Progressive fibrosing interstitial lung diseases: A current perspective

Interstitial lung diseases (ILDs) are a large and diverse group of rare and chronic respiratory disorders, with idiopathic pulmonary fibrosis (IPF) being the most common and best-studied member. Increasing interest in fibrosis as a therapeutic target and the appreciation that fibrotic mechanisms may be a treatable target of IPF prompted the development and subsequent approval of the antifibrotics, pirfenidone and nintedanib. The management of ILDs has changed considerably following an understanding that IPF and some ILDs share similar disease behavior of progressive fibrosis, termed “progressive fibrosing phenotype”. Indeed, antifibrotic treatment has shown to be beneficial in ILDs characterized by the progressive fibrosing phenotype. This narrative review summarizes current knowledge in the field of progressive fibrosing ILDs. Here, we discuss the clinical characteristics and pathogenesis of lung fibrosis and highlight relevant literature concerning the mechanisms underlying progressive fibrosing ILDs. We also summarize current diagnostic approaches and the available treatments of progressive fibrosing ILDs and address the optimization of treating progressive fibrosing ILDs with antifibrotics in clinical practice

Toxicity of antioxidant supplements in patients with male factor infertility: A systematic review and meta-analysis of randomized controlled trials

Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of an-tioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted

Impact of Circadian Desynchrony on Spermatogenesis: A Mini Review

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity

Mixed micelles composed of Peptides and Gadolinium complexes as tumor-specific contrast agents in MRI: a SANS study

A detailed structural investigation on mixed micelle aggregates as target-specific contrast agents for magnetic resonance imaging technique has been carried out by way of small angle neutron scattering measurements. These mixed micelles are formed by two new amphiphilic molecules formed by a bioactive peptide and a claw moiety. The first molecule, C18H37CONH(AdOO)(x)-G-CCK8 (C18LxCCK8, x = 2, 5), contains an 18-carbon-atom alkylic chain bound to the C-terminal of the cholecystokinin octapeptide amide (CCK 26-33 or CCK8) and is able to bind to the overexpressed CCK receptor of some tumor cells. The second molecule, C(18)H(37)CONHLys(DTPAGlu)CONH25- (C18DTPAGlu) or its gadolinium complex [C(18)H(37)CONHLys(DTPAGlu)CONH2Gd](2-), C18DTPAGlu(Gd),contains the same 18-carbon-atom alkylic chain bound, through a lysine residue, to the DTPAGlu chelating agent. Small angle neutron scattering measurements have been performed on ternary systems at different total concentrations and at various ratios of the two molecules. The effect of the concentration on the aggregation number as well as on the shape of the micelle has been investigated. Furthermore in order to optimize the exposure of the peptide on the micelle surface, C18LxCCK8 having the spacer L of different length has been used. The pure binary systems of the synthesized molecules are also presented

Limiting partial molar volume of sodium chloride in 2-methyl-2,4-pentandiol-water mixed solvents at 25 °C

Abstract Herein we report density measurements for the binary system 2-methyl-2,4-pentanediol(MPD,1)-water(0), and for the ternary system MPD(1)-NaCl(2)-water(0), at several fixed MPD/water ratios and at varying NaCl concentrations. The partial molar volume of MPD in the binary system has been discussed according to the McMillan-Meyer theory. At low MPD concentrations, the non-bonding MPD-MPD interactions are related to the overlapping of the hydrophobic parts of the hydration cospheres, whereas at higher concentrations the hydrophilic moieties are also involved in the solute-solute interactions. The ternary density data allowed us to determine the salt partial molar volume at infinite dilution. The trend of this quantity as a function of the MPD content in the MPD-water “mixed solvent” has been interpreted on the basis of the water partial molar volume in the binary MPD-water system

Sodium chloride molar conductance in different poly(ethylene glycol)–water mixed solvents

The molar conductivities of NaCl in several poly(ethylene glycol)(PEG)–water “mixed solvents” are presented as a function of the PEG content in solution. Three different PEG samples, a monodispersed one and two polydispersed ones, have been used. The comparison between the molar conductivity values in the mixed solvents and the corresponding ones in pure water shows that the only effect of PEG on the ions’ motions is an obstruction effect despite the variation of the macroscopic dielectric constant induced by PEG itself. A comparison between the molar conductivities and the corresponding mutual main diffusion coefficients shows a tight correlation between the two quantities. This correlation is possible only in the absence of electrostatic effects due to the presence of PEG

Diffusion in ternary aqueous systems containing human serum albumin and precipitants of different classes

The mutual diffusion coeffs. for two aq. ternary systems, both contg. a protein, human serum albumin (HSA, component 1), were measured. The first system contained a neutral polymer, polyethylene glycol (PEG, component 2), and the second an "org. solvent", 2-methyl-2,4-pentanediol (MPD, component 3). Both PEG and MPD are used as co-precipitants in HSA crystn. protocols. Measurements were performed at const. protein concn., with increasing precipitant content. The results obtained for the two systems were discussed and compared. In both cases, the two main diffusion coeffs., relative to the motion of the protein and of the precipitant under their own concn. gradient, can be interpreted in terms of non-sp. vol. interactions between the solutes. Particularly, it was shown that any possible direct HSA-MPD interaction may not have a significant effect on the values of these two diffusion coeffs. Differences arise between the cross precipitant's diffusion coeffs., relative to the motion of the precipitant under the protein concn. gradient, Di1 with i = 2, 3. In the case of PEG, the D21 trend vs. c2 can be simply interpreted in terms of an "exclude vol." effect. In contrast, in the case of MPD, the D31vs. c3 trend seems to indicate a more complex mechanism of transport. Because the cross precipitant's diffusion coeff. plays an important role in the crystn. process, the implication of the obsd. difference on the crystn. procedure was also discussed