Hyperbaric oxygen therapy in wound healing in mice / [Oxigenoterapia hiperbárica na cicatrização de feridas em camundongos]

We investigated the local and systemic effects of hyperbaric oxygen therapy in BALB/C mice, exposed to two different exposure times, under 2.4 atmosphere (ATM). Fifteen animals were divided into three groups (GI, GII and Control) and underwent a surgical excision of a skin fragment of approximately one square centimeter of the dorsal region. The wounds were treated and monitored for 21 days. In the control group, the wound was cleaned once a day with sterile 0.9% NaCl solution. GI and GII mice were submitted to daily hyperbaric oxygen therapy of 30 or 60minutes sessions, respectively. The wounds were photographed every three days and their surfaces were analyzed by an image analyzer. At 21 days, all animals were euthanatized for histopathological analysis of the skin, lungs and liver in order to identify eventual alterations in wound healing or in the analyzed organs. Animals belonging to GI showed a faster skin wound healing in comparison to the other groups. Animals from GII, however, showed a delayed wound healing process and exhibited lung and microcirculatory alterations. These findings allow us to conclude that the exposure time to the oxygen in hyperbaric environment is crucial and can help or disturb skin wound healing or even be deleterious to other organs.(AU)

Investigaram-se os efeitos locais e sistêmicos da oxigenoterapia hiperbárica em camundongos BALB / C, submetidos a dois tempos de exposição diferentes, sob atmosfera 2,4 (ATM). Quinze animais foram divididos em três grupos (GI, GII e controle) e submetidos à excisão cirúrgica de fragmento de pele de aproximadamente um centímetro quadrado da região dorsal. As feridas foram tratadas e acompanhadas por 21 dias. No grupo controle, a ferida foi limpa uma vez ao dia, com solução estéril de NaCl 0,9%. Camundongos GI e GII foram submetidos à oxigenoterapia hiperbárica diária de 30 ou 60 minutos de sessões, respectivamente. As feridas foram fotografadas a cada três dias, e suas superfícies analisadas por um analisador de imagens. Aos 21 dias, todos os animais foram submetidos à eutanásia para análise histopatológica da pele, do pulmão e do fígado, em busca de eventuais alterações na cicatrização da ferida ou nos órgãos analisados. Animais pertencentes ao GI apresentaram cicatrização mais rápida de feridas cutâneas em comparação aos outros grupos. Já os animais do GII apresentaram retardo na cicatrização da ferida e alterações pulmonares e microcirculatórias. Esses achados permitem concluir que o tempo de exposição ao oxigênio em ambiente hiperbárico é fundamental e pode auxiliar ou atrapalhar a cicatrização de feridas cutâneas ou mesmo ser deletério para outros órgãos.(AU)

Combinação de butafosfan e cianocobalamina no metabolismo da glicose em vacas leiteiras após o parto / Combined of butaphosphan and cyanocobalamin on the glucose metabolism of dairy cows after calving

A hipótese deste estudo é de que o uso da combinação de butafosfan e cianocobalamina pode melhorar a resistência periférica à insulina, aumentar a quantidade de glicose disponível para a glândula mamária e a produção de leite. Assim, o objetivo foi investigar os efeitos combinados de butafosfan e cianocobalamina sobre o metabolismo da glicose em vacas leiteiras no período pós-parto. Vinte e uma vacas leiteiras foram divididas em dois grupos: grupo controle (CON, n= 11), que recebeu cinco aplicações de solução salina (20mL / animal 0,9% NaCl), e grupo Catosal(r) (ABC, n= 10), que recebeu cinco aplicações de 20mL de uma solução contendo as substâncias butafosfan e cianocobalamina (B12 Catosal(r), 100mg da substância butafosfan e 50µg de cianocobalamina por mL). As aplicações foram realizadas por via intramuscular, nos dias sete, 12, 17, 22 e 27 pós-parto. As amostras de sangue foram coletadas para a avaliação das concentrações plasmáticas de fósforo, glicose, ácidos graxos não esterificados (AGNE), albumina, aspartato aminotransferase (AST) e creatina quinase (CK). Nos dias oito e 28 pós-parto, os animais foram pesados e submetidos aos testes de tolerância à glicose e à insulina. O tratamento promoveu perda de peso (ABC 40,4kg, CON 10,73kg, P<0,05) e aumento da AST (ABC 62,92 ±3,31U/L, CON 53,11±3,49 U / L, P<0,05) e dos níveis de CK (ABC 134,09± 19,08U / L, CON 79,43 ± 18,27U / L). Os grupos não diferiram quanto ao metabolismo (área sob a curva) da glicose nos dias oito e 28, porém os animais tratados tiveram um aumento na glicemia (P<0,05) no dia 28 pós-parto (97,54 ± 8,54mg / dL), após a administração de insulina, em comparação ao dia oito (83,01 ± 8,54mg / dL). Assim, pode-se concluir que a combinação de butafosfan e cianocobalamina melhora a adaptação do metabolismo da glicose em vacas leiteiras no início da lactação.(AU)

