胶原诱导性关节炎的评定与T细胞受体-热休克蛋白70DNA疫苗的保护作用

目的:纯化制备含有编码T细胞受体(TCR)Vβ5.2/8.2基因片段与结核杆菌热休克蛋白(HSP)70的一段保守序列P111-125的嵌合DNA疫苗,观察其对胶原诱导性关节炎的保护性作用。方法:实验于2006-07/2007-02在首都医科大学免疫学系实验室完成。①实验分组:36只Lewis大鼠随机分为6组,即正常对照组、胶原诱导性关节炎对照组、空质粒组、pTARGET-TCRVβ5.2-HSP70重组质粒治疗组、pTARGET-TCRVβ8.2-HSP70重组质粒治疗组及pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70重组质粒联合治疗组,每组6只。②实验方法:大量纯化制备重组DNA疫苗pTARGET-TCRVβ5.2-HSP70、pTARGET-TCRVβ8.2-HSP70和空质粒pTARGET,观察重组DNA疫苗对胶原诱导性关节炎的保护效果,包括关节炎指数评分、Eli-spot法测定脾细胞分泌的干扰素γ和白细胞介素4的水平、ELISA法测定血清中抗Ⅱ型胶原抗体的水平;光镜下观察大鼠后肢足关节的病理学变化。结果:36只Lewis大鼠均进入结果分析。重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70对胶原诱导性关节炎有较好的保护性作用,与胶原诱导性关节炎对照组相比,关节炎指数(P<0.05)下降,炎性细胞因子干扰素γ水平(P<0.05)和抗Ⅱ型胶原抗体水平(P<0.01)降低,抑制性细胞因子白细胞介素4水平(P<0.05)升高,病理学改变较轻。且两种重组质粒联合治疗的效果要比单种质粒好。结论:重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70能明显减轻胶原诱导性关节炎大鼠的关节炎症状和病理改变,二者联合应用效果更佳。     

Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.     

