Hydroelectrophoresis for Transdermal Administration of Verapamil or of Hyaluronic Acid in Peyronie's Disease: A Prospective, Open Label, Multicenter Study

Aim & Objective: To assess the efficacy of a new electromotive system for the transcutaneous delivery of verapamil or of hyaluronic acid to improve the symptoms of Peyronie' s disease (PD) in patients with a curvature deformity of < 30° at the beginning of therapy. Methods & Materials: Sixty-one PD patients were studied. Thirty were randomly assigned to receive verapamil 10 mg/session (Isoptin®, BGP Products, Rome-Italy), (Group 1, median age 56 years, range 49-62), and 31 were randomly assigned to receive hyaluronic acid 8 mg/session (Sinovial®, IBSA, Lodi-Italy) (Group 2, median age 58 years, range 51-56). There were ten sessions, 2 sessions/week for each drug. Each drug was transdermally administered using the hydroelectrophoresis technique and carried out using a Hydro4and apparatus (Swiss4Med SA, Morbio Inferiore, Switzerland). With respect to the efficacy of the drugs studied, the endpoints were: side effects, pain, erectile function, penile deviations and plaque area (cm2) before, and 3 and 6 months after drug administration. The differences were assessed using the Mann-Whitney Rank test (unmatched groups) or using the Wilcoxon Signed Rank test (matched groups). The differences between the groups in terms of side effects were assessed using the chi-square test. Results: No significant difference emerged among the baseline values of the two groups. Pain, erectile function, plaque area and penile deformity significantly improved in both groups after treatment, but a notably higher improvement occurred in the patients in whom hyaluronic acid was administered. Only a few negligible side effects occurred in the Group 1 patients treated with Verapamil, with no significant difference between the groups. Conclusion: Administration of both hyaluronic acid and verapamil using the Hydro4and apparatus is a safe and efficient method for PD therapy

Chromatographic Evidence on the Occurrence of Thiotaurine in the Urine of Rats Fed with Cystine

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THE ISOLATION OF PURE HYPOTAURINE FROM THE URINE OF RATS FED CYSTINE

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Experiments with D-cysteine in the rat.

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Development of laser-based powder bed fusion process parameters and scanning strategy for new metal alloy grades: A holistic method formulation

In spite of the fast growth of laser-based powder bed fusion (L-PBF) processes as a part of everyday industrial practice, achieving consistent production is hampered by the scarce repeatability of performance that is often encountered across different additive manufacturing (AM) machines. In addition, the development of novel feedstock materials, which is fundamental to the future growth of AM, is limited by the absence of established methodologies for their successful exploitation. This paper proposes a structured procedure with a complete test plan, which defines step-by-step the standardized actions that should be taken to optimize the processing parameters and scanning strategy in L-PBF of new alloy grades. The method is holistic, since it considers all the laser/material interactions in different local geometries of the build, and suggests, for each possible interaction, a specific geometry for test specimens, standard energy parameters to be analyzed through a design of experiment, and measurable key performance indicators. The proposed procedure therefore represents a sound and robust aid to the development of novel alloy grades for L-PBF and to the definition of the most appropriate processing conditions for them, independent of the specific AM machine applied

The enzymatic oxidation of cysteamine to hypotaurine. Purification and properties of the enzyme.

The enzyme oxidizing cysteamine to hypotaurine has been extracted from horse kidney and purified. The final product behaves as a single protein when analyzed in the ultracentrifuge, by starch gel electrophoresis, and by filtration on dextran gels. The sedimentation coefficient of the pure product is s20, w = 5.9. The molecular weight determined by the Yphantis procedure (22) is 83,000. Nonheme iron is contained in the amount of 1 atom per molecule of enzyme. Spectrophoto-metric analyses indicate absence of nonprotein chromophores in the visible and in the near ultraviolet range. The complete amino acid composition has been determined by ion exchange chromatography. The effect of sulfide, methylene blue, and hydroxylamine, which act as cofactor-like compounds, has been studied. Of the substrates assayed (cysteamine, cysteine, cysteine ethyl and methyl esters, and reduced glutathione), only cysteamine is oxidized to the sulfinic derivative in the presence of the cofactor-like compounds named

Unveiling the morphogenetic code: A new path at the intersection of physical energies and chemical signaling

In this editorial, we discuss the remarkable role of physical energies in the control of cell signaling networks and in the specification of the architectural plan of both somatic and stem cells. In particular, we focus on the biological relevance of bioelectricity in the pattern control that orchestrates both developmental and regenerative pathways. To this end, the narrative starts from the dawn of the first studies on animal electricity, reconsidering the pioneer work of Harold Saxton Burr in the light of the current achievements. We finally discuss the most recent evidence showing that bioelectric signaling is an essential component of the informational processes that control pattern specification during embryogenesis, regeneration, or even malignant transformation. We conclude that there is now mounting evidence for the existence of a Morphogenetic Code, and that deciphering this code may lead to unprecedented opportunities for the development of novel paradigms of cure in regenerative and precision medicine

Corneal incision width after lens implantation: Comparing delivery systems: Corneal incision width and injector systems

Abstract Purpose To compare corneal incision width after phacoemulsification and intraocular lens implantation (IOL) using different delivery systems. Methods One hundred and seventeen patients with cataract and no other anterior segment pathological features or previous eye surgery underwent cataract surgery with IOL implantation through a 2.2 mm incision. Three foldable IOL were implanted with their recommended delivery systems: Acrysof© SN60WF with Monarch© III/cartridge D (Group A, 38 patients); Tecnis© ZCB00 with Unfolder Platinum/cartridge easy load (Group B, 38 patients); Acrysof© SN60WF with Ultrasert™ preloaded system (Group C, 42 patients). Incision width was measured before and after phacoemulsification and IOL implantation. Results Before and after phacoemulsification incision width was, respectively, 2.21 ± 0.02 mm and 2.34 ± 0.08 mm in group A; 2.20 ± 0.02 mm and 2.31 ± 0.06 mm in group B; 2.20 ± 0.02 mm and 2.30 ± 0.07 mm in group C. Incision width was not significantly enlarged after phacoemulsification. Before and after IOL implantation incision width was, respectively, 2.34 ± 0.07 mm and 2.47 ± 0.07 mm in group A; 2.32 ± 0.06 mm and 2.45 ± 0.08 mm in group B; 2.30 ± 0.07 mm and 2.39 ± 0.07 mm in group C. Incision widths in group C were significantly different to groups A and B. No relationship was found between incision sizes and phacoemulsification time, ultrasound energy and IOL powers. Conclusion In cataract surgery Ultrasert™ enlarges the corneal incision less than other delivery systems

Hyaluronan Esters Drive Smad Gene Expression and Signaling Enhancing Cardiogenesis in Mouse Embryonic and Human Mesenchymal Stem Cells

BACKGROUND: Development of molecules chemically modifying the expression of crucial orchestrator(s) of stem cell commitment may have significant biomedical impact. We have recently developed hyaluronan mixed esters of butyric and retinoic acids (HBR), turning cardiovascular stem cell fate into a high-yield process. The HBR mechanism(s) remain still largely undefined. METHODOLOGY/PRINCIPAL FINDINGS: We show that in both mouse embryonic stem (ES) cells and human mesenchymal stem cells from fetal membranes of term placenta (FMhMSCs), HBR differentially affected the patterning of Smad proteins, one of the major conductors of stem cell cardiogenesis. Real-time RT-PCR and Western blot analyses revealed that in both cell types HBR enhanced gene and protein expression of Smad1,3, and 4, while down-regulating Smad7. HBR acted at the transcriptional level, as shown by nuclear run-off experiments in isolated nuclei. Immunofluorescence analysis indicated that HBR increased the fluorescent staining for Smad1,3, and 4, confirming that the transcriptional action of HBR encompassed the upregulation of the encoded Smad proteins. Chromatin immune precipitation and transcriptional analyses showed that HBR increased the transcription of the cardiogenic gene Nkx-2.5 through Smad4 binding to its own consensus Smad site. Treatment of mouse ES cells and FMhMSCs with HBR led to the concomitant overexpression of both Smad4 and α-sarcomeric actinin. Smad4 silencing by the aid of lentiviral-mediated Smad4 shRNA confirmed a dominant role of Smad4 in HBR-induced cardiogenesis. CONCLUSIONS/SIGNIFICANCE: The use of HBR may pave the way to novel combinatorial strategies of molecular and stem cell therapy based on fine tuning of targeted Smad transciption and signaling leading to a high-throughput of cardiogenesis without the needs of gene transfer technologies

Cytochalasin B Modulates Nanomechanical Patterning and Fate in Human Adipose-Derived Stem Cells

Cytoskeletal proteins provide architectural and signaling cues within cells. They are able to reorganize themselves in response to mechanical forces, converting the stimuli received into specific cellular responses. Thus, the cytoskeleton influences cell shape, proliferation, and even differentiation. In particular, the cytoskeleton affects the fate of mesenchymal stem cells (MSCs), which are highly attractive candidates for cell therapy approaches due to their capacity for self-renewal and multi-lineage differentiation. Cytochalasin B (CB), a cyto-permeable mycotoxin, is able to inhibit the formation of actin microfilaments, resulting in direct effects on cell biological properties. Here, we investigated for the first time the effects of different concentrations of CB (0.1–10 μM) on human adipose-derived stem cells (hASCs) both after 24 h (h) of CB treatment and 24 h after CB wash-out. CB influenced the metabolism, proliferation, and morphology of hASCs in a dose-dependent manner, in association with progressive disorganization of actin microfilaments. Furthermore, the removal of CB highlighted the ability of cells to restore their cytoskeletal organization. Finally, atomic force microscopy (AFM) revealed that cytoskeletal changes induced by CB modulated the viscoelastic properties of hASCs, influencing their stiffness and viscosity, thereby affecting adipogenic fat