Syzygium cumini(L.),Skeels fruit extracts: In vitro and in vivo anti-inflammatory properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is an important medicinal plant utilized in the health care systems of Pakistan, India, Sri Lanka, and Bangladesh. S. cumini have been used to treat renal issues, indigestion, diabetes, dysentery, and employed in folk medicine to treat inflammations. It is known to anticipate antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-bacterial, antifungal, activities, and radioprotective activities. MATERIAL AND METHODS: We examined the in vitro anti-inflammatory activities of S. cumini fruit extracts, evaluated using membrane stabilization, egg albumin denaturation, and bovine serum albumin denaturation assays. In vivo anti-inflammatory activity was also assessed, using murine models of carrageenan, formaldehyde, and PGE2 induced paw edema. Fractionation of active extracts was performed using HPLC, followed by LC-ESI-MS/MS analysis to identify the bioactive compounds responsible for anti-inflammatory activity. RESULTS: The crude methanolic extract showed stronger in vitro and in vivo anti-inflammatory activities compared to other extracts. The most potent effects were observed in the formaldehyde induced paw edema assay wherein methanolic extract and standard indomethacin induced 72% and 88% inhibition against paw edema volume in comparison to control (normal saline) respectively. In the bovine serum albumin denaturation assay the methanolic extract induced 82% inhibition against denaturation as compared to control (phosphate buffer) while standard diclofenac sodium induced 98% inhibition. In contrast, 50% v/v MeOH:H2O or 100% dichloromethane extracts displayed moderate to weak effects in the anti-inflammatory models. HPLC fractionation provided 6 active sub-fractions, four (MF2, MF3, MF6, MF7) from the 100% methanolic extract and two (HAF1, HAF3) from the 50% methanolic extract. The MF2, MF7, and HAF1 sub-fractions displayed potent activity in all studied in vitro assays. LC-ESI-MS-MS analysis tentatively identified delphinidin 3-glucoside, peonidin-3,5-diglucoside, gallic acid, liquitrigenin, scopoletin, umbelliferon, and rosmanol from the 100% methanolic fractions. Myricetin, catechin, quinic acid, chlorogenic acid, ellagic acid, gallic acid, and caffeic acid were identified in the 50% methanolic fractions. CONCLUSIONS: These results demonstrate that S. cumini fruit extracts are a rich source of bioactive compounds that are worthy of further investigation as leads for anti-inflammatory drug discovery.

Missed Lisfranc injuries-surgical vs conservative treatment.

INTRODUCTION: Lisfranc injuries form a distinct group of rare but severe injury. Literature suggests a low incidence, but failure to diagnose these injuries early and its subsequent delay in management will affect the patient's mobility and quality of life significantly. The preferred mode of management is said to be surgical. Conversely, the method of intervention for patients not suitable for surgery is less clear. AIM: This study aims to evaluate the effect of delayed diagnosis and the treatment provided on the overall functional outcome for the patients with missed Lisfranc injury. METHODOLOGY: The study was conducted at a specialist centre in the North-West of UK between January 2011 and November 2016. All patients with acute Lisfranc injuries were included in this study. Patient data was collected through electronic notes and analysed to ascertain missed diagnosis. It was also used to evaluate functional and radiological outcome. RESULTS: In our series, 58.8% of Lisfranc injuries were missed on their initial presentation. We report better results for the surgical group when compared with the non-operated group, in spite of the delay in diagnosis. CONCLUSION: We believe that definitive treatment in the form of surgical fixation and anatomical reduction has more influence on the functional outcome than the timing of the surgical fixation in case of subtle Lisfranc injuries.

Joint infection due to Elizabethkingia miricola / Infección articular debida a Elizabethkingia miricola

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Instantaneous Specific Burn Debridement With an Enzymatic Debriding Agent: A New Resource for the Treatment of Burns.

Nexobrid is a new resource for debridement that has emerged in recent years and is gaining relevance in the treatment of all kinds of thermal injuries. This product is an ointment (formed with a mixture of pineapple-derived enzymes enriched with bromelain) that is directly applied over the burn. With a single application, it performs a burned tissue-specific debridement in less than 4 hr, leaving a vital and completely debrided wound bed. In this article, we describe our experience with this product, and through a representative case, we explain the management of these patients in our Burns unit in consonance with national and international consensus.

Treatment by a moisturizer of xerosis and cracks of the feet in men and women with diabetes: a randomized, double-blind, placebo-controlled study.

AIM: To evaluate a moisturizer containing urea, glycerine and petrolatum for healing deep open fissures on the feet of people with diabetes. If left untreated, open fissures, an entry point for bacteria, can lead to infection, ulceration and further complications. METHODS: This randomized, double-blind, multicentre study at 19 hospitals, general practices and diabetologists in France and Belgium included participants with diabetes and a deep open target fissure on their heel. Participants were randomized to test cream or placebo (1 : 1) for 4 weeks. Complete target fissure healing after 4 weeks (primary criterion) and 2 weeks, target fissure closure, overall fissure healing and xerosis were assessed. RESULTS: Some 167 participants were randomized (80 to test cream; 87 to placebo); all were included in the efficacy analyses. The percentage of participants with complete target fissure healing after 4 weeks was higher with test cream than placebo (46.3% vs. 33.3%): the difference did not reach statistical significance (P = 0.088). Fewer participants still had a deep open target fissure with test cream than placebo, the difference was statistically significant and clinically relevant after 2 (24.7% vs. 42.7%, P = 0.027) and 4 weeks (6.4% vs. 24.1%, P = 0.002). The difference in overall fissure healing between test cream and placebo was significant (P < 0.001) and test cream resulted in greater xerosis improvement (P < 0.001 and P = 0.002 at 2 and 4 weeks, respectively). CONCLUSION: The activity of the test cream for treating feet fissures of people with diabetes was confirmed by an improvement in open fissure healing and xerosis. The cream was well tolerated.

Characteristics and clinical assessment of antibiotic delivery by chitosan sponge in the high-risk diabetic foot: a case series.

OBJECTIVE: The local delivery of antimicrobials is attractive for a number of reasons. Chitosan, a biodegradable polysaccharide sponge material, has been proposed as medium to deliver antibiotics directly to wounds. In this report we evaluate the safety and practicality of antimicrobial delivery via chitosan sponge. METHOD: We present the clinical course and systemic absorption characteristics of three cases of people with diabetic foot wounds treated with antibiotic soaked chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN). The antibiotic sponge was made by reconstituting 1.2g tobramycin or 100mg doxycycline in 10-15ml saline and saturating the sponge with the solution. The sponge was then applied to the wounds. Serum levels of each respective antibiotic were evaluated after application. Additional in vitro studies were conducted evaluating elution of antibiotics from the chitosan sponge at established minimum inhibitory concentrations (MIC) for Staphylococcus aureus over 28 days. RESULTS: No patient experienced adverse local or systemic effects due to the sponge treatment. The measured serum levels applied antibiotics remained far less than established minimums after intravenous therapy. Each patient required further treatment, however local infection or contamination resolved during the course of their hospital stay after the chitosan/antibiotic application. CONCLUSION: The use of antibiotic-impregnated chitosan sponges appears a safe and effective mechanism of local delivery of antimicrobials in wounds. Future studies and clinical trials are ongoing to confirm these results and to guide clinical applications.

Plantar and Pedal Puncture Wounds in Children: A Case Series Study From a Single Level I Trauma Center.

OBJECTIVES: The purpose of this study was to describe our experience in treatment of pediatric patient presenting with pedal puncture wound to our level I trauma center and describe our results for the need for hospitalization and/or surgery for these patients. METHODS: Children and adolescents 18 years and younger presenting with pedal puncture wounds from September 2009 to December of 2013 were retrospectively studied. Exclusion criteria included adult patients, wounds related to animal bites, lacerations associated with a motor vehicle collision or all-terrain vehicle accidents, gunshot wounds, degloving injuries, or injuries resulting in complex lacerations to the foot. RESULTS: A total of 147 children presented to emergency department (ED) with a pedal puncture wound. Average age was 9.8 years. Prophylactic antibiotic therapy was administered in 107 cases (72.8%). Fifteen patients (10%) were treated with intravenous or intramuscular antibiotics in the ED or after hospital admission, 81 patients (55%) were treated with oral medications (prescribed for them to be taken after discharge), and 35 patients (24%) received topical antibiotic treatment. Of the 147 patients included in the study, 9 patients (6%) required the need for hospitalization. Two patients were admitted for parenteral antibiotic treatment only, and 7 patients required formal surgical debridement in the operating room in addition to parenteral antibiotic therapy. CONCLUSIONS: The majority of pediatric patients with pedal puncture wounds were treated in the ED with only a small percentage of patients requiring admission for either parenteral antibiotic treatment or formal surgical debridement.

