The intertwining between lead and ethanol in the model organism Caenorhabditis elegans.

Caenorhabditis elegans (C. elegans) is a model organism widely used to evaluate the mechanistic aspects of toxicants with the potential to predict responses comparable to those of mammals. We report here the consequences of developmental lead (Pb) exposure on behavioral responses to ethanol (EtOH) in C. elegans. In addition, we present data on morphological alterations in the dopamine (DA) synapse and DA-dependent behaviors aimed to dissect the neurobiological mechanisms that underlie the relationship between these neurotoxicants. Finally, the escalation to superior animals that parallels the observed effects in both experimental models with references to EtOH metabolism and oxidative stress is also discussed. Overall, the literature revised here underpins the usefulness of C. elegans to evidence behavioral responses to a combination of neurotoxicants in mechanistic-orientated studies.

Inhibidores de histidina decarboxilasa atenúan la actividad proangiogénica de células de Leydig tumorales: ¿Potencial terapia neoadyuvante para el tratamiento de leydigiomas? / Histidine decarboxylase inhibitors attenuate the pro angiogenic activity of Leydig tumor cells: Potential neoadjuvant therapy for the treatment of leydigiomas?

Resumen Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.

ABSTRACT Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.

Probiotic activity of Enterococcus faecalis CECT7121: effects on mucosal immunity and intestinal epithelial cells.

AIMS: To analyse the effect of Enterococcus faecalis CECT7121 on intestinal epithelial cells (IECs) and its effects on the mucosal immune response. METHODS AND RESULTS: Enterococcus faecalis CECT7121 showed a high adhesion capacity to completely and heterogeneously differentiated human intestinal epithelial cell line (Caco-2 cells). In addition, the contact of this bacterium with Caco-2 cells did not induce inflammatory chemokines (IL-8 and CCL-20). The presence of IgA(+) and IL-6(+) cells in the small intestine, as well as the production of inflammatory cytokines (TNFα, IL-6 and IL-12) in the gut, was determined after intragastric inoculation of Ent. faecalis CECT7121 in BALB/c mice. The administration of Ent. faecalis CECT7121 increased the number of IgA(+) cells in the intestinal lamina propria without modifying the percentage of IL-6(+) cells. No differences were observed in the cytokines measured in the intestinal extracts between probiotic-treated and control mice. CONCLUSIONS: Enterococcus faecalis CECT7121 stimulates local mucosal immunity and adheres to IECs without inducing inflammatory signals. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results indicate that, apart from its already reported systemic immune activity, Ent. faecalis CECT7121 has a modulatory effect at a local level.

Melatonin in testes of infertile men: evidence for anti-proliferative and anti-oxidant effects on local macrophage and mast cell populations.

Melatonin acting through the hypothalamus and pituitary regulates testicular function. In addition, direct actions of melatonin at the testicular level have been recently suggested. We have described that melatonin inhibits androgen production in hamster Leydig cells via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. The initial events of the melatonin/CRH signalling pathway have also been established. Melatonin and all components of the melatonergic/CRH system were also detected in Leydig cells of infertile men. This study attempted to search for additional targets of melatonin in the human testis, and to investigate the effects of melatonin on proliferation and the oxidative state in these novel target cells. To this aim, evaluation of human testicular biopsies of patients suffering from hypospermatogenesis or Sertoli cell only syndrome and cell culture studies were performed. Melatonergic receptors were found in macrophages (MACs) and mast cells (MCs) of the human testis. In biopsies of patients suffering idiopathic infertility, melatonin testicular concentrations were negatively correlated with MAC number per mm(2) and TNFα, IL1ß and COX2 expression, but positively correlated with the expression of the anti-oxidant enzymes SOD1, peroxiredoxin 1 and catalase. Melatonin inhibited proliferation and the expression of pro-inflammatory cytokines and cyclooxygenase 2 (COX2) in both the human non-testicular THP-1 MAC cell line and primary cell cultures of hamster testicular MACs. In the human HMC-1 MC line, melatonin increased the expression of anti-oxidant enzymes and decreased reactive oxygen species (ROS) generation. The results reveal new testicular targets of melatonin and describe anti-proliferative and anti-inflammatory effects of this hormone on testicular MACs. Furthermore, melatonin might provide protective effects against oxidative stress in testicular MCs.

Evidence for an adaptation in ROS scavenging systems in human testicular peritubular cells from infertility patients.

