Defects of steroidogenesis

In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed via a 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 block

Versatile and non-cytotoxic GelMA-xanthan gum biomaterial ink for extrusion-based 3D bioprinting

Extrusion-based 3D bioprinting allows the 3D printing of bioinks, composed of cells and biomaterials, to mimic the complex 3D hierarchical structure of native tissues. Successful 3D bioprinting requires bioinks with specific properties, such as biocompatibility, printability, and biodegradability according to the desired application. In the present work, we aimed at developing a new versatile blend of gelatin methacryloyl-xanthan gum (GelMA-XG) suitable for extrusion-based 3D bioprinting with a straightforward process. To this end, we first optimized the process of gelatin methacryloyl (GelMA) synthesis by investigating the impact of different buffer solutions on the degree of functionalization, swelling degree, and degradation rate. The addition of xanthan gum (XG) enabled further tuning of biodegradability and an improvement of GelMA printability. Specifically, an optimal concentration of XG was found through rheological characterization and printability tests. The optimized blend showed enhanced printability and improved shape fidelity as well as its degradation products turned out to be non-cytotoxic, thus laying the foundation for cell-based applications. In conclusion, our newly developed biomaterial ink is a promising candidate for extrusion-based 3D bioprinting

Cyclic Cushing's syndrome: an overview

Cyclic Cushing's syndrome (CS) is a disorder in which glucocorticoid levels are alternately normal and high, the latter occurring in episodes that can last from a few days to several months. It is more common in children than in adults. Cyclic CS may be either of the two different forms of CS (ACTH-dependent or -independent CS). Clinically, it may present with one or many symptoms, depending on the duration of disease activity and the timing of the fluctuations. A serotoninergic influence, cyclic changes in central dopaminergic tone, spontaneous episodic hemorrhage in the tumor, and the action of inflammatory cytokines with antitumor properties are some of the mechanisms suggested to explain the physiopathology of this phenomenon but the exact mechanism remains to be clarified. The cyclic pattern of hypercortisolism can delay the final diagnosis of CS and make it difficult to interpret the results of dynamic tests. Patients may have paradoxical responses to dexamethasone that can reflect increasing or decreasing levels of endogenous activity. Hormone assessments have to be repeated periodically when a diagnosis of CS is suspected. The cyclic pattern can also interfere with medical treatment because patients may show unexpected clinical and biochemical signs of hypocortisolism when cortisol secretion cyclically returns to normal, so an accurate follow-up is mandatory in these patients

Management of severe COPD exacerbations : focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide

The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients' hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization. Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting \u3b22-agonists in combination or not with inhaled corticosteroids. The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials. The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

Severe and poorly controlled asthma still accounts for a great portion of the patients affected. Disease control and future risk management have been identified by international guidelines as the main goals in patients with asthma. The need for new treatment approaches has led to reconsider anticholinergic drugs as an option for asthma treatment. Tiotropium is the first anticholinergic drug that has been approved for children and adults with poorly controlled asthma and is currently considered as an option for steps 4 and 5 of the Global Initiative for Asthma. In large randomized clinical trials enrolling patients with moderate to severe asthma, add-on therapy with tiotropium has demonstrated to be efficacious in improving lung function, decreasing risk of exacerbation and slowing the worsening of disease; accordingly, tiotropium demonstrated to be non inferior compared to long acting beta-agonists in the maintenance treatment along with medium to high inhaled corticosteroids. In view of the numerous ancillary effects acting on inflammation, airway remodeling, mucus production and cough reflex, along with the good safety profile and the broad spectrum of efficacy demonstrated in different disease phenotypes, tiotropium can represent a beneficial alternative in the therapeutic management of poorly controlled asthma. The present extensive narrative review presents the pharmacological and pathophysiological basis that guided the rationale for the introduction of tiotropium in asthma treatment algorithm, with a particular focus on its conventional and unconventional effects; finally, data on tiotropium efficacy and safety. from recent randomized clinical trials performed in all age categories will be extensively discussed

Time evolution of activity concentration of natural emitters in a scenario affected by previous phosphogypsum contamination

The estuary formed by the confluence of Tinto and Odiel river-mouths is located in the South of Spain, close to Huelva town. This estuary has been deeply studied through the years because it has a double particularity. On one hand, since the beginning of the 1960s, the estuary has been affected by direct and indirect phosphogypsum (pg.) releases from two phosphoric acid and fertilizers factories that are working in the area. On the other hand, the pyrite mining operations upstream the Odiel and Tinto rivers has caused historically the formation of H2SO4, through oxidation of the natural sulphur deposits, the acidification of the waters and the consequent mobilisation of heavy metals from the mining area to the Huelva estuary. As a consequence, enhancement contamination levels in natural emitters from the ^'*U series were found in the surroundings of the factories in the previous years to 1998. However, in 1998 the management policy of waste releases drastically changed in the area, and direct discharges to Tinto and Odiel River had to be ceased. A thorough study of the affected zone is being carried out. Riverbed sediments and water samples have been analyzed from four different sampling campaigns in the estuary during the years 1999, 2001, 2002 and 2005. Different radioanalytical techniques have been employed to obtain the activity concentrations of U-isotopes, Th-isotopes, ^^^Ra, ^'"Pb and ^'"Po. Furthermore, the results for the rates of de-contamination of the area are presented. This data will be discussed in order to establish the present status of the contamination in the area, and moreover, to predict the time-evolution of the self-cleanin

Defects of steroidogenesis

In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed via a 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

C-reactive protein but not atrial dysfunction predicts recurrences of atrial fibrillation after cardioversion in patients with preserved left ventricular function

OBJECTIVES: Maintenance of sinus rhythm after cardioversion of atrial fibrillation is a major clinical challenge also in patients with preserved left ventricular function. Subclinical inflammation and atrial strain have been recognized as important contributors to atrial fibrillation onset and perpetuation. Aim of the study was to compare the predictive role of C-reactive protein (CRP) and indices of atrial dysfunction in relation to subacute arrhythmic recurrence rate in patients with persistent atrial fibrillation and normal left ventricular ejection fraction (LVEF). METHODS: We studied 53 patients with a mean LVEF of 58.7 \ub1 6%. Left atrial diameter and area, left atrial auricle emptying velocity, N-terminal pro-b-type natriuretic peptide (NT-proBNP) and CRP levels were determined few hours before electrical cardioversion. NT-proBNP and CRP levels were also measured 1 h and 3 weeks after cardioversion. RESULTS: Subacute atrial fibrillation recurrences were documented in 18 (33.9%) patients. Whereas none of the parameters reflecting atrial dysfunction predicted arrhythmic outcome, higher CRP levels (>3.0 mg/l) were significantly associated with atrial fibrillation recurrences [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.4-2.5; P = 0.031]. No changes in CRP levels were evident after cardioversion independently of underlying rhythm. On the contrary, NT-proBNP levels, which were correlated with left atrial auricle emptying velocity, significantly decreased only in patients who maintained sinus rhythm (from 638 \ub1 329 to 295 \ub1 261 pg/ml; P < 0.001). CONCLUSION: The present study demonstrates that in patients with persistent atrial fibrillation and preserved LVEF, CRP level is an independent predictor of atrial fibrillation subacute recurrence rate, whereas none of the indices of atrial dysfunction is associated with arrhythmic outcome. NT-proBNP levels reflect, instead, the hemodynamic alterations secondary to arrhythmia presence

Contamination and restoration of an estuary affected by phosphogypsum releases

The Huelva Estuary in Huelva, Spain, has been one of the most studied environmental compartments in the past years from the point of view of naturally occurring radioactive material (NORM) releases. It has been historically affected by waste releases, enriched in radionuclides from the U-decay series, from factories located in the area devoted to the production of phosphoric acid and phosphate fertilizers. Nevertheless, changes in national regulations forced a new waste management practice in 1998, prohibiting releases of phosphogypsum into the rivers. The input of natural radionuclides from phosphate factories to rivers was drastically reduced. Because of this there was a unique opportunity for the study of the response of a contaminated environmental compartment, specifically an estuary affected by tidal influences, after the cessation of the contaminant releases to, in this case, the Huelva Estuary (henceforth referred to as the Estuary). To investigate the environmental response to this new discharge regime, the specific activities of radionuclides 226Ra and 210Pb in water and sediment samples collected in four campaigns (from 1999 to 2005) were determined and compared with pre-1998 values. From this study it is possible to infer the most effective mechanisms of decontamination for the Estuary. Decontamination rates of 210Pb and 226Ra in the sediments and water have been calculated using exponential fittings and corresponding half-lives have been deduced from them. The cleaning half-life in the whole area of the Estuary is about 6 and 3.5 years for 226Ra and 210Pb respectively. The observed trend clearly shows that contamination of the Estuary by natural radionuclides is now decreasing and radioactive levels in waters and sediments are approaching the natural background references. This work attempts to evaluate whether it can be expected that the decontamination of the enhanced levels of natural radioactivity in the Estuary can be performed via natural processe