Calcium Hydroxylapatite: Over a Decade of Clinical Experience

Background: Calcium hydroxylapatite is one of the most well-studied dermal fillers worldwide and has been extensively used for the correction of moderate-to-severe facial lines and folds and to replenish lost volume. Objectives: To mark the milestone of 10 years of use in the aesthetic field, this review will consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide a detailed injection protocol for a global facial approach, and examine how the unique properties of calcium hydroxylapatite provide it with an important place in today’s market. Methods: This article is an up-to-date review of calcium hydroxylapatite in aesthetic medicine along with procedures for its use, including a detailed injection protocol for a global facial approach by three expert injectors. Conclusion: Calcium hydroxylapatite is a very effective agent for many areas of facial soft tissue augmentation and is associated with a high and well-established safety profile. Calcium hydroxylapatite combines high elasticity and viscosity with an ability to induce long-term collagen formation making it an ideal agent for a global facial approach.Aesthetic medicine has advanced greatly in the past decade in terms of our understanding of facial anatomy; the cumulative effects of the aging process; and how dermal fillers may be used to repair, reduce, and even reverse these changes. Initially, aesthetic practitioners were “chasing lines and wrinkles,” based on experience with bovine collagen injections beginning in the early 1980s. We now appreciate that a natural and more youthful appearance is dependent on reversing the cumulative effect of age-related changes both on the surface and in the subsurface tissues. For surface aging, restoration of textural and pigmentary alterations is of paramount importance; for the subsurface, restoring lost volume and shape is the key to the more youthful proportions desired by our patients. This focus on facial shape and volume to restore balance, symmetry, and the proportions of youth has led to the development and worldwide clinical use of an ever-expanding list of dermal fillers for treatment of facial aging.Dermal fillers as a category of implantable medical devices, consist of a wide array of products that differ significantly in their chemical composition, mechanism of action, duration, safety, and interaction with host tissues. Many different methods of categorization have been proposed, based in part on these differing characteristics; however, no single, universally agreed upon system exists to date. Of the proposed classification systems, one based on primary mechanism of action (MOA) first proposed by Werschler and Narurkar has been widely used.1 In this approach, dermal fillers are placed into categories of either collagen biostimulation or replacement volume as a primary MOA.In this schema, Radiesse® (calcium hydroxylapatite; CaHA, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a unique product because it provides both replacement volume and collagen biostimulation as a primary MOA. In addition, CaHA is biodegradable and reabsorbed naturally by the host’s metabolic processes. This biostimulatory MOA, with ultimate reabsorption, results in a performance profile that is unique to Radiesse.CaHA is a highly effective agent for many areas of facial soft-tissue augmentation and is associated with a well-established safety profile.2 The year 2013 marked a decade of Radiesse technology, which first received EU approval in 2003 for plastic and reconstructive surgery, including deep dermal and subdermal soft tissue augmentation of the facial area. In the intervening years, the range of uses for CaHA has evolved alongside developments in the field of aesthetic medicine from a surface-oriented two-dimensional approach, concentrating on removal of facial lines and folds, to a three-dimensional approach that also addresses both soft and hard tissue volume loss in both the face and the hands.3With the popularity of dermal fillers demonstrated by increasing numbers of treated patients, public awareness and acceptance of nonsurgical enhancement has greatly increased the treatment options available. Along with botulinum toxin injections and energy-based devices, fillers are the mainstay of most medical aesthetic clinics. With increasing patient demand and the increased availability of aesthetic providers, private practices have become more competitive. Patient retention is now a major objective of most aesthetic businesses. Patient satisfaction is a key element for patient retention and requires a portfolio of safe and effective products. Long-term clinical experience, clinical research, peer-reviewed publications and regulatory approvals have combined to demonstrate the safety and efficacy of CaHA. The product has been evolved to meet the demands of a continuum of aesthetic care in terms of enhancement of youthful patients (ages 25-35); early prevention, rejuvenation, and volume restoration for patients in the middle decades of life (35-55); and for the delay and maintenance as part of restoration for mature (55-75+) patients as well.In this tenth anniversary year, the authors consider the historical milestones of CaHA in aesthetic medicine, propose a protocol for a global facial approach using CaHA, and look at how its unique properties provide it with a place in today’s market and keep it at the forefront of modern aesthetic treatments. Throughout this publication, reference is made to labeled and off-label indications, techniques, and dilution protocols performed by experts in the field of aesthetic medicine. The reader is reminded that some of these are not approved by regulatory authorities and are not endorsed by Merz Pharmaceuticals GmbH.     

Social, emotional, and behavioral functioning of children with cancer

OBJECTIVE: It was hypothesized that children with cancer would have more social problems and difficulties with emotional well-being than case control, same race/gender, similarly aged classmates. STUDY DESIGN: Using a case controlled design, children with any type of cancer requiring chemotherapy except brain tumors (n = 76), currently receiving chemotherapy, ages 8 to 15, were compared with case control classroom peers (n = 76). Peer relationships, emotional well-being, and behavior were evaluated based on peer, teacher, parent, and self-report, and were compared using analysis of variance and structural equation modeling. RESULTS: Relative to case controls, children with cancer were perceived by teachers as being more sociable; by teachers and peers as being less aggressive; and by peers as having greater social acceptance. Measures of depression, anxiety, loneliness, and self-concept showed no significant differences, except children with cancer reported significantly lower satisfaction with current athletic competence. There were also no significant differences in mother or father perceptions of behavioral problems, emotional well-being, or social functioning. Scores on all standardized measures were in the normal range for both groups. Comparisons of the correlation matrices of children with cancer and to the correlation matrix of the comparison children using structural equation modeling suggested they were not significantly different. CONCLUSIONS: Children with cancer currently receiving chemotherapy were remarkably similar to case controls on measures of emotional well-being and better on several dimensions of social functioning. These findings are not supportive of disability/stress models of childhood chronic illness and suggest considerable psychologic hardiness.     

Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury

BACKGROUND: Acute renal failure (ARF) has a high morbidity and mortality. Many therapies have worked in animals but were unsuccessful in clinical trials. The inability to diagnose ARF early may have impaired the success of these trials. METHOD: We screened a subtraction library to search for potential disease markers that would be induced rapidly after renal injury. Mice and rats were subjected to 30 to 40 minutes of bilateral ischemia. RESULTS: mRNA for Cyr61, a secreted growth factor-inducible immediate early gene, was markedly up-regulated at two hours in the kidney but not other organs following renal ischemia. In situ hybridization studies suggested Cyr61 was synthesized in the proximal straight tubule. Cyr61 protein was analyzed by capture with heparin beads followed by Western blotting. Induction of Cyr61 protein could be detected in the kidney within one hour, peaked at four to eight hours, and remained elevated for at least 24 hours following ischemia. Cyr61 protein was detected in urine at three to six hours and peaked at six to nine hours after renal injury. Cyr61 was not detected after volume depletion, which is often difficult to differentiate from ARF. CONCLUSIONS: The secreted, cysteine-rich, heparin binding protein Cyr61 is rapidly induced in proximal straight tubules following renal ischemia, and excreted in the urine where it might serve as an early biomarker of renal injury.     

Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia

We used comparative genomic hybridization (CGH) and conventional cytogenetics (CC) to define chromosomal changes and to evaluate the usefulness of CGH in 65 patients having childhood acute lymphoblastic leukemia (ALL). Subsequently, fluorescence in situ hybridization (FISH) was used to evaluate the CGH and cytogenetic results. Comparative genomic hybridization revealed DNA copy number changes in 49 (75%) patients (including 7 patients with unsuccessful cytogenetics and 2 patients with normal karyotype). A total of 85 losses and 195 gains were detected. The most commonly gained chromosomes were 21 (35%), X (31%), 18 (27%), 10 (26%), 6 (25%), 17 (25%), 4 (23%), and 14 (22%). Losses were most frequently observed on chromosomes 9p (18%) and 12p (11%). Other losses were detected on chromosomes 13q (9%), 6q (9%), 7p (8%), and chromosome X (6%). Conventional cytogenetics revealed chromosomal changes in 53 (82%) patients. The employment of CGH and FISH together with CC analysis revealed chromosomal changes in 62 (95%) of the childhood ALL patients investigated. The CGH completed CC results in 36 patients; in 9 patients, the changes escaped detection without using CGH. The results of our study were compared to 6 other CGH studies previously reported. Our observations underline the benefits of supplementing routine cytogenetic investigation in childhood ALL by FISH and CGH, because small unbalanced changes may escape detection when conventional cytogenetics is the only diagnostic method used.     

Incidence and pattern of 12 years of reported transfusion adverse events in Zimbabwe: a retrospective analysis

Background

Haemovigilance hinges on a systematically structured reporting system, which unfortunately does not always exist in resource-limited settings. We determined the incidence and pattern of transfusion-related adverse events reported to the National Blood Service Zimbabwe.

Materials and methods

A retrospective review of the transfusion-event records of the National Blood Service Zimbabwe was conducted covering the period from 1 January 1999 to 31 December 2011. All transfusion-related event reports received during the period were analysed.

Results

A total of 308 transfusion adverse events (0.046%) were reported for 670,625 blood components distributed. The majority (61.6%) of the patients who experienced an adverse event were female. The median age was 36 years (range, 1–89 years). The majority (68.8%) of the adverse events were acute transfusion reactions consisting of febrile non-haemolytic transfusion reactions (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%) of the adverse events occurred following administration of whole blood, although only 10.6% of the blood was distributed as whole blood. Packed cells, which accounted for 75% of blood components distributed, were associated with 20.1% of the events.

Discussion

The incidence of suspected transfusion adverse events was generally lower than the incidences reported globally in countries with well-established haemovigilance systems. The administration of whole blood was disproportionately associated with transfusion adverse events. The pattern of the transfusion adverse events reported here highlights the probable differences in practice between different settings. Under-reporting of transfusion events is rife in passive reporting systems.