Unexpected activity of saporins.
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Adenine↗
Biomedical subjects
L Barbieri
Publications and source records attributed to L Barbieri.
Isolation and characterization of two new N-glycosidase type-1 ribosome-inactivating proteins, unrelated in amino-acid sequence, from Petrocoptis species.
Two new N-glycosidase type-1 ribosome-inactivating proteins (RIPs), denoted petroglaucin 1 and petrograndin, respectively, were isolated from the plants Petrocoptis glaucifolia (Lag.) Boiss sp. viscosa (Rothm.) Lainz and Petrocoptis grandiflora Rothm. These new RIPs do not share H2N-terminal amino-acid sequence homology with petroglaucin (now denoted as petroglaucin 2), the only other type-1 RIP to be isolated from P. glaucifolia (Arias et al. (1992) Planta 186, 532-540). Petroglaucin 1 shares amino-acid sequence homology with RIPs from Cucurbitaceae while petroglaucin 2 and petrograndin do so with saporins and dianthin 30 (Caryophyllaceae). The new RIPs strongly inhibited protein synthesis at subnanomolar concentrations in rabbit reticulocyte lysates and other eukaryotic cell-free systems, but they were inactive on bacterial ribosomes.
Amino Acid Sequence↗
Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study.
OBJECTIVES: The aim of this study was to determine the effectiveness and safety of yohimbine and trazodone used together for the treatment of pure psychogenic impotence. METHODS: Sixty-three patients who had psychogenic impotence diagnosed on the basis of sexual history, results of physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, partial crossover study comparing placebo with yohimbine (15 mg per day orally) and trazodone (50 mg per day orally) used together. Treatment consisted of two 8-week courses. Patients who initially received placebo for 8 weeks were then switched to the 2-drug combination for 8 weeks. Erectile function, ejaculation, interest in sex, and sexual thoughts were investigated at the end of drug treatment and at 3- and 6-month follow-up. For statistical analysis chi-square, McNemar, and Student's t test for unpaired data were used. RESULTS: Fifty-five patients (87%) completed the whole treatment schedule. Positive clinical results (complete and partial responses) were obtained in 39 (71%) patients at the end of the drug treatment phase. These results were significantly better than those obtained with placebo (p < 0.01). Positive results were maintained in 32 (58%) and 31 (56%) patients at 3- and 6-month follow-up, respectively. Minor drug-related adverse effects occurred in 6 (11%) of the patients in the yohimbine-trazodone group and in 2 (4%) in the placebo group. CONCLUSIONS: The combination of yohimbine and trazodone is a safe and effective first-line treatment for psychogenic impotence.
Administration, Oral↗
Ribosome-inactivating proteins from plants.
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Amino Acid Sequence↗
Distribution and properties of major ribosome-inactivating proteins (28 S rRNA N-glycosidases) of the plant Saponaria officinalis L. (Caryophyllaceae).
We have studied the distribution of the protein synthesis inhibitory activity in the tissues of Saponaria officinalis L. (Caryophyllaceae). Seven major saporins, ribosome-inactivating proteins, were purified to apparent homogeneity from leaves, roots and seeds using a new procedure of RIPs isolation including ion-exchange and hydrophobic chromatography. They all catalysed the depurination of rat liver ribosomes, which generate the Endo's diagnostic rRNA fragment upon treatment with acid aniline, thus indicating that A4324 from the 28S rRNA has been released (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). The molecular mass of saporins by SDS-PAGE ranged between 30.2 and 31.6 kDa and by gel-filtration between 27.5 and 30.1 kDa. Amino acid composition and amino-terminal amino acid sequence indicate that all saporins may be considered isoforms. Only two saporins present in roots were glycosylated (SO-R1 and SO-R3). All saporins are very active on cell-free translation systems derived from rabbit reticulocyte lysates, rat liver, Triticum aestivum L., Cucumis sativus L. and Vicia sativa L. However, they are poor inhibitors of an Escherichia coli translation system. They inhibit protein synthesis in HeLa, BeWo and NB 100 cells, HeLa cells being the most resistant. The enzymatic activity of at least one saporin isoform was dependent on magnesium concentration in the standard rat liver cell-free system.
Amino Acid Sequence↗
Purification and partial characterization of single-chain ribosome-inactivating proteins from the seeds of Phytolacca dioica L.
Three ribosome-inactivating proteins (RIPs) similar to those already known (Stirpe et al. (1992) Bio/Technology 10, 405-412) were purified from the seeds of Phytolacca dioica. These proteins, called Phytolacca dioica RIPs (PD-S1, PD-S2 and PD-S3 RIPs), are glycoproteins, with M(r) approx. 30,000, inhibit protein synthesis by a rabbit reticulocyte lysate and phenylalanine polymerization by isolated ribosomes, and depurinate rat liver rRNA in an apparently identical manner as the A-chain of ricin and other RIPs (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). Part of the purified rat liver ribosomes appeared resistant to the action of PD-S RIPs. The most abundant protein, PD-S2 RIP, gave a weak or nil cross-reaction with sera against various other RIPs, including a pokeweed antiviral protein from the roots of Phytolacca americana. PD-S2 RIP was linked to a monoclonal antibody (Ber-H2) against the CD30 human lymphocyte antigen and the resulting immunotoxin was selectively toxic to the CD30 + Hodgkin's lymphoma-derived L540 cell line.
