Curcumin and Viscum album Extract Decrease Proliferation and Cell Viability of Soft-Tissue Sarcoma Cells: An In Vitro Analysis of Eight Cell Lines Using Real-Time Monitoring and Colorimetric Assays.

BACKGROUND: The cytostatic effects of the polyphenol curcumin and Viscum album extract (VAE) were assessed in soft-tissue sarcoma (STS) cells. METHODS: Eight human STS cell lines were used: fibrosarcoma (HT1080), liposarcoma (SW872, T778, MLS-402), synovial sarcoma (SW982, SYO1, 1273), and malignant fibrous histiocytoma (U2197). Primary human fibroblasts served as control cells. Cell proliferation, viability, and cell index (CI) were analyzed by BrdU assay, MTT assay, and real-time cell analysis (RTCA). RESULTS: As indicated by BrdU and MTT, curcumin significantly decreased the cell proliferation of five cell lines (HT1080, SW872, SYO1, 1273, and U2197) and the viability of two cell lines (SW872 and SW982). VAE led to significant decreases of proliferation in eight cell lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, 1293, and U2197) and reduced viability in seven STS lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, and 1273). As indicated by RTCA for 160 h, curcumin decreased the CI of all synovial sarcoma cell lines as well as T778 and HT1080. VAE diminished the CI in most of the synovial sarcoma (SW982, SYO1) and liposarcoma (SW872, T778) cell lines as well as HT1080. Primary fibroblasts were not affected adversely by the two compounds in RTCA. CONCLUSION: Curcumin and VAE can inhibit the proliferation and viability of STS cells.

Prednisolone but not selenium and rtPA reduces edema and improves angiogenesis after burn in mice.

OBJECTIVE: Despite dramatic improvements in burn care, the major part of the therapy of thermal injuries remains symptomatical in nature. A targeted approach to accelerate angiogenesis and woundhealing and reduce edema formation remains to be found. We therefore aimed to investigate the impact of anti-inflammatory, anti-coagulative and thrombolytic agents on microcirculation after thermal injuries on the mentioned parameters. METHODS: Full thickness burns were inflicted on the ears of hairless mice (n=48). The effects of five intraperitoneal injections of either recombinant tissue plasminogen activator (rtPA), selenium, prednisolone or sodium chloride on microcirculation, edema formation, leukocytes and angiogenesis were investigated over a 13 day period using intravital fluorescent microscopy. RESULTS: Prednisolone slightly improved angiogenesis (100.0% day 0 vs. 91.4% non-perfused area on day 1 post burn, p<0.05) and reduced edema formation (93.3% vs. 123.1% control on day 3, p<0.05). The rtPA-group showed the highest number of sticking leukocytes up to day 7 post burn (233%, 265%, 254% on days 1, 3, and 7, p<0.05 compared to baseline). A post-traumatic expansion of the non perfused area could only be observed in the selenium group (100.0% day 0, 103.1% day 1 post burn). In addition, selenium caused an increase of rolling leukocytes over the complete observation time. CONCLUSION: The often described positive influences of selenium for the treatment of burn patients could not be confirmed, on the contrary we found a post-traumatic expansion of the non perfused area and an increase of leukocytes in this group. The expectations to rtPA did not fulfill. Prednisolone improved angiogenesis and reduced the edema formation, both Parameters are essential for wound healing and survival of burned patients.

Influence of ISDN, L-NAME and selenium on microcirculation, leukocyte endothelium interaction and angiogenesis after frostbite.

BACKGROUND: The body of knowledge regarding the different facets of frostbite injury continues to expand. However, beside the administration of physiological saline, local rewarming, local disinfection and symptomatic medications, today no causal therapy is known which would accelerate angiogenesis and wound healing. The aim of this study was to investigate the influences of dilative acting drugs on microcirculation, angiogenesis and leukocyte behavior. MATERIALS AND METHODS: Ears of male hairless mice (n=40) were inflicted with full thickness frostbites using a cold air jet. Then the affects of four intraperitoneal injections of isosorbitdinitrate (ISDN, n=10), l-nitroarginine-methyl-ester (l-NAME, n=10), selenium (n=10) or sodium chloride (n=10; each administered to one of four corresponding study groups), on microcirculation, leukocyte-endothelial interaction and angiogenesis were investigated over a 12-day period using intravital fluorescent microscopy. RESULTS: Angiogenesis was most improved by ISDN (36.8 vs. 54.5% non-perfused area on day 3, 3.9 vs. 17.0% on day 7 compared to selenium, p<0.006). Venular diameter was most significantly dilated in the ISDN-group, l-NAME showed significantly decreased diameter over the complete time of 12 days. ISDN had positive influences on edema formation, which was significantly reduced compared to control (27% lower values compared to control; p=0.007 on day 3). The l-NAME-group showed the significant highest leukocyte-adhesion compared to control on days 7 and 12 (53% resp. 58% higher, p<0.006). CONCLUSION: Overall, out of all the drugs tested, ISDN improved angiogenesis, dilated venules and decreased edema formation and therefore seems to have the greatest positive impact on these crucial parameters after frostbite injury.

