Tratamiento combinado de Espongostan® y Mepitel® en heridas con pérdida de sustancia y abundante sangrado / Combined treatment of Espongostan® and Mepitel® in wounds with loss of substance and abundant bleeding: a case series

Objetivo: Las heridas por pérdida de sustancia en las yemas de los dedos son dolorosas, incapacitantes y sangran abundantemente. El tratamiento recomendado es a base de Espongostan®, aunque este producto puede combinarse con Mepitel®. La combinación de ambos tratamientos podría reducir el dolor y minimizar el sangrado en curas sucesivas. El objetivo de este estudio es describir la aplicación del tratamiento combinado de Espongostan® y Mepitel®. Además, se describirá la evolución del dolor y el sangrado en estos pacientes. Descripción del caso: Se aplicó el tratamiento combinado a 6 pacientes con heridas de pérdida de sustancia en las yemas de los dedos. Resultados: La escala EVA se mantuvo en valores moderados o se redujo a leve en curas sucesivas. Los pacientes no describen signos de dolor destacables al retirar el Espongostan®. Por otro lado, el sangrado remitió antes de 8 días. La tasa promedio de remisión del sangrado se situó en 1 caso por 4 días. Conclusión: La cura combinada es altamente positiva para minimizar el dolor y el sangrado, reduciendo por consiguiente las molestias derivadas sobre los pacientes. (AU)

Objective: Loss of substance wounds on the pads of the fingers are painful, disabling, and have profuse bleeding. The recommended treatment is based on Espongostan®, although this product may be combined with Mepitel ®. The combination of both treatments could reduce pain and minimize bleeding in successive cures. The objective of this study is to describe the application of the combined treatment of Espongostan® and Mepitel®. In addition, the evolution of pain and bleeding in these patients will be described. Description of the case: We applied the combined treatment to 6 patients with loss of substance wounds on the pads of the fingers. Results: The VAS scale remained at moderate values or was reduced to mild in successive cures. Patients do not describe noticeable signs of pain when removing the Espongostan®. Bleeding subsided before 8 days. The average bleeding remission rate was 1 case per 4 days. Conclusion: The combined cure is highly positive for minimizing pain, bleeding and reducing discomfort caused to patients. (AU)

Emergency Management Strategies and Antimicrobial Considerations for Nonmammalian Marine Vertebrate Penetrating Trauma in North America, the Caribbean, and Hawaii: A Review Article.

There are numerous emergency department visits in the United States for all types of marine animal injuries each year. These injuries may result in significant morbidity or mortality if not managed appropriately. Accurate identification of the offending species, thorough wound hygiene, and judicious use of antibiotics are important for preventing infections. This review aims to describe management strategies and antimicrobial considerations for nonmammalian marine vertebrate penetrating trauma in North America, the Caribbean, and Hawaii. A literature search was performed to identify studies on this subject. This literature consisted of clinical case reports and case series. Reports extracted included those on sharks, barracuda, eels, catfish, stingrays, lionfish, stonefish, and scorpionfish. The majority of reported trauma occurred to beachgoers, fishermen, or commercial aquarium employees who routinely handle these animals. Injury patterns depended on the species but most commonly affected the lower extremities. Infections were seen from saltwater bacteria, human skin flora, or marine animal oral flora. After thorough wound irrigation and exploration, most authors recommended prophylactic antimicrobials to cover Vibrio species, in addition to other gram-negative and gram-positive species. The literature is notable for the lack of controlled studies. Some authors recommended radiographic and/or ultrasonographic imaging to identify retained foreign bodies, such as spines, sand, or teeth.

A feasibility study using sodium alginate injection for penetrating abdominal trauma in a swine model.

Penetrating abdominal injury is a major cause of death in trauma. Sodium alginate hydrogel, a hemostatic agent, offers a platform for targeting both mechanical and biological injuries. The current study assessed the effect of Very Low Viscosity (high) G (VLVG) alginate following abdominal trauma in a swine model of penetrating abdominal injury. Seven anesthetized pigs were instrumented with invasive monitoring catheters and abdominal trauma was introduced by laparoscopic hepatectomy. Ten minutes after the induction of hypovolemic shock, three animals were intra-abdominally administered with VLVG alginate (study group) and four animals with saline (control group). During 8 h of continuous monitoring, various hemodynamic and biochemical variables were measured and liver biopsies for histological evaluation were taken. Hemodynamically, VLVG alginate-treated animals were more stable than controls, as reflected by their lower heart rate and higher blood pressure (p < 0.05 for both). They also had lower levels of liver enzymes and lactate, and less histopathological damage. We show that VLVG alginate might be a promising new agent for reducing penetrating intra-abdominal injury, with hemostatic and biocompatibility efficiency, and tissue preserving properties. Future effort of integrating it with a dispersal device may turn it into a valuable pre-hospital emergency tool to improve survival of trauma casualties.

Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model.

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. ß-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, ß-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the ß-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with ß-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the ß-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1ß and IL-6. After ß-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. ß-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of ß-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.

Evaluation of the Wheat Germ Oil Topical Formulations for Wound Healing Activity in Rats.

Wheat Germ Oil (WGO), the flour-milling by-product of wheat has essential constituents for skin health care as vitamin E, B-complex, squalene and unsaturated fatty acids. Incorporate WGO into polymers of the cream and ointment bases and evaluate the wound healing potential of these WGO formulations in the rat-animal model. <b>Materials and Methods:</b> WGO creams and ointments were prepared in two concentrations, 10 and 20% and evaluated for storage stability, homogeneity and compatibility using Fourier Transform Infrared (FT-IR) spectrometry. An amount of 0.5 g of the WGO formulations was applied daily to the injured area of the rats back. Wounds were observed for any clinical changes and healing compared to the control animal group. <b>Results:</b> The WGO was compatible with the cream and ointment bases and physically stables over 60 days of storage. The formulations of WGO have induced dose-dependent wound healing properties however the ointment formulations were demonstrating wound healing activity significantly better than the creams at all the intervals of the treatment. Within three weeks, 20% WGO ointment has induced a 90%reduction in the wound size diameter. Also, wounds recovered by 50% in 10 and 14 days of treatment with 20% WGO ointment and cream, respectively. <b>Conclusion:</b> The results revealed that WGO is a potential wound-healing agent from the scope that WGO is a common cosmetic ingredient and available at affordable prices.

Wound healing potential of licorice extract in rat model: Antioxidants, histopathological, immunohistochemical and gene expression evidences.

Wound healing is a public health concern. Licorice gained a great attention for its antioxidant and anti-inflammatory properties which expand its valuable effects as a herbal medicine. In this study, we pointed out to the wound healing potential and the mechanism by which licorice alcoholic extract can modulate cutaneous wound healing through immune, antioxidant, histopathological, immunohistochemical (IHC) and molecular studies. 24 Wister rats were assigned into 3 groups (n = 8 each); control group, topical and oral supplied groups. Licorice extract administration significantly increased total and differential leucocyte counts, phagocytic activity of neutrophils, antioxidant biomarkers as superoxide dismutase (SOD), glutathione peroxidase activities (GPx) and reduced glutathione (GSH) content with a notable reduction in oxidative stress marker malondialdehyde (MDA). Moreover, histopathological findings detected complete re-epithelialization with increasing collagen synthesis while IHC results revealed a significant enhancement in the expression of α-SMA, PDGFR-α, FGFR1 and Cytokeratin 14 in licorice treated groups compared with the control group. Licorice extract supplementation accelerated wound healing by increasing angiogenesis and collagen deposition through up-regulation of bFGF, VEGF and TGF-ß gene expression levels compared with the control group. UPLC-PDA-MS/MS aided to authenticate the studied Glycyrrihza species and recognized 101 potential constituents that may be responsible for licorice-exhibited potentials. Based on our observations we concluded that licorice enhanced cutaneous wound healing via its free radical-scavenging potential, potent antioxidant activities, and anti-inflammatory actions. Therefore, licorice could be used as a potential alternative therapy for wound injury which could overcome the associated limitations of modern therapeutic products.

Senkyunolide I protect against lung injury via inhibiting formation of neutrophil extracellular trap in a murine model of cecal ligation and puncture.

