most of the observed patterns and gives robust predictions on phytoplankton mean size and size diversity. CITRATE is suitable for applications in GCMs and constitutes a prototype upon which more sophisticated continuous trait-based models can be developed.

CITRATE 1.0: Phytoplankton continuous trait-distribution model with one-dimensional physical transport applied to the North Pacific

Science.gov (United States)

Chen, Bingzhang; Smith, Sherwood Lan

2018-02-01

Diversity plays critical roles in ecosystem functioning, but it remains challenging to model phytoplankton diversity in order to better understand those roles and reproduce consistently observed diversity patterns in the ocean. In contrast to the typical approach of resolving distinct species or functional groups, we present a ContInuous TRAiT-basEd phytoplankton model (CITRATE) that focuses on macroscopic system properties such as total biomass, mean trait values, and trait variance. This phytoplankton component is embedded within a nitrogen-phytoplankton-zooplankton-detritus-iron model that itself is coupled with a simplified one-dimensional ocean model. Size is used as the master trait for phytoplankton. CITRATE also incorporates trait diffusion for sustaining diversity and simple representations of physiological acclimation, i.e., flexible chlorophyll-to-carbon and nitrogen-to-carbon ratios. We have implemented CITRATE at two contrasting stations in the North Pacific where several years of observational data are available. The model is driven by physical forcing including vertical eddy diffusivity imported from three-dimensional general ocean circulation models (GCMs). One common set of model parameters for the two stations is optimized using the Delayed-Rejection Adaptive Metropolis-Hasting Monte Carlo (DRAM) algorithm. The model faithfully reproduces most of the observed patterns and gives robust predictions on phytoplankton mean size and size diversity. CITRATE is suitable for applications in GCMs and constitutes a prototype upon which more sophisticated continuous trait-based models can be developed.

Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.

Science.gov (United States)

Kim, Ji Won; Kim, Subin; Kim, Songwon; Lee, Haerim; Lee, Jie-Oh; Jin, Mi Sun

2017-05-31

The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

Influence of temperature on flavour compound production from citrate by Lactobacillus rhamnosus ATCC 7469.

Science.gov (United States)

De Figueroa, R M; Oliver, G; Benito de Cárdenas, I L

2001-03-01

The citrate utilization by Lactobacillus rhamnosus ATCC 7469 was found to be temperature-dependent. The maximum citrate utilization and incorporation of [1,5-14C]citrate rate were observed at 37 degreesC. At this temperature, maximum citrate lyase activity and specific diacetyl and acetoin production (Y(DA%)) were observed. The high levels of alpha-acetolactate synthase and low levels of diacetyl reductase, acetoin reductase and L-lactate dehydrogenase found at 37 degreesC led to an accumulation of diacetyl and acetoin. Optimum lactic acid production was observed at 45 degreesC, according to the high lactate dehydrogenase activity. The NADH oxidase activity increased with increasing culture temperature from 22 degreesC to 37 degreesC. Thus there are greater quantities of pyruvate available for the production of alpha-acetolactate, diacetyl and aceotin, and less diacetyl and acetoin are reduced.

Tumor affinity of radiolabeled peanut agglutinin compared with that of Ga-67 citrate in animal models

International Nuclear Information System (INIS)

Yokoyama, K.; Aburano, T.; Watanabe, N.; Kawabata, S.; Ishida, H.; Mukai, K.; Tonami, N.; Hisada, K.

1985-01-01

Peanut agglutinin (PNA) binds avidly to the immunodominant group of the tumor associated T antigen. The purpose of this study was to evaluate oncodiagnostic potential of radiolabeled PNA in animal models. PNA was labeled with I-125 or I-131 by Iodogen and also with In-111 by cyclic DTPA anhydride. The biological activity of PNA was examined by a hemaglutination titer with a photometer before and after labeling. Animal tumor models used were Lewis Lung Cancer(LLC), B-16 Melanotic Melanoma(MM), Yoshida Sarcoma(YS), Ehrlich Ascites Tumor(EAT and Hepatoma AH109A(HAH). Inflammatory tissue induced by turpentine oil was used as an abscess model. Serial scintigraphic images were obtained following IV injections of 100 μCi of I-131 or In-111-DTPA-PNA. The tumor affinity of Ga-67 citrate was studied to compare that of radiolabeled PNA. Tissue biodistribution was studied in EAT bearing mice. All of these tumor models except HAH were clearly visible by radiolabeled PNA without subtraction techniques. In the models of LLC and EAT, PNA showed the better accumulation into the tumor tissue than Ga-67 citrate. In YS and MM, PNA represented almost the same accumulation as Ga-67 citrate. The localization of PNA into abscess tissue wasn't found although Ga-67 citrate markedly accumulated into abscess tissue as well as tumor tissue. The clearance of PNA from tumor was slower than those from any other organs. Tumor to muscle ratio was 5.1 at 48hrs. and tumor to blood ratio increased with time to 2.3 at 96hrs. These results suggested that radiolabeled PNA may have a potential in the detection of tumor

Cumulative response curves to enhance interpretation of treatment differences on the Self-Esteem And Relationship questionnaire for men with erectile dysfunction.

