Search

Introduction: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. Methods: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). Results: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p= 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p= 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. Conclusions: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

Background: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.  Objective: We describe KS clinical presentation in a large Italian cohort. Design: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution. Methods: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients. Results: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p< 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis. Conclusions: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11Apolymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11Asequence in testicular cancer cases. Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11Apolymorphisms using peripheral blood samples. Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11Asequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. Conclusions: Our findings highlight the key role of PDE11Ain testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.

Purpose: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. Methods: This is a case–control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student’s ttest. Mann–Whitney test and Chi-square test. Results: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto’s thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. Conclusions: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

A large body of evidence suggests a role for vitamin D in conditioning cardiovascular risk. Therefore, it can be hypothesized that vitamin D might also play a role in influencing the metabolic profile of hypogonadal men. In this work, we aimed at evaluating if any relationship exists between vitamin D levels and cardiovascular parameters in male hypogonadism. Hypogonadal patients attending our andrology unit were retrospectively reviewed. Clinical and biochemical parameters were evaluated. 103 patients were studied (51 non-diabetic and 52 diabetic subjects). Mean age of the whole sample was 65 years (standard error of the mean: 0.62). Significant correlations of age, total testosterone, parathyroid hormone (PTH), calcemia, and 25-OH vitamin D with the metabolic profile were found. In logistic regression models including age, total testosterone, PTH, calcemia and 25-OH vitamin D as independent variables, lower levels of 25-OH vitamin D were associated with high values of body mass index (BMI) [odds ratio (OR) 0.910, p0.019], insulin (OR 0.918, p0.034), homeostatic model assessment (HOMA) index (OR 0.918, p0.030), total cholesterol (OR 0.819, p< 0.001), triglycerides (OR 0.820, p< 0.001), and low-density lipoprotein cholesterol (OR 0.923, p0.034). In non-diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of BMI, insulin, HOMA, triglycerides, systolic, and diastolic blood pressure. On the other hand, in diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of total cholesterol and triglycerides. Our work shows the influence of vitamin D on cardiovascular profile in male hypogonadism. This effect seems to be more relevant in non-diabetic subjects. If these data were to be confirmed, vitamin D assessment might become mandatory in the clinical evaluation of cardiovascular profile in male hypogonadism.

Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients’ interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.

Hypoparathyroidism and hypocalcemia are two of the most frequent clinical characteristics of 22q11-deletion syndrome (22q11DS). The aim of this study was to evaluate bone metabolism and density in a cohort of patients affected by 22q11DS. In 8 pediatric patients (mean age 11.5 years; range 7–16.4) affected by 22q11DS, creatinine, albumin, total and ionized calcium, phosphate, 25(OH) vitamin D, parathyroid hormone, osteocalcin, C-terminal telopeptide and interleukin 6 were assessed. Furthermore, bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry procedure. 14 healthy children were considered as controls. Most of the studied subjects were overweight and lacked quality physical activity. 40 % of the subjects had reduced calcium levels in the absence of related clinical symptoms and all patients also had inadequate levels of Vitamin D. The values of L1-L4 BMD were within the reference range in all patients (zscore <2). However, after comparing the age-matched indexes of bone mineralization of patients with those of controls, the former had lower bone mineralization indexes than the latter. In pediatric patients with 22q11DS, an initial and slight bone loss is evident. The incidence of hypocalcemia is underestimated because hypocalcemia is asymptomatic. Several factors contribute to bone impairment in children who still have to achieve bone mass peak. Therefore, we suggest strict monitoring of bone metabolism as well as BMD measurement in patients affected by 22q11DS.

We developed clinical practice guidelines to assess the individual risk–benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. Consensus was guided by a systematic review of controlled trials conducted on men with a mean T< 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee. We recommend Tsupplementation (TS) for adult men with severely reduced Tlevels (T< 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T< 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Osteoporosis is a major public health problem also in men and it recognizes hypogonadism as a major cause. To investigate the possible pathogenetic mechanisms on bone impairment in male hypogonadism and on its improvement in response to testosterone replacement treatment (TRT). We retrospectively investigated the hormonal profile and bone mineral density (BMD), evaluated by DXA, in 17 middle-aged hypogonadal men treated for at least 5 years with TRT, compared with 21 recently diagnosed untreated hypogonadal males and 18 age- and BMI-matched healthy subjects. No significant differences in clinical, biochemical and densitometric parameters were found among the three groups, with the exception of 25-OH vitamin D levels that were significantly higher in healthy subjects compared with hypogonadal patients. Untreated patients affected by central hypogonadism, despite similar hormonal levels, displayed significantly lower BMD and decreased LH and 25-OH vitamin D levels, compared with patients with primary hypogonadism. Among the treated patients, BMD parameters were similar regardless of the formulation of TRT. A recent history of central hypogonadism, compared with primary hypogonadism, appears to adversely affect bone health independently of gonadal steroids levels. This could be due to lower LH levels and consequent reduction of vitamin D 25-hydroxylation in the testis.

