Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Fetal liver cells produce both fetal and adult erythrocytes in semiallogeneic radiation chimeras: possible influence of adult environment

Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen- bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells make up all the recipient's red blood cells 2 mo after receipt of the graft, Ft+ cells then being no longer detected. The transient duality of erythropoiesis in irradiated adults grafted with fetal liver cells has been confirmed by studying the kinetics of CFU-E populations, as characterized by their ability to give rise to Ft+ or Ft- erythrocytes. The results are discussed in terms of environmental factors that influenc erythroid differentiation.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Common genetic variants do not associate with CAD in familial hypercholesterolemia

In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49–0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD.     

Clinical approaches to non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.     

Intestinal bacterial translocation and tight junction structure in acute porcine pancreatitis

Background/Aims: To examine whether intestinal bacterial translocation occurs early in acute mild and severe pancreatitis and whether the intestinal expression of tight junction proteins (claudins-2, -3, -4, -5, -7), apoptosis or proliferation would explain the possible translocation. Methodology: Fifteen pigs were randomized to controls (n=5) or to develop mild edematous pancreatitis (n=5, saline infusion to pancreatic duct) or severe necrotic pancreatitis (n=5, taurocholic acid infusion). Translocation was studied by measuring bacterial cultures from portal vein blood and mesenteric lymph nodes. Immunohistochemical expression of the tight junction proteins, apoptosis rate (TUNEL) and Ki-67 were analyzed quantitatively from the epithelium of the jejunum and colon. Results: There was no bacterial translocation during the 6 hours followup, nor changes in the expression of tight junction proteins claudins-2 and -5 in jejunum or colon. Saturation and proportional area of claudin-3 staining decreased in the colon, as did claudins-4 and -7 staining in the jejunum of the necrotic pancreatitis group. Increased apoptosis was found in all samples from controls and the edematous pancreatitis group but not in jejunum in the necrotic pancreatitis group. Ki-67 activity tended to increase in the upper half of the villus in edematous and necrotic pancreatitis. There were no changes in the basic histology. Conclusions: The major finding of this study was that bacterial translocation from the gut is not present at the beginning of acute pancreatitis. Tight junction proteins claudin-2 and -5 do not become altered in the early stages of pancreatitis. Claudin-3 decreases in the colon and claudins-4 and -7 in the jejunum in necrotic pancreatitis. Laparotomy itself causes increased apoptosis in the colon and the jejunum.     

A population based study of outcomes after evacuation of primary supratentorial intracerebral hemorrhage

Background and Purpose

The role of surgery after primary intracerebral hemorrhage (ICH) is controversial. To explore whether hematoma evacuation after ICH had improved short-term survival or functional outcome we conducted a retrospective observational population-based study.

Methods

We identified all subjects with primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland. Hematoma evacuation was carried out by using standard craniotomy or through a burr hole. We compared mortality rates and functional outcomes of patients with hematoma evacuation with those treated conservatively.

Results

Of 982 patients with verified ICH during the study period, 127 (13%) underwent hematoma evacuation. Surgically treated patients were significantly younger (mean ± SD, 63 ± 11 vs. 70 ± 12 years; p < 0.001), had larger hematomas (66 ± 36 vs. 28 ± 40 ml; p < 0.001), lower Glasgow Coma Scale scores (median, 11 vs. 14; p < 0.001) and more frequently subcortical hematomas (68% vs. 24%; p < 0.001) than those treated conservatively. In multivariable analysis, hematoma evacuation independently lowered 3-month mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.43–0.88; p < 0.03), particularly among patients aged ≤70 years with ≥30 ml supratentorial hematomas (adjusted HR, 0.26; 95% CI, 0.14–0.49; p < 0.001). However, poor outcome was not improved by surgery (adjusted odds ratio 0.71; 95% CI 0.29–1.70).

Conclusions

Improved 3-month survival was observed in patients who had undergone hematoma evacuation relative to patients not undergoing evacuation particularly in the subgroup of patients aged ≤70 years with ≥30 ml supratentorial hematomas. Surgery might improve outcome if cases could be selected more precisely and if performed before deterioration.