The hypothesis of this study is that the combined use of butaphosphan and cyanocobalamin could enhance peripheral insulin resistance, increasing the amount of glucose available for the mammary gland and milk production. Thus, our aim was to investigate the combined effects of butaphosphan and cyanocobalamin on the glucose metabolism in dairy cows during the postpartum period. Twenty one dairy cows were divided into two groups: Control Group (CON, n= 11), that received 5 injections of saline solution (20mL/animal 0.9 % NaCl), and Catosal group (ABC, n= 10) which received 5 injections of 20mL of a Butafosfan and Cyanocobalamin solution (Catosal(r) B12, 100mg of Butafosfan and 50µg Cyanocobalamin for mL). The injections were performed by intramuscular route, on days 7, 12, 17, 22 and 27 postpartum. Blood samples were taken on these days to evaluate plasma concentrations of phosphorus, glucose, non-esterified fatty acids (NEFA), albumin, aspartate aminotransferase (AST) and creatine kinase (CK). On days 8 and 28 postpartum, the animals were weighted and subjected to the glucose tolerance and insulin challenge tests. The treatment promoted weight loss (ABC 40.4kg, CON 10.73kg, P< 0.05) and increased AST (ABC 62.92 ±3.31U/L, CON 53.11 ±3.49U/L, P< 0.05) and CK levels (ABC 134.09 ±19.08U/L, CON 79.43 ±18.27U/L). Glucose metabolism (area under the curve) did not differ (P> 0.05) among groups on days 8 and 28; however, ABC animals showed higher serum glucose levels (P< 0.05) after insulin administration on day 28 postpartum (97.54 ±8.54mg/dL) when compared to day 8 (83.01 ±8.54mg/dL). It could be concluded that the combined use of butaphosphan and cyanocobalamin interferes positively with the adaptation of glucose metabolism in dairy cows in early lactation.(AU)

[Case report: fatal diving-accident. Or: accident while diving?]. / Tödlicher Tauchunfall. Oder: Unfall während des Tauchens mit Todesfolge?

This example of a fatal diving accident shows how challenging such cases can be in pre-hospital and clinical care. There is no common mechanism in diving fatalities and more than one group of disorders coming along with decompression sickness. Diving medicine is not an element of medical education, which results in insecurity and hampers adequate therapy of diving incidents. This is aggravated by an insufficient availability of hyperbaric chambers in Germany.

[Treat-to-target (T2T) from the perspective of inpatient rheumatology]. / "Treat-to-Target" (T2T) aus der Sicht der stationären Rheumatologie.

Publication of the treat-to-target (T2T) concept at the end of the Bone and Joint Decade almost coincided with the 15 treatment recommendations of the EULAR as well as with the new classification and revised remission criteria for rheumatoid arthritis (RA).The treat-to-target initiative is solely focused on the description of benchmarks for an effective treatment management of RA to reach its priority target of remission.From the perspective of inpatient rheumatology parallels are shown to the quality projects of the Association of Rheumatology Clinics (VRA), which were initiated in 2001 for the first time.The quality management started up by the VRA not only benefited from the development of the German diagnosis-related groups (G-DRG) system which was also supported by the VRA and the German Society of Rheumatology (DGRh) but also from projects realized to improve the structural and operational quality in inpatient rheumatology units.By launching its own outcome benchmarking project (OBRA) in 2003, which was financially supported by the German Ministry of Health and its continuation with Kobra-1 and future Kobra-2, the VRA already successfully incorporated all benchmarks of management guidelines outlined in the T2T initiative.By steadily improving the outcome, even of RA patients, inpatient rheumatology offers a special quality project for participating clinics who are otherwise competitors, not only to learn from each other but to support each other to find the best way (T2T) to reach a remission and a good quality of life for RA patients and patients with other systemic rheumatic diseases.

