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Chronic wounds result from the body's inability to heal, causing pain, pathogen entry, limited treatment options, and societal burden. Diabetic foot ulcers are particularly challenging, often leading to severe complications like leg amputation. A clinical study tested AMNIODERM+ ® , a new device with a lyophilized human amniotic membrane (HAM), on chronic diabetic foot ulcers. Participants had diabetic neuropathic or neuroischemic leg wounds (2-16 cm 2 ) unhealed by 20% after six weeks of standard care. This study showed significant wound healing improvements with AMNIODERM+ ® . The median wound size reduction after 12 weeks was 95.5%, far exceeding the null hypothesis of 20% change. Additionally, 65% of patients achieved complete ulceration healing, surpassing the 50% efficacy requirement. The median time to full closure was 11.4 weeks, with the proportion of completely healed patients rising progressively, reaching 55% by week 11. These findings, from the clinical trial "Freeze-dried amniotic membrane in the treatment of nonhealing wounds", suggest AMNIODERM+ ® as a promising future treatment for chronic diabetic foot ulcers. The published results were obtained as part of a clinical trial entitled "Freeze-dried amniotic membrane in the treatment of nonhealing wounds: a single-arm, retrospectively-perspective clinical trial", EUDAMED Nr. CIV-SK-22-10-041146.

Nanofibers are well known as a beneficial type of structure for tissue engineering. As a result of the high acquisition cost of the natural polymers and their environmentally problematic treatment (toxic dissolution agents), artificial polymers seem to be the better choice for medical use. In the present study, polycaprolactone nano-sized fibrous structures were prepared by the electrospinning method. The impact of material morphology (random or parallelly oriented fibers versus continuous layer) and the presence of a fraction of hydroxyapatite nanoparticles on cell proliferation was tested. In addition, the effect of improving the material wettability by a low temperature argon discharge plasma treatment was evaluated, too. We have shown that both hydroxyapatite particles as well as plasma surface treatment are beneficial for the cell proliferation. The significant impact of both influences was evident during the first 48 h of the test: the hydroxyapatite particles in polycaprolactone fibers accelerated the proliferation by 10% compared to the control, and the plasma-treated ones enhanced proliferation by 30%.

Electrospinning as a versatile technique producing nanofibers was employed to study the influence of the processing parameters and chemical and physical parameters of solutions on poly(vinylidene fluoride) (PVDF) fibers' morphology, crystallinity, phase composition and dielectric and piezoelectric characteristics. PVDF fibrous layers with nano- and micro-sized fiber diameters were prepared by a controlled and reliable electrospinning process. The fibers with diameters from 276 nm to 1392 nm were spun at a voltage of 25 kV-50 kV from the pure PVDF solutions or in the presence of a surfactant-Hexadecyltrimethylammonium bromide (CTAB). Although the presence of the CTAB decreased the fibers' diameter and increased the electroactive phase content, the piezoelectric performance of the PVDF material was evidently deteriorated. The maximum piezoelectric activity was achieved in the fibrous PVDF material without the use of the surfactant, when a piezoelectric charge of 33 pC N -1 was measured in the transversal direction on a mean fiber diameter of 649 nm. In this direction, the material showed a higher piezoelectric activity than in the longitudinal direction.

