Platelet activation in patients with the Raynaud phenomenon.

BACKGROUND: The Raynaud phenomenon (RP) is an exaggerated and reversible vasospasm of small arteries triggered by cold or emotional stress. Primary RP (PRP) term is used when the underlying condition is unknown. An altered regulation in vascular tone and/or release of soluble mediators from activated platelets plays a role in PRP through an increased oxidative stress. We assessed platelet activation and oxidative stress in patients with PRP by measuring platelet PAC-1, an index of glycoprotein (Gp) IIb/IIIa receptor activation, thromboxane A(2) (TXA(2)), an index of platelet activation and 8-epi-prostaglandin F(2α) (8-epi-PGF(2α)), a marker of endogenous in vivo peroxidation. METHODS: Eighteen asymptomatic patients with PRP (age 41.37 ± 16.94 years; 17 women, 1 man) and 18 healthy subjects (age of 35.11 ± 13.16 years; 16 women, 2 men) were studied. PAC-1 was analysed by flow cytometry while circulating TXB(2) , a stable metabolite of TXA(2) and 8-epi-PGF(2α) levels were assessed by ELISA kit. RESULTS: Our results show a significant platelet activation in PRP patients as indicated by increased PAC-1 expression (65.29 ± 15.24%; P < 0.001), TXB(2) (1477.83 ± 454.04 pg/mL; P= 0.003) and 8-epi-PGF(2α) circulating levels (42.50 ± 14.14 ng/mL; P < 0.001). An inverse correlation between the degree of PAC-1 expression and TXB(2) levels (r=-0.527; P= 0.02) was also found in PRP patients, suggesting that downregulation of GpIIb/IIIa receptor expression may occur during thrombocytopoiesis, as a consequence of the chronic exposure to increased TXB(2) concentration. CONCLUSIONS: Our study for the first time shows a marked activation of GpIIb/IIIa receptor in asymptomatic patients with PRP and supports antiplatelet therapy in PRP patients.

Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp in lean NIDDM men.

OBJECTIVE: To evaluate whether or not insulin stimulates endothelin (ET)-1 secretion in vivo. RESEARCH DESIGN AND METHODS: Plasma ET-1 levels were evaluated in 16 lean normotensive men with non-insulin-dependent diabetes mellitus (NIDDM) (mean age 50.3 +/- 4.1 years) during either a 2-h euglycemic hyperinsulinemic clamp (40 mU insulin.m-2.min-1) or placebo infusion (50 ml isotonic saline) according to a single-blind randomized crossover protocol. RESULTS: Circulating ET-1 levels increased during the euglycemic hyperinsulinemic clamp (from 0.88 +/- 0.38 pg/ml at time 0 to 1.66 +/- 0.22 pg/ml and 1.89 +/- 0.99 pg/ml at 60 and 120 min, respectively [P < 0.05 vs. time 0]) and returned to baseline levels after the discontinuation of insulin infusion (0.71 +/- 0.22 pg/ml after a 30-min period of recovery [NS]). Compared with placebo, the euglycemic hyperinsulinemic clamp induced a significant increase in plasma ET-1 levels at 60 min (P < 0.0001) and 120 min (P < 0.0001). Changes in basal insulin levels and corresponding changes in circulating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp were significantly correlated (r = 0.771, P < 0.0001). A possible unfavorable effect of ET-1 on the tissue sensitivity to insulin-stimulated glucose uptake was suggested by the presence of a negative correlation between total glucose uptake and baseline ET-1 levels (r = -0.498, P < 0.05). CONCLUSIONS: Our findings indicate that circulating ET-1 levels significantly increase during euglycemic hyperinsulinemic clamp in men with NIDDM. The negative correlation between total glucose uptake and circulating ET-1 levels suggests that the peptide might exert negative effects on the insulin sensitivity of target tissues. The consequent increase in insulin secretion as well as the insulin-related ET-1 release from endothelial cells could favor the development of diabetes-related vascular lesions.

Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis.

In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes.

Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo.

Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction could play a significant role in the development of atherosclerotic lesions in hyperinsulinemic conditions.

Blood endothelin-1 levels before and after carotid endoarterectomy for atherosclerotic stenosis.

