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1

Photolysis of the novel inotropes EMD 57033 and EMD 57439: evidence that Ca2+ sensitization and phosphodiesterase inhibition depend upon the same enantiomeric site.  

UK PubMed Central (United Kingdom)

1. We studied the effects of flash photolysis on the novel enantiomeric cardiac inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III inhibitor) in rat isolated ventricular...Full Text Available

1996-08-01

2

Nature of plant stimulators in the production of Acetobacter xylinum ({open_quotes}Tea fungas{close_quotes}) biofilm used in skin therapy  

Energy Technology Data Exchange (ETDEWEB)

Caffeine and related xanthines were identified as potent stimulators for the bacterial cellulose production in A. xylinum. These compounds are present in several plants whose infusions are useful as culture-medium supplements for this acetobacterium. The proposed target for these native purine-like inhibitory substances is the novel diguanyl nucleotide phosphodiesterase(s) that participates in the bacterial cellulogenic complex.

1991-12-31

3

Tadalafil in the treatment of erectile dysfunction  

UK PubMed Central (United Kingdom)

The treatment for erectile dysfunction (ED) was revolutionized with the development of phosphodiesterase type 5 (PDE5) inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis,...Full Text Available

2008-12-01

4

Stochastic simulation of the transducin GTPase cycle.  

UK PubMed Central (United Kingdom)

On rod disc membranes, single photoactivated rhodopsin (R*) molecules catalytically activate many copies of the G-protein (Gt), which in turn binds and activates the effector (phosphodiesterase). We...Full Text Available

1996-12-01

5

Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models  

UK PubMed Central (United Kingdom)

BackgroundThough long known to affect smooth muscle biology, recent studies indicate that phosphodiesterase 5 (PDE5) is also expressed in myocardium. Recognizing that the regulation...Full Text Available

6

Acute change in the cyclic AMP content of rat mammary acini in vitro. Influence of physiological and pharmacological agents.  

UK PubMed Central (United Kingdom)

The cyclic AMP content of acini, freshly prepared from mammary tissue of lactating rats, was measured during incubation in vitro. Neither adrenergic agonists nor cyclic AMP phosphodiesterase inhibitors...Full Text Available

1985-08-15

7

A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy  

UK PubMed Central (United Kingdom)

Selective phosphodiesterase type 5 inhibitors (PDE5Is) have revolutionized the treatment of erectile dysfunction (ED) in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in...Full Text Available

8

Submitochondrial distribution of cAMP in its incubation with rat liver mitochondria  

Energy Technology Data Exchange (ETDEWEB)

When labeled cAMP is incubated with isolated mitochondria from rat liver, it penetrates not only through the outer membrane of the mitochondria but also into the mitoplasts, where it is accumulated chiefly in the matrix. Damage to the mitochondrial membrane by freezing-thawing promotes not an influx but an efflux of cAMP out of the mitoplasts. A substantial part of the labeled nucleotide in all the investigated submitochondrial fractions was identified as intact cAMP by the method of thin-layer chromatography. The transport of cAMP into the mitochondria can explain the activation of their functions by the hormones that activate cytoplasmic adenylate cyclase and by extramitochondrial (cytosol) cAMP, as well as the presence of cAMP-dependent protein kinase and cAMP-phosphodiesterase in the mitochondria.

1986-03-20

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A high-performance liquid chromatography-based radiometric assay for sucrose-phosphate synthase and other UDP-glucose requiring enzymes  

Energy Technology Data Exchange (ETDEWEB)

A method for product analysis that eliminates a problematic step in the radiometric sucrose-phosphate synthase assay is described. The method uses chromatography on a boronate-derivatized high-performance liquid chromatography column to separate the labeled product, (14C)sucrose phosphate, from unreacted uridine 5{prime}-diphosphate-(14C)glucose (UDP-Glc). Direct separation of these compounds eliminates the need for treatment of the reaction mixtures with alkaline phosphatase, thereby avoiding the problem of high background caused by contaminating phosphodiesterase activity in alkaline phosphatase preparations. The method presented in this paper can be applied to many UDP-Glc requiring enzymes; here the authors show its use for determining the activities of sucrose-phosphate synthase, sucrose synthase, and uridine diphosphate-glucose pyrophosphorylase in plant extracts.

1991-05-01

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One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease  

Scientific Electronic Library Online (English)

Abstract in english We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected (more) to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P

2005-02-01

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Long-term Retinal Function and Structure Rescue Using Capsid Mutant AAV8 Vector in the rd10 Mouse, a Model of Recessive Retinitis Pigmentosa  

British Library Electronic Table of Contents (United Kingdom)

The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the ? subunit of rod cGMP-phosphodiesterase (PDE?). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDE? was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed tha...

2011-01-01

12

Local therapies to heal the penis: fact or fiction?  

Science.gov (United States)

Penile rehabilitation has been an area of intense study and debate over the last decade. Interest in this topic was stimulated by the observation that erectile dysfunction remained a significant problem after radical prostatectomy despite meticulous nerve-sparing technique. Smooth muscle alterations and fibrotic changes in the penis were identified as the underlying causes of penile atrophy, veno-occlusive dysfunction, and Peyronie's-like changes that were observed after surgery. Initial observations that intracavernous injection therapies used on a regular basis postoperatively resulted in improvements in the return of spontaneous erectile function led to the development of penile rehabilitation protocols. Chronic dosing of oral type V phosphodiesterase inhibitors is now commonly used by urologists after radical prostatectomy despite a lack of convincing evidence from randomized, placebo-controlled clinical trials. Use of local therapies to heal the penis may have ...

2008-11-20

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Two and 8-azido photoaffinity probes. 1. Enzymatic synthesis, characterization, and biological properties of 2- and 8-azido photoprobes of 2-5A and photolabeling of 2-5A binding proteins  

International Nuclear Information System (INIS)

The 2- and 8-azido trimer 5'-triphosphate photoprobes of 2-5A have been enzymatically synthesized from [#gamma#-"3"2P]2-azidoATP and [#alpha#-"3"2P]8-azidoAPT by 2-5A synthetase from rabbit reticulocyte lysates. Identification and structural determination of the 2- and 8-azido adenylate trimer 5'-triphosphates were accomplished by enzymatic hydrolyses with T2 RNase, snake venom phosphodiesterase, and bacterial alkaline phosphatase. Hydrolysis products were identified by HPLC and PEI-cellulose TLC analyses. The 8-azido photoprobe of 2-5A displaces p_3A_4["3"2P]pCp from RNase L with affinity equivalent to p_3A_3. The 8-azido photoprobe also activates RNase L to hydrolyze poly(U)["3"2P]pCp 50% at 7 /times/ 10/sup /minus/9/ M in core-cellulose assays. The 2- and 8-azido photoprobes and authentic p_3A_3 activate RNase L to cleave 28S and 18S rRNA to specific cleavage products at 10/sup /minus/9/ M in rRNA cleavage assays. The nucleotide binding site(s) of RNase L and/or ...

14

Ophidian envenomation strategies and the role of purines.  

Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to ...

2002-04-01