Vitamin D in Foot and Ankle Fracture Healing: A Literature Review and Research Design.

UNLABELLED: Vitamin D is a generic name for a group of essential vitamins, or secosteroids, important in calcium homeostasis and bone metabolism. Specifically, efficacy of vitamin D with regard to bone healing is in question. A literature review was performed, finding mostly large studies involving vitamin D effects on prevention of fractures and randomized animal model studies consisting of controlled fractures with vitamin D interventions. The prevention articles generally focus on at-risk populations, including menopausal women and osteoporotic patients, and also most often include calcium in the treatment group. Few studies look at vitamin D specifically. The animal model studies often focus more on vitamin D supplementation; however the results are still largely inconclusive. While recent case reports appear promising, the ambiguity of results on the topic of fracture healing suggests a need for more, higher level research. A novel study design is proposed to help determine the efficacy on vitamin D in fracture healing. LEVELS OF EVIDENCE: Therapeutic, Level IV: Systematic Review.

Curcumin treatment attenuates pain and enhances functional recovery after incision.

BACKGROUND: Acute pain after surgery remains moderate to severe for 20% to 30% of patients despite advancements in the use of opioids, adjuvant drugs, and regional anesthesia. Depending on the type of surgery, 10% to 50% of patients experience persistent pain postoperatively, and there are no established methods for its prevention. Curcumin (diferuloylmethane) is one of the phenolic constituents of turmeric that has been used in Eastern traditional medicine as an antiseptic, antioxidant, anti-inflammatory, and analgesic agent. It may be effective for treating postoperative pain. METHODS: We used the hindpaw incision model with C57BL/6 mice. Sensitization to mechanical and thermal stimuli as well as effects on edema and temperature were measured up to 7 days after surgery. Spontaneous pain after incision was assessed by using conditioned place preference (CPP), and alterations in gait function were assessed using multiparameter digital gait analysis. RESULTS: Curcumin (50 mg/kg) significantly reduced the intensity of mechanical and heat sensitization after hindpaw incision in mice. No effects of curcumin on baseline nociceptive thresholds were observed. Curcumin also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. In addition, perioperative curcumin treatment attenuated hyperalgesic priming due to incision when mice were subsequently challenged with hindpaw prostaglandin E2 application. Furthermore, while vehicle-treated mice had evidence of spontaneous pain 48 hours after incision in the CPP paradigm, no evidence of ongoing pain was observed in the mice treated with curcumin. Likewise, hindpaw incision caused changes in several gait-related indices, but most of these were normalized in the curcumin-treated animals. The peri-incisional levels of several pronociceptive immune mediators including interleukin (IL)-1ß, IL-6, tumor necrosis factor α, and macrophage inflammatory protein-1α were either not reduced or were even augmented 1 and 3 days after incision in curcumin-treated mice. The anti-inflammatory cytokine IL-10 was unchanged, while transforming growth factor-ß levels were enhanced under the same conditions. CONCLUSIONS: Our studies suggest that curcumin treatment is effective in alleviating incision-induced inflammation, nociceptive sensitization, spontaneous pain, and functional gait abnormalities. Augmented transforming growth factor-ß production provides one possible mechanism. These preclinical findings demonstrate curcumin's potential as a preventative strategy in postoperative pain treatment.

Safety and efficacy of forefoot surgery under ankle block anaesthesia.

BACKGROUND: Ankle block as the sole anaesthetic for forefoot surgery is not used uniformly throughout the UK despite obvious advantages and widespread use internationally. AIM: Evaluation of safety and effectiveness of performing elective forefoot surgery under ankle block anaesthesia alone in a pilot cohort of patients in a Scottish unit. METHODS: Data were collected from 81 consecutive forefoot procedures (71 patients) using a standardised questionnaire including incremental pain assessment (0-10; 0 no pain, 10 severe pain). RESULTS: Seven patients reported pain during surgery; average score 0.17. Average pain scores 6, 12, 24 and 48 h following surgery were 1.5, 3.09, 2.3 and 1.9, respectively. All patients were discharged home and walking on the same day. CONCLUSION: Forefoot surgery under ankle block alone may be safe and effective. Anaesthesia obtained permitted routine forefoot procedures and provided lasting post-operative analgesia. Combined with intra-operative sedation, use of ankle tourniquet and same day discharge, it had very high patient acceptance and satisfaction.

