On the dose-response association of fine and ultrafine particles in an urban atmosphere: toxicological outcomes on bronchial cells at realistic doses of exposure at the Air Liquid Interface.

Air pollution and particulate matter (PM) are the leading environmental cause of death worldwide. Exposure limits have lowered to increase the protection of human health; accordingly, it becomes increasingly important to understand the toxicological mechanisms on cellular models at low airborne PM concentrations which are relevant for actual human exposure. The use of air liquid interface (ALI) models, which mimic the interaction between airborne pollutants and lung epithelia, is also gaining importance in inhalation toxicological studies. This study reports the effects of ALI direct exposure of bronchial epithelial cells BEAS-2B to ambient PM1 (i.e. particles with aerodynamic diameter lower than 1 µm). Gene expression (HMOX, Cxcl-8, ATM, Gadd45-a and NQO1), interleukin (IL)-8 release, and DNA damage (Comet assay) were evaluated after 24 h of exposure. We report the dose-response curves of the selected toxicological outcomes, together with the concentration-response association and we show that the two curves differ for specific responses highlighting that concentration-response association may be not relevant for understanding toxicological outcomes. Noteworthy, we show that pro-oxidant effects may be driven by the deposition of freshly emitted particles, regardless of the airborne PM1 mass concentration. Furthermore, we show that reference airborne PM1 metrics, namely airborne mass concentration, may not always reflect the toxicological process triggered by the aerosol. These findings underscore the importance of considering different aerosol metrics to assess the toxicological potency of fine and ultrafine particles. To better protect human health additional metrics should be defined, than account for the properties of the entire aerosol mixture including specific as particle size (i.e. particles with aerodynamic diameter lower than 20 nm), the relevant aerosol sources (e.g., traffic combustion, secondary organic aerosol …) as well as their atmospheric processing (freshly emitted vs aged ones).

Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women.

Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5 ng/ml or 35 pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.

Low birth-weight is a PCOS risk factor for Southern-Italian women.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism and insulin-resistance. Initial studies on the genetic basis of this disorder suggested both a maternal and paternal pattern of inheritance. Birth weight has become a main factor to consider when investigating the etiology of an adult-onset disease, since it is a simple indicator of intrauterine adverse conditions. The aim of our study is to validate the "low birth-weight" as risk factor for the development of PCOS. We performed a retrospective study on 188 PCOS patients and 185 controls, showing that Southern-Italian PCOS population have a significant lower birth-weight comparing to the control population; interestingly, PCOS women with low and normal low weight at birth show higher levels of androgens. Taken together, our result highlights the importance of the "birth-weight" factor for PCOS anamnesis.

Myo-inositol vs. D-chiro inositol in PCOS treatment.

AIM: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women in fertile age. It is an endocrine and metabolic disorder characterized by oligo-anovulation, hyperandrogenism and insulin-resistance. Various therapeutic approaches have been attempted in PCOS, including diet and the use of pharmacological agents such as oral contraceptives (OCs) or anti-androgens. Recently, the introduction of inositol in the treatment plan has proved to be as reasonable as useful in countering the endocrine-metabolic disorders of this syndrome. METHODS: The aim of our study was to compare the clinical, endocrine and metabolic response after 6 months of therapy in 137 PCOS women characterized by oligomenorrhea and/or acne and/or mild hirsutism and insulin-resistance. The patients were treated with myo-inositol or with D-chiro-inositol or with placebo. RESULTS: Our study showed that both myo-inositol (MI-PG) and D-chiro inositol (DCI-PG) treatments are able to significantly improve the regularity of the menstrual cycle, the Acne Score, the endocrine and metabolic parameters and the insulin-resistence in young, overweight, PCOS patients. CONCLUSION: Definitely, we assumed that both treatments with myo-inositol and with D-chiro inositol could be proposed as a potential valid therapeutic approach for the treatment of patients with PCOS. Additionally, further examination and for a longer period of treatment are needed.

Source apportionment of particulate matter in a large city of southeastern Po Valley (Bologna, Italy).

