Endogenous Hepatocyte Growth Factor Attenuates Inflammatory Response in Glycerol-Induced Acute Kidney Injury

Background: Hepatocyte growth factor (HGF) is overexpressed after acute kidney injury (AKI). The aim of this study was to evaluate the role of endogenous HGF in the progression of the inflammatory response in glycerol-induced AKI (Gly-AKI) in rats. Methods: Renal and systemic HGF expressions were evaluated during the development of Gly-AKI. Subsequently, the blockade of endogenous HGF was analyzed in rats treated with anti-HGF antibody concomitant to glycerol injection. Apoptosis, cell infiltration and chemokine and cytokine profiles were investigated. Results: We detected an early peak of renal and plasma HGF protein expressions 3 h after glycerol injection. The pharmacological blockade of the endogenous HGF exacerbated the renal impairment, the tubular apoptosis, the renal expression of monocyte chemoattractant protein-1 and the macrophage, CD43+, CD4+ and CD8+ T lymphocytes renal infiltration. The analysis of mRNA expressions of Th1 (t-bet, TNF-alpha, IL-1 beta) and Th2 (gata-3, IL-4, IL-10) cytokines showed a Th1-polarized response in Gly-AKI rats that was aggravated with the anti-HGF treatment. Conclusion: Endogenous HGF attenuates the renal inflammatory response, leukocyte infiltration and Th1 polarization after glycerol injection. The control of cellular immune response may partly explain the protective effect of endogenous HGF in the development of Gly-AKI. Copyright (C) 2008 S. Karger AG, Basel

Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to immunomodulation. To this end, Wistar rats (200-250 g) were submitted to 1-hour ischemia and treated with NPCs (4 x 10(6) cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with carboxyfluorescein diacetate succinimydylester (CFSE). Kidneys were harvested for analysis of cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78mg/dl, p < 0.05) and acute tubular necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-CFSE and glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker) mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-beta and TNF-alpha expression and higher anti-inflammatory IL-4 and IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory cytokines (IL-1 beta, TNF-alpha and INF-gamma). Our data suggested that NPC therapy improved renal function by influencing immunological responses. Copyright (C) 2009 S. Karger AG, Basel

A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury

Ischemic-reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin-3 is a multi-functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro-inflammatory cytokines. The aim of this study was evaluate the role of galectin-3 in the inflammation triggered by IRI. Galectin-3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP-1, IL-6 and IL-1 beta were studied by real-time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 +/- 85.21 mg/dl vs. gal-3 KO = 123.74 +/- 29.64 mg/dl, P = 0.001). Galectin-3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP-1, IL-6, IL-1 beta, less macrophage infiltration and lower ROS production at early time points. Galectin-3 seems to play a role in renal IRI involving the secretion of macrophage-related chemokine, pro-inflammatory cytokines and ROS production.

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720

Ischemia and reperfusion injury (IR) is an antigen independent inflammatory process that causes tissue damage. After IR, kidneys up-regulate leukocyte adhesion molecules and toll-like receptors (TLRs). Moreover, injured kidneys can also secrete factors (i.e. heat shock protein) which bind to TLRs and trigger intracellular events culminating with the increase in the gene expression of inflammatory cytokines. FTY720 is an immunomodulatory compound and protects at least in part kidneys submitted to IR. The mechanisms associated with FTY720`s beneficial effects on kidneys after IR remain elusive. We investigated whether FTY720 administration in mice submitted to kidney IR is associated with modulation of TLR2 and TLR4 expression. C57BL/6 mice submitted to 30 min of renal pedicles clamp were evaluated for serum parameters (creatinine, urea and nitric oxide), kidney histology, spleen and kidney infiltrating cells expression of TLR2 and TLR4, resident kidney cells expression of TLR2 and TLR4 and IL-6 protein expression in kidney. FTY720-treated mice presented decrease in serum creatinine, urea and nitric oxide, diminished expression of TLR2 and TLR4 both in spleen and kidney infiltrating cells, and reduced kidney IL-6 protein expression in comparison with IR non-treated mice. However, acute tubular necrosis was present both in IR non-treated and IR + FTY720-treated groups. Also, FTY720 did not prevent TLR2 and TLR4 expression in kidney resident cells. In conclusion, FTY720 can promote kidney function recovery after IR by reducing the inflammatory process. Further studies are needed in order to establish whether TLR2 and TLR4 down regulation should be therapeutically addressed as protective targets of renal function and structure after IR. (C) 2011 Elsevier B.V. All rights reserved.

Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B(1) receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. (C) 2010 Elsevier B.V. All rights reserved.

Eugenol modifies the excitability of rat sciatic nerve and superior cervical ganglion neurons

Eugenol is a phenylpropene obtained from the essential oils of plants such as clove and basil which has ample use in dentistry. Eugenol possesses analgesic effects that may be related to the inhibition of voltage-dependent Na(+) channels and/or to the activation of TRPV1 receptors or both. In the present study, electrophysiological parameters were taken from the compound action potentials of the isolated rat sciatic nerve and from neurons of the superior cervical ganglion (SCG) impaled with sharp microelectrodes under current-clamp conditions. In the isolated rat sciatic nerve, eugenol inhibited the compound action potential in a concentration-dependent manner. Action potentials recorded from SCG neurons were inhibited by eugenol with an IC(50) of 0.31 mM. At high concentrations (2 mM), during brief applications. eugenol caused significant action potential blockade while it did not interfere with the resting membrane potential or the membrane input resistance. Surprisingly, however, at low eugenol concentrations (0.6 mM), during long time applications, a reversible reduction (by about 50%) in the input membrane resistance was observed, suggesting the possible involvement of a secondary delayed effect of eugenol to reduce neuronal excitability. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Balancing the risk of injury to gymnasts : how effective are the counter measures?

Background—To minimise injury risk and maximise gymnastics performance, coaches, parents, and health professionals working with young gymnasts need to understand and practise safe gymnastics.

Aims—To (a) identify the various injury counter measures specific to gymnastics, (b) critically review the literature describing each injury prevention measure, and (c) assess, using available risk factor and injury data, the weight of evidence to support each of these counter measures. Specific recommendations for further research and implementation strategies to prevent injury and improve safety are also given.

Methods—The relevant literature was identified through the use of Medline (1966 to May 1998) and SPORT Discus (1975 to May 1998) searches, hand searching of journals and reference lists, and discussions with key Australian gymnastics organisations.

Results—The key gymnastics injury counter measures identified in this review include coaching (physical preparation, education, spotting, and performance technique), equipment, and the health support system (medical screening, treatment, and rehabilitation). Categorisation of the type of evidence for the effectiveness of each of these counter measures in preventing injury showed that most of it is based on informal opinion/anecdotal evidence, uncontrolled data based studies, and several prospective epidemiological studies. There is no evidence from formally controlled trials or specific evaluation studies of counter measures for gymnastics.

Conclusions—Although gymnastics is a sport associated with young participants and frequent high volume, high impact training, there is a paucity of information on injury risk factors and the effectiveness of injury practices. Further controlled trials are needed to examine the extent to which injury prevention counter measures can prevent or reduce the occurrence of injury and re-injury. Particular attention should be devoted to improving training facilities, the design and testing of apparatus and personal equipment used by gymnasts, and coaching and the role of spotting in preventing injury.

Quality of life improvements after sports injury

Over the past decade, there has been an increase in available data describing the incidence of sports injuries. However, the outcomes of such injuries remain relatively undocumented. Psychological aspects of sports injury rehabilitation have been documented in elite athletes but not in cohorts of general sports participants. The few studies that have described the financial costs of sports injuries have typically not assessed how these injuries affect quality of life. Despite recent estimates that lost quality of life accounts for 81% of total sports injury costs,1 this has received relatively little attention in the literature. The aim of this paper is to describe the quality of life outcomes associated with sports injuries and to present some preliminary observations about how these change over a six-week period.