Ultrasound-guided interventions of the foot and ankle.

Ultrasound (US) provides excellent delineation of tendons and ligaments in the foot and ankle and provides real-time visualization of a needle during interventions, yielding greater accuracy and efficacy than the traditional blind approach using anatomical landmarks. For this reason, US is rapidly gaining acceptance as the preferred modality for guiding interventions in the foot and ankle where the anatomy is complex, neurovascular structures should be identified, and precise technique is demanded. In the foot and ankle, US is especially useful to guide tendon sheath, bursal, and Achilles paratenon injections, Morton neuroma injections, plantar fascial injections, and joint aspirations and injections.

Delayed presentation of scorpion sting with cardiogenic shock.

A young farmer presented with cardiogenic shock 5 days after a scorpion sting. He was managed with norepinephrine, atropine and supportive measures and made a complete recovery. The role of atropine in treating scorpion sting has to be defined better.

Nonselective and NR2B-selective N-methyl-D-aspartic acid receptor antagonists produce antinociception and long-term relief of allodynia in acute and neuropathic pain.

BACKGROUND: At low dose, the nonselective N-methyl-D-aspartate receptor antagonist ketamine produces potent analgesia. In humans, psychedelic side effects limit its use. To assess whether other N-methyl-D-aspartate receptor antagonist have an improved therapeutic utility index, we compared antinociceptive, side effect, and locomotor activity of three N-methyl-D-aspartate receptor antagonists. METHODS: Ketamine, its active metabolite norketamine, and the NR2B-selective antagonist traxoprodil (CP-101,606) were tested in rat models of acute antinociception (paw-withdrawal response to heat) and chronic neuropathic pain (spared nerve injury). Side effects (stereotypical behavior, activity level) were scored and locomotor function of the nerve-injured paw was assessed using computerized gait analysis. In the chronic pain model, treatment was given 7 days after surgery, for 3 h on 5 consecutive days. RESULTS: All three N-methyl-D-aspartate receptor antagonists caused dose-dependent antinociception in the acute pain model and relief of mechanical and cold allodynia for 3-6 weeks after treatment in the chronic pain model (P < 0.05 vs. saline). In both tests, ketamine was most potent. Norketamine was as much as two times less potent and traxoprodil was up to 8 times less potent than ketamine (based on area under the curve measures). Nerve injury caused an inability to use the affected paw that either did not improve after treatment (ketamine, traxoprodil) or showed only a limited effect (norketamine). Traxoprodil, but not ketamine or norketamine, showed clear separation between effect and side effect. CONCLUSIONS: The observation that traxoprodil causes relief of chronic pain outlasting the treatment period with no side effects makes it an attractive alternative to ketamine in the treatment of chronic neuropathic pain.

Spinal levels of nonprotein thiols are related to nociception in mice.

UNLABELLED: Oxidative stress markers are thought to be related to nociception. Because thiolic compounds are important antioxidants, we investigated the relationship between thiols, endogenous or exogenous, and nociception. Systemic or spinal, but not peripheral, administration of the exogenous thiolic compound N-acetyl-L-cysteine (NAC) reduced nociception induced by intraplantar capsaicin injection. Moreover, we detected an increase in lipid peroxidation and 3-nitrotyrosine and a decrease in nonprotein thiolic levels in the lumbar spinal cord of capsaicin-injected animals. All these effects were prevented by NAC treatment (i.p. and i.t.). Our findings confirm a role for the spinal cord in NAC actions because systemic NAC administration also reduced the nociception trigged by intrathecal injection of capsaicin. Moreover, adjuvant-induced arthritis, but not paw incision, also -decreases nonprotein thiol levels in the spinal cord. Similarly, NAC produced antinociception in adjuvant-treated animals, but not in paw-incised animals. Finally, we investigated the role of endogenous thiol compounds in the nociceptive process administrating buthionine-suphoxamine (BSO), an inhibitor of glutathione-synthesis. Intrathecal BSO treatment decreased nonprotein thiol levels in the spinal cord, as well as induced mechanical allodynia and chemical and thermal hyperalgesia. In conclusion, our results indicate a critical role for nonprotein thiols in nociception at the level of the spinal cord. PERSPECTIVE: The results presented here indicate that the loss of nonprotein thiols in the spinal cord is involved in pain development. Therefore, the administration of thiolic compounds or other strategies allow thiol levels to be maintained and could be a beneficial action in the therapy of painful conditions.