This study reports the results of an experimental research project carried out in Bologna, a midsize town in central Po valley, with the aim at characterizing local aerosol chemistry and tracking the main source emissions of airborne particulate matter. Chemical speciation based upon ions, trace elements, and carbonaceous matter is discussed on the basis of seasonal variation and enrichment factors. For the first time, source apportionment was achieved at this location using two widely used receptor models (principal component analysis/multi-linear regression analysis (PCA/MLRA) and positive matrix factorization (PMF)). Four main aerosol sources were identified by PCA/MLRA and interpreted as: resuspended particulate and a pseudo-marine factor (winter street management), both related to the coarse fraction, plus mixed combustions and secondary aerosol largely associated to traffic and long-lived species typical of the fine fraction. The PMF model resolved six main aerosol sources, interpreted as: mineral dust, road dust, traffic, secondary aerosol, biomass burning and again a pseudo-marine factor. Source apportionment results from both models are in good agreement providing a 30 and a 33% by weight respectively for PCA-MLRA and PMF for the coarse fraction and 70% (PCA-MLRA) and 67% (PMF) for the fine fraction. The episodic influence of Saharan dust transport on PM10 exceedances in Bologna was identified and discussed in term of meteorological framework, composition, and quantitative contribution.

[Clinical effects of treatment with phytoestrogens in postmenopausal women]. / Effetti clinici del trattamento con fitoestrogeni in donne in post-menopausa.

AIM AND METHODS: Phytoestrogens are plant substances that have estrogenic properties; they haven't steroid structure but they are heterocyclic phenols and for this reason are similar to 17 ß estradiol from the functional and structural point of view; they compete for the same receptor sites of endogenous estrogens, but with an activating capacity a thousand times lower. For this reason, the isoflavones are an alternative to hormone-replacement treatment: they are prescribed to all those women who cannot be treated with HRT for several contraindications, such as thrombosis or breast tumor familiarity. The aim of our study was to demonstrate the effectiveness of soy isoflavones on menopausal symptoms. RESULTS AND CONCLUSION: In our experience, literature data were confirmed, with a 40% reduction of the vasomotor symptoms after 6 months of treatment. Associated with this improvement, there is also the reduction in the degree of insomnia and depressive symptoms. The musculoskeletal pains, however, are not reduced significantly as no positive change was found on vaginal dryness, a major cause of dyspareunia in postmenopausal period.

[Polycystic ovarian syndrome incidence in young women with non-alcoholic fatty liver disease]. / Incidenza di sindrome dell'ovaio policistico in giovani donne affette da steatosi epatica non alcolica.

AIM: Recently, numerous studies have shown significant correlation between hyperandrogenism and elevated insulin levels in many patients with polycystic ovarian syndrome (PCOS). Insuline-Resistance (IR) results in increased circulating levels of this hormone and it is the basis of the metabolic syndrome, characterized by the presence of fatty liver disease (NAFLD), which is pathologically characterized by the accumulation of triglycerides as macro or micro vesicles, in more than 5% of hepatocytes. The aim of our study was to evaluate the incidence of NAFLD in young women with PCOS, who were lean, overweight or obese. METHODS: Particularly, the levels of glucose and insulin, the lipidic profile, and all liver function indices were evaluated; the severity and degree of steatosis were established on the basis of parenchymal echogenicity and the view of intrahepatic venous circulation. RESULTS: Our study showed that NAFLD is a common disease in women with polycystic ovaries, especially with high BMI, but an incidence rate of 40% in lean women too was found. Because steatohepatitis is a risk factor for the developmente of cirrhosis and hepatocellular carcinoma, it is therefore prudent to carry out an ultrasound evaluation of liver in all young patients suffering from polycystic ovary syndrome, regardless of their BMI and the results of serological evaluation of liver. CONCLUSION: This collateral diagnosis that accompanies the diagnosis of Polycystic Ovary Syndrome seems important since this type of patients could be treated with metformin or with thiazoles to reduce insulin-resistance and steatosis as well.

Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial.

BACKGROUND: Polycystic ovary syndrome is the most common cause of chronic anovulation infertility in women in fertile period, and it's characterized by an increased production of androgens and estrogens. The administration of myo-inositol, a B complex vitamin, was associated with a decreased of serum testosterone and simultaneously, due to its ability to increase insulin sensitivity, women who received myo-inositol showed a great improvement of the ovulary function. Besides, the supplementation of inositol improves the oocytes' quality and increase the number of oocytes collected after ovarian stimulation in patients undergoing IVF (in vitro fertilization). AIM: The aim of this study is to determine the effects of myo-inositol on oocyte's quality on a sample of women with polycystic ovary syndrome. MATERIAL AND METHODS: The patients were divided into two groups: patients of Group A in-took 2 g of myo-inositol + 200 microg of folic acid (Inofolic, LO.LI. Pharma, Rome, Italy) while Group B only 200 microg of folic acid, both groups took the treatment twice a day, continuously for 3 months. RESULTS: At the end of treatment, the number of follicles of diameter > 15 mm, visible at ultrasound during stimulation, and the number of oocytes recovered at the time of pick-ups were found to be significantly greater in the group treated with myo-inositol, so as the aver-age number of embryos transferred and embryo Score S1. Significantly reduced was the average number of immature oocytes (vesicles germ and degenerated oocytes) too. CONCLUSIONS: These data suggest that myoinositol may be useful in the treatment of PCOS patients undergoing ovulation induction, both for its insulin-sensitizing activity, and its role in oocyte maturation.