[Microvascular effects of burn plasma transfer and therapeutic options in a rat model]. / Mikrovaskuläre Effekte des Verbrennungsplasma-transfers und therapeutische Optionen im Tiermodell.

INTRODUCTION: Thermal injuries with more than 20% of burned body surface area (BSA) lead to systemic shock with generalised oedema in addition to local tissue destruction. This condition, known as burn injury, is caused by immunmodulative mediators whose individual significance is not known in detail. We present an experimental model where plasma of burned animals (burn plasma) is transmitted to healthy animals, to trigger burn iniury without performing direct burn trauma. MATERIAL AND METHODS: The systemic oedema is measured by extravasation of fluorescent albumin in mesenterial venules of Wistar rats. In addition, leukocyte-endothelial interactions ("leukocyte rolling and sticking") is examined. RESULTS: The systemic capillary leak is induced by both direct thermal trauma as well as by infusion of burn plasma. This is evident even after plasma dilution (1% in Ringer's lactate) of the burn plasma. In addition, topical therapy for burned animals (donors) with cerium nitrate led to a significant reduction of plasma extravasation in receiver animals. In addition, systemic antioxidant therapy with high-dose vitamin C of receiver animals, led to a significant reduction of the capillary leak. Leukocyte-endothelial interactions are not significantly affected in either case. CONCLUSION: In summary, for the first time a reliable model of burn injury has been established, which eliminates mediator-independent effects. In addition, our studies show that antioxidant therapy with high doses of vitamin C and topical treatment with cerium nitrate both reduce the systemic capillary leak in receiver animals. Their positive influence could therefore soon be integrated in clinical treatment algorithms.

[The medical treatment of Kim Phúc at the BG Unfallklinik Ludwigshafen]. / Die Behandlung von Kim Phúc an der BG Unfallklinik Ludwigshafen.

The Vietnam War was a military conflict in Vietnam during the Cold War that followed the First Indochina War. This war was fought between North Vietnam, supported by its communist allies, and the government of South Vietnam, supported by the USA and other anti-communist countries. Kim Phúc is the child depicted in the Pulitzer Prize winning photograph taken on June 8, 1972 by AP photographer Nick Út. The iconic photo shows her at about nine years of age running naked on a road amid the chaos after being severely burned by a napalm attack. After 14 months of hospital stay and 17 surgical procedures Kim Phúc was able to return home. Since then, she was used as a propaganda symbol by the communist government of Vietnam. To continue her studies, Kim was granted permission to move to Cuba where she met her future husband. However, the sequelae of her burn wounds affected her everyday life enormously. In 1984, with the support of the international aid organization "terre des hommes" and the German magazine "STERN", Kim Phúc got the opportunity to meet and get treated by Professor Zellner. Professor Peter Rudolph Zellner was the first chief of the Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, and one of the founder members of the German Society of Plastic Surgeons. The reconstructive surgeries provide Kim Phúc an almost normal life. Later on, she was involved in international aid organizations; she was named a UNESCO Goodwill Ambassador and she was awarded several honorary Doctorates of Law. Kim Phúc became a Canadian citizen. Today, she lives with her husband and two children in Ontario, Canada.

[Current state of neoadjuvant therapy of soft tissue sarcoma]. / Aktueller Stand der neoadjuvanten Therapie bei Weichteilsarkomen.

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.

Activity of histone H1.2 in infected burn wounds.

OBJECTIVES: Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity. METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria. RESULTS: Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control. CONCLUSIONS: These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.