A critical role for collagen II in cartilage matrix degradation: Collagen II induces pro‐inflammatory cytokines and MMPs in primary human chondrocytes

We report a process that results in the acceleration of matrix degradation in human articular cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro‐inflammatory signaling cascades. We first tested the collagen II‐dependent induction of pro‐inflammatory cytokines and matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT‐PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL‐1β. ELISA was used to quantify IL‐6 and IL‐8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38‐inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose‐dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL‐1β, IL‐6, and IL‐8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II‐dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II‐dependent feed‐forward mechanism whereby collagen II induces first MMPs and pro‐inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro‐inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of cartilage matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009     

Is there an Upgrading to Malignancy at Surgery of Mucocele‐Like Lesions Diagnosed on Percutaneous Breast Biopsy?

Management of pure mucocele‐like lesion (MLL) diagnosed on percutaneous breast biopsy (PBB) is controversial. To assess surgical upgrade rate and clinical outcome of pure MLL obtained as sole diagnosis on PBB. Patients diagnosed with a MLL as the most advanced lesion on PBB from April 1997 to December 2010 were reviewed for radiologic presentation, biopsy technique, and pathologic and clinical outcomes. Of the 21,340 image‐guided PBB performed during the study period, 50 women with 51 MLL (0.24%) were identified. Mean age was 53.1 ± 7.7 years. Radiologic findings were mostly microcalcifications (n = 47, 92.2%). Stereotactic PBB was performed for 49 lesions (96.1%). Surgery was performed shortly after biopsy in 35 women, with benign final pathology in 33, and upgrade to ductal carcinoma in situ (DCIS) in two patients (2/35, 5.7%). Mean follow‐up was 4.2 ± 2.5 years (3.7 ± 2.1 years for surgical patients; 5.9 ± 2.9 years for follow‐up only patients); three women were lost to follow‐up (3/50). Three invasive cancers (3/47, 6.4%) were diagnosed 1.2, 1.2, and 2.8 years after biopsy: two in surgical patients, and one in a follow‐up only patient. No cancer occurred at the same site as the original MLL. Pure MLL lesion of the breast is a rare entity and is mostly associated with a benign outcome. We observed an upgrade to DCIS slightly superior to 5%, but no invasive cancer. It is therefore unclear if these lesions should be excised or clinically and radiologically followed up when such lesions are found at PBB.     

Treatment options for spontaneous and postoperative sclerosing mesenteritis

Sclerosing mesenteritis is a rare pathology with only a few described cases in the literature. The etiology is unclear; however, several potential triggers, including abdominal surgery and abdominal trauma, have been discussed. The pathology includes a benign acute or chronic inflammatory process affecting the adipose tissue of the mesenterium. Despite it being a rare disease, sclerosing mesenteritis is an important differential diagnosis in patients after abdominal surgery or patients presenting spontaneously with signs of acute inflammation and abdominal pain. We present here three cases with sclerosing mesenteritis. In two cases, sclerosing mesenteritis occurred postoperatively after abdominal surgery. One patient was treated because of abdominal pain and specific radiological signs revealing spontaneous manifestation of sclerosing mesenteritis. So far there are no distinct treatment algorithms, so the patients were treated differently, including steroids, antibiotics and watchful waiting. In addition, we reviewed the current literature on treatment options for this rare disease.     

Clear cell papillary cystadenoma of the epididymis and mesosalpinx: immunohistochemical differentiation from metastatic clear cell renal cell carcinoma

Clear cell papillary cystadenoma is a rare epithelial tumor of the epididymis, which may present as an isolated lesion or as a component of von Hippel-Lindau disease (VHLD). Recently, tumors have also been described in the female genital tract with similar histology. Recognition of clear cell papillary cystadenoma is critical because of its association with VHLD and its potential diagnostic confusion with metastatic renal cell carcinoma because of a shared architecture and clear cells. In this study, we report on the immunohistochemical differentiation of 5 clear cell papillary cystadenomas, 3 of the epididymis and 2 of the mesosalpinx, from metastatic renal cell carcinoma. In 2 cases, there was a history of renal cell carcinoma in the setting of VHLD; and in 1 of these cases, an epididymal papillary cystadenoma was initially considered to be metastatic renal cell carcinoma. Immunohistochemically, tumor cells were moderately intensely positive for cytokeratin AE1/AE3 and epithelial membrane antigen, strongly positive for CK7 and negative for CK20 and RCC. Four of 5 cases were negative for CD10. This staining profile contrasts with that reported for clear cell renal cell carcinomas, which are typically negative for CK7 and immunoreactive for renal cell carcinoma (RCC) and CD10. Our findings indicate that, in cases where there is uncertainty about the histologic diagnosis of clear cell papillary cystadenoma, the above immunohistochemical panel helps to rule out metastatic renal cell carcinoma.     

Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.     