[Clinical effectiveness of N-oleyl-phosphatidyl-ethanolamine (NOPE) in obesity: our experience]. / Efficacia clinica della n-oleil-fosfatidil-etanolamina (NOPE) nella terapia dell'obesita: nostra esperienza.

Adjustment and maintenance of body weight are the result of many process combination, that affect both the gastrointestinal system and other mechanisms in the central nervous system. Often a diet modification alone is not sufficient to guarantee significant changes in body weight. For this reason, it sometimes necessary to make other interventions, in order to help an individual to adhere to the diet as much as possible and to achieve the objectives established. The N-oleyl-phosphatidyl-ethanolamine (NOPE) is a phospholipid. It can be endogenous or exogenous, and it is present in cell membranes and in much of the food. Food intake increases its production; in fact, because of certain stimuli, it is sometimes produced by the epithelial intestine cells too. Another substance whose activity is comparable to NOPE is the epigallocatechin gallate (EGCG), an abundant catechin present in the green tea, which allows a lipid lowering and antioxidant action, and acts on energy consumption as well. The aim of our study was to evaluate the effectiveness of NOPE and EGCG pharmaceutical formulation in a population of obese women, administering the supplement twice daily before meals, for a period of 60 days. The comparison between the effectiveness of the results in a homogeneous group of patients treated with diet and placebo, allows to confirm the data reported in the literature regarding the effectiveness of the pharmaceutical formulation and the absence of side effects.

[Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus]. / Aspetti psichici del disturbo disforico della fase luteale: nuove prospettive terapeutiche, il vitex agnus castus. Nostra esperienza.

AIM: The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. METHODS AND RESULTS: Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). CONCLUSION: This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

[Innovative genetic, clinical and endocrinologic aspects in young females affected by premature ovarian insufficiency]. / Innovativi aspetti genetici, clinici ed endocrini in una giovane popolazione femminile affetta da insufficienza ovarica prematura.

AIM: Heterogeneity premature ovarian insufficiency (POI) is one of the reasons why there are different causes that contribute in determining this type of hormonal disorder. Although the causes have already been established for many types of premature ovarian failure, are still uncertain causes in most cases of idiopathic forms, despite the description of several candidate genes, including BMP-15 gene. The gene under study is precisely the BMP-15, which is part of the superfamily of Transforming Growth Factors-beta or the TGF-ß, which also belong to the growth differentiation factors (GDFs). METHODS: This study examined a sample of Sicilian women suffering from POI, carefully selected according to their age, since in these cases, the genetic factor probably has a greater impact. RESULTS AND CONCLUSION: Identify a mutant gene that causes ovarian failure may be important to make a diagnosis that can predict the possible future development of the disease. The outcome of the studies, however, has not found the gene in question, but it is hypothesized that this may be a direct consequence of the limited amount of women that was done the study, a case which may be rebutted by increasing the number of patients.

[Effects of inositol on oocyte quality in patients affected with polycystic ovary syndrome]. / Effetti dell'inositolo sulla qualità ovocitaria in pazienti affette da sindrome dell'ovaio policistico.

AIM: Polycystic ovary syndrome is the most common cause of chronic anovulation infertility in women in fertile period. The supplementation of inositol, due to its ability to increase insulin sensitivity, improves the oocytes' quality and increase the number of oocytes collected after ovarian stimulation in patients undergoing IVF (In Vitro Fertilization). The aim of our study is to determine the effects of myo-inositol on oocyte's quality on a sample of women with polycystic ovary syndrome. METHODS: The patients were divided into two groups: patients of Group A intook 2 g of myo-inositol + 400 µg of folic acid 2 times a day, continuously for 3 months, while Group B only 400 µg of folic acid. RESULTS AND CONCLUSION: At the end of treatment, the number of follicles of diameter >15 mm, visible at ultrasound during stimulation, and the number of oocytes recovered at the time of pick-ups were found to be significantly greater in the group treated with myo-inositol, so as the average number of embryos transferred and embryo Grade G1. Significantly reduced was the average number of immature oocytes (vesicles germ and degenerated oocytes) too.

Protection of ovarian tissue from radiotherapy.

Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47).