Glucagon-like peptide 1 (GLP-1) is an intestinal hormone secreted after the ingestion of various nutrients. The main role of GLP-1 is to stimulate insulin secretion in a glucose-dependent manner. However, the expression of GLP-1 receptor was found to be expressed in a variety of tissues beyond pancreas such as lung, stomach, intestine, kidney, heart and brain. Beyond pancreas, a beneficial effect of GLP-1 on body weight reduction has been shown, suggesting its role for the treatment of obesity. In addition, GLP-1 has been demonstrated to reduce cardiovascular risk factors and to have a direct cardioprotective effect, fostering heart recovery after ischemic injury. Further, data from both experimental animal models and human studies have shown beneficial effect of GLP-1 on bone metabolism, either directly or indirectly on bone cells. We review here the recent findings of the extra-pancreatic effects of GLP-1 focusing on both basic and clinical studies, thus opening future perspectives to the use of GLP-1 analogs for the treatment of disease beyond type 2 diabetes. Finally, the GLP-1 has been demonstrated to have a beneficial effect on both vascular, degenerative diseases of central nervous system and psoriasis.

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

Background:Hirsutism is defined as the presence of excessive terminal hair in androgen-dependent areas of a woman’s body. Regarding this it has been suggested that Lavender and Tea tree oils may have antiandrogenic activities. Aim:To evaluate therapy based on Lavender and Tea tree oils in women suffering from mild idiopathic hirsutism (IH). Subjects and methods:A prospective, open-label, placebo-controlled, randomized study was performed: women affected by mild IH were randomly assigned to receive oil spray containing Lavender and Tea tree oils (group T) (no.=12) or placebo (group P) (no.=12) twice a day for 3 months in areas affected by hirsutism. Evaluation of hirsutism was carried out at baseline and after 3 months by Ferriman-Gallwey score and by measuring hair diameter taken from some body areas. A hematological and hormonal evaluation was carried out at baseline and after 3 months. Results:No significant variations were found in any of the hormones studied in groups T and P between baseline and after 3 months. A statistically significant decrease of hirsutism total score and of hair diameter was found in group T, while no statistically significant difference in these two parameters was observed in group P; in group T percentual reduction of hair diameter was significantly greater than in group P. Conclusions:Lavender and Tea tree oils applied locally on skin could be effective in reducing mild IH; this treatment could represent a safe, economic and practical instrument in the cure of this disease.

Background:Despite their efficacy in the treatment of benign prostatic hyperplasia (BPH) the popularity of inhibitors of 5α-reductase (5ARI) is limited by their association with adverse sexual side effects. However, the real impact of 5ARI on sex hormones and sexual function is controversial. Aim:To investigate the role of 5ARI therapy on hormonal parameters and sexual function in men already complaining of sexual problems. Materials and methods:A consecutive series of 3837 men (mean age 63.5±12.8 yr) attending our outpatient clinic for sexual dysfunction was retrospectively studied. Several clinical, biochemical, and instrumental (penile color doppler ultrasound) factors were evaluated. Results:Among the patients studied, 78.7% reported erectile dysfunction, 51.1% hypoactive sexual desire (HSD), 86.7% perceived reduced sleep-related erections (PR-SRE) and 19.1 % premature ejaculation. The use of 5ARI was associated with an increased risk of HSD and PR-SR whereas no relationship was found with erectile dysfunction and ejaculation disturbances. Subjects using 5ARI also more frequently had gynecomastia along with reduced SHBG and higher calculated free testosterone levels. All these associations were confirmed in a case-control study comparing 5ARI users with age-body mass index-smoking status and total testosterone-matched controls. Conclusions:Our data indicates that use of 5ARI in men with sexual dysfunction does not significantly exacerbate pre-existing ejaculatory or erectile difficulties, but can further impair their sexual life by reducing sexual drive and spontaneous erection.

Background:The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified. Aim:To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification. Material and methods:A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study. Results:After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m2), all the aforementioned associations were confirmed only in non obese patients. Conclusions:Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism.