BACKGROUND: Elevated plasma levels of endothelin-1 (ET-1) have been reported in advanced atherosclerosis. Further in vivo demonstration of cause-effect relationship between atherosclerotic lesion and high levels of ET-1 needs to be carried out. The aim of this study was to determine whether circulating levels of ET-1 are influenced by removing haemodynamically significant atherosclerotic stenosis in selected patients with mono or bilateral carotid atherosclerotic stenosis. METHODS: Cubital venous ET-1-immunoreactive (IR) levels were measured in 20 patients: 11 (mean age+/-S.D. 63.1+/-5.36 years; range 53-70 years) were affected by monolateral, and nine patients (mean age+/-S.D. 64.7+/-9.8 years; range 52-78 years) by bilateral extracranial carotid artery atherosclerotic stenosis. ET-1-IR levels were evaluated before and 7 days after monolateral surgical endoarterectomy. Pre-surgery levels of ET-1-IR were compared with those obtained from 18 healthy younger volunteers (mean age+/-S.D. 27.8+/-2.7 years; range 20-50 years). FINDINGS: The mean cubital venous levels of ET-1-IR in the atherosclerotic patients before endoarterectomy (mean+/-S.D. 4.50+/-3.35 pg/ml; range 1.28-10.66 pg/ml) were significantly higher than those observed in healthy subjects (mean+/-S.D. 0.641+/-0.137 pg/ml; range 0.36-1.02 pg/ml) (P=0.000). The mean ET-1-IR level decreased significantly after endoarterectomy in the group of patients with monolateral stenosis (pre-surgery: mean+/-S.D. 4.35+/-3.11 pg/ml; range 1.28-10.66 pg/ml; post-surgery: mean+/-S.D. 3.05+/-2.94 pg/ml, range 0.28-8.86 pg/ml) (P=0.005), but not in patients with bilateral extracranial carotid stenosis submitted to monolateral endoarterectomy (pre-surgery: mean+/-S.D. 4.77+/-3.79 pg/ml; range 2.18-10.3 pg/ml; post-surgery: mean+/-S.D. 4.60+/-3.70 pg/ml; range 2.20-11.10 pg/ml). INTERPRETATION: The removal of a haemodynamically significant atherosclerotic vascular stenosis is associated with a decrease in the circulating ET-1-IR levels 7 days after surgery when haemodynamically significant atherosclerotic lesions are absent.

Effect of thyroid hormone on the pre- and post-natal development of the rat testis.

The relationship between thyroid function and testicular development in the rat was investigated. Hypothyroidism was induced during fetal or post-natal life by adding methimazole (MMI) to the drinking water of pregnant or lactating mothers. A group of newborn rats was treated with MMI and i.p. injections of L-tri-iodothyronine (L-T3). Hypothyroidism was shown by the reduced serum levels of total T3 and of total thyroxine (T4) in pregnant mothers and in pubertal rats. Testes were studied using light microscopy at 18 and 21 days post coitum or during puberty (21, 35 and 50 days after birth); serum levels of gonadotrophins were also evaluated in pubertal rats. Hypothyroidism had no effect on testicular development during fetal life and when induced in newborn rats it was associated at puberty with reduced serum levels of FSH and LH and with delayed maturation of the testis compared with control rats. The delay in maturation consisted of a reduction in the diameter of seminiferous tubules, and a reduction in the number of germ cells per tubule; this was associated with increased degeneration and arrested maturation of germ cells. In addition, Sertoli cells demonstrated retarded development, as indicated by a delay in the appearance of cytoplasmic lipids and in the development of a tubule lumen. Hormonal and morphological abnormalities were absent in rats treated with MMI plus L-T3. In conclusion, hypothyroidism occurring soon after birth caused reduced levels of gonadotrophins in the serum and a delay in pubertal spermatogenesis, possibly due to retarded differentiation of the Sertoli cells.

Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.

To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating endothelin-1 concentrations in patients with chronic hypoxia.

