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The role of oxidative stress (OS) in male infertility as a primary etiology and/or concomitant cause in other situations, such as inflammation, varicocele and gonadotoxin effects, is well documented. While reactive oxygen species (ROS) are implicated in many important roles, from spermatogenesis to fertilization, epigenetic mechanisms which are transmissible to offspring have also recently been described. The present review is focused on the dual aspects of ROS, which are regulated by a delicate equilibrium with antioxidants due to the special frailty of spermatozoa, in continuum from physiological condition to OS. When the ROS production is excessive, OS ensues and is amplified by a chain of events leading to damage of lipids, proteins and DNA, ultimately causing infertility and/or precocious pregnancy termination. After a description of positive ROS actions and of vulnerability of spermatozoa due to specific maturative and structural characteristics, we linger on the total antioxidant capacity (TAC) of seminal plasma, which is a measure of non-enzymatic non-proteic antioxidants, due to its importance as a biomarker of the redox status of semen; the therapeutic implications of these mechanism play a key role in the personalized approach to male infertility.

Popper’s original definition of truthlikeness relied on a central insight: that truthlikeness combines truth and information, in the sense that a proposition is closer to the truth the more true consequences and the less false consequences it entails. As intuitively compelling as this definition may be, it is untenable, as proved long ago; still, one can arguably rely on Popper’s intuition to provide an adequate account of truthlikeness. To this aim, we mobilize some classical work on partial entailment in defining a new measure of truthlikeness which satisfies a number of desiderata. The resulting account has some interesting and surprising connections with other accounts on the market, thus shedding new light on current attempts of systematizing different approaches to verisimilitude.

Background & aims: Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. Methods: We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m2), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H2O2-metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. Results: Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60 ± 8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. Conclusions: These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remai

According to the Bayesian view, scientific hypotheses must be appraised in terms of their posterior probabilities relative to the available experimental data. Such posterior probabilities are derived from the prior probabilities of the hypotheses by applying Bayes'theorem. One of the most important problems arising within the Bayesian approach to scientific methodology is the choice of prior probabilities. Here this problem is considered in detail w.r.t. two applications of the Bayesian approach: (1) the theory of inductive probabilities (TIP) developed by Rudolf Carnap and other epistomologists and (2) the analysis of the multinational inferences provided by Bayesian statstics (BS). ... Zie: Summary

Oxidative stress is a mechanism underlying different kinds of infertility in human males. However, different results can be observed in relation to the method used for its evaluation. Varicocele patients show a number of biochemical abnormalities, including an altered distribution of coenzyme Q between seminal plasma and sperm cells and also an apparent defect in the utilization of antioxidants. Moreover, an influence of systemic hormones on seminal antioxidant system was observed too. Finally, the effects of surgical treatment on oxidativestress indexes and the possible usefulness of some medical therapies, like coenzyme Q supplementation, are discussed. In conclusion, published data show a role of oxidative stress in varicocele-related male infertility, but at present we do not know the precise molecular mechanisms underlying these phenomena.

Coenzyme Q(10) (CoQ(10)), also known as ubiquinone for its presence in all body cells, is an essential part of the cell energy-producing system. However, it is also a powerful lipophilic antioxidant protecting lipoproteins and cell membranes. Due to these two actions, CoQ(10) is commonly used in clinical practice in chronic heart failure, male infertility, and neurodegenerative disease. However, it is also taken as an anti-aging substance by healthy people aiming for long-term neuroprotection and by sportsmen to improve endurance. Many hormones are known to be involved in body energy regulation, in terms of production, consumption and dissipation, and their influence on CoQ(10) body content or blood values may represent an important pathophysiological mechanism. We summarize the main findings of the literature about the link between hormonal systems and circulating CoQ(10) levels. In particular the role of thyroid hormones, directly involved in the regulation of energy homeostasis, is discussed. There is also a link with gonadal and adrenal hormones, partially due to the common biosynthetic pathway with CoQ(10), but also to the increased oxidative stress found in hypogonadism and hypoadrenalism.