Science.gov (United States)

Cappelleri, Joseph C; Zou, Kelly H; Bushmakin, Andrew G; Carlsson, Martin O; Symonds, Tara

2013-03-01

What's known on the subject? and What does the study add? Studies on erectile dysfunction (ED) therapies rely heavily on patient-reported outcomes (PROs) to measure efficacy on treatment response. A challenge when using PROs is interpretation of the clinical meaning of changes in scores. A responder analysis provides a threshold score to indicate whether a change in score qualifies a patient as a responder. However, a major consideration with responder analysis is the sometimes arbitrary nature of defining the threshold for a response. By contrast, cumulative response curves (CRCs) display patient response rates over a continuum of possible thresholds, thus eliminating problems with a rigid threshold definition, allowing for a variety of response thresholds to be examined simultaneously, and encompassing all data. With respect to the psychosocial factors addressed in the Self-Esteem And Relationship questionnaire in ED, CRCs clearly, distinctly, and meaningfully highlighted the favourable profiles of responses to sildenafil compared with placebo. CRCs for PROs in urology can provide a clear, transparent and meaningful visual depiction of efficacy data that can supplement and complement other analyses. To use cumulative response curves (CRCs) to enrich meaning and enhance interpretation of scores on the Self-Esteem And Relationship (SEAR) questionnaire with respect to treatment differences for men with erectile dysfunction (ED). This post hoc analysis used data from all patients who took at least one dose of study drug and had at least one post-baseline efficacy evaluation in a previously published 12-week, multicentre, randomized, double-blind, placebo-controlled trial of flexible-dose (25, 50, or 100 mg) sildenafil citrate (Viagra) in adult men with ED who had scored ≤ 75 out of 100 on the Self-Esteem subscale of the SEAR questionnaire. CRCs were used on the numeric change in transformed SEAR scores from baseline to end-of-study for each SEAR component. The

Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase.

Science.gov (United States)

Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

2017-06-01

The protein methylome in mammalian mitochondria has been little studied until recently. Here, we describe that lysine-368 of human citrate synthase is methylated and that the modifying enzyme, localized in the mitochondrial matrix, is methyltransferase-like protein 12 (METTL12), a member of the family of 7β-strand methyltransferases. Lysine-368 is near the active site of citrate synthase, but removal of methylation has no effect on its activity. In mitochondria, it is possible that some or all of the enzymes of the citric acid cycle, including citrate synthase, are organized in metabolons to facilitate the channelling of substrates between participating enzymes. Thus, possible roles for the methylation of Lys-368 are in controlling substrate channelling itself, or in influencing protein-protein interactions in the metabolon. © 2017 The Authors FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

DEFF Research Database (Denmark)

Pels, A; Kenny, L C; Alfirevic, Z

2017-01-01

randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants......BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate...... Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre...

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.

Corrosion behavior of Ti and TI6Al4V in citrate buffers containing fluoride ions

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Anelise Marlene Schmidt

2010-03-01

Full Text Available The effect of fluoride ions concentration on the electrochemical behavior of Ti grade 2 and Ti6Al4V in citrate buffers was studied. Open circuit potential (OCP measurements and voltammetric studies of the samples in the fluoride containing citrate buffers revealed a dissolution process when the pH falls below 5.0 and the NaF content is higher than 0.01 M. However, in citrate pH 7.6 the materials showed a passive behavior even in 0.1 M NaF. Some micrographs of Ti grade 2 obtained after longer immersion times in citrate pH 5.0 with 0.01 M NaF showed a surface attack. EIS (Electrochemical Impedance Sprectroscopy data obtained at the OCP revealed that the film resistance decreases when the immersion time is increased in pH 5.0 containing 0.1 M NaF. In the citrate pH 7.6 the EIS data indicated a two-layer model of an oxide film consisting of a more compact inner layer and a porous outer layer. On the other hand, the EIS results in citrate pH 4.0 change significantly when the fluoride ions concentration increases from 0.01 to 0.05 M. The electrochemical data revealed that the corrosion behavior of Ti grade 2 and Ti6Al4V in the citrate buffers depends on the pH, the fluoride content and the exposure time.

PDE5 Inhibitors-Loaded Nanovesicles: Physico-Chemical Properties and In Vitro Antiproliferative Activity

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Roberta F. De Rose

2016-05-01

Full Text Available Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP. Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase. Nanoliposomes, made up of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine monohydrate (DPPC, cholesterol, and N-(carbonyl-methoxypolyethylene glycol-2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-mPEG2000 (6:3:1 molar ratio, were characterized by a mean diameter of ~100 nm, a very low polydispersity index (~0.1 and a negative surface charge. The drugs did not influence the physico-chemical properties of the systems and were efficiently retained in the colloidal structure. By using cell count and MTT assay, we found a significant reduction of the viability in both cell lines following 24 h treatment with both nanoliposomal-encapsulated drugs, notably greater than the effect of the free drugs. Our findings demonstrate that nanoliposomes increase the antiproliferative activity of phosphodiesterase-5 inhibitors, providing a useful novel formulation for the treatment of thyroid carcinoma.

[Perinatal clomiphene citrate treatment changes sexual orientations of male mice].

Science.gov (United States)

He, Feng-Qin; Zhang, Heng-Rui

2013-10-01

Perinatal period and adolescence are critical for brain development, which is the biological basis of an individual's sexual orientation and sexual behavior. In this study, animals were divided into two groups and their sexual orientations were observed: one group experienced drug treatments during the perinatal period, and the other group was castrated at puberty. The results showed that estradiol treatment had no effect on mature male offspring's sexual orientations, but 9 days and 14 days of clomiphene citrate treatment significantly increased the chance of homosexuality and effeminized behavior. In addition, the sexual orientation of mature normal male offspring, which were castrated when they were 21 days old,was not significant different from the control animals. These findings suggest that the inhibition of perinatal estrogen activities could suppress individual male-typical responses, enhance female-typical responses and induce homosexual orientations. Moreover, the masculinizing effects of estrogen were more obvious during perinatal period than adolescence.

Renal Localization of 67Ga Citrate in Noninfectious Nephritis

International Nuclear Information System (INIS)

Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu

1992-01-01

67 Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of 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 67 Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of 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 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 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 67 Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, 67 Ga citrate scan is useful in predicting renal involvement.