BACKGROUND: Senkyunolide I (SEI), a component of a Chinese herb named Ligusticum Chuanxiong hort, which is included in the formulation of Xuebijing Injection, a medication used to treat sepsis in China. Our previous study showed that SEI was protective against sepsis-associated encephalopathy and the present study was performed to investigate the role of SEI in sepsis-induced lung injury in a murine model of cecal ligation and puncture (CLP). METHODS: SEI (36 mg/kg in 200 µl) or vehicle was administered immediately after CLP surgery. The lung injury was assessed 24 h later by histopathological tests, protein concentration in the bronchoalveolar lavage fluid (BALF), neutrophil recruitment in the lung tissue (myeloperoxidase fluorescence, MPO), pro-inflammatory cytokines and oxidative responses. Platelet activation was detected by CD42d/GP5 immunofluorescence and neutrophil extracellular trap (NET) were determined by immunofluorescence assays and enzyme linked immunosorbent assay (ELISA) of MPO-DNA. In vitro experiments were performed to detect the level of MPO-DNA complex released by SEI-treated neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) or co-cultured with platelets from CLP mice. RESULTS: SEI administration relieved the injury degree in CLP mice according to the histopathological tests (P < 0.05 compared with DMSO + CLP group). Protein level in the BALF and neutrophil infiltration were remarkably reduced by SEI after CLP surgery (P < 0.05 compared with DMSO + CLP group). TNF-α, IL-1ß and IL-6 were decreased in the plasma and lung tissues from CLP mice treated with SEI (P < 0.05 compared with DMSO + CLP group). The phosphorylation of JNK, ERK, p38 and p65 were all inhibited by SEI (P < 0.05 compared with DMSO + CLP group). Immunofluorescence of MPO showed that neutrophil number was significantly lower in SEI treated CLP mice than in vehicle treated CLP mice (P < 0.05). The CD42d/GP5 staining suggested that platelet activation was significantly reduced and the NET level in the lung tissue and plasma was greatly attenuated by SEI treatment (P < 0.05 compared with DMSO + CLP group). In vitro experiments showed that the MPO-DNA level stimulated by PMA was significantly reduced by SEI treatment (P < 0.05 compared with DMSO treatment). Co-culture neutrophils with platelets from CLP mice resulted in higher level of MPO-DNA complex, while SEI partly reversed such effects of platelet on NET formation. CONCLUSIONS: SEI was protective against lung injury induced by CLP in mice. The NET formation was significantly reduced by SEI treatment, which might be involved in the mechanism of the protective effect.

Electrospun PLGA/SF/artemisinin composite nanofibrous membranes for wound dressing.

Combining biodegradable materials with natural plant components for wound dressing has been receiving significant attention. ART is a sesquiterpene lactone compound extracted from Artemisia annua L., possessing multiple pharmacological effects including antibacterial activity and anti-inflammatory property. Herein, the blended polylactic acid glycolic acid (PLGA)/silk fibroin (SF) membranes loaded with artemisinin (ART) are fabricated through electrospinning. With aid of SF, the fabricated membranes have a good sustained-release effect, and the accumulated ART release can reach 69% after three weeks. PLGA/SF/ART membranes exhibit favorable anti-inflammatory and cell compatibility in vitro evaluations. The in vivo experiment indicates that PLGA/SF/ART2 membranes can shorten the inflammation period and enhance skin regeneration in a full-thickness wound model through down-regulating the expressions of pro-inflammatory cytokines IL-1ß and TNF-α. To sum up, the fabricated PLGA/SF/ART2 composite membranes with anti-inflammatory properties can be a proposal wound dressing for chronic wound healing.

An All-in-One Tannic Acid-Containing Hydrogel Adhesive with High Toughness, Notch Insensitivity, Self-Healability, Tailorable Topography, and Strong, Instant, and On-Demand Underwater Adhesion.

Hydrogels that are mechanically tough and capable of strong underwater adhesion can lead to a paradigm shift in the design of adhesives for a variety of biomedical applications. We hereby innovatively develop a facile but efficient strategy to prepare hydrogel adhesives with strong and instant underwater adhesion, on-demand detachment, high toughness, notch-insensitivity, self-healability, low swelling index, and tailorable surface topography. Specifically, a polymerization lyophilization conjugation fabrication method was proposed to introduce tannic acid (TA) into the covalent network consisting of polyethylene glycol diacrylate (PEGDA) of substantially high molecular weight. The presence of TA facilitated wet adhesion to various substrates by forming collectively strong noncovalent bonds and offering hydrophobicity to allow water repellence and also provided a reversible cross-link within the binary network to improve the mechanical performance of the gels. The long-chain PEGDA enhanced the efficacy and stability of TA conjugation and contributed to gel mechanics and adhesion by allowing chain diffusion and entanglement formation. Moreover, PEGDA/TA hydrogels were demonstrated to be biocompatible and capable of accelerating wound healing in a skin wound animal model as compared to commercial tissue adhesives and can be applied for the treatment of both epidermal and intracorporeal wounds. Our study provides new, critical insight into the design principle of all-in-one hydrogels with outstanding mechanical and adhesive properties and can potentially enhance the efficacy of hydrogel adhesives for wound healing.