AIMS: To evaluate the behavior of plasma endothelin-1 in patients with chronic hypoxia. METHODS: Fifteen male patients (mean age 52.1 +/- 3.1 years) with mild chronic obstructive pulmonary disease (COPD) were studied. Twelve healthy men (mean age 48.3 +/- 5.4 years) served as controls. Both patients and controls underwent standard pulmonary function tests, echocardiographic evaluation, and arterial blood gas evaluation. Blood samples for endothelin-1 assay were taken from a previously incannulated antecubital vein after 60 minutes of rest in the supine position. Endothelin-1 was measured by radioimmunoassay after extraction from plasma. RESULTS: Patients with chronic hypoxia had lower PaO2 values (66.1 +/- 6.2 mmHg) than controls (83.8 +/- 2.7 mmHg) but PaCO2 values were similar (38.1 +/- 2.5 v 36.7 +/- 3.1 mmHg, respectively). Arterial pulmonary pressure, therefore, was higher in patients (18.1 +/- 3.7 mmHg) than in controls (10.4 +/- 2.7 mmHg) as were circulating endothelin-1 concentrations (1.22 +/- 0.36 v 0.57 +/- 0.1 pg/ml). Furthermore, plasma endothelin-1 concentrations were negatively correlated with PaO2 and directly correlated with pulmonary pressure levels. No significant correlations were found in controls. CONCLUSIONS: These results show a clear relation between chronic hypoxia and circulating endothelin-1 concentrations. Therefore, chronic hypoxia may be regarded as an important stimulus for endothelin-1 release and as one of the main contributors to increased vasoconstriction in the vascular pulmonary bed which often accompanies lung disease.

Interference of antisperm antibodies with the induction of the acrosome reaction by zona pellucida (ZP) and its relationship with the inhibition of ZP binding.

OBJECTIVE: To determine whether antisperm antibodies can interfere with the induction of the acrosome reaction (AR) by the zona pellucida (ZP) and whether this interference also can occur in the absence of an inhibitory effect on ZP binding. DESIGN: Prospective in vitro study. SETTING: A tertiary care center, the Andrologic Clinic, University of L'Aquila. PATIENT(S): Sera from 12 infertile patients with high titers of circulating antibodies directed against the sperm head were studied. INTERVENTION: None MAIN OUTCOME MEASURE(S): The effect of antisperm antibodies on ZP binding was evaluated by matching antibody-exposed and nonexposed donor sperm suspensions labeled with fluorescein or rhodamine, respectively, and incubated with the same salt-stored human ZPs. The effect of antibodies on ZP-induced AR was determined by challenging antibody-exposed and nonexposed donor sperm suspensions with human ZPs disaggregated with acidic NaH2PO4. Acrosomal status was evaluated using fluorescein-labeled Pisum sativum agglutinin and supravital stain Hoechst 33258. In some selected cases, the effect of antisperm antibodies on the acrosomal status of sperm bound to intact ZP also was evaluated using transmission electron microscopy. RESULT(S): Five of 12 sera exhibited an inhibitory effect on ZP binding. An inhibition of AR induction by disaggregated ZPs (ranging from 64% to 98%) was produced by all 5 sera with an inhibitory effect on ZP binding and by 2 of 7 sera without an inhibitory effect on ZP binding. The different effects of antisperm antibodies on AR induction by disaggregated ZP were confirmed by comparing with ultrastructural evaluations on the acrosomal status of sperm bound to intact ZP. CONCLUSION(S): Antisperm antibodies can interfere with the induction of AR by ZP. This inhibition can occur even in the absence of an inhibitory effect on ZP binding. Neither effect may occur.

Nongenomic progesterone receptor on human spermatozoa: biochemical aspects and clinical implications.

Progesterone (P) is a physiological stimulus of human sperm functions. It is present in high levels at the site of fertilization (cumulus oophorus) and has been described to affect several sperm functions, including motility, capacitation, acrosome reaction, and the ability to bind and to respond to zona proteins. The effects of the steroid are mediated essentially by an increase of intracellular calcium concentrations, stimulation of activity of phospholipases, phosphorylation of proteins, efflux of chloride. These effects are due to activation of a rapid, nongenomic pathway. Whether the effects of progesterone are mediated or not by specific interactions with sperm membrane proteins is questioned. By using an antibody directed against the C-terminal region (P-binding region) of the genomic receptor, we have recently identified two sperm proteins with molecular weights distinct from the classic genomic receptors. In addition, ligand blot analysis with peroxidase-conjugated P demonstrated that P specifically binds these two proteins. Classical ligand binding experiments demonstrated the presence of two specific binding sites with affinity in the nanomolar and in the micromolar range, respectively. The involvement of progesterone in the physiological process leading to fertilization of the oocyte is suggested by several studies. In particular, the demonstration that sperm responsiveness to progesterone is impaired in subfertile patients and that is strictly correlated to the ability of fertilizing the oocyte represents a further indication of the participation of the steroid in this process. In addition, the determination of sperm responsiveness may be predictive of fertilizing ability with a positive predictive value of 90% and can be clinically useful for the preliminary assessment of the male partner to select the appropriate assisted reproductive technique.