Narratives of recovery from traumatic injury: issues in the nursing care of patients in rehabilitation

Patients who sustain multiple orthopaedic injuries through trauma frequently undergo lengthy rehabilitation. There is little information available about how patients experience hospital rehabilitation programs. In particular, not much is known about factors that inhibit or facilitate the rehabilitation process. This paper describes a qualitative study that explored the rehabilitation  experiences of thirteen patients who had serious orthopaedic injuries.  In-depth interviews revealed issues about good and bad care, the importance of mateship, getting through the day and living with pain. In addition, participants spoke of the impact that the accident and resulting injuries had on their relationships, their experience of loss, how difficult it was to manage everyday issues and the ways in which the accident changed them. The findings of the study have been set into a framework of therapeutic emplotment, a novel way to view the role of the rehabilitation nurse.

Influences of spatial practices on pressure ulcer management in the context of spinal cord injury

Nursing practice is significantly influenced by the type and use of space in which nursing is practised. While investigating current patterns of service delivery for the management of pressure ulcers from the perspective of people with spinal cord injuries and their families, the space in which care was delivered was identified as a central determinant of care. Qualitative methods were used to investigate consumer perspectives among patients residing in both metropolitan and rural communities who had been hospitalized for the management of pressure ulcers. Issues related to the spatial practices of the hospital are discussed, demonstrating a link between well-being and the creation of an appropriate caring milieu. It is concluded that service could be improved markedly if health-care professionals placed more consideration on the impact of space on their service delivery.

The use of injury surveillance databases to identify emerging injury hazards

Among the many valuable uses of injury surveillance is the potential to alert health authorities and societies in general to emerging injury trends, facilitating earlier development of prevention measures. Other than road safety, to date, few attempts to forecast injury data have been made, although forecasts have been made of other public health issues. This may in part be due to the complex pattern of variance displayed by injury data. The profile of many injury types displays seasonality and diurnal variance, as well as stochastic variance. The authors undertook development of a simple model to forecast injury into the near term. In recognition of the large numbers of possible predictions, the variable nature of injury profiles and the diversity of dependent variables, it became apparent that manual forecasting was impractical. Therefore, it was decided to evaluate a commercially available forecasting software package for prediction accuracy against actual data for a set of predictions. Injury data for a 4-year period (1996 to 1999) were extracted from the Victorian Emergency Minimum Dataset and were used to develop forecasts for the year 2000, for which data was also held. The forecasts for 2000 were compared to the actual data for 2000 by independent t-tests, and the standard errors of the predictions were modelled by stepwise hierarchical multiple regression using the independent variables of the standard deviation, seasonality, mean monthly frequency and slope of the base data (R = 0.93, R² = 0.86, F_{(3, 27)} = 55.2, p < 0.0001). Significant contributions to the model included the SD (β = 1.60, p < 0.001), mean monthly frequency (β =  - 0.72, p < 0.002), and the seasonality of the data (β = 0.16, p < 0.02). It was concluded that injury data could be reliably forecast and that commercial software was adequate for the task. Variance in the data was found to be the most important determinant of prediction accuracy. Importantly, automated forecasting may provide a vehicle for identifying emerging trends.

Pressure injury: an exploration of the relationship between risk factors and interface pressure

