High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

ObjectiveIdentifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.MethodsPlasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.ResultsA significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = −0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.ConclusionsHigh levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.     

Use of biomimetic microtissue spheroids and specific growth factor supplementation to improve tenocyte differentiation and adaptation to a collagen-based scaffold in vitro

Tenocytes represent a valuable source of cells for the purposes of tendon tissue engineering and regenerative medicine and as such, should possess a high degree of tenogenic differentiation prior to their use in vivo in order to achieve maximal efficacy. In the current report, we identify an efficient means by which to maintain differentiated tenocytes in vitro by employing the hanging drop technique in combination with defined growth media supplements. Equine tenocytes retained a more differentiated state when cultured as scaffold-free microtissue spheroids in low serum-containing medium supplemented with l-ascorbic acid 2-phosphate, insulin and transforming growth factor (TGF)-β1. This was made evident by significant increases in the expression levels of pro-tenogenic markers collagen type I (COL1A2), collagen type III (COL3A1), scleraxis (SCX) and tenomodulin (TNMD), as well as by enhanced levels of collagen type I and tenomodulin protein. Furthermore, tenocytes cultured under these conditions demonstrated a typical spindle-like morphology and when embedded in collagen gels, became highly aligned with respect to the orientation of the collagen structure following their migration out from the microtissue spheroids. Our findings therefore provide evidence to support the use of a biomimetic microtissue approach to culturing tenocytes and that in combination with the defined growth media described, can improve their differentiation status and functional repopulation of collagen matrix.     

An updated review on pathophysiology and management of burning mouth syndrome with endocrinological,psychological and neuropathic perspectives

Burning mouth syndrome (BMS) is a chronic oro‐facial pain disorder of unknown cause. It is more common in peri‐ and post‐menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line–derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network–related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first‐line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well‐designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands.     

Bone and joint alterations in acromegaly

Growth hormone (GH) is fundamental for the maintenance of bone mass and metabolism both during childhood and in adulthood. This effect is due to a complex interaction between circulating GH and IGF-I produced peripherally. In vitro data and experimental animal models have clarified many of the regulatory mechanisms underlying the characteristic skeletal changes occurring in acromegaly. This review focuses on the effects of GH excess on bone metabolism and mass in acromegalic patients and, in particular, on the influence of factors such as hypogonadism, gender, age and therapy on bone metabolism and arthropathy.     

钛对大肠杆菌生长影响的实验研究

以草酸钛钾溶液为受试物，用无菌操作法在不同浓度试验水样及不含钛的对照水样中加入大肠杆菌稀释液1ml（含菌300个），观察6小时和1－7天的细菌生长情况。结果各受试组与对照组比较，10.0mg／L和1．0mg／L组接触6小时至7天大肠杆菌生长均有明显的抑制作用；0．1mg／L组接触6－24小时显示抑制作用，但第4天开始菌落减少的速度比对照组缓慢。提示钛对大肠杆菌的生长有抑制作用，其作用阈浓度为1．0mg／L，阈下浓度为0，1mg／L。     

Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa.     

国产rhGH的免疫原性及其对临床疗效的影响

目的　通过测定生长激素缺乏症 (GHD)患儿用国产重组人生长激素 (recom bined hum angrowth horm one,rh GH)治疗时血清生长激素抗体 (GH- Ab)水平及其结合特性 ,探讨 rh GH的免疫原性及其对疗效的影响。方法　对 6 1例 (男 49例 ,女 12例 ) GHD患儿用国产 rh GH治疗 ,每晚睡前皮下注射 rh GH 0 .1IU /kg共6个月 ;用放射免疫法测定治疗期间患儿血清 GH- Ab水平和滴度 ,并计算抗体结合容量、亲和常数 (Ka)。结果　48%患儿 (2 9/6 1)用药后 3个月血清 GH - Ab呈阳性至试验结束时仍未消失 ,其中 2 0例抗体为弱阳性 (结合率 <10 % ) ,9例呈强阳性 (结合率 >15 % ) ;5 2 %患儿 (32 /6 1)治疗期间抗体为阴性 ;血清 GH- Ab的结合容量、Ka及滴度均为低水平 ,分别为 (0 .1～ 4.8) pmol/L、(1.7× 10 7～ 6 .5× 10 8) L /mol和 1∶ 4～ 1∶ 8。GH- Ab阳性患儿治疗后的身高、身高增长速率及身高落后于正常 SD值的变化与同期阴性者比较无统计学差异 (P>0 .0 5 )。结论　本试验所用国产 rh GH对 GHD患儿身高增长具有确切的促进作用 ,其免疫原性所导致产生的 GH - Ab未对患儿体格线性增长产生负性影响