Serum 90K/MAC-2BP glycoprotein in patients with liver cirrhosis and hepatocellular carcinoma: a comparison with alpha-fetoprotein.

Glycoprotein 90K/MAC-2BP is a member of the scavenger receptor cystein-rich protein superfamily, which is thought to be involved in immune surveillance, defending the body against pathogens and cancer. 90K serum levels are elevated in patients with cancer of various origins and in viral infections, such as human immunodeficiency virus and hepatitis C virus (HCV). Because in patients with HCV-related cirrhosis the incidence of hepatocellular carcinoma (HCC) is high, in the present paper we examined, by means of an enzyme-linked immunosorbent assay, the 90K serum levels in 103 patients with liver cirrhosis, and in 69 with HCC, and compared them to alpha-fetoprotein, the reference tumor marker for this neoplasm. Serum levels of 90K (cut-off 14 microg/ml) were elevated both in cirrhosis (39%) and HCC (46%) compared to controls (14.1 microg/ml vs. 10.6 microg/ml in cirrhosis, and 14.8 microg/ml vs. 9.1 microg/ml in HCC, p < or = 0.001). There was a significant association with the presence of anti-HCV antibodies. 90K was found to be a non-specific tumor marker which is complementary to alpha-fetoprotein on the basis of its probable different biological significance. In fact, 74% of HCC patients had at least one positive marker. Combined use of 90K and alpha-fetoprotein could improve the sensitivity of a single test in the diagnosis of HCC.

Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome.

Hirsutism is a common symptom of women affected by polycystic ovary syndrome (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25 patients affected by PCOS with severe hirsutism for a period of 24 months. Seventeen of these patients had not been treated before and eight had had previous but unsatisfactory therapy. Nineteen patients showed a normal body weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and endocrinological evaluation and an assessment of the degree of hirsutism, assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under baseline conditions. Patients started treatment with flutamide (Eulexin, Schering-Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological assessment of gonadotropin episodic secretion and of gonadotropin response to GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide administration. During treatment, our patients showed a marked and significant reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 + 2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly and markedly respond to treatment with flutamide alone without important side-effects even if administered for a long period.

Sodium nitroprusside induces internalization of muscarinic receptors stably expressed in Chinese hamster ovary cell lines.

We have characterized the internalization of muscarinic acetylcholine receptors induced by the nitric oxide (NO)-generating compound sodium nitroprusside. When Chinese hamster ovary cells, stably transfected with the human m4 muscarinic receptor subtype, were incubated for 1 h in the presence of 700 microM sodium nitroprusside, the number of receptors measured in intact cells with the hydrophilic ligand N-[3H]methylscopolamine was reduced by 30%. The effect was dose dependent, beginning with a concentration of sodium nitroprusside as low as 45 microM. Removal of sodium nitroprusside from the incubation medium did not result in a recovery of the binding sites. The phenomenon was temperature dependent and was blocked by the muscarinic antagonist atropine. No receptor diminution was detected when the number of binding sites was evaluated with the lipophilic antagonist [3H]quinuclidinyl benzilate. This indicates that sodium nitroprusside induces a redistribution of the muscarinic receptors between the plasma membrane and an internal compartment of the cell. Receptor loss was readily reversed by treatment with the sulfhydryl reducing agent diethyldithiocarbamate. Our data provide evidence that muscarinic receptors are internalized by sodium nitroprusside through the oxidation of sulfhydryl groups; they also suggest that NO could play a role in muscarinic receptor desensitization.

[Efficacy of enoxacin in the treatment of prostatitis-vesiculitis: its absence of toxicity on spermatogenesis]. / Efficacité de l'énoxacine dans le traitement des prostato-vésiculites: son absence de toxicité sur la spermatogénèse.

OBJECTIVES: The ability of enoxacin, a second generation quinolone, to diffuse into the seminal fluid both of normal volunteers (n = 10, protocol A) and patients with prostato-vesiculitis and positive sperm cultures (n = 10, protocol B) was investigated. In addition, the microbiological effectiveness and the occurrence of adverse effects on spermatogenesis were evaluated in the patient group. METHODS: Enoxacin was administered in oral doses of 300 mg b.i.d. for two and seven days to volunteers and patients, respectively. Two hours after the last drug administration, blood, semen and urine samples were collected to determine seminal fluid antibiotic concentrations by microbiological agar diffusion assay. In protocol B, sperm cultures and sperm analyses were performed at the end of treatment and repeated at 30 and 90 days follow-ups. RESULTS: In both protocols significant seminal fluid antibiotic concentration was achieved, thus providing evidence for considerable diffusion of the drug into prostate gland and seminal vesicles. Moreover, sperm cultures were sterile in all patients, and semen analysis demonstrated that spermatogenesis was not impaired by antibiotic treatment; on the contrary, 30 days after drug withdrawal percentage sperm motility improved, and the rate of abnormal forms decreased. CONCLUSIONS: The absence of adverse effects, both general and specifically on spermatogenesis, may be related to the restriction of indications and the brevity of the therapeutic cycles. Our results suggest that enoxacin may be successfully and safely used, in short term courses, for the treatment of documented genital tract infection by sensitive organisms. Further studies are needed to thoroughly evaluate the potential adverse effects on fertility of this quinolone, particularly when used for long-term suppressive therapy in patients with chronic urological infections.

Inter and intra-individual variability of sperm morphology after selection with three different techniques: layering, swimup from pellet and percoll.