The structure and binding mode of citrate in the stabilization of gold nanoparticles

KAUST Repository

Al-Johani, Hind; Abou-Hamad, Edy; Jedidi, Abdesslem; Widdifield, Cory M.; Viger-Gravel, Jasmine; Sangaru, Shiv; Gajan, David; Anjum, Dalaver H.; Ould-Chikh, Samy; Hedhili, Mohamed N.; Gurinov, Andrei; Kelly, Michael J.; El Eter, Mohamad; Cavallo, Luigi; Basset, Jean-Marie; Basset, Jean-Marie

2017-01-01

Elucidating the binding mode of carboxylate-containing ligands to gold nanoparticles (AuNPs) is crucial to understand their stabilizing role. A detailed picture of the three-dimensional structure and coordination modes of citrate, acetate, succinate and glutarate to AuNPs is obtained by 13C and 23Na solid-state NMR in combination with computational modelling and electron microscopy. The binding between the carboxylates and the AuNP surface is found to occur in three different modes. These three modes are simultaneously present at low citrate to gold ratios, while a monocarboxylate monodentate (1κO1) mode is favoured at high citrate:gold ratios. The surface AuNP atoms are found to be predominantly in the zero oxidation state after citrate coordination, although trace amounts of Auδ+ are observed. 23Na NMR experiments show that Na+ ions are present near the gold surface, indicating that carboxylate binding occurs as a 2e− L-type interaction for each oxygen atom involved. This approach has broad potential to probe the binding of a variety of ligands to metal nanoparticles.

The structure and binding mode of citrate in the stabilization of gold nanoparticles

KAUST Repository

Al-Johani, Hind

2017-03-27

Elucidating the binding mode of carboxylate-containing ligands to gold nanoparticles (AuNPs) is crucial to understand their stabilizing role. A detailed picture of the three-dimensional structure and coordination modes of citrate, acetate, succinate and glutarate to AuNPs is obtained by 13C and 23Na solid-state NMR in combination with computational modelling and electron microscopy. The binding between the carboxylates and the AuNP surface is found to occur in three different modes. These three modes are simultaneously present at low citrate to gold ratios, while a monocarboxylate monodentate (1κO1) mode is favoured at high citrate:gold ratios. The surface AuNP atoms are found to be predominantly in the zero oxidation state after citrate coordination, although trace amounts of Auδ+ are observed. 23Na NMR experiments show that Na+ ions are present near the gold surface, indicating that carboxylate binding occurs as a 2e− L-type interaction for each oxygen atom involved. This approach has broad potential to probe the binding of a variety of ligands to metal nanoparticles.

Citrate effects on amorphous calcium carbonate (ACC) structure, stability, and crystallization

DEFF Research Database (Denmark)

Tobler, Dominique Jeanette; Rodriguez Blanco, Juan Diego; Dideriksen, Knud

2015-01-01

Understanding the role of citrate in the crystallization kinetics of amorphous calcium carbonate (ACC) is essential to explain the formation mechanisms, stabilities, surface properties, and morphologies of CaCO3 biominerals. It also contributes to deeper insight into fluid-mineral inte......Understanding the role of citrate in the crystallization kinetics of amorphous calcium carbonate (ACC) is essential to explain the formation mechanisms, stabilities, surface properties, and morphologies of CaCO3 biominerals. It also contributes to deeper insight into fluid...

A study of 153Sm-citrate-hydroxyapatite synovectomy in knee synovitis with rheumatoid arthritis

International Nuclear Information System (INIS)

Fan Yanggang; Li Guohua; Yao Guozhong; Zhang Qingcheng; Li Guangming

2006-01-01

Objective: To investigate the efficacy and safety of 153 Sm-citrate-hydroxyapatite (HA) synovectomy in knee synovitis with rheumatoid arthritis (RA). Methods: In 43 RA patients ineffective to routine anti-rheumatic drugs (DMMARDs) therapy, radiation synovectomy was performed by 153 Sm-citrate-HA in 67 joints and its efficacy and safety were evaluated. Results: Radioactivity was evenly distributed as observed by gamma camera after injection. In 8 cases leakage of radioactivity was detected after 24 h, and accounted to 153 Sm-citrate-HA synovectomy is effective after short-term and medium-term follow-up and it is a safe procedure. (authors)

77 FR 47370 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Intent To Rescind...

Science.gov (United States)

2012-08-08

... DEPARTMENT OF COMMERCE International Trade Administration [C-570-938] Citric Acid and Certain... citric acid and certain citrate salts from the People's Republic of China.\\1\\ On May 31, 2012, we... order includes all grades and granulation sizes of citric acid, sodium citrate, and potassium citrate in...

Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment.

Science.gov (United States)

Eisner, Brian H; Asplin, John R; Goldfarb, David S; Ahmad, Ardalanejaz; Stoller, Marshall L

2010-06-01

Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH. Copyright

Cupric citrate as growth promoter for broiler chickens in different rearing stages

Energy Technology Data Exchange (ETDEWEB)

Brainer, Monica Maria de Almeida [EAFCe, Ceres, GO (Brazil). Dept. de Zootecnia; Menten, Jose Fernando Machado; Vale, Marcos Martinez do; Morais, Sonia Cristina Daroz de [Universidade de Sao Paulo (USP), Piracicaba, SP (Brazil). Escola Superior de Agricultura Luiz de Queiroz (ESALQ). Dept. de Zootecnia]. E-mail: jfmmente@esalq.usp.br

2003-07-01

Feeding cupric citrate as alternative to cupric sulfate to broilers has been suggested in the literature. Day-old male broiler chicks (1,200) were used in an experiment to evaluate the efficacy of cupric citrate supplementation (75 mg Cu kg-1) during the 1-21, 22-42 or 1-42 d periods in comparison to an unsupplemented diet and a diet supplemented with cupric sulfate (200 mg Cu kg-1, 1-42 d). A randomized block design was used, with five treatments, six replicates and 40 birds per pen. The diets, based on corn and soybean meal, and water were offered ad libitum during the 42-day experimental period. Over the entire period, there was no effect of copper supplementation (P > 0.05) on bird live weight, weight gain, feed intake, feed conversion and mortality. Cupric citrate supplementation on the 22-42 d period resulted in worse feed conversion as compared to broilers receiving cupric sulfate (2.014 vs. 1.967, P < 0.05). Copper residues in the litter were reduced when broilers were fed cupric citrate, as compared to cupric sulfate (P < 0.01). The absence of response to copper supplementation can be attributed to the environmental and sanitary rearing conditions.