The role of adrenal steroids in antioxidant regulation is not known. Previously, we demonstrated some Coenzyme Q(10) (CoQ(10)) alterations in pituitary diseases, which can induce complex pictures due to alterations of different endocrine axes. Therefore we determined CoQ(10) and Total Antioxidant Capacity (TAC) in pituitary-dependent adrenal diseases: 6 subjects with ACTH-dependent adrenal hyperplasia (AH); 19 with secondary isolated hypoadrenalism (IH), 19 with associated hypothyroidism (multiple pituitary deficiencies, MPH). CoQ(10) was assayed by HPLC; TAC by the system metmyoglobin-H(2)O(2), which, interacting with the chromogenous 2,2(I)-azinobis-(3-ethylbenzothiazoline-6-sulphonate), generates a spectroscopically revealed radical compound after a latency time (Lag) proportional to the antioxidant content. CoQ(10) levels were significantly lower in IH than AH and MPH, with a similar trend when adjusted for cholesterol. Also TAC was lower in IH than in AH and MPH, suggesting that adrenal hormones can influence antioxidants. However, since thyroid hormones modulate CoQ(10) levels and metabolism, when thyroid deficiency coexists it seems to play a prevalent influence.

Oxidative stress, a condition defined as unbalancing between production of free radicals and antioxidant defenses, is an important pathogenetic mechanism in different diseases. Despite the abundant literature, many aspects of hormone role in regulating antioxidant synthesis and activity still remain obscure. Therefore, we reviewed experimental data, in vivo and in vitro, about the effects of the different pituitary- dependent axes on antioxidant levels, trying to give a broad view from hormones which also have antioxidant properties to the classic antioxidants, from the lipophilic antioxidant Coenzyme Q10, strictly related to thyroid function, to total antioxidant capacity, a measure of non-protein non-enzymatic antioxidants in serum and other biological fluids. Taken together, these data underline the importance of oxidative stress in various pituitary-dependent disorders, suggesting a possible clinical usefulness of antioxidant molecules.

Infertility is associated with oxidative stress, normally counterbalanced by different antioxidant systems. In order to explore the hormonal control of seminal plasma total antioxidant capacity (TAC) we evaluated TAC and hormone patterns in a group of unselected infertile patients and control subjects. One hundred and ten infertile patients (divided in three groups: inflammation, varicocele, other etiologies) and 31 fertile men were examined, evaluating blood serum gonadotropins, testosterone, estradiol, FT3, FT4, TSH, PRL, seminal parameters and TAC. TAC was measured using the H2O2-metmyoglobin system which generates the spectroscopically detectable radical cation of the chromogenous compound 2,2I-Azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS). The lag time of its appearance is proportional to the antioxidant activity. Lag phase was significantly higher in varicocele vs controls, whereas it was lower in patients with inflammation vs varicocele or other kinds of infertility. The correlation analysis between hormones and seminal parameters showed an inverse correlation between PRL and sperm motility, and a direct correlation of TAC with PRL and FT4, but not with gonadotropins or gonadal steroids. Our data suggest that systemic hormones may play a role in regulating seminal antioxidant capacity. This is interesting also because some hormones, such as thyroid and pituitary ones, are not usually tested in the first level evaluation of male patients with fertility problems.

Oxidative stress is involved both in metabolic syndrome and male infertility. Hypogonadism is also associated with increased risk for cardiovascular disease. To investigate the role of gonadal steroids in systemic antioxidant regulation, we determined plasma CoenzymeQ10 (CoQ10) and total antioxidant capacity (TAC) in postsurgical hypopituitaric patients. Twenty-six patients aged 28 55 years were studied 6 12 months after surgery. CoQ10 levels were measured by high-performance liquid chromatography and TAC by spectroscopy with the use of the mioglobin-H2O2 system, which, in interacting with chromogen 2,2I-azinobis-(3- ethylbenzothiazoline-6-sulfonate), generates a radical after a latency time (LAG) that is proportional to antioxidant content. Sixteen patients presented low testosterone values; in 10 patients hypogonadism was isolated, and in 6 patients hypothyroidism also was present. CoQ10 levels were significantly lower in isolated hypogonadism than in normogonadism. Testosterone treatment, performed in those patients with isolated hypogonadism, induced a significant enhancement both in CoQ10 level and LAG. CoQ10 and LAG values correlated significantly, suggesting an interrelationship between different antioxidants. Our data suggest that hypogonadism could represent a condition of oxidative stress, in turn related with augmented cardiovascular risk.