Recombinant GH therapy is normally administered to GH-deficient children in order to achieve a satisfactory height — the main target during childhood and adolescence. However, the role of GH does not end once final height has been reached, but continues during the so-called transition period. In this phase of life, the body undergoes several changes, both physical and psychological, that culminate in adulthood. During this period, GH has a part in numerous metabolic functions. These include the lipid profile, where it increases HDL and reduces LDL, with the global effect of cardiovascular protection. It also has important effects on body composition (improved muscle strength and lean body mass and reduced body fat), the achievement of proper peak bone density, and gonad maturation. Retesting during the transition period, involving measurement of IGF-I plus a provocative test (insulin tolerance test or GHRH + arginine test), is thus necessary to establish any persistent GH deficiency requiring additional replacement therapy. The close cooperation of the medical professionals involved in the patient’s transition from a pediatric to an adult endocrinologist is essential. The aim of this review is to point out the main aspects of GH treatment on body composition, metabolic and gonad functions in the transition period.

Nearly 70 years after its description, Klinefelter syndrome (KS) remains a largely undiagnosed condition. As its clinical presentation may be subtle, many of those affected may be unaware or diagnosed only during evaluation for hypogonadism and/or infertility. In February 2010 an interdisciplinary panel of specialists met in Abano Terme (Padua, Italy) in a workshop on “Klinefelter Syndrome: diagnosis and clinical management”. The main aim of this meeting was to discuss several aspects related to the epidemiology, pathogenesis, and evaluation of KS and to develop a consensus defining its early diagnosis and treatment. In the present consensus we have highlighted the features that may prompt the physicians to look after patients with KS both for the syndrome and correlated diseases. We have provided evidences that, during the different phases of life, there might be some advantages in establishing the diagnosis and starting proper follow-up and treatment. The workshop was carried out under the auspices of the Italian Society of andrology and Sexual Medicine (SIAMS).

In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed viaa series of hydroxylation, oxidation, and reduction steps into a vast array of biologically active compounds: mineralocorticoids, glucocorticoids, and sex hormones. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Sex hormones are essential for sex differentiation in male and support reproduction. They include androgens, estrogens, and progestins. A block in the pathway of steroid biosynthesis leads to the lack of hormones downstream and accumulation of the upstream compounds that can activate other members of the steroid receptor family. This review deals with the clinical consequences of these blocks.

Hypogonadotropic hypogonadism (HH), or secondary hypogonadism, is a clinical condition due to an impairment of the pituitary function, characterized by low testosterone plasma levels associated with normal or low FSH and LH plasma levels. An impairment of gonadotropin secretion and, therefore, a reduced efficiency of spermatogenesis was reported to be frequently associated to conditions different from the classical causes of secondary hypogonadism. These conditions (metabolic, endocrine and eating disorders, physical exercise etc.)have been associated with a non-classical form of HH that could be called “functional” HH (FHH). FHH differs from the classical one by the evidence that gonadotropin levels are in the low-normal range, but are inadequate for the testosterone levels, that often are also in the low-normal range. This commentary aims at reviewing knowledge on the forms of male HH in order to indicate and discuss clinical context, diagnostic and therapeutic approach in the less known non-classical form, i.e. FHH.

We had previously demonstrated that Coenzyme Q10[(CoQ10) also commonly called ubiquinone]is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10on sperm motility and function had been addressed only through some in vitroexperiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia

General dynamic penile color doppler ultrasound (D-PCDU) screening in patients with erectile dysfunction (ED) has been questioned due to an inadequate cost-benefit ratio. The aim of the present study is to evaluate the validity of different risk scores in the identification of patients being screened for arteriogenic ED (AED) at D-PCDU. A consecutive series of 738 patients with ED was studied. AED was defined when peak systolic velocity (PSV) was lower than 25 cm/sec. The assessment of cardiovascular risk was evaluated using different risk engines, derived from the Framingham, the PROCAM and the Progetto Cuore studies. An iterative receiver operator characteristic (ROC) curve analysis was used to determine the most proper threshold for different scales for the screening of AED. Among the patients studied, 52 (7%) had PSV<25 cm/sec. The area under the ROC curves for pathological PSV in relation to cardiovascular risk estimated with different engines was 0.762±0.03, 0.716±0.03, and 0.667±0.03 for Progetto Cuore, Framingham, and PROCAM engines, respectively. Sensitivity and specificity of Progetto Cuore estimated risk were 67%, 71 % when a threshold of 15% was chosen. Corresponding figures for Framingham and PROCAM engine were 74%, 57% and 69%, 55%, respectively. If D-PCDU is performed only on patients with cardiovascular risk >15%, who represent about 1/4 of all patients (26.8%), as estimated by Progetto Cuore, about 70% of cases of arteriogenic ED can be identified. Estimated cardiovascular risk, assessed through risk engines, could be used to identify patients who should undergo D-PCDU evaluation for the diagnosis of AED.