Circulating endothelin-1 levels in obese patients with the metabolic syndrome.

We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome.

Light microscopic, immunocytochemical and ultrastructural study of a case of Sertoli cell tumor of the testis.

A case of testicular specialized gonadal stroma tumor was evaluated by histologic, ultrastructural and immunohistochemical techniques in a young adult male patient. The neoplastic cells were organized in cords or tubular structures delimited by a basement membrane. The ultrastructural findings suggested a diagnosis of a partially differentiated Sertoli cell tumor. This was also supported by the presence of a vimentin rich cytoskeleton, which is normally present in Sertoli and Leydig cells. The tumor cells did not secrete steroid hormones, as suggested by clinical findings, as well as by hormonal, immunohistochemical, and ultrastructural observations.

Ultrastructure of fetal human gonad before sexual differentiation and during early testicular and ovarian development.

The development of the human gonad was investigated by light and transmission electron microscopy in 20 embryos and fetuses between 4.5 and 11.5 weeks of gestation, i.e. during the stages of sex-indifferent gonad, initial testicular and ovarian development. The gonadal blastema in 4.5-week-old embryos appeared formed by poorly differentiated somatic mesothelial cells, and by specialized germ cells (PGCs) with signs of ameboidism, cellular structures suggesting active protein biosynthesis and mitotic activity. The sexual differentiation of the gonads was clearly observed in 7-week-old embryos and involved at the same time the testis and the ovary. The former contained seminiferous cords formed by palisades of poorly differentiated Sertoli cells, which were segregated from the mesothelium by a rudimentary albuginea. The interstitial tissue at this age contained mesenchymal cells. Between 8 and 11.5 weeks of gestation, there was a synchronous cytodifferentiation of both Sertoli and Leydig cells. The latter acquired features of steroidogenic elements. The ovaries of 7-week-old fetuses contained packed ovigerous cords formed by somatic and germ cells (oogonia). The former embraced the oogonia with thin overlapping cytoplasm projections, and acquired features similar to those of cells in primary follicles, already at this early fetal age. At the same time the sexual differentiation of the gonads involved somatic and germ cells. In the female, the oogonia continued to show the main features they had during migration and colonization, including a high mitotic rate, signs of ameboidism and a developed apparatus for protein synthesis. On the contrary Gonocytes enclosed in the seminiferous cords progressively entered a quiescent phase characterized by a reduced mitotic rate, a decrease of endoplasmic reticulum and nucleolar complexity. The chronological relationship between the cytodifferentiation of Sertoli and Leydig cells, and changes of germ cells, suggest that somatic components of the testis may contribute to a male type of differentiation of germ cells from the very beginning of sexual differentiation.

Vitamin D protects human endothelial cells from H2O2 oxidant injury through the Mek/Erk-Sirt1 axis activation.

Endothelium homeostasis alterations govern the pathogenesis of cardiovascular diseases. Several studies show that vitamins anti-oxidant proprieties rescue the endothelial functions adversely affected by oxidative stress in several diseases. We investigated the vitamin D anti-oxidant potential in human endothelial cells exposed to H2O2 oxidative stress. Vitamin D protected endothelial cells against H2O2 oxidative stress counteracting the superoxide anion generation, the apoptosis and blocking the extrinsic caspase cascade by positively controlling phospho-active ERKs level. MEKs/ERKs inhibitor U0126 reverted the vitamin D anti-oxidant effects. Characterizing the vitamin D downstream effector, we found that vitamin D up-regulated SirT-1 and reverted the SirT-1 down-regulation induced by H2O2. ERKs activation by vitamin D strictly correlated with SirT-1 protein accumulation since both MEKs/ERKs inhibition and ERK1/2 silencing decreased SIRT-1. SirT-1 inhibition by Sirtinol reverted the vitamin D anti-oxidant effects. Thus, vitamin D significantly reduced the endothelial malfunction and damage caused by oxidative stress, through the activation of MEKs/ERKs/SirT-1 axis.

Postnatal development and distribution of peptide-containing nerves in the genital system of the male rat. An immunohistochemical study.

The distribution and relative density of peptide-containing nerves was studied in the rat in order to assess the progression of neuronal changes during the postnatal development of the male genital system from the prepubertal age to adulthood. Testis, caput and cauda epididymis, ductus deferens, seminal vesicles, prostate and penis from 8-, 20-, 38-, and 70-day-old rats were sectioned and were immunostained with antisera to the neuropeptides calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and to a general neuronal marker, protein gene product 9.5 (PGP 9.5). The testicular parenchyma and caput epididymis did not show any immunoreactivity. Very scattered CGRP-containing nerves were present in 8-day-old rats; numerous VIP-, CGRP-, and NPY-peptide-containing nerves were observed in the cauda epididymis, ductus deferens, accessory glands and penis of 20-day-old rats. The number of nerves increased in 35-day-old rats while no changes were observed in more adult rats. A parallel increase was seen for the immunostain for PGP 9.5. These data suggest that peptide-containing nerves appear in the genital system after birth and reach a full development before the completion of puberty. Peptide-containing nerves were visible first in the interstitial area and then spread in the muscular coat of the ducts, glands and of the blood vessels. While CGRP- and NPY-containing nerves were distributed in the vicinity of the muscle cells, VIP-containing nerves were also observed in the subepithelial regions, suggesting a possible role of this neuropeptide in the control of epithelial functions.

Quantitative parameters of seminiferous epithelium in secretory and excretory oligoazoospermia.

Testicular biopsy specimens from infertile men (sperm count, less than 10(6)/ml) were evaluated on 1-micron thick sections, and counts of stem cells and differentiated spermatogonia, primary spermatocytes, early and late spermatids, and Sertoli cells were compared to counts in six fertile men. Biopsy specimens were also compared for the appearance of seminiferous tubule wall, blood vessels, and interstitium. Infertile men were grouped according to the following diagnoses: hypospermatogenesis (n = 5), spermatocyte arrest of spermatogenesis (n = 5), and obstruction of the genital tract (n = 7). A low productivity of spermatogenesis in cases of hypospermatogenesis appeared to be due to an exaggerated degeneration of primary spermatocytes and to a yield of abnormal spermatids. A block of meiosis in spermatocyte arrest was associated with a degeneration of primary spermatocytes and with a reduced number of staminal spermatogonia. Abnormal spermiogenesis was observed in cases of obstruction of the genital tract and was associated with an increase in stem cell spermatogonia. A thickening of seminiferous tubule and blood vessel walls could be responsible for the limited functional capacity of Sertoli cells, causing altered spermiogenesis in cases of excretory azoospermia. A severe primitive failure of Sertoli cells in secretory oligoazoospermia could account for a deranged maturation and degeneration of premeiotic and postmeiotic germ cells.

[Gonadotropin response to acute stimulation with LHFSHRH in idiopathic oligospermia. Preliminary results]. / Risposta gonadotropinica alla stimolazione acuta con GN-RH nell'oligosppermia idiopatica. Risultati preliminari.

Serum FSH and LH levels in basal conditions and after Gn-RH test were investigated in 15 idiopathic oligozoospermic patients. Basal FSH was significantly higher in oligospermic than in normal subjects and a negative relationship was found between basal FSH and sperm count. Basal LH was not different in oligozoospermic and in normal subjects. Both FSH and LH responses to GN-RH were significantly higher in oligozoospermic patients. In idiopathic oligozoospermia the presence of a testicular defect involving both the seminiferous epithelium and Leydig cells is suggested.

[Development and differentiation of the rat epididymis. II: histochemical aspects of the peritubular zone]. / Sviluppo e differenziazione dell'epididimo di ratto. II: aspetti istochimici della zona peritubulare.

Development of the contractile peritubular structures of rat testis, from birth to full maturation, was investigated by histochemical evaluation of alkaline phosphatase activity (A.P.A.) at 0, 16, 22 e 35 days of age. A.P.A. appeared at 6 days, age of appearance also of the cytoplasmic microfilaments of peritubular cells. The correlation between cytoplasmic microfilaments and A.P.A. was confirmed by the pattern of A.P.A. positivity at 6 degree day, when the inner peritubular cells layer, in which the microfilaments are present, are more positive than the outer layer in which the microfilaments are not yet present. These findings give further support to the belief that the cytoplasmic microfilaments of peritubular cells are contractile structures.