Cupric citrate as growth promoter for broiler chickens in different rearing stages

International Nuclear Information System (INIS)

Brainer, Monica Maria de Almeida; Menten, Jose Fernando Machado; Vale, Marcos Martinez do; Morais, Sonia Cristina Daroz de

2003-01-01

Feeding cupric citrate as alternative to cupric sulfate to broilers has been suggested in the literature. Day-old male broiler chicks (1,200) were used in an experiment to evaluate the efficacy of cupric citrate supplementation (75 mg Cu kg-1) during the 1-21, 22-42 or 1-42 d periods in comparison to an unsupplemented diet and a diet supplemented with cupric sulfate (200 mg Cu kg-1, 1-42 d). A randomized block design was used, with five treatments, six replicates and 40 birds per pen. The diets, based on corn and soybean meal, and water were offered ad libitum during the 42-day experimental period. Over the entire period, there was no effect of copper supplementation (P > 0.05) on bird live weight, weight gain, feed intake, feed conversion and mortality. Cupric citrate supplementation on the 22-42 d period resulted in worse feed conversion as compared to broilers receiving cupric sulfate (2.014 vs. 1.967, P < 0.05). Copper residues in the litter were reduced when broilers were fed cupric citrate, as compared to cupric sulfate (P < 0.01). The absence of response to copper supplementation can be attributed to the environmental and sanitary rearing conditions

Functional analysis of the citrate activator CitO from Enterococcus faecalis implicates a divalent metal in ligand binding

Directory of Open Access Journals (Sweden)

Victor S. Blancato

2016-02-01

Full Text Available The regulator of citrate metabolism, CitO, from Enterococcus faecalis belongs to the FCD family within the GntR superfamily. In the presence of citrate, CitO binds to cis-acting sequences located upstream of the cit promoters inducing the expression of genes involved in citrate utilization. The quantification of the molecular binding affinities, performed by isothermal titration calorimetry (ITC, indicated that CitO has a high affinity for citrate (KD= 1.2±0.2 µM, while it did not recognize other metabolic intermediates. Based on a structural model of CitO where a putative small molecule and a metal binding site were identified, it was hypothesized that the metal ion is required for citrate binding. In agreement with this model, citrate binding to CitO sharply decreased when the protein was incubated with EDTA. This effect was reverted by the addition of Ni2+, and Zn2+ to a lesser extent. Structure-based site-directed mutagenesis was conducted and it was found that changes to alanine in residues Arg97 and His191 resulted in decreased binding affinities for citrate, as determined by EMSA and ITC. Further assays using lacZ fusions confirmed that these residues in CitO are involved in sensing citrate in vivo. These results indicate that the molecular modifications induced by a ligand and a metal binding in the C-terminal domain of CitO are required for optimal DNA binding activity, and consequently, transcriptional activation.

Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and live birth in anovulatory women: systematic review and meta-analysis

NARCIS (Netherlands)

Gadalla, M. A.; Huang, S.; Wang, R.; Norman, R. J.; Abdullah, S. A.; El Saman, A. M.; Ismail, A. M.; van Wely, M.; Mol, B. W. J.

2018-01-01

To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane

Studies on ligand exchange reaction of functionalized mercaptothiadiazole compounds onto citrate capped gold nanoparticles

International Nuclear Information System (INIS)

Kalimuthu, Palraj; John, S. Abraham

2010-01-01

Mercaptothiadiazole ligands functionalized with thiol (2,5-dimercapto-1,3,4-thiadiazole (DMT)) and methyl (5-methyl-2-mercapto-1,3,4-thiadiazole (MMT)) groups capped onto citrate capped gold nanoparticles (C-AuNPs) by ligand exchange reaction was investigated by UV-vis spectroscopy, FT-IR spectroscopy and transmission electron microscopy (TEM) techniques. The surface plasmon resonance band at 522 nm for C-AuNPs was shifted to 530 nm after capping with DMT whereas an additional band was observed at 630 nm due to aggregation in addition to a shift in the band at 522 nm after capping of MMT onto C-AuNPs. Thus, capping of DMT onto C-AuNPs leads to the formation of stable AuNPs while capping of MMT leads to the formation of unstable AuNPs. FT-IR studies show that the citrate ions were completely replaced by both DMT and MMT ligands from the AuNPs. TEM images indicate that the size and shape of the AuNPs remain same after capping of these ligands.

Intense muscle uptake of Ga-67 citrate and Tc-99m MDP in a patient with aplastic anemia

International Nuclear Information System (INIS)

Batte, W.G. Jr.; Yeh, S.D.; Rosenblum, M.K.; Larson, S.M.

1991-01-01

An unusual distribution of Tc-99m MDP and Ga-67 citrate in several muscle groups is described in a 14-year-old boy with aplastic anemia and normal renal function at the time of imaging. Although the patient did not develop musculo-skeletal signs or symptoms, a subsequent autopsy revealed widespread muscle calcification

Myositis ossificans with Ga-67 citrate positivity

International Nuclear Information System (INIS)

Moreno, A.J.; Yedinak, M.A.; Spicer, M.J.; Turnbull, G.L.; Byrd, B.F.; Brown, T.J.

1985-01-01

A 16 year-old boy presented with a firm mass within the left thigh. Ga-67 citrate and bone scintigraphy revealed soft tissue radiotracer accumulation within the mass lesion. Radiographs and xerography of the left thigh revealed calcification within the soft tissue mass typical of myositis ossificans. The patient's clinical course was uneventful

Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS

DEFF Research Database (Denmark)

Westergaard, Niels; Waagepetersen, Helle S; Belhage, Bo

2017-01-01

Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and 13C-NMR to investigate...... metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles...

