MR Features of Juxta-Articular Venous Malformations of the Knee to Predict the Clinical Outcome of Sclerotherapy

PurposeTo analyze and correlate preinterventional magnetic resonance (MR) imaging findings with clinical symptoms after percutaneous sclerotherapy of venous malformations (VMs) adjacent to the knee.Materials and MethodsTwenty-five patients (mean age, 24 y; range, 7–55 y; 11 female) with 26 VMs adjacent to the knee undergoing sclerotherapy (direct puncture, diagnostic angiography, sclerosant injection) were identified, and MR imaging findings were analyzed. The VM involved the synovium of the knee joint in 19 of 26 cases (76%). These lesions were associated with joint effusion (3 of 19; 16%), hemarthrosis (4 of 19; 21%), or synovial thickening (16 of 19; 84%). Follow-up ended 6–8 weeks after the first or second sclerotherapy session if complete pain relief was achieved or 3 months after the third sclerotherapy session. Treatment outcomes were categorized as symptom improvement (complete or partial pain relief) or poor response (unchanged or increased pain).ResultsForty-nine percutaneous sclerotherapy sessions were performed. Despite the absence of signs of knee osteoarthritis, patients with a VM involving the synovium (8 of 14; 57%) showed a poor response to sclerotherapy (1 of 8 [13%] pain-free after 1 sclerotherapy session). Among patients with VMs with no associated joint alteration and no synovial involvement (6 of 14; 43%), 5 of 6 (83%) showed improvement of symptoms after 1 sclerotherapy session (P < .05).ConclusionsJuxta-articular VMs of the knee are frequently associated with hemarthrosis and synovial thickening. Patients with signs of osteoarthritis and synovial involvement of the VM on presclerotherapy MR imaging deserve special consideration, as these findings predict worse clinical symptoms after sclerotherapy.     

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.     

Effects of Mistletoe (Viscum Album L., Loranthaceae) Extracts on Arterial Blood Pressure in Rats Treated with Atropine Sulfate and Hexocycline

Acute effects of different extracts of mistletoe stem (Viscum album) were investigated on values of arterial blood pressure in Wistar rats. Arterial blood pressure was registered by direct method in the left carotid artery and the investigated extracts (total ethanol, ether and ethyl acetate) of mistletoe stem were administered into the right jugular vein. The total ethanol extract exhibited the best effect even on the lowest applied concentration (3.33 × 10^?5 mg kg^?1) and significantly decreased the blood pressure after applied concentration 1.00 × 10^?3 mg kg^?1. On the contrary, the ether and ethyl acetate extracts exhibited notable activity only by higher administered doses. Atropine as a nonselective blocker of muscarinic receptors reduced the hypotensive effects of ethanol extract of mistletoe. Hexocycline, a selective blocker of muscarine receptors, significantly raised blood pressure and decreased the hypotensive effect of ethanol extract of mistletoe on arterial blood pressure in rats.     

PI-88: a novel inhibitor of angiogenesis

Growth factors that stimulate angiogenesis are vital in tumor development and maintenance. Inhibitors of angiogenesis are emerging as key elements in anticancer treatments, and now antibodies and small molecule kinase inhibitors are approved in the treatment of a variety of solid tumors. These have shown modest but statistically significant benefit in colon, breast and lung cancers. PI-88 has a novel mechanism of action compared to the drugs on the market today. By inhibiting heparanase, PI-88 blocks angiogenesis on several different cellular and biological levels. Promising results from Phase I/II trials are being seen with PI-88 in a variety of tumor types including melanoma and hepatocellular carcinoma. However, the development of antibody-induced thrombocytopenia has limited its use in some patients.     

Inhibitory Effects of Fermented Brown Rice on Induction of Acute Colitis by Dextran Sulfate Sodium in Rats

Although the pathogenic mechanisms of inflammatory bowel diseases are not fully understood, colonic microbiota may affect the induction of colonic inflammation, and some probiotics and prebiotics have been reported to suppress colitis. The inhibitory effects of brown rice fermented by Aspergillus oryzae (FBRA), a fiber-rich food, on the induction of acute colitis by dextran sulfate sodium (DSS) were examined. Feeding a 5% and 10% FBRA-containing diet significantly decreased the ulcer and erosion area in the rat colon stained with Alcian blue. In another experiment, 10% FBRA feeding decreased the ulcer index (percentage of the total length of ulcers in the full length of the colon) and colitis score, which were determined by macroscopic observation. It also decreased myeloperoxidase activity in the colonic mucosa. Viable cell numbers of Lactobacillus in the feces decreased after DSS administration and was reversely correlated with severity of colitis, while the cell number of Enterobacteriaceae increased after DSS treatment and was positively correlated with colitis severity. These results indicate that FBRA has a suppressive effect on the induction of colitis by DSS and suggest FBRA-mediated modification of colonic microbiota.     