Amino Acid Sequence↗
Is there a role for transrectal microwave hyperthermia of the prostate in the treatment of abacterial prostatitis and prostatodynia?
Transrectal microwave hyperthermia of the prostate was administered to 54 patients with chronic abacterial prostatitis or prostatodynia, who failed to respond to several courses of conventional therapies. Hyperthermia was delivered in 60-min long sessions with three randomly chosen regimens (1 session/week for 4 weeks; 1 session/week for 6 weeks; 2 sessions/week for 3 weeks). A prostatic temperature of 42.5 +/- 0.5 degrees C was maintained throughout the entire duration of each session. Patients were assessed pre- and postoperatively by scoring of subjective symptoms, uroflowmetry with flow nomograms, determination of residual urine volume, and transrectal ultrasonography of the prostate. At the long-term follow-up, the subjective symptom score was significantly improved in all patients. Fifty percent of the patients also reported an improvement of life quality, 47% reported their condition unchanged, and 3% reported deterioration, despite therapy. Urodynamic parameters improved but did not reach statistical significance. No major complications were encountered. Our preliminary data indicate that transrectal microwave hyperthermia of the prostate is a safe therapy that can be beneficial as a second line treatment in selected patients with recurring symptoms of abacterial prostatitis or prostatodynia, which do not respond to medical therapy.
Adult↗
Intracavernous vasoactive pharmacotherapy: the impact of a new self-injection device.
The clinical effects of a new self-injection pen were investigated in 160 impotent patients undergoing intracavernous vasoactive pharmacotherapy. Of the patients previously using insulin syringes for self-injection 90% switched to the pen, since it was considered easier to use and several injections could be performed with the same drug cartridge, thus avoiding the preparation necessary before every single injection with the syringe. Dropout rates were 36% and 12% for patients using the syringe and the pen, respectively (p < 0.05). This self-injection pen can be used for any drug, either singly or in combination with others. It is well accepted by patients, and greatly increases acceptance of and satisfaction with intracavernous pharmacotherapy.
Alprostadil↗
Four-drug intracavernous therapy for impotence due to corporeal veno-occlusive dysfunction.
Although veno-occlusive dysfunction is a frequent cause of impotence, a definitive therapeutic strategy has not yet been clearly defined. A total of 56 patients with corporeal veno-occlusive dysfunction diagnosed by dynamic infusion cavernosometry-cavernosography (flow to maintain erection greater than 10 ml. per minute and rate of corporeal pressure decrease after interruption of intracavernous infusion greater than 50 mm. Hg for 30 seconds) not considered suitable candidates for surgery underwent self-injection therapy. A vasoactive mixture composed of 12.1 mg./ml. papaverine hydrochloride, 10.1 micrograms./ml. prostaglandin E1, 1.01 mg./ml. phentolamine mesylate and 0.15 mg./ml. atropine sulfate was used. After dose titration of the drug mixture 54 patients (95%) were able to obtain sustained rigid erections that guaranteed satisfactory sexual activity. Mean (plus or minus standard error of mean) volume of injected mixture was 0.42 +/- 0.09 ml. (range 0.25 to 0.90 ml.). Four patients (7%) reported transient hypotension that did not recur after the application of a penile rubber band before injection. At a mean followup of 16 months 6 patients (11%) discontinued use of injections, 37 (69%) were satisfied and using the mixture, and 11 (20%) maintained rigid erections using a lower than initial dose. No major complications were encountered. The association of drugs with different mechanisms of action caused a synergism that potentiated the therapeutic activity and reduced side effects by decreasing the total drug dose.
Alprostadil↗
Effects of ribosome-inactivating proteins on Escherichia coli and Agrobacterium tumefaciens translation systems.
The effects of 30 type 1 and of 2 (ricin and volkensin) type 2 ribosome-inactivating proteins (RIPs) on Escherichia coli and Agrobacterium tumefaciens cell-free translation systems were compared with the effects on a rabbit reticulocyte translation system. The depurinating activity of RIPs on E. coli ribosomes was also evaluated. Only six type 1 RIPs inhibited endogenous mRNA-directed translational activity of E. coli lysates, with submicromolar 50% inhibitory concentrations. Four RIPs had similar activities on poly(U)-directed phenylalanine polymerization by E. coli ribosomes, and three RIPs inhibited poly(U)-directed polyphenylalanine synthesis by A. tumefaciens ribosomes, with submicromolar 50% inhibitory concentrations.
Agrobacterium tumefaciens↗
Long-term clinical reliability of transurethral and open prostatectomy for benign prostatic obstruction: a term of comparison for nonsurgical procedures.
To elucidate the long-term reliability of prostatectomy, we evaluated 92 benign prostatic hyperplasia patients who had been submitted to either transurethral or open surgery at the 5-year follow-up. Ninety-five percent of the patients were still nonobstructed and subjectively satisfied of their urinary status. Postoperative mortality was presumably not related to the previous operation. Until now, nonsurgical procedures did not guarantee the results achieved by surgical treatment and should thus be reserved for patients at high operative risk or refusing surgery.
Follow-Up Studies↗
Velocity and flow volume gradients along the cavernosal artery: a duplex and color Doppler sonography study.
Duplex and color Doppler sonography were used to assess 130 impotent patients and 8 potent controls. Cavernosal artery diameter, peak flow velocity and volume flow rate were evaluated at the level of the crura of the corpora cavernosa and 1 cm proximal to the corona penis. Potent controls and nonarteriogenic impotent patients showed a 20% reduction in hemodynamic parameters at the periphery of the cavernosal arterial tree. In patients with occlusive disease, involving either the upper arterial tree or the entire course of the cavernosal artery, the gradient was maintained. In patients with selective occlusive disease of the distal segment of the cavernosal artery the hemodynamic gradient almost doubled. Hemodynamic gradients can be identified along the cavernosal artery and provide additional information to arteriographic data for the selection of candidates for penile vascular reconstructive surgery.
Arterial Occlusive Diseases↗
Morphodynamic assessment of penile circulation in impotent patients: the role of duplex and color Doppler sonography.
Duplex and color Doppler sonography were used to assess the vascular status of 240 impotent patients. The tests were performed before and after intracorporal injection of a standard dose of a vasoactive mixture and measurements were done both at the crura and at the midshaft of the penis. Particular care was taken in the evaluation of cavernosal arteries diameter, wall pulsatility, morphology of spectral waveform, blood flow acceleration, systolic and diastolic flow velocity and flow volume. Resistance and pulsatility indexes of the cavernosal arteries were also measured. Flow along the deep dorsal vein was quantified when possible. Cavernosal artery peak systolic flow velocity, flow volume and acceleration were the best indicators of arterial penile circulation. Persistently elevated (> 10 cm/s) diastolic flow in the cavernosal arteries positively correlated with a diagnosis of venogenic impotence obtained by dynamic infusion cavernosometry--cavernosography in almost 80% of cases. Duplex and color Doppler sonography permit to thoroughly evaluate cavernosal arteries function and seem to have a promising role in the study of the veno-occlusive mechanism of the corpora cavernosa.
Blood Flow Velocity↗
[Coronary stenting: indications and results].
Intracoronary stenting has been introduced to overcome the 2 main limitations of balloon angioplasty:acute vessel closure and late restenosis. Palmaz-Schatz stent is today the most diffuse prosthesis; the incidence of subacute occlusion and of restenosis reported by various Authors are acceptable. The risk of major complications however is definite and anticoagulation mandatory. Only controlled clinical studies and improvements in the stent design and in the knowledge of thrombotic processes will permit an enlargement of stent indications.
Arterial Occlusive Diseases↗
A new 'solid phase' procedure to synthesize immunotoxins (antibody-ribosome inactivating protein conjugates).
A method to produce immunotoxins (conjugates comprising of a monoclonal antibody and toxin) using ribosome inactivating protein anchored on an affinity gel derivatized with triazinic dye is described. The adsorbed toxins were activated with 2-imino-thiolane and then conjugated to monoclonal antibody activated by SPDP. The "heterogeneous phase" system offered several advantages, reducing the usually required purification steps and opening a way to automatize the conjugation procedure.
Antibodies, Monoclonal↗
[Doppler color echography in the diagnosis of impotence].
This study reports the experience achieved with duplex and color Doppler ultrasonography in 120 impotent patients. The following morphodynamic parameters of the cavernosal arteries were studies before and after intracorporal injection of a mixture of vasoactive drugs: arterial diameter, wall pulsatility, morphology of the spectral waveform, peak systolic velocity, end diastolic velocity and flow volume. The veno-occlusive mechanism of the corpora cavernosa was studied directly by determination of flow along the deep dorsal vein of the penis and indirectly by serial evaluation of the diastolic flow of the cavernous arteries.
Adult↗
Immunological properties of ribosome-inactivating proteins and a saporin immunotoxin.
Antibodies have been raised in rabbits against plant ribosome-inactivating proteins (RIPs) and used to demonstrate cross-reactivity between RIPs from plants belonging to the same family, but little or no cross-reactivity between RIPs from taxonomically unrelated plants. When an immunotoxin consisting of saporin conjugated to bovine IgG was injected into rabbits, the animals formed antibodies against both saporin and bovine IgG.
Animals↗
Some ribosome-inactivating proteins depurinate ribosomal RNA at multiple sites.
Saporin-S6, a ribosome-inactivating protein (RIP) from Saponaria officinalis released more than 1 mol of adenine/mol of ribosomes from house fly (Musca domestica) larvae and from rat liver. The release of adenine from rat liver ribosomes by several RIPs (plant enzymes with RNA N-glycosidase activity) was examined. Saporins, pokeweed antiviral protein from roots of Phytolacca americana (PAP-R), and trichokirin from Trichosanthes kirilowii seeds depurinated rat liver ribosomes at more than one site. Up to 33 mol of adenine were released from 1 mol of ribosomes. This property is not common to all RIPS.
Animals↗