Biliopancreatic diversion (BPD) is a surgical procedure performed in patients with untreatable obesity and insulin resistance. The demonstrated metabolic and hormonal results of this procedure include: the reversal of insulin resistance, an increase in diet-induced thermogenesis and modifications of gut hormones, such as gastrin, enteroglucagone, neurotensin and cholecystokinin. On the other hand, obesity is a condition of increased oxidative stress; however few studies have investigated antioxidant systems in obese persons with BPD. In order to evaluate the metabolic status and antioxidant systems in such patients, we studied a group of 11 morbidly obese patients, aged 28-62 years, with a mean BMI of 54.71± 2.52 kg/m2, before and after successful BPD (mean post-BPD BMI 44.68 ± 1.51 kg/m2). A control group composed of ten slightly overweight women, with a mean BMI of 28.5±0.72 kg/m2, was also studied. Coenzyme Q10 (CoQ10) levels (also normalized for cholesterol levels) and Total Antioxidant Capacity (TAC) in blood plasma were assessed in these populations. The most striking datum was the extremely low level of CoQ10 in postoperative period (0.34±0.16 vs 0.66±0.09µg/ml, p=0.04); also the data corrected for cholesterol levels presented the same pattern, with a more marked significance (152.46±11.13 vs 186.4±17.98 nmol/mmol, p=0.001).This could be due to lipid malabsorption after surgery. In fact, the pre-BPD data present all the metabolic and hormonal characteristics of severe obesity and, after BPD, there was a net improvement in the metabolic parameters. The first pathophysiological phenomenon seems to be lipid malabsorption that has been argued to be cause of insulin resistance reversion. This metabolic interpretation is also confirmed by the absence of significant variations of TAC (57.5±5.3 vs 66±5.3). The mechanisms of these phenomena remain to be established. These data suggest the importance of correcting post-surgical metabolic complications, in these clinica

BACKGROUND: Maleness associated with 45,X karyotype is a very rare condition: Male differentiation implicates translocation of Y material on different autosomes (11,15,14,18 are described in literature). Previously, in our Institute of Genetics, a 25-year-old male with 45,X karyotype, was examined: testes and normal external genitalia were present. High resolution analysis of prometaphase chromosomes revealed additional euchromatic matherial on the short arm of one 15 chromosome; after in situ hybridisation with Y-specific probe pDP105, a significant grain accumulation was observed distal to 15p11.2, suggesting a Y/15 translocation. After 20 years, the patient again returned to our center with requests on sexual and fertility potential; he was re-examined, at clinical, genetical, hormonal metabolic level. METHODS: FISH analyses were performed on metaphase chromosomes. We also performed: standard oral glucose tolerance test (OGTT); basal and dynamic hormones assays; standard semen analysis according to WHO criteria; DEXA. RESULTS: FISH studies with LSI SRY (Vysis) probe showed positive signal on terminal p arm of chromosome 15; CEP Y (Vysis), and acro p-arm probe (Vysis) signals were both present on the derivative chromosome 15; RP11-75F5 BAC probe (Yq11.21) signal was present between the Y-specific and 15-specific centromeres. The patient had clinical criteria for metabolic syndrome; hypergonadotropinemic hypotestosteronemia was discovered. DISCUSSION: The interest of this case, other than natural history of such a rare condition, strongly reinforces metabolic role of testosterone and suggest that hypogonadism could play a role in the development of metabolic syndrome in our patient.

According to the Bayesian view, scientific hypotheses must be appraised in terms of their posterior probabilities relative to the available experimental data. Such posterior probabilities are derived from the prior probabilities of the hypotheses by applying Bayes'theorem. One of the most important problems arising within the Bayesian approach to scientific methodology is the choice of prior probabilities. Here this problem is considered in detail w.r.t. two applications of the Bayesian approach: (1) the theory of inductive probabilities (TIP) developed by Rudolf Carnap and other epistomologists and (2) the analysis of the multinational inferences provided by Bayesian statstics (BS). ... Zie: Summary