Results of a Community-based, Randomized Study Comparing a Clear Liquid Diet With a Low-residue Diet Using a Magnesium Citrate Preparation for Screening and Surveillance Colonoscopies.

Science.gov (United States)

Thukral, Chandrashekhar; Tewani, Sumeet K; Lake, Adam J; Shiels, Aaron J; Geissler, Kathy; Popejoy, Sara; Stafford, Megan; Vicari, Joseph J

2017-11-03

Current bowel preparations for colonoscopy include a clear liquid diet (CLD) along with consumption of a laxative. This dietary restriction along with large volume bowel preparations are barriers to compliance and willingness among patients in scheduling screening examinations. The aim of our study was to compare the efficacy and tolerability of a low-volume split dose magnesium citrate bowel preparation in patients on a low-residue diet (LRD) with those on a CLD. In this single center, single blinded, randomized controlled trial, patients scheduled for outpatient colonoscopies were assigned to either a CLD or a LRD 1 day before the examination. Both groups received a split dose magnesium citrate preparation. The quality of the preparation was rated using the Boston Bowel Preparation Scale (BBPS). Patient satisfaction and side effects were evaluated using a questionnaire. We were unable to detect a significant difference in the BBPS scores between the LRD and CLD groups (P=0.581). A significantly higher percentage of patients in the LRD group rated the diet as easy compared with the CLD group (PCLD group (PCLD in patients using a magnesium citrate bowel preparation for screening and surveillance colonoscopies. Patient satisfaction scores were higher with a LRD compared with a CLD. We believe the LRD should be the recommended diet in patients using a standard bowel preparation for screening and surveillance colonoscopy.

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas

International Nuclear Information System (INIS)

Ziegels, P.; Nocaudie, M.; Huglo, D.; Deveaux, M.; Detourmignies, L.; Wattel, E.; Marchandise, X.

1995-01-01

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxy-isobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkin's disease and non-Hodgkin's lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of 99m Tc-MIBI and 72 h after injection of 185 MBq of 67 Ga citrate. The overall sensitivity of 99m Tc-MIBI and 67 Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with 99m Tc-MIBI and 53% with 67 Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for 99m Tc-MIBI and 2 for 67 Ga citrate. At present, 99m Tc-MIBI cannot replace 67 Ga citrate in the assessment of lymphomas. (orig.)

Quality of drug information on the World Wide Web and strategies to improve pages with poor information quality. An intervention study on pages about sildenafil.

Science.gov (United States)

Martin-Facklam, Meret; Kostrzewa, Michael; Martin, Peter; Haefeli, Walter E

2004-01-01

The generally poor quality of health information on the world wide web (WWW) has caused preventable adverse outcomes. Quality management of information on the internet is therefore critical given its widespread use. In order to develop strategies for the safe use of drugs, we scored general and content quality of pages about sildenafil and performed an intervention to improve their quality. The internet was searched with Yahoo and AltaVista for pages about sildenafil and 303 pages were included. For assessment of content quality a score based on accuracy and completeness of essential drug information was assigned. For assessment of general quality, four criteria were evaluated and their association with high content quality was determined by multivariate logistic regression analysis. The pages were randomly allocated to either control or intervention group. Evaluation took place before, as well as 7 and 22 weeks after an intervention which consisted of two letters with individualized feedback information on the respective page which were sent electronically to the address mentioned on the page. Providing references to scientific publications or prescribing information was significantly associated with high content quality (odds ratio: 8.2, 95% CI 3.2, 20.5). The intervention had no influence on general or content quality. To prevent adverse outcomes caused by misinformation on the WWW individualized feedback to the address mentioned on the page was ineffective. It is currently probably the most straight-forward approach to inform lay persons about indicators of high information quality, i.e. the provision of references.

Flexible biodegradable citrate-based polymeric step-index optical fiber.

Science.gov (United States)

Shan, Dingying; Zhang, Chenji; Kalaba, Surge; Mehta, Nikhil; Kim, Gloria B; Liu, Zhiwen; Yang, Jian

2017-10-01

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ion exchange behaviour of citrate and EDTA anions on strong and weak base organic ion exchangers

International Nuclear Information System (INIS)

Askarieh, M.M.; White, D.A.

1988-01-01

The exchange of citrate and EDTA ions with two strong base and two weak base exchangers is considered. Citrate and EDTA analysis for this work was performed using a colorimetric method developed here. The ions most selectively exchanged on the resins are H 2 cit - and H 2 EDTA 2- , though EDTA is generally less strongly sorbed on strong base resins. In contact with weak base resins, deprotonation of the resin occurs during ion exchange with a noticeable drop in solution pH. Although EDTA sorption can be reversed by nitric acid, citrate ions are significantly held on the resin at low pH. The exchange of citrate can be made reversible if bicarbonate is added to the initial solutions. Alkaline regeneration of exchangers loaded with EDTA proved to be very effective. (author)

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

Science.gov (United States)

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

Sodium citrate blood contamination by K2 -ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing.

Science.gov (United States)

Lima-Oliveira, G; Salvagno, G L; Danese, E; Favaloro, E J; Guidi, G C; Lippi, G

2015-06-01

The potential cross-contamination of additives between primary blood tubes is a well-known problem during sample collection. The aim of this study was to assess the impact of citrated blood contamination with different amounts of dipotassium ethylenediaminetetraacetic (K2 EDTA blood) on activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. Blood was collected from 15 ostensibly healthy volunteers into four 0.109 m citrate blood tubes followed by one K2 EDTA blood tube. The citrate tubes of each subject were pooled and divided in five aliquots. The whole blood of the K2 EDTA tube was then added in scalar amounts to autologous citrated blood aliquots, to obtain K2 EDTA contamination ranging from 0% to 43%, and thus mimic potential pre-analytical contamination. A statistically and clinically significant prolongation was observed for both APTT and PT between 29% and 43% K2 EDTA contamination, whereas the decrease of fibrinogen values became statistically and clinically significant at 43% K2 EDTA contamination. The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management. © 2014 John Wiley & Sons Ltd.

