Charge Disproportionation, Mixed Valence, and Janus Effect in Multiorbital Systems: A Tale of Two Insulators.

Multiorbital Hubbard models host strongly correlated "Hund's metals" even for interactions much stronger than the bandwidth. We characterize this interaction-resilient metal as a mixed-valence state. In particular, it can be pictured as a bridge between two strongly correlated insulators: a high-spin Mott insulator and a charge-disproportionated insulator which is stabilized by a very large Hund's coupling. This picture is confirmed comparing models with negative and positive Hund's coupling for different fillings. Our results provide a characterization of the Hund's metal state and connect its presence with charge disproportionation, which has indeed been observed in chromates and proposed to play a role in iron-based superconductors.

Treatment of male infertility.

Male factor infertility is a general term that describes a situation in which the inability to conceive is associated with an alteration identified in the male partner. This dysfunction may be associated with low sperm concentration (oligozoospermia), poor sperm motility (asthenozoospermia) or abnormal sperm morphology (teratozoospermia); however, generally, a disturbance of all these variables, oligoasthenoteratozoospermia, is mostly frequent in male subfertility. For many andrological disorders, it is not possible to find a reasonable cause and various uncontrolled treatments have been applied to infertile men, often just on an empirical basis. More recently, after the explosive development of modern assisted reproduction techniques (ARTs), feasible with a single spermatozoon [intracytoplasmic sperm injection (ICSI)], the treatment of male infertility has received new meaning and andrologists are no longer expected to achieve a quantitative increase in sperm number but are instead asked to improve the fertility potential of the single sperm cell in order to achieve better results in both in vitro fertilization and ICSI. Additional prospective studies are needed to better understand the possible role of therapy in ART candidate patients.

[Clinical and diagnostic approach to erectile dysfunction]. / Approccio clinico e diagnostico alla disfunzione erettile.

Erectile dysfunction (ED), defined as the inability to achieve and/or maintain an erection sufficiently long for a satisfactory sexual performance or intercourse, is an important and common medical problem. ED is not a life-threatening disorder, but it influences the daily routine, social interactions, well-being and quality of life of the patient. Recent epidemiological data have shown a high prevalence and incidence of ED. The Massachusetts Male Aging Study found that 52% of men between the ages of 40 and 70 years reported ED with 9.6% having mild, 22.2% moderate and 17.2% complete or severe ED. In a large Italian cross-sectional study the overall prevalence of self-reported ED was 12.8% and the frequency of ED increases with age. ED may signal serious underlying and potentially life-threatening diseases, such as diabetes, hypertension, cardiovascular disease, peripheral vascular disease and other neurological and endocrine disorders. Also well documented is the role of some drug groups, certain types of surgery, injuries and the role of risk factors related to lifestyle such as smoking, alcohol consumption and inappropriate dietary habits accompanied by an abnormal serum level of cholesterol. The current availability of effective and safe oral drugs for ED in conjunction with the tremendous media interest in the condition, have resulted in an increasing number of men seeking help for ED. As a consequence, many physicians without background knowledge and clinical experience in the diagnosis of ED are involved in making decisions concerning the evaluation of such patients. The result of this is that some males with ED may undergo little or no evaluation before treatment is initiated and, in such circumstances, the disease causing the symptom (ED) may remain untreated. Baseline diagnostic evaluation for ED can identify the underlying pathological condition or the risk factors associated with ED in 80% of patients. This article reports a sequential approach for the diagnosis of ED that may diagnose reversible causes of ED and also unmask medical conditions that manifest with ED as the first symptom.

Androgen modulation of pro-inflammatory and anti-inflammatory cytokines during preadipocyte differentiation.

BACKGROUND: Macrophages and adipocytes contribute to release of cytokines resulting in the chronic inflammatory profile of the metabolic syndrome. The local increase of proinflammatory cytokines impairs adipogenesis, resulting in formation of dysfunctional adipocytes that are unable to store and handle lipids. The altered lipid fluxes in/from adipocytes affect whole-body metabolism. We investigated the role of androgens on adipocyte-derived proinflammatory and anti-inflammatory cytokines during preadipocyte differentiation. MATERIALS AND METHODS: Various differentiation methods were used to obtain full conversion of 3T3-L1 into mature adipocytes. The degree of adipocyte conversion in the presence/absence of dihydrotestosterone (DHT) was analyzed by measuring intracellular triglycerides (Oil Red O staining). The effects of DHT administration on interleukin 1ß (IL-1ß), IL-2, IL-6, IL-10, IL-12, interferon γ (IFNγ) and tumor necrosis factor α (TNFα) secretion was measured at days 0, 4, 6 and 8 of differentiation using the SearchLight multiplex protein array. RESULTS: DHT regulates a number of cytokines in committed and mature 3T3-L1 adipocytes. IL-1ß and TNFα were readily suppressed at the very early stages of differentiation. IFNγ release was inhibited at day 4, but the effect was no longer detectable on day 8. IL-6 and IL-12 were significantly reduced at day 8 of differentiation. Conversely, the differentiation-dependent increase of IL-2 and IL-10 was further stimulated by DHT since day 0. CONCLUSIONS: We provide evidence that androgens promote an anti-inflammatory profile that parallels the acquisition of a functional adipocyte phenotype. The crosstalk between androgens, adipocyte-derived mediators of inflammation and intracellular lipid fluxes could have profound implications on metabolism of men with obesity and metabolic syndrome.

Medical treatment to improve sperm quality.

Approximately 30% of cases of couple infertility are due to a male factor. Several conditions can interfere with spermatogenesis and reduce sperm quality and production. Treatable conditions, such as hypogonadism, varicocele, infections and obstructions, should be diagnosed and corrected, but many aspects of male factor infertility remain unclear. Various agents have been used in the attempt to increase the fertility potential of subjects with idiopathic oligoteratoasthenozoospermia. The rationale of medical treatment to improve sperm quality in these subjects has been questioned by the introduction of assisted reproductive technologies. However, there is now growing awareness of the importance of good quality spermatozoa for embryonic development and higher birth rates. Confounding factors in assessing the efficacy of male infertility treatments have erroneously inflated the superiority of assisted reproductive technologies over conventional approaches. A systematic review is given of relevant randomized controlled trials and effects on semen parameters. The analysis reveals that although results are heterogeneous, gonadotrophins, anti-oestrogens, carnitine and trace elements may be beneficial in improving sperm quality, although their effect on pregnancy rate remains controversial. The most common drug regimens are compared and an estimate of the results expected from these treatments provided.

Altered melatonin secretion in hypogonadal men: clinical evidence.

The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary-gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release.

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.

OBJECTIVES: Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. CONCLUSION: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Effects of testosterone on sexual function in men: results of a meta-analysis.

OBJECTIVES: The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta-analysis of placebo-controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed in MEDLINE, the Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, a total of 17 randomized placebo-controlled trials were found to be eligible. For each domain of sexual function we calculated the standardized mean difference relative to T and reported the results of pooled estimates of T treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross-over. The median study length was 3 months (range 1-36 months). Our meta-analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut-off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta-regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta-analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low-normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long-term safety data are not available. The present meta-analysis highlights the need, and pitfalls, for large-scale, long-term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle-aged and elderly men with reduced T levels and ED.

Acute electroretinographic changes during sildenafil (Viagra) treatment for erectile dysfunction.

The authors describe their findings on 12 subjects who were treated with 50 mg of sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka-Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in Vmax (higher rod response to light stimuli) and a decrease in K (higher sensitivity).