Sperm morphology has been suggested to be one of the most reliable factor in predicting male fertility potential both in spontaneous cycles and in assisted reproduction. In this work the morphology of spermatozoa selected with three different techniques (layering, swimup from pellet and mini-percoll) has been assessed and compared in 20 infertile patients. All the techniques allowed the recovery of sperm populations of a better quality than in basal samples, with a higher percentage of normal forms (p < 0.001). No significant differences were observed among the three different techniques in selecting sperm populations. The scatter diagrams comparing pairwise differences between the methods against their means regard the percentage of normal forms selected show a great (over 20%) inter and intra-individual variability. These data demonstrate that the three techniques select different percentages of normal spermatozoa, even in the same patient. Since it is crucial to obtain the highest number of morphologically normal and motile spermatozoa and each technique may provide different results in a given patient, we suggest that at least two techniques of sperm selection be performed before assisted reproduction procedures. This combined testing could also be relevant in the prognostic evaluation of the infertile male, since it explores the different characteristics of sperm function.

Cortisol and heart rate changes in first- and fourth-time donors.

It is well-known that during blood donation some subjects experience mild, moderate, or severe stress reactions. The frequency of these reactions is higher in first-time donors than in experienced ones. However, hormonal variations might nevertheless be present in subjects who show no clinical reaction. Cortisol is the hormone classically involved in response to stress. The aim of this study was to evaluate cortisol behavior in blood donors who did not manifest clinical reaction. Cortisol was studied before and after the first and fourth blood donation in 20 blood donors, aged 25-45 years. Blood pressure and heart rate were also evaluated. Plasma cortisol concentrations decreased during the first (from 202.6 +/- 9.2 ng/ml at -15 min, to 147.5 +/- 8.0 ng/ml, at +30 min; p < 0.001), but not during the fourth (142.5 +/- 7 ng/ml vs. 153.0 +/- 10.1 ng/ml) blood donation; blood pressure remained stable throughout donations, while the heart rate significantly decreased (from 78 to 68 beats/min; p < 0.001) only during the first experience. The increased cortisol levels observed before the first donation are apparently due to emotional components, since they were not observed in experienced donors. We may conclude that blood donation per se is not a stressful event and that moderate stress, as suggested by the increased cortisol levels and heart rate at the first donation, is secondary to emotional rather than to physical factors and occurs during a never-experienced-before event.

Treatment of complicated benign prostatic hyperplasia with LHRH-analogues in aged patients.

The effect of administration of an LHRH-analogue (LHRH-a) was evaluated in 11 patients with benign prostatic hyperplasia (BPH) in whom there were contraindications for surgery. These patients, who already had impaired potency due to age or serious illness, were given 1500 micrograms LHRH-a in the first week and 1200 micrograms from the eighth day onwards. They all improved significantly (P less than 0.001) with regard to their urological symptoms on day 60 of treatment. Our results demonstrate the influence of androgen in maintaining established BPH, the effectiveness of LHRH-a therapy in selected patients with BPH and the usefulness of a salivary testosterone assay for the follow-up of treatments expected to lower the bioavailability of androgen to target tissues.

Influence of conjugated oestrogens on circulating oestradiol, oestrone, LH, FSH and prolactin levels in postmenopausal women.

The effects on plasma 17-beta-oestradiol (E2), oestrone (E1), LH, FSH and prolactin (PRL) levels of 1.5 mg conjugated oestrogen, administered daily per os for 20 consecutive days, was investigated in six postmenopausal women aged 60-68. Both E2 and E1 increased progressively and significantly (p less than 0.001) from 18 and 28 pg/ml to 32 and 108 pg/ml, respectively, at the end of treatment; five days after the last dose both E2 and E1 had fallen to pretreatment levels (p greater than 0.05). LH and FSH decreased progressively and significantly (p less than 0.001) from 114 and 105 mlU/ml (before therapy) to 43 and 36 mIU/ml, respectively, after oestrogen administration. One week after interruption of treatment, both LH and FSH were significantly higher (p less than 0.001) than that obtained at the end of therapy. No significant variation (0.05 greater than p greater than 0.02) was observed for plasma PRL during and after oestrogen administration. Such results indicate that in postmenopausal women the specific enzymatic mechanism of oestrogen interconversion are maintained and that there is no increase of prolactin. IN this was, the possible effects on the development of breast cancer by elevated levels of this hormone, usually observed during long-term oestrogen therapy, would be avoided.

Amplification of LH response to LHRH by dopamine infusion in eugonadal women.

Although the role of biogenic amines in the regulation of gonadotropin release has been studied extensively, the precise role of dopamine (DA) in stimulating LHRH and/or LH release is still controversial. In the present study 6 eugonadal women, aged 20-30, were given an LHRH infusion on day 6 of the menstrual cycle and the pattern and magnitude of LH and FSH responses were estimated. On day 6 of the next cycle, the experiment was repeated and DA was also infused beginning 60 min after the start of the LHRH infusion. Following LHRH infusion plasma LH showed a marked and significant rise with a mean peak increment at 4 h, and with a cumulative response (CR) of 9136 +/- 955 mIU/ml/6h. The pattern of FSH response tended to parallel that of LH; however, mean peak increment at 4 h and a CR of 2640 +/- 169 mIU/ml/6h were markedly lower. Plasma prolactin levels remained unchanged. Addition of DA to LHRH at 60 min evoked a significantly greater mean peak LH increment at 4 h and a CR of 15514 +/- 1836 mIU/ml/6h (p less than 0.001). There were no significant changes in either mean FSH peak at 4 h or in the CR (3257 +/- 309 mIU/ml/6h). As expected, a highly significant (p less than 0.001) decrease in circulating PRL from 12.1 +/- 3.1 to 3.0 +/- 1.5 ng/ml was seen during DA infusion. In conclusion, DA given by iv infusion enhancement LH response to LHRH in eugonadal women under the conditions of the present investigation, supporting a role for a dopaminergic component in the control of LH release in women.