[Amendment of the structural quality for inpatient rheumatology. A forward-looking concept]. / Neufassung der Strukturqualität der akut-stationären Rheumatologie. Ein zukunftsweisendes Projekt.

In 2010 a total of 9 guidelines on structural quality were endorsed by the Association of Rheumatology Clinics in Germany (VRA). These 9 structural criteria replace the regulations published in 2002 and were elaborated with the support of the German Rheumatology League. With guideline number 9 even the structural requirements for university hospitals are defined for the first time.Along with taking part in the quality project "Kobra" (continuous outcome benchmarking in rheumatology inpatient treatment) compliance with the new structural criteria constitutes a prerequisite for acquiring a quality certificate, which is awarded by an external institution.By this means the VRA sets the stage for its members to be prepared for future challenges and quality competition among hospitals. Furthermore, the provision of a high quality treatment for chronically diseased patients in rheumatology clinics will be effectively supported.

Insights from a novel three-dimensional in vitro model of lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia burgdorferi and synovial explants and fibroblasts.

OBJECTIVE: To develop a novel 3-dimensional (3-D) in vitro model of Lyme arthritis to use in the study of the interactions between Borrelia burgdorferi (Bb) and human synovial host cells with respect to phagocytosis and potential persistence of Bb as well as the induction of proinflammatory cytokines and chemokines. METHODS: Two distinct culture systems, consisting of synovial membrane explants or interactive synovial cells embedded in 3-D fibrin matrices, were chosen. Both systems were artificially infected with Bb, and the interactions between Bb and synovial tissue/cells were studied by histology, immunohistochemistry, and electron microscopy. Functional analyses included the induction/secretion of cytokines by Bb in the model system. RESULTS: Both culture systems proved to be stable and reproducible. The host cells and spirochetes showed high levels of viability and maintained their physiologic shape for >3 weeks. Bb invaded the synovial tissue and the artifical matrix in a time-dependent manner. Host cells were activated by Bb, as indicated by the induction of interleukin-1beta and tumor necrosis factor alpha. Electron microscopic analysis revealed Bb intracellularly within macrophages as well as synovial fibroblasts, suggesting that not only professional phagocytes, but also resident synovial cells are capable of phagocytosing Bb. Most interestingly, the uptake of the spirochetes appeared to cause severe damage of the synovial fibroblasts, since the majority of these cells displayed ultrastructural features of disintegration. CONCLUSION: A novel 3-D in vitro model has been established that allows the study of distinct aspects of Lyme arthritis under conditions that resemble the pathologic condition in humans. This reproducible, standardized model supplements animal studies and conventional 2-D cultures. The disintegration of synovial fibroblasts containing Bb or Bb fragments challenges the concept of an intracellular persistence of Bb and may instead reflect a mechanism that contributes to the inflammatory processes characteristic of Lyme arthritis.

Cytokines derived from alveolar macrophages induce fever after bronchoscopy and bronchoalveolar lavage.

As much as one-third of patients develop fever and flu-like symptoms after fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown reasons. The aim of the present study was to investigate factors mediating these side effects. Fifty consecutive patients with various pulmonary diseases who underwent FOB without further interventions (n = 30) or combined with BAL (n = 20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6 h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at t2. At to and t1, generally only low cytokine concentrations could be detected. At t2, however, significant increases of cytokine levels were found. IL-6 and TNF-alpha were significantly higher in patients after BAL than in patients after FOB. Comparing patients who developed fever (n = 12) with those who did not (n = 38), irrespective of the endoscopic procedures performed, dramatic increases of all three cytokines were detected in febrile patients that were significantly higher than in patients without fever. In the FOB group only patients who received local anesthesia by prilocaine bolus injection into the airways via the working channel of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile and had slight IL-6 increases only. There was a highly significant correlation between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98). All blood cultures remained sterile. These results indicate that fever after FOB and BAL is induced by proinflammatory cytokines derived from alveolar macrophages activated by instillation of fluid into the airways.