Biodegradation of metal citrate complexes and implications for toxic-metal mobility

International Nuclear Information System (INIS)

Francis, A.J.; Dodge, C.J.; Gillow, J.B.

1992-01-01

The presence of synthetic and naturally occurring chelating agents in nuclear and toxic-metal wastes is a major concern because of their potential to enhance mobilization of metal ions away from the disposal sites. Of particular interest is citric acid, which is present in low-level and transuranic radioactive wastes and in domestic and industrial wastes (as washing fluids, for instance), as well as being found naturally. Citrate ions form multidentate, stable complexes with a variety of toxic metals and radionuclides; but biodegradation of these complexes, precipitating the metal ions as insoluble hydroxides, oxides or other salts, may retard migration. Here we report a study of the biodegradation of citrate complexes of Ca, Fe(II), Fe(III), Cd, Cu, Ni, Pb and U. Several of these complexes were not readily degraded by bacteria, and the biodegradability depended on the chemical nature of the complex, not on the toxicity of the metal to the bacteria. This resistance to biodegradation implies that citrate complexation may play an important part in migration of these hazardous wastes. (author)

Highly selective and sensitive macrocycle-based dinuclear foldamer for fluorometric and colorimetric sensing of citrate in water.

Science.gov (United States)

Rhaman, Md Mhahabubur; Hasan, Mohammad H; Alamgir, Azmain; Xu, Lihua; Powell, Douglas R; Wong, Bryan M; Tandon, Ritesh; Hossain, Md Alamgir

2018-01-10

The selective detection of citrate anions is essential for various biological functions in living systems. A quantitative assessment of citrate is required for the diagnosis of various diseases in the human body; however, it is extremely challenging to develop efficient fluorescence and color-detecting molecular probes for sensing citrate in water. Herein, we report a macrocycle-based dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for anion binding by fluorescence and colorimetric techniques in water at neutral pH. Results from the fluorescence titrations reveal that the 1·EY ensemble strongly binds citrate anions, showing remarkable selectivity over a wide range of inorganic and carboxylate anions. The addition of citrate anions to the 1·EY adduct led to a large fluorescence enhancement, displaying a detectable color change under both visible and UV light in water up to 2 μmol. The biocompatibility of 1·EY as an intracellular carrier in a biological system was evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent cell viability. The strong binding properties of the ensemble allow it to be used as a highly sensitive, detective probe for biologically relevant citrate anions in various applications.

Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

Science.gov (United States)

Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

2017-02-01

Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

In men with erectile dysfunction, satisfaction with quality of erections correlates with erection hardness, treatment satisfaction, and emotional well-being.

Science.gov (United States)

Kaminetsky, Jed C; Depko, Andrzej J; Ströberg, Peter; Buvat, Jacques; Tseng, Li-Jung; Stecher, Vera J

2009-03-01

The validated Quality of Erection Questionnaire (QEQ) evaluates satisfaction with erection quality. To collate QEQ data, including correlations between QEQ outcomes and outcomes assessing emotional well-being, treatment satisfaction, and erection hardness after sildenafil citrate treatment. In four trials, men older than 18 years and with erectile dysfunction, a stable sexual partner, and no recent phosphodiesterase type 5 inhibitor use were randomized to double-blind flexible-dose sildenafil or placebo (1:1 ratio) for 6 or 10 weeks (two trials), fixed-dose 50 mg, 100 mg, and placebo (1:1:1 ratio) for 8 weeks (one trial), and 50 mg and 100 mg (1:1 ratio) for 4 weeks after 4 weeks of single-blind sildenafil 50 mg. Exclusion criteria included recent significant cardiovascular disease, use of nitrates, nitric oxide donors, cytochrome P450 3A4 inhibitors, or other erectile dysfunction treatment, and sildenafil hypersensitivity or previous severe or serious treatment-related adverse event. Scores on the QEQ, QEQ Question 5 (satisfaction with erection hardness), the Self-Esteem and Relationship Questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction; the percentage of occasions with Erection Hardness Score 3 (EHS 3, hard enough for penetration but not completely hard) and/or EHS 4 (completely hard and fully rigid); and Pearson correlation coefficients. 1,296 men (18-80 years) were randomized. Except for the percentage of occasions with EHS 3, all outcomes improved in men treated with sildenafil and correlated positively with the change in QEQ scores in all trials. Satisfaction with the quality of erections, which is easily monitored with the QEQ, correlated positively with measures of emotional well-being and treatment satisfaction and with the change in percentage of erections that were completely hard and fully rigid, but not with the change in percentage of erections that were hard enough for penetration but not completely hard.

21 CFR 172.370 - Iron-choline citrate complex.

Science.gov (United States)

2010-04-01

....370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline...

Photometric determination of the composition and dissociation constants of niobium (5) citrate complexes

International Nuclear Information System (INIS)

Grigor'eva, V.V.; Golubeva, I.V.

1979-01-01

Niobium (5) citrate complexes in aqueous solution (pH 1-6) are investigated. To determine the complexes composition the metal-indicator method has been applied. Experimental data have been treated by the method of equilibrium shift using somewhat changed variant of the metal-indicator method. The complex ion charge in the solution has been determined by the ion-exchange method. Dissociation constants of citrate complexes have been determined photometrically

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.

The role of tannic acid and sodium citrate in the synthesis of silver nanoparticles

Science.gov (United States)

Ranoszek-Soliwoda, Katarzyna; Tomaszewska, Emilia; Socha, Ewelina; Krzyczmonik, Pawel; Ignaczak, Anna; Orlowski, Piotr; Krzyzowska, Małgorzata; Celichowski, Grzegorz; Grobelny, Jaroslaw

2017-08-01

We describe herein the significance of a sodium citrate and tannic acid mixture in the synthesis of spherical silver nanoparticles (AgNPs). Monodisperse AgNPs were synthesized via reduction of silver nitrate using a mixture of two chemical agents: sodium citrate and tannic acid. The shape, size and size distribution of silver particles were determined by UV-Vis spectroscopy, dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM). Special attention is given to understanding and experimentally confirming the exact role of the reagents (sodium citrate and tannic acid present in the reaction mixture) in AgNP synthesis. The oxidation and reduction potentials of silver, tannic acid and sodium citrate in their mixtures were determined using cyclic voltammetry. Possible structures of tannic acid and its adducts with citric acid were investigated in aqueous solution by performing computer simulations in conjunction with the semi-empirical PM7 method. The lowest energy structures found from the preliminary conformational search are shown, and the strength of the interaction between the two molecules was calculated. The compounds present on the surface of the AgNPs were identified using FT-IR spectroscopy, and the results are compared with the IR spectrum of tannic acid theoretically calculated using PM6 and PM7 methods. The obtained results clearly indicate that the combined use of sodium citrate and tannic acid produces monodisperse spherical AgNPs, as it allows control of the nucleation, growth and stabilization of the synthesis process. [Figure not available: see fulltext.

A fundamental study on brain scanning with sup(99m)Tc-citrate

International Nuclear Information System (INIS)

Ishii, Katsumi; Kobayashi, Takeshi; Yamada, Nobuaki; Horiike, Shigeharu; Nakazawa, Keiji

1978-01-01

We examined the sup(99m)Tc-citrate obtained by labelling citrate with sup(99m)Tc-pertechnetate using Solcocitran Kit. For our fundamental study--we measured the ratio of labelling by means of paper chromatography. By picking out each organs of each rats we also measured the velocity at which radiopharmaceuticals disappeared in each of their organs, and the distribution of radio-pharmaceuticals in their organs. For our clinical study--we performed brain scanning on 47 patients. The following are the results; Citrate was labelled as much as 99 - 95% into sup(99m)Tc-pertechnetate. The velocity of disappearance in each organ of the rats was quicker than in the case of sup(99m)TcO 4 - . Accumulation in the choroid plexus and salivary gland was not obserbed despite the fact that we did not use KClo 4 , and images of brain tumor were obtainable to a high degree. (author)

Morphology of embryonic liver under the influence of silver and gold citrates on a background of lead intoxication

OpenAIRE

Harets V.I.; Shatorna V.F.; Belska Iu.O.

2016-01-01

Morphological state of embryonic liver under the influence of silver and gold citrates on a background of lead intoxication was studied. We found that  values of the hepatofetal index in the groups Pb+Ag and Pb+Au had significant differences as compared to the group exposed to lead intoxication, but did not differ significantly from the control group and made up 0,086±0,001 and 0,083±0,001, respectively. Value of the relative area of blood vessels in groups Pb+Ag and Pb+Au was 13.08±0.53% and...

The Effect of Polymer Molecular Weight on Citrate Crosslinked ...

African Journals Online (AJOL)

Erah

Purpose: To develop citrate crosslinked chitosan films using chitosan of different molecular weights. (MW) in .... left to stand until trapped air bubbles ... blotted out carefully with filter paper from the .... potential as biodegradable stent coatings. J.

A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

Science.gov (United States)

Wheeler, Karen M; Smith, Ryan P; Kumar, Raj A; Setia, Shaan; Costabile, Raymond A; Kavoussi, Parviz K

2017-04-01

We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Citrate biodegradation. Mid-year status report, [January 1994--June 1994

International Nuclear Information System (INIS)

Francis, A.J.; Dodge, C.J.; Chatterjee, S.; Landry, M.F.

1994-07-01

The Uranium Soils Integrated Demonstration (USID) Program was established to demonstrate advanced technologies for the remediation of uranium contaminated soils. This program, managed by the Fernald Environmental Restoration Management Corporation (FERMCO), focuses on the development and demonstration of new soil remediation processes which are faster, safer, and more economical for use at the Fernald site and throughout the DOE complex for cleanup of similar contaminants. Brookhaven National Laboratory (BNL) has developed a process which uses citric acid to treat contaminated soils and wastes with the subsequent recovery of toxic metals and uranium. Citric acid, a naturally occurring organic chelating agent, forms multidentate stable complexes with the transition metals and actinides, and has been effectively used to extract uranium and other metals from solid wastes via the formation of soluble metal citrate complexes. Further studies have also shown that several of the metal citrate complexes are readily biodegraded by microorganisms. During this process, the metals form a precipitate or become associated with the biomass and are recovered at the end of the biodegradation. Although uranyl citrate is recalcitrant to biodegradation, upon exposure to visible light it undergoes photochemical degradation resulting in the formation of an insoluble, stable polymeric form of uranium

Comparison of pre-filter and post-filter ionised calcium monitoring in continuous veno-venous hemodiafiltration (CVVHD-F with citrate anti-coagulation.

Directory of Open Access Journals (Sweden)

Matthew J Brain

Full Text Available It is widespread practice during citrate anticoagulated renal replacement therapy to monitor circuit ionised calcium (iCa2+ to evaluate the effectiveness of anticoagulation. Whether the optimal site to sample the blood path is before or after the haemofilter is a common question.Using a prospectively collected observational dataset from intensive care patients receiving pre-dilution continuous veno-venous haemodiafiltration (CVVHD-F with integrated citrate anticoagulation we compared paired samples of pre and post filter iCa2+ where the target range was 0.3-0.5 mmol.L-1 as well as concurrently collected arterial iCa2+. Two nested mixed methods linear models were fitted to the data describing post vs pre filter iCa2+, and the relationship of pre, post and arterial samples.An 11 bed general intensive care unit.450 grouped samples from 152 time periods in seven patients on CRRT with citrate anticoagulation.The relationship of post to pre-filter iCa2+ was not 1:1 with post = 0.082 + 0.751 x pre-filter iCa2+ (95% CI intercept: 0.015-0.152, slope 0.558-0.942. Variation was greatest between patients rather than between circuits within the same patient or citrate dose. Compared to arterial iCa2+ there was no significant difference between pre and post-filter sampling sites (F-value 0.047, p = 0.827.These results demonstrate that there is minimal difference between pre and post filter samples for iCa2+ monitoring of circuit anticoagulation in citrate patients relative to the arterial iCa2+ in CVVHD-F however compared to pre-filter sampling, post filter sampling has a flatter response and greater variation.