Background.Liver ischemia/reperfusion is frequently associated with organ injury to which reactive oxygen species contribute. The aim of our study was to evaluate cytosolic and mitochondrial glutathione levels and morphological changes in hepatocytes of rat liver in an experimental model of ischemia/reperfusion.

Summary The ependymal lining of the diencephalic third ventricle is known to exhibit significant variation in zonal architecture and the relations of neurites to the ventricular surface in different regions remains obscure. The present study explores the fine structural organization of the ependymal region of the thalamic paraventricular nucleus. Methodology was developed for tracing neurites of cells retrogradely labelled with horseradish peroxidase based on our recent observation that paraventricular neurons projecting to the amygdaloid complex cluster near the ventricle and emit numerous dendrites extending toward the ependymal surface.

A role for sex hormones in the pathogenesis of solid-cystic tumour (SCT) of the pancreas is suggested by its predilection for young fertile women. Controversial data have been provided for the presence of progesterone receptors (PR) and/or oestrogen receptors (ER) in SCT. We report the immunohistochemical detection of PR in ten cases of SCT. Eight were from young women. The remaining two were from a post-menopausal woman and a young boy. All cases showed PR immunoreactivity in the large majority of neoplastic cells, whereas none exhibited ER positivity. In one tumour two types of cell populations were noted, the more anaplastic invasivetype being PR negative, whereas the more typical was PR positive. PR immunoreactivity in the absence of ER may simply reflect a lower sensitivity of ER antibody failing to reveal the biochemically detectable ER, or that the PR in cells of SCT are constitutively synthesized in an oestrogen-independent way, as in T47D breast carcinoma cell line, meningioma cells and some gastric cancer cells. Our findings support the hypothesis of a possible pathogenetic role of progesterone in SCT, independent of the patient's sex and age.

The distribution of lanthanum on the taste disc of the frog,Rana esculenta, afteren blocstaining of the tongue with lanthanum nitrate was studied at the ultrastructural level by means of scanning electron microscopy (in the secondary electron mode or in the back scattered electron mode), energy-dispersive X-ray microanalysis, transmission electron microscopy and electron spectroscopic imaging. It was consistently found that lanthanum distribution on the surface of the taste disc is not homogeneous and that the surface of putative receptor cells is in contact with strongly lanthanum-positive material. Calcium co-localizes with lanthanum at that level. These results suggest that different microenvironments exist at the surface of the taste disc and that this could be relevant to the receptor function.

Summary: The ultrastructure of the centromedian nucleus of the monkey thalamus was analysed qualitatively and quantitatively and projection neurons, local circuit neurons, and synaptic bouton populations identified. Projection neurons were mostly medium-sized, with oval-fusiform or polygonal perikarya, few primary dendrites, and frequent somatic spines; local circuit neurons were smaller. Four basic types of synaptic boutons were distinguished: (1) Small- to medium-sized boutons containing round vesicles (SR) and forming asymmetric contacts, identified as corticothalamic terminals. (2) Heterogeneous medium-sized boutons with asymmetric contacts and round vesicles, similar to the so-called large round (LR) boutons, which were in part of cortical origin. (3) Heterogeneous GAD-positive small- to medium-sized boutons, containing pleomorphic vesicles and forming symmetric contacts (F1 type), which included pallidothalamic terminals. (4) Presynaptic profiles represented by GAD-positive vesicle-containing dendrites of local circuit neurons. Complex synaptic arrangements, serial synapses and triads with LR and SR boutons engaging all parts of projection neuron dendrites and somata, were seen consistently, whereas classical glomeruli were infrequent. LR and SR boutons also established synapses on dendrites of local circuit neurons. F1 boutons established synapses on projection neuron somata, dendrites and initial axon segments. Compared to other previously studied motor-related thalamic nuclei, differences in synaptic coverage between proximal and distal projection neuron dendrites were less pronounced, and the density of synapses formed by local circuit dendrites on projection neuron dendrites was lower. Thus, compared to other thalamic nuclei, the overlap of different inputs was higher on monkey centromedian cells, and centromedian inhibitory circuits displayed a different organization.