Fibrosis, increased amounts of immune cells and expression of COX-2 in the testes of infertility patients provide circumstantial evidence for a specific testicular milieu, in which reactive oxygen species (ROS) could be increased. If ROS level increase and/or ROS scavengers decrease, the resulting testicular oxidative stress may contribute to human male infertility. Primary peritubular cells of the human testis, from men with normal spermatogenesis (HTPCs) and infertile patients (HTPC-Fs), previously allowed us to identify an end product of COX-2 action, a prostaglandin derivative (15dPGJ2), which acts via ROS to alter the phenotype of peritubular cells, at least in vitro. Using testicular biopsies we now found 15dPGJ2 in patients and hence we started exploring the ROS scavenger systems of the human testis. This system includes catalase, DJ-1, peroxiredoxin 1, SOD 1 and 2, glutathione-S-transferase and HMOX-1, which were identified by RT-PCR/sequencing in HTPCs and HTPC-Fs and whole testes. Catalase, DJ-1, peroxiredoxin 1 and SOD 2 were also detected by Western blots and in part by immunohistochemistry in testicular samples. Western blots of cultured cells further revealed that catalase levels, but not peroxiredoxin 1, SOD 2 or DJ-1 levels, are significantly higher in HTPC-Fs than in HTPCs. This particular difference is correlated with the improved ability of HTPC-Fs to handle ROS, which became evident when cells were exposed to 100 µm H(2)O(2). H(2)O(2) induced stronger responses in HTPCs than in HTPC-Fs, which correlates with the lower level of the H(2)O(2)-degrading defence enzyme catalase in HTPCs. The results provide evidence for an adaptation to elevated ROS levels, which must have occurred in vivo and which persist in vitro in HTPC-Fs. Thus, in infertile men with impaired spermatogenesis elevated ROS levels likely exist, at least in the tubular wall.

Abnormal assembly of annulate lamellae and nuclear pore complexes coincides with fertilization arrest at the pronuclear stage of human zygotic development.

BACKGROUND: The assembly of nuclear pore complexes (NPC) and their cytoplasmic stacks, annulate lamellae (AL), promote normal nucleocytoplasmic trafficking and accompany pronuclear development within the mammalian zygote. Previous studies showed that a percentage of human oocytes fertilized in vitro failed to develop normal pronuclei and cleave within 40-48 h post insemination. We hypothesized that an aberrant recruitment of NPC proteins, nucleoporins and/or NPC preassembled into AL, might accompany human fertilization arrest. METHODS AND RESULTS: We explored NPC and AL assembly in unfertilized human oocytes, and fertilized and arrested zygotes by immunofluorescence with an NPC- and AL-specific antibody, mAb 414, and by transmission electron microscopy. Major NPC or AL assembly was not observed in the unfertilized human oocytes. Once fertilization took place, the formation of AL was observed throughout the cytoplasm and near the developing pronuclei with NPC. On the contrary, NPC assembly was disrupted in the arrested zygotes, whereas AL were clustered into large sheaths. This was accompanied by the lack of NPC incorporation into the nuclear envelopes. CONCLUSIONS: We conclude that the aberrant assembly of NPC and AL coincides with early developmental failure in humans.

[Use of sildenafil in the chronic uremic patient]. / L'uso del sildenafil nel paziente uremico.

BACKGROUND: Erectile dysfunction is one of the factors influencing negatively the quality of life of patients in hemodialytic treatment. The international literature shows that erectile dysfunction is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialytic treatment. Fertility, libido and erectile dysfunction, suffer progressive worsening with time, in spite of hemodialysis. The availability of a drug like Sildenafil can improve the quality of life of the patient and give him a normal sexual activity. METHODS: Twenty patients between 29 and 51 years, were selected; 2 of these had been subjected to renal transplant, with a dialytic treatment time varying from 3 to 13 years. Before the treatment all the patients have been subjected to an andrological screening (testosterone, prolactin, penile color Doppler ultrasound) and proposed the IIEF test. Therapeutic strategy included the assumption of the drug in the days in which the patients were not subjected to dialysis, with an interval from 1 to 3 weeks between assumption and another. The dose was 25-50 mg. At the end of three months of therapy the patients were again subjected to the IIEF test. RESULTS: All patients reported an improvement in sexual activity and sexual desire with very good repercussions on general and psychophysical conditions. CONCLUSIONS: The results demonstrate at least that Sildenafil is also effective in uremic patients in dialytic treatment or after renal transplant and that it can therefore resolve one of the main problems for the normal development of the life of such patients.

Controversies in the evolution of paediatric-adolescent varicocele: clinical, biochemical and histological studies.