In-vivo wound healing activity of a novel composite sponge loaded with mucilage and lipoidal matter of Hibiscus species.

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

Dose Assessment Following a 238Pu-contaminated Wound Case with Chelation and Excision.

The urinary excretion and wound retention data collected after a Pu-contaminated wound were analyzed using Markov Chain Monte Carlo (MCMC) to obtain the posterior distribution of the intakes and doses. An empirical approach was used to model the effects of medical treatments (chelation and excision) on the reduction of doses. It was calculated that DTPA enhanced the urinary excretion, on average, by a factor of 17. The empirical analysis also allowed calculation of the efficacies of the medical treatments-excision and chelation averted approximately 76% and 5.5%, respectively, of the doses that would have been if there were no medical treatment. All bioassay data are provided in the appendix for independent analysis and to facilitate the compartmental modeling approaches being developed by the health physics community.

Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake via Wound and Treatment with DTPA.

The administration of chelation therapy to treat significant intakes of actinides, such as plutonium, affects the actinide's normal biokinetics. In particular, it enhances the actinide's rate of excretion, such that the standard biokinetic models cannot be applied directly to the chelation-affected bioassay data in order to estimate the intake and assess the radiation dose. The present study proposes a new chelation model that can be applied to the chelation-affected bioassay data after plutonium intake via wound and treatment with DTPA. In the proposed model, chelation is assumed to occur in the blood, liver, and parts of the skeleton. Ten datasets, consisting of measurements of C-DTPA, Pu, and Pu involving humans given radiolabeled DTPA and humans occupationally exposed to plutonium via wound and treated with chelation therapy, were used for model development. The combined dataset consisted of daily and cumulative excretion (urine and feces), wound counts, measurements of excised tissue, blood, and post-mortem tissue analyses of liver and skeleton. The combined data were simultaneously fit using the chelation model linked with a plutonium systemic model, which was linked to an ad hoc wound model. The proposed chelation model was used for dose assessment of the wound cases used in this study.

Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17ß-Estradiol.

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17ß-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERß. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERß receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.

Drupin, a cysteine protease from Ficus drupacea latex accelerates excision wound healing in mice.

Wound healing is a tightly regulated physiological process that restores tissue integrity after injury. Plant latex proteases (PLPs) are considered an integral part in herbal wound care as it interferes at different phases of the wound healing process. Although many studies have reported the involvement of PLPs in healing process, an in-depth investigation is required to understand the molecular mechanism. Hence, the effect of PLPs with fibrinolytic activity on wound healing was investigated systematically using mouse excision wound model. Among 29 latices from Ficus genus tested, Ficus drupacea exhibited potent fibrinolytic activity. Cysteine protease responsible for fibrinolysis was purified from the F. drupacea latex named it as drupin, tested for its wound healing efficacy. The accelerated wound healing was mediated by downregulation of matrix metalloprotease (MMP)-9 without altering MMP-8 expression. Besides, drupin enhanced the rate of collagen synthesis at the wound site by increasing arginase 1 activity. And also, drupin increased the expression of arginase 1 in macrophages and involved in cell proliferation, and migration via MAP kinase and PI3K/Akt pathways. Overall, the present study highlights the interference of drupin in wound healing by increased arginase 1 activity and collagen synthesis, and cell proliferation and migration.

A Supersaturated Oxygen Emulsion for Wound Care and Skin Rejuvenation.

