Testosterone replacement therapy does not promote priapism in hypogonadal men with sickle cell disease: 12-month safety report.

Hypogonadism, which is highly prevalent in men with sickle cell disease (SCD), affects quality of life and causes great morbidity. The safety of testosterone replacement therapy (TRT) in SCD in relation to priapism episodes is relatively unknown. Our aim was to monitor the safety of TRT in a cohort of seven hypogonadal men with SCD. Testosterone undecanoate (Nebido) 1 g was administered intramuscularly to adult men with homozygous SCD (Hb SS) having hypogonadism [serum total testosterone ≤12.0 nmol/L (346 ng/dL), reference range 12.5-38.1 nmol/L (360-1098 ng/dL)] for 12 months. Serum total testosterone, haemoglobin, haematocrit, renal and liver function tests, glucose and PSA measurements were done at baseline and 12-month follow-up. Trough serum total testosterone, haemoglobin and haematocrit were measured three monthly. Priapism events and adverse drug events were assessed every 3 months. International Index of Erectile Function (IIEF), Androgen Deficiency in the Ageing Male (ADAM) and World Health Organization Quality of Life (WHOQOL) questionnaires were administered at baseline, 6 and 12 months. Seven men with a mean age of 34.4 years were treated. Median total testosterone increased from 10.6 to 11.2 nmol/L (p = 0.46). Median serum lactate dehydrogenase levels decreased from 1445 to 1143.5 IU/L (p < 0.05), while all other laboratory indices remained stable. Injection site pain was the most frequently reported adverse event, with no increases in painful crises, hypersensitivity or oedema. After TRT, there was no significant increase in priapism frequency. Median questionnaire scores were increased for the IIEF (46-68, p = 0.018), reduced for ADAM (5.0-2.0, p = 0.016) and unchanged for WHOQOL (98-103, p = 0.086). TRT using testosterone undecanoate with eugonadal intent for hypogonadism appears to be safe in men with SCD. This treatment does not appear to promote priapism occurrences and rather it possibly improves sexual function. Future prospective evaluations in larger groups of hypogonadal men with SCD are necessary to confirm these findings.

Priapismo secundario a antipsicóticos: a propósito de un caso asociado a risperidona / Priapism associated with risperidone use: Report of one case

Background: The use of drugs with α-adrenergic antagonistic effect is one of the most prominent etiologies of priapism. We report a 32-year-old schizophrenic male in treatment with risperidone who consulted in the emergency room for a painful priapism. A low flow priapism was diagnosed. Medical treatment was unsuccessful and the patient was subjected to a proximal corporo-spongiosal shunt (Quackels technique), with good results. The patient was discharged in good conditions.

Phoneutria nigriventer spider toxin Tx2-6 causes priapism and death: a histopathological investigation in mice.

Phoneutria nigriventer spider bite causes priapism, an effect attributed to the peptide toxins Tx2-5 and Tx2-6 and involving nitric oxide. Tx2-6 (MW = 5287) is known to delay the inactivation of Sodium channels in the same fashion as many other venom toxins. In the present study we evaluated the i.p. dose that induces priapism and the other symptoms in mice. Animals killed by the toxin or crude venom (0.85 mg/kg) were autopsied and a pathological study of brain, lung, kidney, liver and heart was undertaken using standard techniques. The same protocol was employed with animals injected with crude venom. Results showed that priapism is the first sign of intoxication, followed by piloerection, abundant salivation and tremors. An i.p. injection of about 0.3 µg/kg induced only priapism with minimal side-effects. The most remarkable histological finding was a general vascular congestion in all organs studied. Penis showed no necrosis or damage. Lungs showed vascular congestion and alveolar hemorrhage. Heart showed also sub-endothelial hemorrhage. Brain showed only a mild edema and vascular congestion. Results obtained with crude venom closely resemble those of purified toxin. We conclude that Tx2-6 have profound effects on the vascular bed especially in lungs and heart, which may be the cause of death. Interestingly brain tissue was less affected and the observed edema may be attributed to respiratory impairment. To the best of our knowledge this is the first histopathological investigation on this toxin and venom suggesting a possible cause of death.

[Priapism associated with risperidone use: Report of one case]. / Priapismo secundario a antipsicóticos: a propósito de un caso asociado a risperidona.

The use of drugs with α-adrenergic antagonistic effect is one of the most prominent etiologies of priapism. We report a 32-year-old schizophrenic male in treatment with risperidone who consulted in the emergency room for a painful priapism. A low flow priapism was diagnosed. Medical treatment was unsuccessful and the patient was subjected to a proximal corporo-spongiosal shunt (Quackels technique), with good results. The patient was discharged in good conditions.

Adrenergic α-blockers: an infrequent and overlooked cause of priapism.

A systematic review of the literature about the causal relationship between priapism and adrenergic α-blockers used for the treatment of lower urinary tract symptoms (LUTS) and arterial hypertension was accomplished. While opportunely describing a case of tamsulosin-induced priapism, we reviewed the literature using MEDLINE, COCHRANE and LILACS libraries, selecting all the articles until the present time addressing the association between priapism and α-blockers. Our patient was a healthy 32-year-old man who reported LUTS. His prostate was firm and moderately enlarged on digital rectal examination, measuring 30 grams on transabdominal ultrasound. Empirical treatment with tamsulosin was initiated and he developed priapism the day after the first dose of the drug. Erection was reverted by aspiration of the corpora and intracavernosal injection of adrenaline. Despite the late presentation (40 h of erection), he had no ED on follow-up. In the systematic review, among 2157 articles on priapism, only 13 similar cases reported α-blockers as the etiology of priapism. Therefore, adrenergic α-blockers are effective and safe drugs, with few serious adverse reactions. Nevertheless the association with priapism is well documented and related to substantial morbidity, this is an infrequent event and should not preclude their use, considering that the patient be sufficiently informed.

Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6

Brain areas expressing c-fos messenger RNA were mapped by quantitative in situhybridization after 1–2 h of intoxication with 10 mg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, includingthe supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus,locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NO stimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamicn. failed to induce penile erection, arguing against CNS involvement in thisparticular effect.

Functional expression of a recombinant toxin - rPnTx2-6 - active in erectile function in rat.

In the current study, the putative cDNA for PnTx2-6 toxin of the Phoneutria nigriventer spider venom was cloned and expressed as tioredoxin fusion protein in the cytoplasm of Escherichia coli. The fusion protein was purified from the bacterial extracts by combination of immobilized Ni-ion affinity and gel filtration chromatographies. Then, it was cleaved by enterokinase and the generated recombinant PnTx2-6 (rPnTx2-6) was further purified by reverse-phase HPLC. Likewise the native toxin purified from the spider venom, rPnTx2-6 potentiates the erectile function when injected in rats. This result indicates that the production of functional recombinant PnTx2-6 might be an alternative to provide this basic and valuable tool for study, as well as for further understanding such complex physiological system, including its correlation with the central nervous system and local tissue factors.

Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5, a lethal Phoneutria nigriventer spider toxin.

The primary goal of this study was to determine whether Tx2-5, a sodium channel selective toxin obtained from the venom of the spider Phoneutria nigriventer, produced penile erection by means of nitric oxide mechanism. Toxin identity was analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse) injection challenged the hypothesis above. Controls were injected with the D-isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile erections in about half the animals treated, while 7-NI completely abolished this effect. Interestingly 7-NI also abolished all the other symptoms of intoxication induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5 killed all the animals of the control group and no one in the 7-NI-treated group. We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome that include penile erection, hypersalivation and death by respiratory distress or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME reduces the penile erection and partially protects from the lethal effects of Tx2-5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes all the toxic effects of Tx2-5, including penile erection and death suggesting that nNOS is the major player in this intoxication; (4) toxins from other animals that affect sodium channels in the same way as Tx2-5 and induce similar toxic syndromes may have as a major common target, the activation of nitric oxide synthases.

Stuttering priapism associated with withdrawal from sustained-release methylphenidate.

Stuttering priapism is intermittent, prolonged, painful, pathologic erections with intervening periods of detumescence. An adolescent had stuttering priapism associated with withdrawal from sustained-release methylphenidate. To our knowledge, this is the first such report of stuttering priapism associated with stimulant drugs for treatment of attention deficit hyperactivity disorder.

Nonadrenergic, noncholinergic relaxation of human isolated corpus cavernosum induced by scorpion venom.

OBJECTIVES: To examine the effects of Tityus serrulatus scorpion venom (TSV) on human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally observed in scorpion envenomation, mostly in children. METHODS: HCC strips were suspended in a cascade system and superfused with aerated and warmed Krebs' solution at 5 mL/min. Noradrenaline (3 micromol/L) was infused to induce a submaximal contraction of the HCC strips. The release of cyclooxygenase products was prevented by infusing indomethacin (6 micromol/L). RESULTS: N(omega)-nitro-L-arginine methyl ester (10 micromol/L; n = 10) increased the tone of the preparations and significantly reduced (P <0.01) the acetylcholine (ACh) and TSV-induced relaxations. Subsequent infusion of L-arginine (300 micromol/L) partially reversed the increased tone and significantly restored the relaxations induced by TSV and ACh (P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 micromol/L; n = 8) markedly reduced (P <0.01) the relaxations induced by TSV, ACh, glyceryl trinitrate, and bradykinin. 7-Nitroindazole (10 micromol/L; n = 8) inhibited the relaxations induced by TSV by 84% (P <0.01) and also caused small, but significant, reductions in the ACh and bradykinin-induced HCC relaxations (P <0.05). Atropine (1 micromol/L; n = 6) abolished the relaxations evoked by ACh (P <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 micromol/L; n = 6) abolished the relaxations induced by TSV (P <0.01) and also reversed the established TSV-induced relaxation (n = 4). CONCLUSIONS: Our results indicate that TSV relaxes HCC through the release of nitric oxide from nonadrenergic, noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for the TSV-induced relaxations might be useful for a better understanding of the development of priapism in cases of scorpion envenomation.

Unusual complications of warfarin therapy: skin necrosis and priapism.

Skin necrosis and priapism are unusual complications of warfarin therapy. We report a teenager with warfarin-associated skin necrosis and priapism who was subsequently found to be a compound heterozygote for protein C deficiency and a heterozygote for the factor V Leiden mutation.

[Priapism induced by intracavernous injection]. / Priapismo provocado por inyección intracavernosa.

We report 16 cases of priapism in 13 of 404 patients who received intracavernous injection of vasoactive drugs to induce erection. In 10 patients the complication presented following injection of papaverine and phentolamine in combination. Despite reducing the dose of both agents, one patient had another episode of priapism. One patient who had been receiving papaverine alone in increasing doses with no results, developed priapism after the first injection of the combined treatment modality and again after the dose of both drugs had been reduced. Three cases presented priapism after injection with papaverine alone. One presented the complication again after injection of a reduced dose. The patients were seen after a sustained erection of 20 hours maximum on 15 occasions and one patient was seen after a sustained erection of 36 hours.

Tratamiento de la erección prolongada secundaria a inyección intracavernosa de medicamentos / Treatment of the prolonged erection induced by an intracavernous drug injection

La erección prolongada es la principal complicación de la inyección intracavernosa de papaverina y/o phentolamina. En 1700 inyecciones tuvimos esta complicación en un 3,06%(52/1700). Cuando se usa papaverina mezclada con Phentolamina sube a 19%. Se tratan a las 6 horas con medicamentos simpaticomiméticos con excelente rendimiento. 5 de ellas se trataron con Ketamina 30 mg en IIC con resultados espectaculares y sin complicaciones secundarias.

Erección peneana sostenida y raquinestesia: detumescencia por inyección intracavernosa de etilefrina / Prolonged penile erection and rachianesthesia: detumescence by intracavernous etilefrine inyection

Se presentan 11 enfermos con erección peneana sostenida por raquianestesia con 20 mg de bupivacaine, que fueron tratados con 10 mg de etilefrina inyectados por vía intracavernosa. En 10 casos se obtuvo detumescencia total y un paciente en forma parcial. No se registraron complicaciones, solo un leve hematoma en el sitio de la inyección en 1 enfermo. Todos presentaron hipertensión arterial fácilmente controlable. Se analiza el mecanismo de la erección y la bibliografía