OBJECTIVE: To study hormonal and histological parameters of paediatric-adolescent varicocele in order to know certain aspects of its natural history, in an attempt to find prognostic markers of testicular damage. DESIGN AND METHODS: In a prospective cross-sectional study, we evaluated 93 children and adolescents with left unilateral varicocele and 29 healthy males as control group. All of them were classified according to Tanner stage. Scrotal Doppler in both testes and GnRH and human chorionic gonadotrophin (hCG) tests were performed in all subjects. Surgery was performed in 28 patients and homolateral testicular biopsy in 18. RESULTS: Hormonal measurements of patients with varicocele were compared with a control group for each Tanner stage. Testicular biopsy specimens were analysed by light and electron microscopy. We only observed statistical differences in Tanner III patients in basal FSH (median and range) controls=1.70 (1.10-3.70) IU/l vs varicocele=4.20 (1.00-7.50) IU/l, P<0.05 and in Tanner IV patients in LH post-GnRH: controls=11.0 (7.50-15.0) IU/l vs varicocele=18.0 (5.10-29.0) IU/l, P<0.05 and in testosterone post-hCG: controls=9.50 (7.7-10.0) ng/ml vs varicocele=12.0 (6.2-23.0) ng/ml, P<0.01. No correlation was found between the various clinical grades of varicocele and hormonal measurements for each Tanner stage. No statistically significant differences were found between pre- and post-operative hormonal findings, either in basal levels or in maximal responses. On the other hand, no morphological abnormalities were observed by electron microscopy in germ cells, tubular wall and interstice. CONCLUSIONS: There appears to be no reliable biochemical marker in children and adolescents that may predict impaired testicular function. A significant size discrepancy between both testes, testicular pain and a hyperresponse to GnRH stimulation should continue to be, for the time being, the indications for surgery.

Passive immunization with anti-laminin immunoglobulin G modifies the integrity of the seminiferous epithelium and induces arrest of spermatogenesis in the guinea pig.

In the testis, the base of the Sertoli cells is in contact with the basement membrane matrix, in which the laminins constitute the major noncollagenous components. We have previously demonstrated that antibodies against a preparation enriched in basement membranes of seminiferous tubules (STBM) or a noncollagenous fraction of STBM passively transferred induced modifications to the basement membranes and focal sloughing of the seminiferous epithelium in the rat. In the present report, we tested the effect of passive immunization with anti-laminin IgG on the limiting membrane of the seminiferous tubules, spermatogenesis, and maintenance of the blood-testis barrier in the adult guinea pig. Rabbit antibodies to laminin 1 (IgG fraction) were injected in adult male guinea pigs (GP). Nonimmunized GP and GP immunized with normal rabbit serum IgG were used as controls. Measurements of variations in the diameter and lumen of the tubules and in the size of individual components of the tubular limiting membrane showed that the highest percentage of tubules with reduced lumen occurred 30 days after passive immunization with anti-laminin, when the limiting membrane was thickest and lesions to the seminiferous epithelium were most severe. The lesions included thickening of the limiting membrane, infolding in the basal lamina, deposits of immune complexes coincident with sloughing of pachytene spermatocytes and spermatids, and vacuolization of the Sertoli cells. Mononuclear cell infiltration of the tubules was rare. Permeability tracer studies revealed that Sertoli cell tight junctions remained impermeable. Fifty and 80 days after treatment, the basement membrane of the tubules and the progression of the spermatogenesis were normal. Passive immunization with anti-laminin IgG provided a valuable experimental model for the in vivo study of the influence of the basement membrane on the issue of spermatogenesis and the integrity of the seminiferous epithelium.

Aggressive treatment of 119 open fracture wounds.

BACKGROUND: The purpose of this study was to determine whether immediate primary closure of open fracture wounds can be performed without increasing the incidence of infections and delayed unions/nonunions. Although the traditional management of these injuries has been open treatment, a trend toward immediate primary closure has evolved on our service. METHODS: All open fractures presenting to an urban Level I trauma center during a 42-month period were reviewed. Of the 127 patients with open fractures, 90 patients (119 open fractures) were initially treated at the above institution within 24 hours of injury, had fractures proximal to the carpus or tarsals, and were followed-up until fracture union. All patients underwent emergent wound irrigation and debridement. The method of fracture immobilization and timing of wound closure was left to the discretion of the attending orthopedic surgeon. Immediate primary closure was used in 22 of 25 Grade I open fractures (88%), 37 of 43 Grade II fractures (86%), 24 of 32 Grade IIIa fractures (75%), 4 of 12 Grade IIIb fractures (33%), and 0 of 7 Grade IIIc fractures (0%). RESULTS: Eight fractures (7%) were complicated by a deep wound infection/osteomyelitis, and 19 fractures (16%) developed a delayed union/nonunion. Statistical analysis revealed no significant difference in delayed/nonunion and infection rates between immediate and delayed closures. CONCLUSION: Immediate primary closure of open fracture wounds after a thorough debridement by an experienced fracture surgeon appears to cause no significant increase in infections or delayed union/nonunions. In addition, early closure may decrease the requirement for subsequent debridements and soft-tissue procedures, thereby minimizing surgical morbidity, shortening hospital stays, and reducing costs. We feel that a randomized, prospective study of this aggressive approach to open fracture care is warranted.