Although oxygen is essential for proper wound healing, wounds are often hypoxic with diminished oxygen delivery to the healing tissue. Since oxygenation of the outer layers of skin is almost exclusively provided by the atmosphere, increasing the presence of external oxygen enhances the healing process. Hyperbaric oxygen therapy is beneficial for treating nonhealing wounds, such as diabetic ulcers, and has been used to speed post-treatment recovery following aesthetic procedures; however, it is not suitable for home use. Recently, perfluorocarbon emulsions have been developed that can absorb large amount of oxygen. Preparations containing 2% of these compounds can absorb up to seven-times more oxygen than water at 37°C. A topical perfluorocarbon emulsion consisting of perfluorodecalin, water, plant derived emulsifiers, and a preservative, has been developed for use in dermatology (Cutagenix™ & Cutavive™ Professional Skin Care Emulsion; Cutagenesis, Niwot, CO). Designed to be applied 2 to 4 times daily following skin rejuvenation procedures, this topical oxygen emulsion reduces the incidence of post-procedure complications. The application of a topical emulsion is well-suited for patient application to enhance recovery following energy-based aesthetic procedures. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4728.

Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post-CRASH-2 Era.

OBJECTIVES: The CRASH-2 trial demonstrated that tranexamic acid (TXA) in adults with significant traumatic hemorrhage safely reduces mortality. Given that the CRASH-2 trial did not include U.S. sites, our objective was to evaluate patient characteristics, TXA dosing strategies, and the incidence of mortality and adverse events in adult trauma patients receiving TXA at a U.S. Level I trauma center in the post-CRASH-2 era. METHODS: We conducted a retrospective study that included patients aged 18 years or older who received TXA after an acute injury from July 2014 to June 2017. We excluded patients who received TXA orally, patients who received TXA for elective surgical procedures or nontrauma indications, patients who received it 8 hours or longer after the time of injury, and patients with cardiac arrest at time of emergency department arrival. Trained abstractors collected data from the trauma registry and hospital electronic medical records. Our primary outcome measures were in-hospital death and acute thromboembolic events within 28 days from injury. RESULTS: We included 273 patients with a mean (±SD) age of 43.8 (±18.7)  years. The mean (±SD) time of administration of TXA from time of injury was 1.55 (±1.2)  hours with 229 patients (83.9%) receiving TXA within 3 hours. The overall mortality within 28 days from injury was 12.8% (95% confidence interval [CI] = 8.9% to 16.7%), which was similar compared to that in the CRASH-2 trial (14.5%, 95% CI = 13.9% to 15.2%). The incidence of acute thromboembolic events was 6.6% (95% CI = 3.7% to 9.5%), which was higher than that in the CRASH-2 trial (2.0%, 95% CI = 1.73% to 2.27%). Patients in our cohort also received surgery (64.8% vs. 47.9%) and blood transfusions (74.0% vs. 50.4%) more frequently than those in the CRASH-2 cohort. CONCLUSIONS: Adult trauma patients receiving TXA had similar incidences of death but higher incidences of thromboembolic events compared to the CRASH-2 trial. Variation in patient characteristics, injury severity, TXA dosing, and surgery and transfusion rates could explain these observed differences. Further research is necessary to provide additional insight into the incidence and risk factors of thromboembolic events in TXA use.

Incisional Injury Modulates Morphine Reward and Morphine-Primed Reinstatement: A Role of Kappa Opioid Receptor Activation.

BACKGROUND: Persistent use of prescription opioids beyond the period of surgical recovery is a large part of a public health problem linked to the current opioid crisis in the United States. However, few studies have been conducted to examine whether morphine reward is influenced by acute pain and injury. METHODS: In a mouse model of incisional injury and minor trauma, animals underwent conditioning, extinction, and drug-primed reinstatement with morphine to examine the rewarding properties of morphine in the presence of acute incisional injury and drug-induced relapse, respectively. In addition, we sought to determine whether these behaviors were influenced by kappa opioid receptor signaling and measured expression of prodynorphin messenger RNA in the nucleus accumbens and medial prefrontal cortex after conditioning and before reinstatement with morphine and incisional injury. RESULTS: In the presence of incisional injury, we observed enhancement of morphine reward with morphine-conditioned place preference but attenuated morphine-primed reinstatement to reward. This adaptation was not present in animals conditioned 12 days after incisional injury when nociceptive sensitization had resolved; however, they showed enhancement of morphine-primed reinstatement. Prodynorphin expression was greatly enhanced in the nucleus accumbens and medial prefrontal cortex of mice with incisional injury and morphine conditioning and remained elevated up to drug-primed reinstatement. These changes were not observed in mice conditioned 12 days after incisional injury. Further, kappa opioid receptor blockade with norbinaltorphimine before reinstatement reversed the attenuation induced by injury. CONCLUSIONS: These findings suggest enhancement of morphine reward as a result of incisional injury but paradoxically a protective adaptation with incisional injury from drug-induced relapse resulting from kappa opioid receptor activation in the reward circuitry. Remote injury conferred no such protection and appeared to enhance reinstatement.