78 FR 34648 - Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing Duty Administrative...

Science.gov (United States)

2013-06-10

... citric acid and citrate salts from the People's Republic of China for the period January 1, 2011, through... and Certain Citrate Salts from the People's Republic of China: Notice of Countervailing Duty Order, 74... subsidy, i.e., a government-provided financial contribution that gives rise to a benefit to the recipient...

Neptunium speciation (complexation and redox behaviour) in aqueous citrate medium

International Nuclear Information System (INIS)

Bonin, L.; Ansoborlo, E.; Moisy, Ph.

2005-01-01

Full text of publication follows: In the framework of the French Environmental Nuclear Toxicology programme, additional experiments related to the decorporation of actinides are planned. The lack of information on the neptunium behaviour within blood and the inefficiency of therapeutic treatments, led us to study the complexation of this element with basic anions. Within this purpose, the in vitro behaviour of Np IV and Np V in simple media simulating biological media was studied: blood plasma is one of the media of interest and it can be simulated, from a chemical point of view, by an aqueous solution with pH 7.4, containing ions such as citrate (1.6 10 -4 mol/L), lactate (1.5 10 -3 mol/L), CO 3 2- (2.5 10 -2 mol/L), PO 4 3- (1.1 10 -3 mol/L), SO 4 2- (3.3 10 -4 mol/L) and Cl - (9 10 -2 mol/L). This study was more specifically focused on the behaviour of neptunium with citrate ion, which is also a basic ligand to consider when one wishes to study the migration of actinides in the environment, since it exists in significant amounts in the ground due to its production by the plants. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np V with various acid-basic forms of the citrate anion was observed; regarding Np IV , two complexes, with 1:1 and 1:2 stoichiometry, have been respectively observed. The reactivity of Np VI is probably similar to the behaviour of U VI , which is reported in literature to form a complex with a 1:1 stoichiometry with the Cit 3- anion From the quantitative study of these equilibria, it has been possible to determine the values of various equilibrium constants. Concerning the stability of neptunium towards oxido-reduction, it was confirmed that Np VI was very quickly reduced to Np V by the citrate anions, whereas Np IV was stable. In the case of Np V , it was observed that, depending on the pH and the citrate

Bright luminescence of Vibrio fischeri aconitase mutants reveals a connection between citrate and the Gac/Csr regulatory system.

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Septer, Alecia N; Bose, Jeffrey L; Lipzen, Anna; Martin, Joel; Whistler, Cheryl; Stabb, Eric V

2015-01-01

The Gac/Csr regulatory system is conserved throughout the γ-proteobacteria and controls key pathways in central carbon metabolism, quorum sensing, biofilm formation and virulence in important plant and animal pathogens. Here we show that elevated intracellular citrate levels in a Vibrio fischeri aconitase mutant correlate with activation of the Gac/Csr cascade and induction of bright luminescence. Spontaneous or directed mutations in the gene that encodes citrate synthase reversed the bright luminescence of aconitase mutants, eliminated their citrate accumulation and reversed their elevated expression of CsrB. Our data elucidate a correlative link between central metabolic and regulatory pathways, and they suggest that the Gac system senses a blockage at the aconitase step of the tricarboxylic acid cycle, either through elevated citrate levels or a secondary metabolic effect of citrate accumulation, and responds by modulating carbon flow and various functions associated with host colonization, including bioluminescence. © 2014 John Wiley & Sons Ltd.

A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome

Directory of Open Access Journals (Sweden)

Kallol Kumar Roy

2012-01-01

Full Text Available Objectives: To compare the efficacy of letrozole and clomiphene citrate (CC in patients of anovulatory polycystic ovarian syndrome (PCOS with infertility. Materials and Methods: This prospective randomized clinical trial included 204 patients of PCOS. 98 patients (294 cycles received 2.5-5 mg of letrozole; 106 patients (318 cycles received 50-100 mg of CC (both orally from Days 3-7 of menstrual cycle. The treatment continued for three cycles in both the groups. Main outcome measures: ovulation rate, endometrial thickness, and pregnancy rate. Statistical analysis was done using SPSS 13 software. P value less than 0.05 was considered significant. Results: The mean number of dominant follicles in letrozole groups and CC groups was 1.86±0.26 and 1.92±0.17, respectively (P=0.126. Number of ovulatory cycle in letrozole group was 196 (66.6% versus 216 (67.9% in CC group (P=0.712. The mean mid-cycle endometrial thickness was 9.1±0.3 mm in letrozole group and 6.3±1.1 in CC group, which was statistically significant (P=0.014. The mean Estradiol [E2] level in clomiphene citrate group was significantly higher in CC group (364.2±71.4 pg/mL than letrozole group (248.2± 42.2 pg/mL. 43 patients from the letrozole group (43.8% and 28 patients from the CC group (26.4% became pregnant. Conclusion: Letrozole and CC have comparable ovulation rate. The effect of letrozole showed a better endometrial response and pregnancy rate compared with CC.

Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome.

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Roy, K K; Baruah, Jinee; Moda, Nidhi; Kumar, Sunesh

2009-10-01

Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.

Three-dimensional models of Mycobacterium tuberculosis proteins Rv1555, Rv1554 and their docking analyses with sildenafil, tadalafil, vardenafil drugs, suggest interference with quinol binding likely to affect protein's function.