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Carboxyalkyl peptides containing a biphenylylethyl group at the P1‘ position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10−50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P1‘, a tert-butyl group at P2‘, and a methyl group at P3‘ produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P1‘-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P1‘ proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4‘-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl-1,5-pentanedioic acid 1-(α(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a Ki of 10 nM against MMP-3 and an ED50 of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1β injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED50 = 6 mg/kg iv).

A case of pseudohermaphroditism with persistence of Mullerian duct derivates in a 77-year-old patient is reported. The patient was phenotypically male and the caryotype was 46 XY. He had a normal penile size and normal sexual function until 3 years previously. The vagina and uterus communicated with the posterior urethra. Laparatomy showed an almost normal uterus with the testicles at the end of the fallopian tubes. Problems concerning embryogenesis and management are discussed.

The Authors describe a case of urachal adenocarcinoma. The patient was a 36-year-old man who had already undergone segmentai (cupula) cystectomy at another hospital. The result of the histological test was: urachal adenocarcinoma. Afterwards a C.T. scan was taken which was negative. Then the patient had a cystoscopy with biopsy (negative) in our hospital, and underwent a new segmentai cystectomy releasing the urachus. The result of the second histological test was urachal adenocarcinoma. The Authors underline the rareness of this pathology, and the importance of total or segmentai cystectomy for treatment of the above.

The authors report their experience in 10 cases of giant calculosis of the bladder. Their formation secondary to obstructive cervico-urethral pathology is highlighted and treatment of the latter remains of prime importance.

In view of the lack of spinal units in Calabria and Institutes from which information can be obtained on the conditions of patients with injuries to the spinal cord, we researched such patients (approx. 500,000) with urological risk in our territory. We included in our study 81 patients, 62 men and 19 women, aged between 18 and 78 years. Significant uro-andrological problems were found in 42 patients. It is to be hoped that the survey contributes to improving the poor assistance at present provided for persons with injuries to the spinal cord in Calabria.