Differences among Three Branded Formulations of Hyaluronic Acid: Data from Environmental Scanning Electron Microscope Profile, Rheology Behavior and Biological Activity

Background: This study has analysed the viscosupplemental proprieties of three commercially available formulations of Hyaluronic Acid (HA) suspension (F1: Synvisc, Hylan G-F 20; F2: Hyalgan; F3: Donegal HA 2.0), which differ in composition, Molecular Weight (MW) and HA content. Methods: Analyses were conducted using rheology measurements and Environmental Scanning Electron Microscope (ESEM). The capacity of the three tested formulations to inhibit specific Metalloproteases (MMPs) was also evaluated. Results: F1 is the only sample showing viscoelastic properties but may have increased immunogenicity attributable to the subsequent chemical cross-linking process that enhances the MW. F2 and F3 show a lower viscosity compared to F1. F2 has the lowest viscosity at low shear rate, the lower independence from the oscillatory stress and a solution-like rheology behaviour. F3 display a solution behaviour. However, unlike F2, F3 crossover point falls in the middle of the frequency range of interest showing a considerable rheological behaviour. The internal structure of F3 (pseudo-spongy thick filaments) suggests that it has the ability to interact with a great water content. The crossover points of the examined samples clearly reveal their different rheological behaviour, allowing their classification in gel-like or solution-like materials. F3 has higher ability in inhibiting MMP- 2 and MMP-9 activity compared to F1 and F2, probably due to its specific MW and/or higher HA concentration. Conclusion: The three tested HA formulations differ in rheological properties and inhibition of MMP-2 and MMP-9 activity. F3 seems to be the most appropriate formulation for the treatment of osteoarthritis and rheumatoid arthritis

Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: A pharmacogenetic study

Study question: Does the spermDNAfragmentation index (DFI) improve depending on the FSH receptor (FSHR) genotype as assessed by the nonsynonymous polymorphisms rs6166 (p.N680S) after 3 months of recombinant FSH treatment in men with idiopathic infertility? summary answer: FSH treatment significantly improves sperm DFI only in idiopathic infertile men with the p.N680S homozygous N FSHR. what is known already: FSH, fundamental for spermatogenesis, is empirically used to treat male idiopathic infertility and several studies suggest that DFI could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is known that the FSHR single nucleotide polymorphism (SNP) rs6166 (p.N680S) influences ovarian response in women and testicular volume in men. study design, size and duration: Amulticenter, longitudinal, prospective, open-label, two-arm clinical trial was performed. Subjects enrolled were idiopathic infertile men who received 150 IU recombinant human FSH s.c. every other day for 12 weeks and were followed-up for a further 12 weeks after FSH withdrawal. Patients were evaluated at baseline, at the end of treatment and at the end of follow-up. participants/materials, setting, methods: Eighty-nine men with idiopathic infertility carrier of the FSHR p.N680S homozygousNor S genotype, FSH 64 8 IU/l and DFI >15%,were enrolled. A total of 66 patients had DFI analysis completed on at least two visits. DFI was evaluated in one laboratory by TUNEL/PI (propidium iodide) assay coupled to flow cytometry, resolving two different fractions of sperm, namely the 'brighter' and 'dimmer' sperm DFI fractions. main results and the roleof chance: Thirty-eightmen(57.6%)were carriers of the p.N680S homozygousNand 28 (42.4%) of the homozygous S FSHR. Sperm concentration/number was highly heterogeneous and both groups included men ranging from severe oligozoospermia to normozoospermia. Total DFI was significantly lower at the end of the study in homozygous carriers of the p.N680SNversus p.N680S S allele (P = 0.008). Total DFI decreased significantly from baseline to the end of the study (P = 0.021) only in carriers of the p.N680S homozygous N polymorphism, and this decrease involved the sperm population containing vital sperm (i.e. brighter sperm) (P = 0.008). The dimmer sperm DFI fraction, including only nonvital sperm, was significantly larger in p.N680S S homozygous patients than in homozygous N men (P = 0.018). Total DFIwas inversely related to total sperm number (P = 0.020) and progressive sperm motility (P = 0.014).Whenpatients were further stratified according to sperm concentration (normoozospermic versus oligozoospermic) or -211G>T polymorphism in the FSHB gene (rs10835638) (homozygous Gversus others), the significant improvement of sperm DFI in FSHR p.N680S homozygousNmen was independent of sperm concentration and associated with the homozygous FSHB -211G>T homozygous G genotype. limitations, reasons for caution: The statistical power of the study is 86.9% with alpha error 0.05. This is the first pharmacogenetic study suggesting that FSH treatment induces a significant improvement of total DFI in men carriers of the p.N680S homozygousNFSHR; however, the results need to be confirmed in larger studies using a personalized FSH dosage and treatment duration. wider implications of the findings: The evaluation of sperm DFI as a surrogate marker of sperm quality, and of the FSHR SNP rs6166 (p.N680S), might be useful to predict the response to FSH treatment in men with idiopathic infertility. study funding/competing interest(s): The study was supported by an unrestricted grant to M.S. and H.M.B. from Merck Serono that provided the drug used in the study. MS received additional grants from Merck Serono and IBSA as well as honoraria from Merck Serono. The remaining authors declare that no conflicts of interest are present. trial registration number: EudraCT number 2010-020240-35