Sorocea guilleminiana Gaudich.: Wound healing activity, action mechanisms, and chemical characterization of the leaf infusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorocea guilleminina Gaudich. is a tree or shrub endemic to Brazil. Its leaves are used in Brazilian folk medicine for the healing of wounds, stomach problems, inflammation and as diuretic. The present study evaluates the activity and action mechanisms of the healing properties of the aqueous extract of S. guilleminiana leaves (AESg), in experimental models in vivo and in vitro, as well as performs a phytochemical analysis of the extract. MATERIALS AND METHODS: The AESg was prepared by infusion: Ten g of dry leaves powder in 1 L hot water, soaked for 15 min, filtered, lyophilized, and stored at -30 °C. Phytochemical analyses were realized by colorimetry and HPLC/ESI/MS. Its' in vitro cytotoxicity was evaluated on fibroblastic N3T3 cells. The potential of the wound healing activity in vivo was evaluated using excision and incision wound rat models, by histopathology of the injured skin along with the determination of nitric oxide, cytokines (IL-1ß, IL-10, and TNF-α), and antioxidant parameters (GSH, MPO and CAT). In vitro wound healing activity was also demonstrated in scratched N3T3 cells, by measuring the proliferation/migration rate. RESULTS: The phytochemical analysis of the AESg revealed a strong presence of polar compounds, especially flavonoids (4 majoritarian), as well as terpenes and/or sterols (2 majoritarian). The AESg showed no toxicity in the N3T3 cell line (IC50 > 800 µg/mL). Topical treatment with the AESg showed an increase (p < 0.05) in wound contraction with 2 mg/g cream on days 5 and 9 (43.56% and 6.70% increase, respectively), and with 50 mg/g on days 7 and 9 (10.88% and 7.91%, respectively), compared to the vehicle (non-ionic neutral cream). Topical application of AESg (2 or 50 mg/g non-ionic cream) in incised wounds caused an increase in the force necessary for the rupture of the wound when compared to the vehicle group. No changes in cytokines (IL-1ß, IL-10, or TNF-α) or NO accumulation was found with up to 50 mg/g AESg treatment. For antioxidant activity on the incision wound, an increase in GSH levels was denoted with the AESg use, at the lowest and highest dose (2 and 50 mg/g) by 75.86% and 61.20% respectively, when compared to the vehicle. Also, the CAT activity was accentuated by AESg at the highest dose (50 mg/g) by 85.87%. Finally, the AESg at all doses attenuated MPO activity significantly in the incision wound by 71.35%, 73.21%, 78.08%, respectively. In the scratch test on N3T3 cells, the treatment with AESg resulted also in an increase in fibroblast proliferation/migration rate, compared to the vehicle. CONCLUSION: AESg is not cytotoxic. The results confirm the popular use of the leaf infusion of S. guilleminiana for the treatment of cutaneous wounds, possibly by stimulating the proliferation of fibroblasts with a consequent deposition of collagen, fastening rearrangement of collagen fibers, and greater transformation into myofibroblasts, essential in the healing process. Preliminary chemical analyzes of AESg revealed the presence mainly of phenolic compounds, being salicylic acid, gallic acid, pinocembrin and isoquercitrin the majoritarian ones.

Prophylactic antibiotics for penetrating abdominal trauma: duration of use and antibiotic choice.

BACKGROUND: Penetrating abdominal trauma (PAT) is a common type of trauma leading to admission to hospital, which often progresses to septic complications. Antibiotics are commonly administered as prophylaxis prior to laparotomy for PAT. However, an earlier Cochrane Review intending to compare antibiotics with placebo identified no relevant randomised controlled trials (RCTs). Despite this, many RCTs have been carried out that compare different agents and durations of antibiotic therapy. To date, no systematic review of these trials has been performed. OBJECTIVES: To assess the effects of antibiotics in penetrating abdominal trauma, with respect to the type of agent administered and the duration of therapy. SEARCH METHODS: We searched the following electronic databases for relevant randomised controlled trials, from database inception to 23 July 2019; Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE Ovid, MEDLINE Ovid In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily and Ovid OLDMEDLINE, Embase Classic + Embase Ovid, ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), and two clinical trials registers. We also searched reference lists from included studies. We applied no restrictions on language or date of publication. SELECTION CRITERIA: We included RCTs only. We included studies involving participants of all ages, which were conducted in secondary care hospitals only. We included studies of participants who had an isolated penetrating abdominal wound that breached the peritoneum, who were not already taking antibiotics. DATA COLLECTION AND ANALYSIS: Two study authors independently extracted data and assessed risk of bias. We used standard Cochrane methods. We aggregated study results using a random-effects model. We also conducted trial sequential analysis (TSA) to help reduce type I and II errors in our analyses. MAIN RESULTS: We included 29 RCTs, involving a total of 4458 participants. We deemed 23 trials to be at high risk of bias in at least one domain. We are uncertain of the effect of a long course of antibiotic prophylaxis (> 24 hours) compared to a short course (≤ 24 hours) on abdominal surgical site infection (RR 1.00, 95% CI 0.81 to 1.23; I² = 0%; 7 studies, 1261 participants; very low-quality evidence), mortality (Peto OR 1.67, 95% CI 0.73 to 3.82; I² = 8%; 7 studies, 1261 participants; very low-quality evidence), or intra-abdominal infection (RR 1.23, 95% CI 0.84 to 1.80; I² = 0%; 6 studies, 111 participants; very-low quality evidence). Based on very low-quality evidence from fifteen studies, involving 2020 participants, which compared different drug regimens with activity against three classes of gastrointestinal flora (gram positive, gram negative, anaerobic), we are uncertain whether there is a benefit of one regimen over another. TSA showed the majority of comparisons did not cross the alpha adjusted boundary for benefit or harm, or reached the required information size, indicating that further studies are required for these analyses. However, in the three analyses which crossed the boundary for futility, further studies are unlikely to show benefit or harm. AUTHORS' CONCLUSIONS: Very low-quality evidence means that we are uncertain about the effect of either the duration of antibiotic prophylaxis, or the superiority of one drug regimen over another for penetrating abdominal trauma on abdominal surgical site infection rates, mortality, or intra-abdominal infections. Future RCTs should be adequately powered, test currently used antibiotics, known to be effective against gut flora, use methodology to minimise the risk of bias, and adequately report the level of peritoneal contamination encountered at laparotomy.

Stem cells and metformin synergistically promote healing in experimentally induced cutaneous wound injury in diabetic rats.

INTRODUCTION: Diabetes mellitus (DM) is a serious, chronic metabolic disorder commonly complicated by diabetic foot ulcers with delayed healing. Metformin was found to have a wound healing effect through several mechanisms. The current study investigated the effect of both bone marrow-derived mesenchymal stem cells (BM-MSCs) and metformin, considered alone or combined, on the healing of an experimentally induced cutaneous wound injury in streptozotocin-induced diabetic rats. MATERIAL AND METHODS: Forty adult male albino rats were used. Diabetes was induced by single intravenous (IV) injection of streptozotocin (STZ). Next, two circular full thickness skin wounds were created on the back of the animals, then randomly assigned into 4 groups, ten rats each. BM-MSCs were isolated from albino rats, 8 weeks of age and labeled by PKH26 before intradermal injection into rats of Group III and IV. Groups I (diabetic positive control), II (metformin-treated, 250 mg/kg/d), III (treated with 2×106 BM-MSCs), and IV (wounded rats treated both with metformin and BM-MSCs cells). Healing was assessed 3, 7, 14, and 21 days post wound induction through frequent measuring of wound diameters. Skin biopsies were obtained at the end of the experiment. RESULTS: Gross evaluation of the physical healing of the wounds was done. Skin biopsies from the wound areas were processed for hematoxylin and eosin (H&E), Masson's trichrome staining and immunohistochemical staining for CD31. The results showed better wound healing in the combined therapy group (IV) as compared to monotherapy groups. CONCLUSIONS: Although both metformin and BM-MSCs were effective in the healing of experimentally induced skin wounds in diabetic rats, the combination of both agents appears to be a better synergistic option for the treatment of diabetic wound injuries.