Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy

Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.     

Smell in cystic fibrosis

In cystic fibrosis (CF), the most frequent life threatening inherited disease in Caucasians, sinonasal mucosa is regularly affected by defective mucociliary clearance. This facilitates pathogen colonization into CF airways and causes frequent symptoms of rhinosinusitis, including an impaired sense of smell. Despite probable effects on nutrition and overall health, CF–rhinosinusitis is little understood: CF-associated smelling deficiencies reported in literature vary between 12 and 71 %. The aim of this study was to assess olfactory and gustatory function in relation to sinonasal symptoms and sinonasal colonization, and lung function and nutrition. Thirty-five CF patients of different ages were compared to 35 age-matched healthy controls. Olfactory function was assessed by ‘Sniffin’Sticks’, gustatory qualities by “Taste-strips”, and symptoms by sino-nasal outcome test 20 (SNOT-20). Normosmia was found in 62.8 % of healthy controls but only in 28.6 % of CF patients. In contrast the majority of CF patients exhibited a smell loss; almost 62.9 % of them were hyposmic, and 8.6 % functionally anosmic. Importantly, reduced olfactory function only affected odor thresholds, which were significantly increased in CF, not odor identification. This suggests that the olfactory dysfunction in CF results from the olfactory periphery due to either problems in conduction and/or a functional lesion due to the inflammatory process. SNOT-20 scores increased continuously from normosmic to hyposmic and anosmic CF patients (means 7.2/11.1/28.3 points). Neither sinonasal pathogen colonization, gender, pulmonary function, nor allergy or sinonasal surgery appeared to have significant effects on olfactory function and taste. Olfactory disorders are considerably more frequent in CF patients than in age-matched healthy controls. Assessing these parameters within CF-routine care should be considered because of their importance to nutrition and, thus, overall therapy outcome.     

Efficacy of intra-tendinous injection of platelet-rich plasma in treating tendinosis: comprehensive assessment of a rat model

Objectives

To assess the potential of intra-tendinous injection of platelet rich plasma (PRP) to treat tendinosis (T+) in a rat model of patellar and Achilles T+, and evaluate its local toxicity.

Methods

Thirty rats (120 patellar and Achilles tendons) were used. We induced T+ into 80 tendons (patellar?=?40, Achilles?=?40) by injecting collagenase at day 0 under ultrasound (US) guidance. Clinical examination and US at day 3, followed by US-guided intra-tendinous injection of either PRP (PRPT+, n?=?40) or physiological serum (ST+, n?=?40, control). Follow-up was at days 6, 13, 18 and 25 using clinical, US and histological evaluation. To study PRP toxicity, we injected PRP into 40 normal tendons (PRPT-) and compared with 40 untreated normal tendons (T-).

Results

All PRPT+ showed better joint mobilisation compared with ST+ at day 6 (P?=?0.005), day 13 (P?=?0.02), day 18 (P?=?0.003) and day 25 (P?=?0.01). Similar results were found regarding US and histology, with smaller collagen fibre diameters (day 6, P?=?0.003, day 25, P?≤?0.004), less disorganisation and fewer neovessels (day 6, P?=?0.003, day 25, P?=?0.0003) in PRPT+ compared with ST+. Comparison between PRPT- and T- showed no PRP toxicity (P?=?0.18).

Conclusions

Our study suggests that mono-injection of PRP in T+ improves tendon healing, with no local toxicity.

Key Points

? We assessed the potential of platelet rich plasma (PRP) to treat tendinosis. ? We treated patellar and Achilles tendinosis in a rat model. ? We evaluated clinical, imaging and histological data. ? Intra-tendinous PRP injection could be useful in the treatment of tendinosis.     

Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

Purpose

Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity.

Materials and method

Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1^® (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−).

Results

All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18).

Conclusion

Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.     

Dysfunction of the chemical senses smell and taste

Dysfunction of the senses of taste and smell may strongly affect our lives. During the last years reliable techniques for the standardized investigation of the 2 senses have been introduced to clinical routine. These techniques are highly standardized and can be easily used, for example, for quality control before and after surgery. Although there are proven therapeutic approaches to taste or smell loss, by far not all patients can be helped. New ideas need to tested within rigorous double-blind studies. The regenerative capacity within the chemical senses provides a major basis for hopes on therapeutic success.     

Application of the intelligent techniques in transplantation databases: a review of articles published in 2009 and 2010

The replacement of defective organs with healthy ones is an old problem, but only a few years ago was this issue put into practice. Improvements in the whole transplantation process have been increasingly important in clinical practice. In this context are clinical decision support systems (CDSSs), which have reflected a significant amount of work to use mathematical and intelligent techniques. The aim of this article was to present consideration of intelligent techniques used in recent years (2009 and 2010) to analyze organ transplant databases. To this end, we performed a search of the PubMed and Institute for Scientific Information (ISI) Web of Knowledge databases to find articles published in 2009 and 2010 about intelligent techniques applied to transplantation databases. Among 69 retrieved articles, we chose according to inclusion and exclusion criteria. The main techniques were: Artificial Neural Networks (ANN), Logistic Regression (LR), Decision Trees (DT), Markov Models (MM), and Bayesian Networks (BN). Most articles used ANN. Some publications described comparisons between techniques or the use of various techniques together. The use of intelligent techniques to extract knowledge from databases of healthcare is increasingly common. Although authors preferred to use ANN, statistical techniques were equally effective for this enterprise.