Tissue engineering in plastic reconstructive surgery

Tissue engineering (TE) is a new interdisciplinary field of applied research combining engineering and biosciences together with clinical application, mainly in surgical specialities, to develop living substitutes for tissues and organs. Tissue engineering approaches can be categorized into substitutive approaches, where the aim is the ex vivo construction of a living tissue or organ similar to a transplant, vs. histioconductive or histioinductive concepts in vivo. The main successful approaches in developing tissue substitutes to date have been progresses in the understanding of cell-cell interactions, the selection of appropriate matrices (cell-matrix interaction) and chemical signalling (cytokines, growth factors) for stimulation of cell proliferation and migration within a tissue-engineered construct. So far virtually all mammalian cells can be cultured under specific culture conditions and in tissue specific matrices. Future progress in cell biology may permit the use of pluripotent stem cells for TE. The blueprint for tissue differentiation is the genome: for this it is reasonable to combine tissue engineering with gene therapy. The key to the progress of tissue engineering is an understanding between basic scientists, biochemical engineers, clinicians, and industry.     

Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor

The purpose of this study was to characterize a new chemical entity, desvenlafaxine succinate (DVS). DVS is a novel salt form of the isolated major active metabolite of venlafaxine. Competitive radioligand binding assays were performed using cells expressing either the human serotonin (5-HT) transporter (hSERT) or norepinephrine (NE) transporter (hNET) with K(i) values for DVS of 40.2 +/- 1.6 and 558.4 +/- 121.6 nM, respectively. DVS showed weak binding affinity (62% inhibition at 100 microM) at the human dopamine (DA) transporter. Inhibition of [3H]5-HT or [3H]NE uptake by DVS for the hSERT or hNET produced IC50 values of 47.3 +/- 19.4 and 531.3 +/- 113.0 nM, respectively. DVS (10 microM), examined at a large number of nontransporter targets, showed no significant activity. DVS (30 mg/kg orally) rapidly penetrated the male rat brain and hypothalamus. DVS (30 mg/kg orally) significantly increased extracellular NE levels compared with baseline in the male rat hypothalamus but had no effect on DA levels using microdialysis. To mimic chronic selective serotonin reuptake inhibitor treatment and to block the inhibitory 5-HT(1A) autoreceptors, a 5-HT(1A) antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo hexanecarboxamide maleate salt (WAY-100635) (0.3 mg/kg s.c.), was administered with DVS (30 mg/kg orally). 5-HT increased 78% compared with baseline with no additional increase in NE or DA levels. In conclusion, DVS is a new 5-HT and NE reuptake inhibitor in vitro and in vivo that demonstrates good brain-to-plasma ratios, suggesting utility in a variety of central nervous system-related disorders.     

Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation

In murine macrophages, as a result of arginine catabolism during activation, citruline is produced under the effect of IFN-gamma and LPS, and ornithine and polyamines by IL-4 and IL-10. For proliferation, arginine is required from the extracellular medium and is used for protein synthesis. During activation, most arginine (>95% in 6 h) was metabolized, while under proliferation only half was incorporated into proteins. Under basal conditions, this amino acid was preferentially transported by y(+)L activity. During activation, arginine transport increased drastically (4-5-fold) through y(+) cationic amino acid transporter (CAT) activity. By contrast, M-CSF induced only a modest increase in uptake (0.5-fold). The increase in arginine transport during activation, but not proliferation, was mediated by the SLC7A2/Cat2 gene. SLC7A1/Cat1 is constitutively expressed, and is not modified by proliferating or activating agents. M-CSF-dependent proliferation was not affected in the macrophages of SLC7A2 knockout mice; however, these cells showed a drastic reduction in the production of citruline or ornithine and polyamines during activation. The data show that a large increase in a specific transport system (CAT2) is necessary for activation-induced arginine metabolism, while arginine is in excess for the requirements of proliferation and a modest increase in transport occurs.     

Laboratory strength of glass ionomer cement, compomers, and resin composites

PURPOSE: The study evaluates the compressive, flexural, and diametral tensile strengths of 8 core build-up materials from different material classes (highly viscous glass ionomer cement, autocured resin composite, and compomers). MATERIALS AND METHODS: All materials were manipulated according to the manufacturers' recommendations for use as core materials. At a temperature of 23.0 +/- 1.0 degrees C the properties of compressive, diametral tensile and flexural strength were determined using a universal testing machine at 15 minutes, 1 hour, and 24 hours after material preparation. Using one-way analysis of variance (ANOVA), multiple mean value comparisons were performed to determine significant differences (p< or =.05) between the core restoration materials. RESULTS: The values for compressive strength varied from 40.3 +/- 5.2 MPa (compomer) to 237.4 +/- 37.3 MPa (autocured resin composite) for the 3 measurement times. At 15 minutes, 1 hour, and 24 hours after first mixing, the ANOVA showed significant differences (p < or =.05) between the resin composite Core Paste and all of the other materials. Diametral tensile strengths ranged from 5.5 +/- 1.1 MPa for glass ionomer cement to 39.1 +/- 2.9 MPa for composite core material. Three-point flexural strength showed values ranging from 12.1 +/- 2.5 MPa for glass ionomer cement to 92.1 +/- 9.7 MPa for compomer between the 3 measurement times. CONCLUSIONS: Setting time influences the mechanical properties of the materials tested in this study. Autopolymerizing resin composite Core Paste demonstrated greater compressive and flexural strengths at the 3 measurement times than the other materials tested. Reinforced composites, in comparison to the autocured resin composites, yielded no improvement in tensile strength. Flexural and tensile strengths of the glass ionomer cement were lower than those of autocured resin composites and compomers.     

Patellofemoral pain syndrome

The patellofemoral pain syndrome (PFPS) is a possible cause for anterior knee pain, which predominantly affects young female patients without any structural changes such as increased Q-angle or significant chondral damage. This literature review has shown that PFPS development is probably multifactorial with various functional disorders of the lower extremity. Biomechanical studies described patellar maltracking and dynamic valgus in PFPS patients (functional malalignment). Causes for the dynamic valgus may be decreased strength of the hip abductors or abnormal rear-foot eversion with pes pronatus valgus. PFPS is further associated with vastus medialis/vastus lateralis dysbalance, hamstring tightness or iliotibial tract tightness. The literature provides evidence for a multimodal non-operative therapy concept with short-term use of NSAIDs, short-term use of a medially directed tape and exercise programmes with the inclusion of the lower extremity, and hip and trunk muscles. There is also evidence for the use of patellar braces and foot orthosis. A randomized controlled trial has shown that arthroscopy is not the treatment of choice for treatment of PFPS without any structural changes. Patients with anterior knee pain have to be examined carefully with regard to functional causes for a PFPS. The treatment of PFPS patients is non-operative and should address the functional causes. Level of evidence V.     

Clinical features of Guillain–Barré syndrome and factors associated with mortality during the 2019 outbreak in Peru

Journal of Neurology - Peru has suffered an increase of Guillain Barre Syndrome incidence since 2015, being the biggest outbreak during 2019. We aimed to describe the clinical features, outcomes,...     

Nuevas dianas terapéuticas en el melanoma

Research into molecular targets for drug development in melanoma is starting to bear fruit. Of the drugs tested to date in patients with metastatic melanoma, those that have yielded the best results are V600E BRAF inhibitors in melanomas carrying the V600E mutation; c-kit tyrosine kinase activity inhibitors in melanomas carrying c-kit mutations; and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, which block the mechanisms involved in immune tolerance. Many problems have yet to be resolved in these areas, however, such as the rapid development of resistance to BRAF and c-kit inhibitors and the lack of biomarkers to predict treatment response in the case of CTLA-4 blockers. We review the results of targeted therapy with these and other drugs in metastatic melanoma and discuss what the future holds for this field.