Promotion and inhibition of neurite regeneration in cultured neurons

The majority of neurons belonging to the central nervous system of the mollusc Planorbarius corneus is capable of neurite regeneration in vitro only in presence of factors released from the periesophageal ganglionic ring. Even each individual ganglion produces unknown stimulating factors sufficient for a complete neurite regeneration. The percentage of neurons showing neurite regeneration is nearly the same independent of ganglionic type and it increases following a rise in the concentration of promoting factors. We identified by RIA an insulin -like molecule among the released substances. Adding antisera against molluscan insulin -like neuropeptides to the culture medium we obtained an almost complete inhibition of neurite regeneration when the factors are released by cerebral or pedal ganglia. No inhibition occurs if the neural factors are released by visceroparietal ganglia

GH response to GHRH plus Arginine in lipodistrophic patients with human immunodeficiency virus: gender differences

GH deficiency is more frequent in men with HIV than in HIV-infected wome

Probiotics ingestion does not directly affect thyroid hormonal parameters in hypothyroid patients on levothyroxine treatment

Purpose: The relationship between probiotics and levothyroxine (LT4) requirement has not yet been investigated. The aim of this study was to assess whether a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3\uc2\uae) is able to influence LT4metabolism acting on the gut microbiota. Methods: A prospective, randomized, single-blind, controlled, investigator-started clinical trial was carried out. Patients with primary hypothyroidism were randomly assigned to the study (VSL#3\uc2\uae + LT4) and the control group (LT4). A 2-month treatment phase was followed by 2 months of follow-up. Clinical examination, blood tests for thyroid function and for peripheral tissue markers of thyroid hormones (PTM) were performed monthly. LT4dose adjustments were performed when necessary. Results: Thirty-nine patients were enrolled in the study group and 41 in the control group. No difference in thyroid function [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)] and PTM was found between groups and among visits. FT3/fT4ratio was directly correlated to TSH at each visit in both groups, with the exception of the first evaluation of probiotics-treated subjects (rho = 0.287, p = 0.076). LT4daily dose adjustments occurred more frequently in the control than in the study group (p = 0.007), despite no differences in the mean LT4daily dose. In particular, LT4doses were increased six times in the control group and decreased four times in the study group. Conclusion: VSL#3\uc2\uae does not directly alter thyroid functional compensation. A probiotics-mediated influence on thyroid hormones homeostasis is suggested since probiotics supplementation could be able to prevent serum hormonal fluctuations

Congenital estrogen deficiency: in search of the estrogen role in human male reproduction

Recently, a remarkable progress has been made in our understanding about the role of sex steroids in male physiology. In this paper, we consider the clinical aspects of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - in men and we discuss both well-established and supposed estrogen roles in the human male reproductive function. These topics include the role of estrogens in the control of gonadotropin secretion, in male fertility determination and psychosexual behavior. Briefly, estrogens play a pivotal role in the control of serum gonadotropin concentrations in the human male. Furthermore, a possible role of estrogens on both human male fertility and sexuality has also been suggested by recent studies, even though the available data are far from being conclusive. Conversely, for what concern Fertility and sexual behavior, a well-established effect of estrogens has been provided by recent studies on male rodents, which show impaired sexual behavior and fertility as a consequence of estrogen defect. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved

Ruolo del dosaggio di calcitonina (Ct) nei liquidi di lavaggio da agoaspirato (FNA-B) nella diagnosi di carcinoma midollare della tiroide (MTC): confronto con la calcitonina basale, la citologia e il test di stimolo alla pentagastrina (Pg-test)

Ruolo diagnostico del dosaggio della calcitonina nel liquido di lavaggio ottenuto mediante agoaspirato ecoguidato dei noduli tiroidei sospetti per carcinoma midollare tiroideo

Multilevel approach to male fertility by machine learning highlights a hidden link between haematological and spermatogenetic cells

Male infertility represents a complex clinical condition requiring an accurate multilevel assessment, in which machine learning (ML) technology, combining large data series in nonlinear and highly interactive ways, could be innovatively applied

Untargeted and Targeted Metabolomic Profiling of Preterm Newborns with EarlyOnset Sepsis: A Case-Control Study

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as “cases” if they developed EOS, and as “controls”if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis

Prevalence of secondary causes of osteoporosis among HIV infected individuals

Although osteopenia/osteoporosis is very frequent among HIV infected individuals. Vitamin D deficiency is frequent in this Italian population and might be a contrib- utor to this problem