[Role of color Doppler ultrasonography with contrast media in the monitoring of hepatocarcinoma after intralesional treatment]. / Ruolo dell'eco color Doppler con mezzo di contrasto nel monitoraggio dell'epatocarcinoma dopo trattamento intralesionale.

INTRODUCTION: We investigated the accuracy of contrast-enhanced color Doppler US in the assessment of the effectiveness of intralesional treatment of hepatocarcinomas. MATERIAL AND METHODS: Eight cirrhotic patients (HCV+), Child-Pugh class B, with a single hepatocarcinoma (< 4 cm O) and ineligible for surgical resection for various reasons (age > 70 years, reduced partial hepatic reserve, esophageal varices at risk, postoperative recurrence, no consent to the operation) were submitted to radiohyperthermia (6 patients) and percutaneous alcoholization (2 patients). The diagnosis was made with alpha-fetoprotein titration. CT, B-mode and color Doppler US with the administration of Levovist (Schering AG, Berlin, Germany). Thirty and 60 days after the treatment, both the alpha-fetoprotein titration and contrast-enhanced color Doppler US were repeated. RESULTS: Baseline color Doppler was carried out before intralesional treatment in the 8 patients and was followed by Levovist color Doppler which showed some intralesional signals, afferent vessels and rich vascularization in all the lesions. At the first follow-up (30 days), no intralesional vascular signals or afferent vessels were detected in any patient, while rich peripheral vascularization persisted in all cases, even after radiofrequency and alcoholization treatments. At 60 days' follow-up, the color Doppler pattern of all cases was the same as at 30 days. CONCLUSIONS: The absence of any intralesional vascular signals in all the treated patients and the possible demonstration of complete tumor necrosis seem to confirm the important role of contrast-enhanced color Doppler US in monitoring focal hepatic lesions after intralesional treatment.

[An update in the diagnosis and treatment of tumors of the hepatic portal]. / Attualità nella diagnosi e nel trattamento dei tumori della placca ilare.

BACKGROUND: Cholangiocarcinoma affecting the cross of the bile ducts is a tumour which has, although treatments, a high rate of mortality. METHODS: Between January 1986 and January 1996 six patients affected by Klatskin's tumor were studied; three of them underwent operation and were treated with insertion of a T tube (Kerr), whereas the other three were managed endoscopically with trans-tumoral stenting. RESULTS: The survival rate was about seven months for patients who underwent operation and fifteen months for patients managed with endoscopic stenting. CONCLUSIONS: After a review of the literature and according to personal experience, it is underlined that only an early diagnosis can achieve best results, since the latest knowledge about hepatic anatomy derived from transplants allows more extensive resections.

Atypical cilia in testicular cells from normal rats.

During our observations solitary cilia have been noted in Sertoli cells, fibroblasts and myoid cells of the rat testes. They mostly presented a 9 + 0 pattern and appeared similar to those previously reported in other cell types. In the present report, we describe their structure and analyze their putative functional significance.

Reconstruction of the dysplastic spastic hip with peri-ilial pelvic and femoral osteotomy followed by immediate mobilization.

All children with cerebral palsy who had a pelvic osteotomy performed by the senior author (F.M.) from 1989 through 1991 were reviewed. Indications for operative reconstruction were failed muscle lengthening in a child younger than 8 years or a painful hip. The operative procedure included adductor muscle lengthening, varus shortening femoral osteotomy, and peri-ilial pelvic osteotomy. Patients were immediately mobilized after surgery by physical therapy. Fifty-one children had reconstruction of 49 subluxated and 21 dislocated hips. Femoral and pelvic osteotomies were performed on 59 hips, and 11 hips had only a femoral osteotomy. Forty-nine hips had adductor muscle lengthening, and 27 hips had femoral osteotomy to provide for relief of contractures. At mean follow-up of 34 months, two hips in two patients had redislocated, requiring repeated surgery. Two hips remained subluxated and asymptomatic. Twenty-three hips in 18 patients were painful before surgery. One hip continued with severe pain after surgery, requiring further surgery. Three hips continued with mild pain not requiring surgery, and 14 (82%) hips had complete pain relief. Of 37 caretakers interviewed, 80% felt the procedure was beneficial and would recommend it to others. Eight percent were uncertain, and 6% (two caretakers) thought it was not helpful.

