Impaired cutaneous wound healing in mice lacking tetranectin

Tetranectin was originally purified from human serum on the basis of plasminogen kringle 4-binding properties. Tetranectin enhances plasminogen activation by a tissue-type plasminogen activator so that it has been suggested to play a role in tissue remodeling. We have generated mice with a targeted disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision. However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process.     

Detailed Analysis of Mucosal Restoration of the Small Intestine After the Cavitary Two-Layer Cold Storage Method

Small bowel transplantation (SBT) is associated with a high incidence of infectious complications because of ischemia/reperfusion (I/R) mucosal injury concomitant with potent immunosuppression. In this study, we evaluated whether the cavitary two-layer method (cTLM) could reduce I/R injury and allow early mucosal restoration, particularly after prolonged preservation and transplantation. Canine heterotopic segmental SBT was performed immediately without preservation (group 1), after 24-h preservation in UW solution (group 2) or by the cTLM (group 3). The graft samples were taken 1 h after reperfusion and on days 1, 4 and 7. We assessed graft mucosa with detailed microscopic and electromicroscopic analyses. In Group 3, histological injury and cell apoptosis after transplantation were significantly alleviated and rapidly recovered to a similar level of group 1. The mucosal restoration was morphologically completed within 4 days. In contrast, in group 2, more pronounced mucosal injury and delayed recovery were noted. Crypt cell proliferation activity was well maintained in groups 1 and 3 throughout the experimental period. Our ultrastructural analysis suggested that mitochondrial integrity achieved by the cTLM was a basal mechanism under the prompt mucosal restoration. The cTLM could reduce I/R injury, facilitate mucosal regeneration and restore the nearly normal structure early after SBT.     

Functional outcomes after arthroscopic treatment of lateral epicondylitis

Background  The purpose of this study was to evaluate surgical outcomes of arthroscopic débridement for lateral epicondylitis using a validated, patient-assessed scoring system as well as conventional outcome measures. We also wanted to identify potential predictive factors that may be associated with the outcomes. Methods  A total of 20 elbows in 18 patients with chronic lateral epicondylitis who underwent arthroscopic surgery were included. There were nine men and nine women with a mean age of 54 years (range 42–71 years). Operative treatment consisted of débridement of the extensor carpi radialis brevis (ECRB) origin and resection of the radiocapitellar synovial plica interposed in the joint. Outcomes were assessed using a patient rating, visual analogue scale (VAS) pain score, the Japanese Orthopaedic Association (JOA) elbow score, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire. The average length of follow-up was 28 months (range 24–40 months). Results  After surgery, according to the patients’ reports, 14 of 20 elbows were much better, and 6 elbows were better. A mean preoperative VAS pain score at rest of 3.9 points improved to 0.3 points (P < 0.0001), and that during activity improved from 7.8 points to 0.9 points (P < 0.0001). The mean preoperative JOA elbow score of 29 points was improved to 90 points (P < 0.0001). The mean postoperative DASH score was 10.6 (range 0–50). Absent of T2-weighted high signal focus of the ECRB origin on preoperative magnetic resonance imaging (MRI) (P = 0.02) and receiving public assistance (P = 0.01) were significantly associated with worse DASH scores. Conclusions  Arthroscopic release was a satisfactory procedure for chronic lateral epicondylitis. Preoperative MRI of the ECRB origin and socioeconomic factors were significantly associated with postoperative residual symptoms evaluated with the DASH score.     

The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.

STUDY DESIGN: Apoptosis in cervical intervertebral disc cells and cartilaginous endplate cells was examined by the nick end labeling (TUNEL) technique during the process of natural aging and in a mouse experimental spondylosis model. OBJECTIVES: To determine the role of apoptosis in aging and degeneration of intervertebral discs by monitoring chronologic changes in the quantity and localization of apoptotic cells. SUMMARY OF BACKGROUND DATA: Apoptosis occurs within human intervertebral discs, but little is known about the pathologic significance of this process. On the other hand, the cartilaginous endplate is known to decrease in thickness and to disappear with aging and degeneration. The cause of this age-related change remains unclear. METHODS: A mouse spondylosis model was prepared via surgical resection of the posterior spinal element in 12 mice to examine the experimentally induced spondylosis process. Eighteen naturally aged mice were also used to examine the influence of aging. Paraffin-embedded midsagittal sections of the cervical spine were obtained 2, 3, 6, and 12 months after surgery in the spondylosis model and in the age-matched naturally aged mice, as well as in 4-week-old and 18-month-old naturally aged mice. Sections were stained with hematoxylin and eosin, safranin-O, and the TUNEL procedure. The number of apoptotic cells and vital cells were counted in the cartilaginous endplate of the intervertebral disc excluding the growth cartilage, and the degree of disappearance of the cartilaginous endplate was evaluated. RESULTS: Apoptosis, particularly noticeable in the cartilaginous endplate, increased with age and resulted in a marked decrease in cell density. Subsequently, the structure of the cartilaginous endplate began to disappear. Apoptosis was more evident and the structure of the cartilaginous endplate began to disappear more rapidly in the surgically treated group than in the naturally aged group. CONCLUSIONS: TUNEL-positive cells in the cartilaginous endplate increased with age, with destruction of the cartilaginous endplate after apoptosis (TUNEL-positive cell death). The application of the spondylosis model increased the incidence of apoptosis preceding the development of spondylosis. This suggests that apoptosis plays a role in the age-related changes seen in the cartilaginous endplate of the intervertebral disc and in the experimentally induced spondylosis process.     

Treatment of pyoderma gangrenosum with granulocyte and monocyte adsorption apheresis

Pyoderma gangrenosum is an intractable skin disorder characterized by the development of erythematous pustules or nodules that rapidly progress to destructive, necrotizing, non-infective ulcers. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy in two new patients, a 67-year-old man with ulcerations on his lower leg, and a 44-year-old man with turgid erythematous lesions with burrowing abscesses and sinus formation on his hip, groin, and thighs. Both patients received 10 GCAP treatments at 5-day intervals. Their skin lesions responded well. The 9 cmx6 cm ulcer on the lower right leg of the 67-year-old patient was completely covered by regenerated skin at the completion of therapy. The turgid skin lesions containing pustules and ulcers of the other patient showed amelioration and a marked decrease in the volume of exudate. Our results suggest that GCAP is a useful treatment modality for pyoderma gangrenosum.     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis

International Journal of Clinical Pharmacy - Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients...