Stimulated healing of recalcitrant wounds by topical application of enriched cell culture medium: a clinical report.

This study was designed to test the efficacy of enriched cell culture medium as a wound dressing. The rationale was to create within the wound space an optimal microenvironment, conducive to cellular proliferation, vascular granulation tissue formation, and epithelialization. This study was performed on various wounds that failed to respond to previous conventional treatments.A total of 288 wounds were within the inclusion criteria, with only contaminated and neoplastic wounds excluded. Most of the patients (80 percent) were ambulatory, and the wounds were examined by the attending physician once every 7 to 14 days at an outpatient clinic. The remaining 20 percent of patients were admitted to the study while hospitalized.Cell culture medium MCDB, supplemented with insulin, thyroxin, and growth hormone, was gelled. The gel was self-applied once a day to freshly washed wounds, covered with a gauze pad, and anchored with netting.Healing started 7 to 14 days after the initiation of treatment with enriched cell culture medium. However, the criterion for success of the treatment was determined on complete wound closure, which was achieved in 189 of 288 wounds (65.6 percent). Wound closure was correlated with the initial wound volume, stage, and origin. The average time required for closure of wounds caused by systemic pathologies (n = 181) and those based on regional status (n = 107) were 12.0 and 4.4 weeks, respectively, compared with 290 and 10.3 weeks of the previous conventional treatment. In 19 extensive wounds, when vascularized granulation tissue was established, a successful surgical closure was attained.Most wounds of patients who did not continue the enriched cell culture medium treatment (34.4 percent) manifested reduced wound volume, ranging from 11 to 98 percent of initial volume. Discontinuation of treatment was associated with difficulties in reaching the clinic for the weekly examination, rather than for reasons directly related to the treatment itself, and occurred significantly earlier during the treatment period.Thus, enriched cell culture medium was effective in stimulating wound healing in recalcitrant wounds. The healing was rapid with minimum scarring and pain. No side effects or allergic reactions were reported or observed.     

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial

Background

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments.

Methods and Findings

The trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements.

Conclusions

HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00715052","term_id":"NCT00715052"}}NCT00715052     

An Immunomodulating Motif of the HIV-1 Fusion Protein Is Chirality-independent: IMPLICATIONS FOR ITS MODE OF ACTION*

An immunosuppressive motif was recently found within the HIV-1 gp41 fusion protein (termed immunosuppressive loop-associated determinant core motif (ISLAD CM)). Peptides containing the motif interact with the T-cell receptor (TCR) complex; however, the mechanism by which the motif exerts its immunosuppressive activity is yet to be determined. Recent studies showed that interactions between protein domains in the membrane milieu are not always sterically controlled. Therefore, we utilized the unique membrane leniency toward association between d- and l-stereoisomers to investigate the detailed mechanism by which ISLAD CM inhibits T-cell activation. We show that a d-enantiomer of ISLAD CM (termed ISLAD d-CM) inhibited the proliferation of murine myelin oligodendrocyte glycoprotein (MOG)-(35–55)-specific line T-cells to the same extent as the l-motif form. Moreover, the d- and l-forms preferentially bound spleen-derived T-cells over B-cells by 13-fold. Furthermore, both forms of ISLAD CM co-localized with the TCR on activated T-cells and interacted with the transmembrane domain of the TCR. FRET experiments revealed the importance of basic residues for the interaction between ISLAD CM forms and the TCR transmembrane domain. Ex vivo studies demonstrated that ISLAD d-CM administration inhibited the proliferation (72%) and proinflammatory cytokine secretion of pathogenic MOG(35–55)-specific T-cells. This study provides insights into the immunosuppressive mechanism of gp41 and demonstrates that chirality-independent interactions in the membrane can take place in diverse biological systems. Apart from HIV pathogenesis, the d-peptide reported herein may serve as a potential tool for treating T-cell-mediated pathologies.     

Epizootic Hemorrhagic Disease Virus Induces and Benefits from Cell Stress,Autophagy, and Apoptosis

The mode and timing of virally induced cell death hold the potential of regulating viral yield, viral transmission, and the severity of virally induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process, and the consequence of their inhibition have yet to be characterized. Here, we report that the Ibaraki strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular protein synthesis, the activation of c-Jun N-terminal kinase (JNK), and the phosphorylation of the JNK substrate c-Jun. The production of infectious virions decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone), upon inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy regulator Atg5, or upon treatment of infected cells with the JNK inhibitor SP600125 or the cyclin-dependent kinase (CDK) inhibitor roscovitine, which also inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125, and roscovitine partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV induces and benefits from the activation of signaling pathways involved in cell stress and death.     

The effect of body size on the thermoregulation of lizards on hot,dry Mediterranean islands

Body size shapes the overall biology of organisms. We assessed the impact of size on temperature regulation in populations of normal-sized and large-bodied insular Mediterranean lizards (Podarcis gaigeae, Lacertidae). We hypothesized that large lizards would achieve higher body temperatures and thermoregulate more effectively than their smaller kin. Large- and small-bodied lizards share the same thermoregulation pattern, achieving similar body temperatures in the field. Large lizards, however, prefer higher set-point temperatures. Lizards in both populations thermoregulate effectively, but large lizards thermoregulated less effectively than normal-sized lizards. The particular conditions at the islet that harbors the large-bodied population (harsh intraspecific competition) seem to account for this pattern.     

Underwater linear polarization: physical limitations to biological functions

Polarization sensitivity is documented in a range of marine animals. The variety of tasks for which animals can use this sensitivity, and the range over which they do so, are confined by the visual systems of these animals and by the propagation of the polarization information in the aquatic environment. We examine the environmental physical constraints in an attempt to reveal the depth, range and other limitations to the use of polarization sensitivity by marine animals. In clear oceanic waters, navigation that is based on the polarization pattern of the sky appears to be limited to shallow waters, while solar-based navigation is possible down to 200-400 m. When combined with intensity difference, polarization sensitivity allows an increase in target detection range by 70-80% with an upper limit of 15 m for large-eyed animals. This distance will be significantly smaller for small animals, such as plankton, and in turbid waters. Polarization-contrast detection, which is relevant to object detection and communication, is strongly affected by water conditions and in clear waters its range limit may reach 15 m as well. We show that polarization sensitivity may also serve for target distance estimation, when examining point source bioluminescent objects in the photic mesopelagic depth range.