In vivo and in vitro evaluation of the use of a newly developed melatonin loaded emulsion combined with UV filters as a protective agent against skin irradiation

BackgroundMelatonin has attracted attention because of their high antioxidant and anticarcinogenic activity. Otherwise, the use of sunscreens is recommended for patients after chemotherapy and radiotherapy treatments or to prevent UV radiation-induced skin damages that may result in pre-cancerous and cancerous skin lesions.ObjectiveTo evaluate the beneficial influence of melatonin in topical sunscreen emulsions combined with three common ultraviolet filters.MethodsAfter the formulation characterization in terms of rheology, stability studies were performed. Release studies let us to evaluate its mechanism of delivery and ex vivo permeation study through human skin, the amount of melatonin retained. The antioxidant activity assay was also carried out, and finally the in vivo photoprotective effect in rats was tested as transepidermal water loss and erythema formation.ResultsThe rheological behaviour of formulations was pseudoplastic fluid, all emulsions had good physical stability. Release studies showed a trend of enhancement in melatonin release from emulsions incorporating UV filters and followed a Weibull model. Melatonin permeation was higher from the emulsion containing melatonin combined with a mixture of three ultraviolet filters (MMIX) formulation. Equally this formulation exhibited the highest radical scavenging activity. Finally the photoprotective assay showed that only skin areas treated with this formulation were statistically equivalent to the unirradiated control area.ConclusionMMIX formulation would be a promising formulation for preventing the undesirable adverse effects of UV skin irradiation because melatonin not only acts as a potent antioxidant itself, but also is capable of activating an endogenous enzymatic protective system against oxidative stress.     

Myostatin inhibits proliferation but not differentiation of trout myoblasts

The muscle growth in mammals is regulated by several growth factors including myostatin (MSTN), a member of the transforming growth factor-beta (TGF-beta) superfamily. To date, it is unknown in fish whether MSTN could have any effect on proliferation or differentiation of myogenic cells. Using culture of trout satellite cells, we showed that mstn1a and mstn1b mRNA are expressed in myoblasts and that their expression decreased in differentiating myoblasts. We also demonstrated that a treatment with huMSTN decreased the proliferation of IGF1-stimulated myoblasts in a dose-dependent manner. By contrast, treatment of myoblasts with 100 nM of huMSTN for three days, did not affect the percentage of positive cells for myogenin neither the percentage of nuclei in myosin positive cells. Moreover, our results clearly indicated that huMSTN treatment had no effect on MyoD and myogenin protein levels, which suggests that huMSTN did not strongly affect MyoD activity. In conclusion, we showed that huMSTN inhibited proliferation but not differentiation of trout myoblasts, probably resulting from a lack of huMSTN effect on MyoD activity. Altogether, these results show high interspecies differences in the function of MSTN.     

Early postoperative transtibial articular fistula formation after anterior cruciate ligament reconstruction: a review of three cases

Introduction

This is a retrospective case report of three cases with an early postoperative transtibial fistula after anterior cruciate ligament reconstruction (ACL).

Materials and methods

The patients had undergone ACL reconstruction and complained of fluid drainage through the not-healed wound or swelling localized on the anteromedial aspect of the ipsilateral proximal tibia during the early postoperative. Magnetic resonance imaging showed a multilocular fluid-filled cyst arising from the distal hole of the tibial bone tunnel. Open resection of the fistula and the cyst was performed in all cases and communication between the tibial tunnel and the joint space was confirmed. During revision surgery the distal hole of the tibial tunnel was covered with a fascio-periosteal flap.

Results

All wounds healed without complications. There was no recurrence of drainage or cyst formation. At 2 years follow-up the knee function was normal and was not affected by the complication in any of the patients. Early postoperative transtibial fistulae after ACL reconstruction are rare complications that clinically present either as anterior tibial cysts or persistent wound drainage. Surgical treatment is required, and some delay in the rehabilitation routine is required, but the final outcome is not affected.     

Lipid-based drug delivery systems for cancer treatment

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concluded that biodistribution profiles of chemotherapy agents can be controlled by their loading to such nanoplatforms. Lipid-based nanomedicines offer an interesting approach to the delivery of anticancer drugs to brain tumors, and to reverse multi-drug resistance of cancer cells. Finally, a deep evaluation of the applicability of drug delivery strategies in the formulation of lipid-based nanoplatforms is carried out. They involve active drug targeting (including ligand-mediated delivery, and stimuli-sensitive carriers), and passive drug targeting (through the enhanced permeability and retention effect) to tumors.     

Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP‐43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP‐43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP‐43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer’s disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non‐FTLD related findings can influence the cognitive status, particularly in older age groups.     

Accumulation of prion protein in the vagus nerve in creutzfeldt–jakob disease

Disease‐associated proteins are thought to propagate along neuronal processes in neurodegenerative diseases. To detect disease‐associated prion protein (PrP^Sc) in the vagus nerve in different forms and molecular subtypes of Creutzfeldt–Jakob disease (CJD), we applied 3 different anti‐PrP antibodies. We screened the vagus nerve in 162 sporadic and 30 genetic CJD cases. Four of 31 VV‐2 type sporadic CJD and 7 of 30 genetic CJD cases showed vagal PrP^Sc immunodeposits with distinct morphology. Thus, PrP^Sc in CJD affects the vagus nerve analogously to α‐synuclein in Parkinson disease. The morphologically diverse deposition of PrP^Sc in genetic and sporadic CJD argues against uniform mechanisms of propagation of PrP^Sc. Ann Neurol 2019;85:782–787     

Evaluation of novel nystatin nanoemulsion for skin candidosis infections

One of the most common fungal skin infections is candidosis. Topical application of drugs at the pathological sites offers potential advantage of direct drug delivery to the site of action. The main aim of this work was to evaluate an optimal nystatin nanoemulsion for topical application avoiding undesirable side effects as systemic absorption and toxicity. Surface morphology and droplet size distribution of nystatin nanoemulsion was determined by transmission electronic microscopy and dynamic light scattering. Vertical diffusion Franz‐type cells and high‐performance liquid chromatography were used to perform the in vitro release and ex vivo human skin permeation studies. Transdermal permeation parameters were estimated from the permeation values using different theoretical approaches. Microbiological studies were performed to evaluate the antifungal effect. Nanoemulsion exhibited a spherical shape with smooth surface and mean droplet size between 70 and 80 nm. The pharmacokinetic release showed the nanoemulsion is faster than commercial ointment Mycostatin^® improving the potential therapeutic index. Permeation studies demonstrated nystatin was not absorbed into systemic circulation and the retained amount in the skin was sufficient to ensure an antifungal effect. This antifungal effect was higher for nystatin loaded nanoemulsion than nystatin itself. A therapeutic improvement of the nystatin nanoemulsion treatment compared with the classical ones was achieved.