颞下颌关节紊乱病患者关节滑液硫酸软骨素含量变化及意义

目的观察颞下颌关节紊乱病(TMD)患者关节滑液中硫酸软骨素(CS)的含量变化,探讨其在TMD诊断中的价值.方法用高效液相色谱法检测10例正常人颞下颌关节(对照组)、32例颞下颌关节结构紊乱病(ID组)、28例颞下颌关节骨关节病(OA组)患者关节滑液中CS不饱和二糖ΔDi-6S与ΔDi-4S.结果三组关节滑液中均能检测出ΔDi-6S,ID组及OA组均检测到ΔDi-4S,对照组仅有3例检测到痕量ΔDi-4S.ΔDi-6S与ΔDi-4S含量在ID组及OA组均高于对照组(P均＜0.001),OA组亦高于ID组(P＜0.01).结论 TMD患者关节滑液中CS含量增加,且随病变的加重CS含量增加,其可以作为一种生化标志用于TMD的早期诊断.     

IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice

Aim:

To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD).

Methods:

The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-IL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses.

Results:

In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b administration increased the percentage of myeloid-derived suppressor cells (MDSCs) among total splenic mononuclear cells as well as the percentage of regulatory T cells (Tregs) among splenic CD4+ T cells in the mice. Moreover, MSC-IL37b administration increased the IL-2+ cells and decreased the IFN-γ+ cells among splenic CD4+ T cells.

Conclusion:

IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS-induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.     

Sulfate metabolism in the alloxan-diabetic rat: relationship of altered sulfate pools to proteoglycan sulfation in heart and other tissues

Summary The incorporation of [³⁵S]sulfate into heart proteoglycans has been studied in normal and alloxan-diabetic rats by perfusion and in vivo administration of the isotope; in the latter situation, comparison was also made of radiolabeled sulfate utilization by several other tissues (kidney, liver, lung, muscle, testes and skin). The radiolabeled products were characterized by sodium dodecylsulfate polyacrylamide gel electrophoresis and anion exchange chromatography, as well as by sizing of the glycosaminoglycan chains by gel filtration both before and after nitrous acid treatment. The most prominent band observed in the heart guanidine extract by electrophoresis had a molecular weight of 85,000 and minor components (M_r=360,000 and 170,000) were also detected; approximately 20% of the proteoglycan associated [³⁵S]sulfate was present in heparan sulfate chains. After perfusion the pattern, as well as the amount of radioactivity recovered from the diabetic heart, was similar to the normal heart. In contrast, after intraperitoneal injection of the [³⁵S]sulfate, a substantial reduction in incorporation was found not only in heart but in several other tissues studied, although no qualitative differences were noted in the macromolecules formed by the two groups of animals. Measurement of the serum sulfate concentration indicated that the level in the alloxan-diabetic rat (1.23 mmol/l) was significantly less (p<0.01) than that of the normal rat (1.67 mmol/l). Moreover, when serum specific activity curves were prepared between 10 min and 24 h after isotope injection, the decline in the diabetic curve was found to be much more rapid than that of the normal curve, with the area under the diabetic specific activity curve between 0 and 4 h being 0.61 that of normal (p<0.005). Since the amount of free [³⁵S]sulfate recovered in the tissues was also considerably lower in the diabetic animals, the specific activity differences of the precursor appear to account for the reduced incorporation of sulfate observed in vivo in contrast to perfusion, where pool sizes and specific activity can be controlled. Measurement of renal sulfate clearance indicated that it is enhanced in the alloxan-diabetic rats, suggesting that handling of sulfate in diabetes is similar to that previously described in this disease for inorganic phosphate.     

Effect of Iron Supplementation on Oxidative Stress and Intestinal Inflammation in Rats with Acute Colitis

In this study, we investigated the effect of intraperitoneal iron dextran (100mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma -tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats.