Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.

Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (

Dehydroepiandrosterone metabolism in human plasma.

The possibility that dehydroepiandrosterone (DHEA) is metabolized in human plasma was studied by column and thin-layer chromatography. The results obtained indicate that a time-dependent disappearance of DHEA is matched by the appearance of newly-formed species that may represent DHEA conversion by-products. Neither disappearance of DHEA, nor formation of the alleged conversion by-products was observed when reactions were performed under conditions in which plasma enzymes were removed or inactivated. These results suggest that, in plasma, DHEA is partially transformed into different substances, and that the conversion reactions are catalyzed by enzymes present in this tissue. The observed kinetics of appearance and partial disappearance of the radiolabeled species can be interpreted as indicating that some of the by-products formed are further converted into other substances. The data shown appear to indicate that plasma can be added to the list of the already known compartments that are involved in steroid metabolism.

Neuropeptide degradation in naive and steroid-treated allergic saliva.

The hydrolysis of neuropeptides and possible variations in hydrolysis following steroidal treatment, were examined in the presence of saliva collected from allergic volunteers; data obtained were compared to those obtained with a age and sex-matching group of healthy controls. The results reported indicate the presence of a statistically significant increase in the hydrolysis of the model substrate in allergic as compared to control saliva, and a reduction of substrate hydrolysis in treated as compared to naive allergic saliva. Total enzyme activity, the relative activity of the three classes of substrate-active enzymes (aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases), the allergy-associated variations of these activities, and the variations associated to therapy were found to be different in male and female saliva. Specifically, in the controls, the lower level of hydrolysis evident in female as compared to male saliva appeared to be principally induced by lower activity of aminopeptidases. Under allergic conditions, a sex-different increase in the activity of all three classes of substrate-active enzymes modified the hydrolysis pattern differently in samples obtained from male and female donors. Finally, pharmacological treatment induced opposite effects on the enzymes present in each sex: in male saliva, the activity of all three classes of substrate-active enzymes--and, thus, of substrate hydrolysis--was reduced near to the levels measured in the controls. In female saliva, the reduction in the activity of aminopeptidases was coupled with an increase in the activity of dipeptidylaminopeptidases, causing substrate hydrolysis to remain near the levels measured in naive allergic, rather than control, saliva.

[Flowmetry analysis in patients undergoing transurethral resection of the prostate for BPH]. / Análisis flujométrico en pacientes sometidos a RTU de próstata por HBP.

Transurethral resection (TUR) is the most frequent surgical treatment for symptomatic benign prostate hyperplasia (BPH). Prostate size is a significant factor for choosing TUR versus prostate adenomectomy. Analysis of flowmetry results obtained with TUR in 203 patients, based on weight of resected prostate tissue. Flowmetry was performed prior to TUR and prostate size was estimated with transabdominal ultrasound. Prostate tissue was weighed after TUR and a new flowmetry was performed 6 months after treatment. Mean weight of resected tissue was 31.34 g. When all flowmetry parameters analyzed pre-and post TURs were compare, there were significant differences (p < 0.001). Increased maximum flow (Qmax) and increased mean flow (Qmed) occurred in 91.7% and 96.31% patients, respectively. Mean increase of post-surgical Qmax was significantly higher (p > 0.01) in patients with Qmax prior to surgery lower than 8 ml/s. No significant correlation was demonstrated between prostate volume measured by ultrasound or resected prostate tissue and increased post-surgical Qmax. TUR improves flowmetry parameters, mainly in patients with pre-surgical Qmax lower than 8 mL/s. Extensive prostate resection does not appear to improve the flowmetry results obtained with a sufficient functional TUR.

[Prevention of prolonged drug-induced erection by intracavernous injection of etilefrine]. / Prevención de la erección farmacológica prolongada mediante la inyección intracavernosa de etilefrina.

Here in we report the results of intracavernous injection of etilefrine hydrochloride in a group of 12 patients who developed rigid erection after a diagnostic test with intracavernous PGE1 injection or cavernosometry. Etilefrine reversed erection in all cases. No side-effects or significant changes in blood pressure were noted. Etilefrine is believed to be a safe and low cost alternative to other alpha-adrenergic agents in the prevention of drug-induced priapism.

[Flubiprofen vs dipyrone combined with hyoscine: the analgesic efficacy in renal colic]. / Flubiprofeno vs dipirona asociada a hioscina: eficacia analgésica en el cólico nefrítico.

OBJECTIVE: We compared the efficacy of flurbiprofen (NSAID) versus dipirone + hyoscine N-butylbromide in the treatment of nephric colic. METHODS: The study comprised 135 patients, aged 18 to 75 yrs, with intense nephric colic. The patients were observed 60 min after a single IM dose of 150 mg flurbiprofen (n = 67) or 2 gm dipirone + 20 mg hyoscine N-butylbromide. RESULTS: Both treatment modalities were well-tolerated and afforded significant pain relief. Flurbiprofen, however, was faster-acting and superior to dipirone + hyoscine in the overall evaluation of good and excellent therapeutic response rates. CONCLUSION: The results of the study show that IM flurbiprofen is a useful alternative to dipirone + hyoscine N-butylbromide in the treatment of nephric colic.

[Primary mucinous adenocarcinoma of the prostate]. / Adenocarcinoma mucinoso prostático primario.

Contribution of a new case of prostatic mucinous adenocarcinoma of primary origin. Diagnosis was established by histochemical techniques alcian blue, PAS and alcian-PAS) processing the fragments from the prostate transurethral resection (PTUR). Neither the existence of extraprostatic tumoration, local infiltration, or metastasis was recognized. No correlation between preoperative prostatic acid phosphatase (PAP) (50) and prostatic specific antigen (PSA) values (3ng/m) was evidenced. After radical prostatectomy both markers remain undetected one year after surgery.

[Foreign bodies in the bladder and urethra]. / Cuerpos extraños en vejiga y uretra.

Many cases have been published in the urological literature of foreign bodies apparent in the bladder and urethra. Based on the five cases we are now presenting, we review this chapter of urology. We discuss the clinico-pathological aspects of this pathology and provide diagnostic and therapeutical guidance. We recall the role urologists have to play in preventing such events in the course of their diagnostic and therapeutic activity.