Induction of chalcone synthase expression by rhizobia and nod factors in root hairs and roots.

Chalcone synthase (CHS) of Vigna unguiculata is encoded by a gene family that is abundantly transcribed in leaves and nodules. Inoculation with Rhizobium sp. NGR234, which nodulates V. unguiculata, or with NGR delta nodABC, a mutant deficient in Nod factor production, induced rapid accumulation of CHS mRNAs in roots and root hairs. As both Nod+ and Nod- bacteria provoke responses, induction of CHS gene expression may involve symbiotic or defense responses. Four days after inoculation with the wild-type Rhizobium sp., the transcript levels increased in roots but decreased in root hairs. Use of a region unique to the 5' end of a specific CHS gene (VuCHS1) showed that increases of transcript levels in root hairs 24 h after inoculation with both rhizobia were specific to this gene. Transcripts of this gene in roots were only detectable 4 days after treatment with NGR234. It is possible therefore that accumulation of VuCHS1 follows the infection pathway of rhizobia entering legume roots. Purified Nod factors induced accumulation of transcripts, showing that they might be part of the signal transduction pathway leading to CHS expression.

Potential infectious agents in the induction of arthritides.

In the multifactorial etiology of rheumatic diseases, infectious agents are regarded as the major environmental factors that may cause inflammatory arthritides in genetically susceptible hosts. Two not mutually exclusive pathogenetic pathways are hypothesized to explain the initiation and perpetuation of chronic arthritides by infectious agents: persistent infection and induction of immunopathology. In this review we focus on the role of infections in the etiopathogenesis of rheumatoid arthritis. Retroviruses and enteropathogenic bacteria continue to be the most intensively discussed candidates as possible etiologic factors of rheumatoid arthritis. Although there is ample indirect evidence for the involvement of infections in the pathogenesis of autoimmune disease, direct proof is still missing. There may be no single infectious trigger for rheumatoid arthritis, but multiple infectious agents that share antigenic motifs. The "reverse immunology" approach addresses this issue and is discussed in our outlook on future research directions.

[Responsibility for patient education and incidence of homologous blood transfusions in unilateral breast cancer operations]. / Zur Aufklärungspflicht und Häufigkeit homologer Bluttransfusionen bei einzeitigen Mammakarzinom-Operationen.

According to a judgement by the German Federal Court of 17 December 1991 the surgeon is legally bound to inform the patient before hand of the risk of a possible homologous blood transfusion during surgery. If the transfusion probability exceeds 5%, this obligation is really relevant, 228 patients with primary breast cancer of stage pT1 - 3N0 - 2M0 had been treated either radically (n = 146) or by a breast-preserving operation (n = 82) from January 1989 to December 1993. 400 to 800 ml erythrocyte preparations had been placed at disposal in advance for each patient. The rate of blood transfusions, pre- and postoperative haemoglobin (Hb), age, tumour size, lymph node involvement, kind and duration of operation as well as postoperative course have been analysed 43 of 228 (18.9%) patients received a homologous blood transfusion within 24 hours after operation. Transfusion rate per year decreased from 39.4% (1989) to 44.8% (1990), 12.2% (1991), 16.6% (1992) and 3.1% in 1993. On the contrary mean pre-and postoperative haemoglobin levels did not differ significantly (p < 0.05) between the different years: 13.4 +/- 0.8 respectively 12.1 +/- 1.1 g/dl (1989) and 13.5 +/- 1.3 respectively 12.1 +/- 1.3 g/dl (1993). Patients who had transfusions were significantly (p < 0.05) more likely to suffer from preoperative anaemia and larger tumors, and they have been treated by mastectomy more frequently compared to patients without transfusion. There were no correlations between transfusions and age, tumour size, lymph node involvement, kind and duration of operation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Transfusion incidence and indications for homologous blood sparing measures in single stage breast carcinoma operations]. / Transfusionshäufigkeit und Indikationen für fremdblutsparende Massnahmen bei einzeitigen Mammakarzinom-Operationen.