Pressure injuries are a serious risk for patients admitted to hospital and are thought to result from a number of forces operating on skin tissue (pressure, shear and friction). Most research on interface pressure (IP) has taken place using healthy volunteers or mannequins. Little is currently known about the relationship between pressure injury risk and IP for hospital patients. This relationship was investigated with a sample of 121 adult hospital patients. Pressure injury risk was evaluated using the Waterlow Risk Assessment Tool (WRAT) and IP was measured at the sacrum using a Tekscan ClinSeatTM IP sensor mat. Other factors considered were body mass index (BMI), blood pressure, reason for hospital admission, comorbidities and admission route to hospital. Patients were classified according to WRAT categories (‘low risk’, ‘at risk’, ‘high risk’, ‘very high risk’) and then remained still on a standard hospital mattress for 10 minutes while IP was measured. Participants in the ‘low risk’ group were significantly younger than all other groups (p<0.001) and there were some group differences in BMI. IP readings were compared between the ‘low risk’ group and all of the participants at greater risk. The ‘low risk’ group had significantly lower IP at the sacrum on a standard hospital mattress than those at greater risk (p=0.002). Those at greater risk tended to have IP readings at the low end of the compromised IP range. This study is significant because it describes a new, clinically relevant methodology and presents findings that challenge clinician assumptions about the relationships between pressure injury risk assessment and IP.

Best buys in fall injury prevention

More than 4,400 Victorian children are admitted to hospital for fall related injuries annually. Of these, 1,967 are known to have fallen from playground equipment. These 1,967 children consume 5,620 bed days. Another 3,934 children are treated in Emergency Departments for falls from playground equipment. In total, the direct cost borne by government is estimated at more than 4.7 million dollars. The cost in bed days and Emergency services is also considerable.

Teaching landing skills in elite junior Australian football: evaluation of an injury prevention strategy

Objective: To evaluate the effectiveness of a preseason physical training programme that taught landing and falling skills in improving landing skills technique and preventing injury in junior elite Australian football players.

Methods: 723 male players who participated in an under 18 elite competition were studied prospectively in a non-randomised controlled trial over two consecutive football seasons. There were 114 players in the intervention group and 609 control players. The eight session intervention programme taught players six landing, falling, and recovery skills, which were considered fundamental for safe landing in Australian football. Landing skills taught in these sessions were rated for competence by independent and blinded assessors at baseline and mid-season.

Results: Evaluation of landing skills found no significant differences between the groups at baseline. Evaluation after the intervention revealed overall improvement in landing skills, but significantly greater improvement in the intervention group (z = –7.92, p = 0.001). Players in the intervention group were significantly less likely (relative rate 0.72, 95% confidence interval 0.52 to 0.98) to sustain an injury during the season than the control group. In particular, the time to sustaining a landing injury was significantly less for the intervention group (relative rate 0.40, 95% confidence interval 0.17 to 0.92) compared with the control group.

Conclusions: Landing and falling ability can be taught to junior elite Australian football players. Players in the intervention group were protected against injury, particularly injuries related to landing and falls.

The sport Injury Rehabilitation Adherence Scale : a reliable scale for use in clinical physiotherapy

Objective
To evaluate, through two studies, the factor structure, inter-rater agreement, and test–retest and inter-rater reliability of the Sport Injury Rehabilitation Adherence Scale (SIRAS).

Design
Repeated measures design in both Study 1 (video evaluation) and Study 2 (clinical evaluation).

Setting
University department (Study 1) and outpatient physiotherapy department (Study 2).

Participants
Sixty physiotherapists and physiotherapy students in Study 1 and 45 patients undergoing physiotherapy treatment for a musculoskeletal injury in Study 2.

Intervention
In Study 1, participants rated the adherence of a simulated videotaped patient demonstrating high, moderate and low adherence during rehabilitation. In Study 2, two physiotherapists rated the adherence of patients at two consecutive rehabilitation sessions.

Main outcome measure
The SIRAS.

Results
In Study 1, principal components analysis confirmed a single factor for the SIRAS, and inter-rater agreement values ranged from 0.87 to 0.93. In Study 2, inter-rater and test–retest reliability coefficients ranged from 0.76 [95% confidence interval (CI) 0.54 to 0.83] to 0.89 (95% CI 0.79 to 0.95), and from 0.63 (95% CI 0.36–0.82) to 0.76 (95% CI 0.55–0.88), respectively.

Conclusion
The SIRAS is a reliable measure with high inter-rater agreement when used to evaluate clinic-based adherence to physiotherapy rehabilitation for musculoskeletal injury.