Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought.

OBJECTIVE: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. DESIGN: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. RESULTS: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. CONCLUSIONS: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors.

Fibromyalgia and bipolar disorder: extent of comorbidity and therapeutic implications.

Fibromyalgia (FM) is a syndrome that affects muscles and soft tissues. Presenting symptoms include chronic muscle pain, fatigue, sleep problems and psychological symptoms, including depression and anxiety. There exists strong evidence of a comorbidity between FM and Bipolar Disorder (BD). In this study, papers from 2006 to February 2016 that examined the comorbidity and etiological similarities of FM and BD were reviewed, as well as the therapeutic implications of these findings. The reviewed articles showed that an adequate psychiatric screening for BD is recommended in FM patients with depressive symptoms, in order to decrease administration of antidepressants for BD, due to the lack of proven efficacy, and to limit antidepressant-induced mania. Alternative therapies, such as agomelatine, memantine and psychotherapic treatment should be considered.

Is vitamin E an anti-allergic compound?

Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.

Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with abdominal obesity. Growing evidence suggests that inflammation in specific depots of white adipose tissue (WAT) has a key role in NAFLD progression, but experimental evidence for a causal role of WAT is lacking. METHODS: A time-course study in C57BL/6J mice was performed to establish which WAT depot is most susceptible to develop inflammation during high-fat diet (HFD)-induced obesity. Crown-like structures (CLS) were quantified in epididymal (eWAT), mesenteric (mWAT) and inguinal/subcutaneous (iWAT) WAT. The contribution of inflamed WAT to NAFLD progression was investigated by surgical removal of a selected WAT depot and compared with sham surgery. Plasma markers were analyzed by enzyme-linked immunosorbent assay (cytokines/adipokines) and lipidomics (lipids). RESULTS: In eWAT, CLS were formed already after 12 weeks of HFD, which coincided with maximal adipocyte size and fat depot mass, and preceded establishment of non-alcoholic steatohepatitis (NASH). By contrast, the number of CLS were low in mWAT and iWAT. Removal of inflamed eWAT after 12 weeks (eWATx group), followed by another 12 weeks of HFD feeding, resulted in significantly reduced NASH in eWATx. Inflammatory cell aggregates (-40%; P<0.05) and inflammatory genes (e.g., TNFα, -37%; P<0.05) were attenuated in livers of eWATx mice, whereas steatosis was not affected. Concomitantly, plasma concentrations of circulating proinflammatory mediators, viz. leptin and specific saturated and monounsaturated fatty acids, were also reduced in the eWATx group. CONCLUSIONS: Intervention in NAFLD progression by removal of inflamed eWAT attenuates the development of NASH and reduces plasma levels of specific inflammatory mediators (cytokines and lipids). These data support the hypothesis that eWAT is causally involved in the pathogenesis of NASH.

Sclerotherapy of malignant pleural effusion through sonographically placed small-bore catheters.

Pleural sclerosis after drainage with a small-bore catheter was performed in 21 patients with malignant pleural effusions. Intrapleural catheters 7- to 24-French in size were placed by using sonographic guidance. Tetracycline (18 patients) and bleomycin (four patients) were used as sclerosing agents (one patient had both). Clinical and radiologic follow-up was available on all patients until they died (range, 2 weeks to 25 months; mean, 3.6 months). Pleural sclerosis was successful in 15 (71%) of 21 patients. Two patients in whom pleurodesis failed had pleural sclerosis repeated, with one success and one failure. All of the failures were in patients in whom the amount of chest-tube drainage was more than 100 ml/day. Pleurodesis with tetracycline was painful in six patients; no pain was associated with use of bleomycin. Small pneumothoraces developed in four patients at the time of chest-tube placement, without consequence. A superimposed infection that developed in a patient having continuous drainage of pleural fluid was successfully treated with antibiotics. Pleural sclerotherapy can be performed through sonographically placed small-bore catheters with results comparable to those seen with large-bore, surgically placed catheters.

Malignant small bowel obstruction and ascites: not a contraindication to percutaneous gastrostomy.

Percutaneous gastrostomy (PG) with gastropexy was performed for relief of malignant small bowel obstruction in 12 patients with extensive ascites. Abdominal paracentesis was performed before PG in nine patients and after PG in one patient. Gastrostomy catheters were inserted without complication in all patients. Clinical follow up revealed that pericatheter leakage of ascitic fluid and skin excoriation occurred only in the three patients who did not have paracentesis performed before PG. No dislodgement of gastrostomy catheters occurred but mild peritonitis was noted in one patient. Our experience suggests that although in the past extensive ascites was a relative contraindication for PG, these patients can now be successfully treated with a combination of ultrasound-guided paracentesis to reduce pericatheter leakage of ascitic fluid, and gastropexy to prevent catheter dislodgement.

Percutaneous balloon dilatation of benign biliary strictures.

Percutaneous biliary dilatation is an effective alternative to surgical management of benign biliary strictures that has low morbidity and no reported mortality. Reported success rates for this procedure range from 40% to 90% depending on the size of the series, the type of patient being treated, and the length of follow-up period. The procedure is done in the fluoroscopy suite with an angioplasty balloon catheter. Transhepatic access is most common, but the procedure may be done via existing T-tube tracts or specially created jejunal loops. As the frequency of radical liver surgery such as liver transplant and radical trisegmentectomy rises, so too, the rate of biliary stricture is likely to rise, making percutaneous balloon dilatation an increasingly important tool in the interventional radiologist's armamentarium.

Occlusion of biliary endoprostheses: presentation and management.

A retrospective review of 20 cases of endoprosthesis occlusion in 17 patients was performed. The average length of stent patency before occlusion was 3.7 months. Clinical manifestations included one or a combination of the following: cholangitis (n = 17), jaundice (n = 9), and leakage of bile or purulent material from the percutaneous insertion site (n = 6). Eighteen of 20 episodes of endoprosthesis occlusion were successfully managed with normalization of biochemical parameters and alleviation of clinical manifestations. No therapy was attempted in two episodes of stent occlusion due to widespread metastatic disease. All 17 patients received intravenous fluid replacement and broad-spectrum antibiotic therapy. This was sufficient therapy to relieve symptoms in two cases of occlusion. Occluded stents were removed in the other 16 patients by means of radiologic (n = 10) or endoscopic (n = 6) methods. After the acute septic episode had subsided (2-5 days; mean, 3 days), new endoprostheses were percutaneously inserted in 10 cases of occlusion, long-term internal-external catheters were placed in five, and surgical bypass was performed in one. The authors conclude that endoprosthesis occlusion should not be considered a terminal event in patients with malignant biliary disease.

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.