Background and Purpose: NMDA receptors are glutamatergic ionotropic receptors involved in excitatory neurotransmission, synaptic plasticity and excitotoxic cell death. Many allosteric modulators can influence the activity of these receptors positively or negatively, with behavioural consequences. 20-Oxo-5β-pregnan-3α-yl sulphate (pregnanolone sulphate; PA-6) is an endogenous neurosteroid that inhibits NMDA receptors and is neuroprotective. We tested the hypothesis that the interaction of PA-6 with the plasma membrane is critical for its inhibitory effect at NMDA receptors., Experimental Approach: Electrophysiological recordings and live microscopy were performed on heterologous HEK293 cells expressing GluN1/GluN2B receptors and cultured rat hippocampal neurons., Key Results: Our experiments showed that the kinetics of the steroid inhibition were slow and not typical of drug-receptor interaction in an aqueous solution. In addition, the recovery from steroid inhibition was accelerated by β- and γ-cyclodextrin. Values of IC(50) assessed for novel synthetic C3 analogues of PA-6 differed by more than 30-fold and were positively correlated with the lipophilicity of the PA-6 analogues. Finally, the onset of inhibition induced by C3 analogues of PA-6 ranged from use-dependent to use-independent. The onset and offset of cell staining by fluorescent analogues of PA-6 were slower than those of steroid-induced inhibition of current responses mediated by NMDA receptors., Conclusion and Implications: We conclude that steroid accumulation in the plasma membrane is the route by which it accesses a binding site on the NMDA receptor. Thus, our results provide a possible structural framework for pharmacologically targeting the transmembrane domains of the receptor., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

20-Oxo-5β-[9,12,12-(2)H(3)]pregnan-3α-yl-l-glutamyl 1-ester 11 was synthesized as an internal standard for quantification of a neuroprotective NMDA receptor ligand, 20-oxo-5β-pregnan-3α-yl-l-glutamyl 1-ester 18 and its metabolites, in plasma and tissue. 11α-Hydroxy-progesterone (1) was reduced under basic conditions to yield the corresponding 5β-steroid. Protection of the 3- and 20-oxo groups and oxidation of the 11α-hydroxy group was then followed by a deuterium exchange, conducted under basic conditions using deuterated methanol. Next, the carbonyl moiety at C-11 was reduced and the 11α-hydroxyl group removed through utilization of the Barton-McCombie reaction. Subsequent deprotection of the 3- and 20-acetals and stereoselective reduction of the 3-oxo group gave the desired trideuterated pregnanolone (8). This was coupled with protected glutamic acid, which was then deprotected to yield [9,12,12-(2)H(3)]-pregnanolone glutamate (11) with >99% isotopic purity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Expansion of the D-ring of 19-norsteroids with incorporation of the steroid C-18 methyl group into a newly formed six-membered ring provides easy access to the chrysene ring system. By taking advantage of the symmetry of the chrysene ring system and avoiding meso chrysene intermediates, four optically pure 2,8-difunctionalized (C-2 hydroxyl group and C-8 oxo group) hexadecahydrochrysene diastereomers, and their corresponding optically pure enantiomers were prepared from 19-nortestosterone. The eight chrysene stereoisomers are of interest as starting materials for preparing chrysene analogues of physiologically important neurosteroids.

This study addresses the hypothesis that the lack of anesthetic activity for (3α,5α)-3-hydroxypregn-16-ene-11,20-dione (Δ(16)-alphaxalone) is explained by the steroid Δ(16) double bond constraining the steroid 20-carbonyl group to a position that prevents it from favorably interacting with γ-aminobutyric acid type A (GABA(A)) receptors. A series of Δ(16) and Δ(17(20)) analogues of Δ(16)-alphaxalone was prepared to evaluate this hypothesis in binding, electrophysiological, and tadpole anesthesia experiments. The results obtained failed to support the hypothesis. Instead, the results indicate that it is the presence of the C-21 methyl group in Δ(16)-alphaxalone, not the location of the constrained C-20 carbonyl group, that prevents Δ(16)-alphaxalone from interacting strongly with the GABA(A) receptor and having anesthetic activity. Consistent with this conclusion, a Δ(17(20)) analogue of Δ(16)-alphaxalone without a C-21 methyl group was found to be very similar to the anesthetic steroid (3α,5α)-3-hydroxypregnane-11,20-dione (alphaxalone) with regard to time of onset and rate of recovery from anesthesia when administered to mice by tail vein injection.

The synthesis of several novel 5alpha- and 5beta-20-oxo-pregnane derivatives substituted in the position 3 and 7 of the steroid skeleton is described. Activity of synthesized compounds was studied in voltage-clamped cultured rat hippocampal neurons. Substituted derivatives inhibited NMDA-elicited neuronal activity. The relationship between biological activity and structure is discussed.