Under a ruling by the Bundesgerichtshof from December 17, 1991 (AZ VI ZR 40/91), the surgeon is obliged to inform a patient about the risks of a possible blood transfusion if the transfusion frequency is 5% or more. Between January 1989 and December 1994, 273 patients with primary breast cancer at the stages pT1-3, N1-2, M0 underwent one-time modified radical mastectomy (n = 164) or a breast conserving operation (n = 109) in our hospital. The number of blood transfusions, pre- and postoperative haemoglobin, age, tumour size, lymph node involvement, kind and duration of the operation and the postoperative course were analysed. In all, 44 of the 273 patients (16.1%) received an homologous blood transfusion perioperatively. The annual transfusion rates were 39.4% (1989), 44.8% (1990), 12.2% (1991), 16.6% (1992) and 3.1% (1993), falling to 2.2% in 1994. The mean pre- and postoperative haemoglobin concentrations did not differ significantly (p > 0.05) over the years: 13.4 +/- 1.0 g/dl and 12.0 +/- 1.1 g/dl in 1989 and 13.7 +/- 1.2 g/dl and 11.8 +/- 1.2 g/dl in 1994. Patients who received transfusions had preoperative anaemia (p < 0.021), bigger tumours (p < 0.0005) and mastectomy operations significantly more frequently than patients not given transfusions. There were no correlations between transfusions and age, lymph node involvement and kind and duration of operation. We conclude that, cognizant of a transfusion frequency of 2.2% in our hospital in one-time breast cancer operations, only patients with anaemia or large tumours require blood transfusions, for which autologous blood donations or normovolaemic haemodilution are the choices. The patients' attention is to be drawn to these. In cases of normal preoperative haemoglobin and small tumours, the physician should inform the patient that experience has shown that in all probability a blood transfusion will not be necessary and so a preoperative autologous blood donation or normovolaemic haemodilution can be dispensed with.

Accumulation of transcripts encoding a lipid transfer-like protein during deformation of nodulation-competent Vigna unguiculata root hairs.

A cDNA library was constructed from RNA of Vigna unguiculata root hairs harvested 1 day and 4 days after inoculation with Rhizobium sp. NGR234. A heterologous probe was used to identify a cDNA clone, the predicted 99-amino-acid sequence of which shares homology with a nonspecific lipid transfer protein (LTP) of Hordeum vulgare. Other characteristics, including an estimated molecular weight of 10.4 kD, an isoelectric point of 8.6, and a signal peptide with a hydrophobic region at the amino-terminal end, are shared by most LTPs. A transcript of 630 nt was found in all tissues tested, except nodules. Levels of mRNA increased in root hairs 24 hr after treatment with Rhizobium sp. NGR234, with different hormones, or with Nod factors. Amounts of transcripts were dependent on the concentration of Nod factors. Accumulation of transcripts during nodule development correlated with root hair deformation, the first visible step in the Rhizobium-legume symbiosis.

Effects of unilateral and bilateral auricular transcutaneous electrical nerve stimulation on cutaneous pain threshold.

This study compared the effects of unilateral and bilateral auricular transcutaneous electrical nerve stimulation on cutaneous pain threshold. Auricular acupuncture points were stimulated with low frequency, high intensity TENS for 45 seconds. Sixty healthy, adult subjects were assigned randomly to one of two treatment groups or to a control group. The two treatment groups received low frequency, high intensity TENS either unilaterally or bilaterally. The control group did not receive auricular stimulation. Experimental pain threshold at the left wrist was determined with a painful stimulus before and after auricular stimulation. Both unilateral and bilateral auricular stimulation groups exhibited a significant increase (p less than .05) in experimental pain threshold, but the control group did not. The mean change values between the unilateral and bilateral stimulation groups were not statistically different. These results suggest that both unilateral and bilateral auricular TENS can increase pain threshold.