The abnormal development of male sex organs in the rat using a pure antiandrogen and a 5 alpha-reductase inhibitor during gestation.

The effects of a pure antiandrogen flutamide and the 5 alpha-reductase inhibitor finestaride on both prenatal differentiation of prostate and external genitalia were studied in the rat. In control male offspring the mean value of anogenital distance was 3.1 +/- 0.24 mm, and in control female was 1.2 +/- 0.10 mm. In control male newborn rats, histological sections at cranial portion of the urethra revealed prostate bud formation. Male offspring prenatally exposed to 6 mg/Kg/day of flutamide had a significant decrease in anogenital distance, but no alteration in prostate bud formation. At higher dosages of flutamide, the external genitalia were virtually feminizated and the prostatic budding was completely inhibited. In male offspring treated 'in utero' with doses of finestaride of 2, 8 and 16 mg/Kg/day, the anogenital distance became progressively reduced, but complete abolition of prostate development never occurred. However, in male offspring given finestaride at a dose of 2 mg/Kg/day concomitantly with flutamide at a dose of 6 mg/Kg/day, prostate differentiation was completely abolished.

Serum luteinizing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal follicle stimulating hormone serum concentrations.

The purpose of the study was to evaluate pulsatile luteinizing hormone (LH) release and intratesticular concentrations of testosterone and oestradiol in infertile men, to determine if alterations in gonadotrophin secretion are associated with changes in the testicular concentrations of steroids. Patients with idiopathic oligo/azoospermia were divided into a high follicle stimulating hormone (FSH) group (n = 5) and a normal FSH group (n = 6). Blood samples were taken every 15 min for 6 h to determine LH, FSH, testosterone, oestradiol, sex hormone binding globulin, bioactive LH and bioavailable testosterone. The patients underwent a bilateral testicular biopsy for histological assessment and to determine testosterone and oestradiol concentrations. Serum measurements were compared with those of seven fertile men. The high FSH group had a higher concentration of serum LH and oestradiol than normal men (P < 0.01) and showed a lower frequency of LH pulses than the normal FSH group and control men (P < 0.01). Intratesticular oestradiol was higher in the high FSH group (P < 0.001), with a lower testosterone/oestradiol ratio (P < 0.01). Patients showed a negative correlation between the serum testosterone/LH ratio and FSH (r = -0.75; P < 0.01) and a positive correlation between the testicular oestradiol concentration and serum FSH (r = 0.86; P < 0.01). The histopathological examination only showed a smaller tube diameter in the high FSH group (P < 0.05). These data seem to indicate that a higher intratesticular concentration of oestradiol with a lower testosterone/oestradiol ratio in the high FSH group could have a deleterious effect on spermatogenesis.

[Hormonal markers of early-stage osteitis fibrosa in patients on hemodialysis]. / Indici ormonali di osteite fibrosa in fase iniziale nel paziente emodializzato.

The diagnosis of renal osteodystrophy is straightforward when the disease has reached an advanced stage and the pathology is extremely difficult to treat, whereas it is considerably more complex during the early stages. A study was carried out to assess the sensitivity of some biochemical, hormonal and instrumental markers in the early diagnosis of osteitis fibrosa in patients undergoing hemodialysis due to chronic renal insufficiency. Of these markers, the assay of whole molecule PTH appeared to be the most sensitive and specific biological marker.

[Use of ultrafiltration in refractory cardiac decompensation]. / Impiego dell'ultrafiltrazione nello scompenso cardiaco refrattario.

Traditional therapy for heart failure (diuretics, digitalic compound, vasodilators, inodilatory ACE-inhibitors) cannot arrest the progressive overloading of the circulatory system so that it is inevitable that a refractory stage to all forms of treatment will be reached when more specialised techniques, such as heart transplant and ultrafiltration will be needed. The paper reports the results obtained in 13 patients in ultrafiltration treatment for refractory heart failure: in the majority of these, a marked improvement in general conditions (edema, dyspnea) was recorded together with a regression from class 5 to class 3 NYHA in 5 patients, and to class 2 for others. The ultrafiltration method in spite of not altering the prognosis which remains negative in these patients, allow those waiting for heart transplant to survive and may improve their chances of surviving heart surgery.