Conditioning stimulus can influence an external urethral sphincter contraction evoked by a magnetic stimulation

AIMS: To study the effect of a conditioning stimulus on an external urethral sphincter (EUS)contraction evoked by a magnetic stimulation at different time intervals. METHODS: Seven healthy male volunteers underwent EUS pressure measurement. At baseline, magnetic stimulation of the lumbosacral spinal cord above the motor threshold was performed and evoked EUS pressure responses were recorded. The lumbosacral magnetic stimulation was repeated with same intensity, while a selective electrical dorsal penile nerve stimulation below the bulbocavernosus reflex (BCR) threshold was preceding at five different intervals (10, 20, 30, 50, 100 msec). The protocol was performed with empty and full bladder (BLA), and baseline responses were statistically compared to those with combined stimulation. RESULTS: When the dorsal penile nerve electrical stimulation preceded the lumbosacral magnetic stimulation by 20 msec (P=0.0048), 50 msec (P=0.0039), or 100 msec (P=0.0002), the amplitudes of the EUS pressure response with empty BLA were significantly reduced compared to lumbosacral magnetic stimulation alone. With a filled BLA, the amplitudes of the EUS were significantly reduced only at an interval of 50 msec (P<0.0001). CONCLUSIONS: A conditional sensory pudendal stimulation seems to have the capacity to inhibit the external urethral sphincter contraction induced by a magnetic stimulation. The inhibitory effect seems to depend on the latency between the peripheral and lumbosacral stimulation as well as on the degree of BLA filling. It remains to be proved if the neuromodulative effect of the conditional stimulus occurs at a spinal or supraspinal level.     

A Cross-Cultural Comparison of ICD-11 Complex Posttraumatic Stress Disorder Symptom Networks in Austria,the United Kingdom,and Lithuania

The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) includes a new disorder, complex posttraumatic stress disorder (CPTSD). The network approach to psychopathology enables investigation of the structure of disorders at the symptom level, which allows for analysis of direct symptom interactions. The network structure of ICD-11 CPTSD has not yet been studied, and it remains unclear whether similar networks replicate across different samples. We investigated the network models of four different trauma samples that included a total of 879 participants (M age = 47.17 years, SD = 11.92; 59.04% women) drawn from Austria, Lithuania, and Scotland and Wales in the United Kingdom. The International Trauma Questionnaire was used to assess symptoms of ICD-11 CPTSD in all samples. The prevalence of PTSD and CPTSD ranged from 23.7% to 37.3% and from 9.3% to 53.1%, respectively. Regularized partial correlation networks were estimated and the resulting networks compared. Despite several differences in the symptom presentation and cultural background, the networks across the four samples were considerably similar, with high correlations between symptom profiles (ρs = .48–.87), network structures (ρs = .69–.75), and centrality estimates (ρs = .59–.82). These results support the replicability of CPTSD network models across different samples and provide further evidence about the robust structure of CPTSD. The most central symptom in all four sample-specific networks and the overall network was “feelings of worthlessness.” Implications of the network approach in research and practice are discussed.     

Comparative evaluation of two different Artemisia dracunculus L. cultivars for blood sugar lowering effects in rats

Recent concerns about the potential carcinogenicity of estragole and methyleugenol led a number of regulatory bodies to call for restrictions on the use of herbs that contain these constituents. A number of medicinal plants produce essential oils that contain estragole and methyleugenol, including Artemisia dracunculus L. (tarragon). Previous studies have proven the antidiabetic properties of tarragon. In order to address the safety concerns of estragole containing tarragon extracts, an extraction procedure was developed to minimize the estragole and methyleugenol content in tarragon extracts and the ethanol versus aqueous extracts from two Artemisia dracunculus cultivars (French and Russian tarragon) were tested for blood glucose lowering effects in rats. It could be demonstrated that aqueous extracts of both Artemisia cultivars did not contain detectable amounts of estragole and methyleugenol, whereas ethanol extracts (60% v/v) of the French cultivar contained higher levels of the aforementioned compounds than those of the Russian cultivar. Further testing revealed that Russian tarragon lowered blood glucose levels in rats after glucose challenge, with the ethanol extract being as active as the aqueous extract. The results suggest that by using adequate production procedures the amount of potentially harmful compounds in extracts can be limited without affecting the overall pharmacological activities of these preparations.     

Long-term bonding to eroded dentin requires superficial bur preparation

Objectives

This study aims to evaluate the influence of different surface preparation techniques on long-term bonding effectiveness to eroded dentin.

Materials and methods

Dentin specimens were eroded by pH cycling or were left untreated as control, respectively. Five different “preparation” techniques were applied: (1) cleaning with pumice, (2) air abrasion, (3) silicon polisher, (4) proxo-shape, and (5) diamond bur. The three-step etch-and-rinse adhesive OptiBond FL (O-FL; Kerr) and the mild two-step self-etch adhesive Clearfil SE Bond (C-SE; Kuraray) were evaluated. Micro-tensile bond strength was measured after water storage for 24?h and 1?year. Fracture analysis was performed by stereomicroscopy and SEM. Interfaces were characterized by TEM. Differences were statistically analyzed with a linear mixed effects model (α?=?0.05).

Results

Erosion reduced bond strength in all groups, but this effect was less prominent when eroded dentin was prepared by diamond bur. Storage lowered bond strength in almost all groups significantly, but this ageing effect was more prominent for the eroded surfaces than for non-eroded controls. Whereas after 1-year control specimens revealed superior bond strength with the three-step etch-and-rinse adhesive (O-FL), the mild two-step self-etch adhesive (C-SE) revealed a better 1-year bond strength to eroded dentin. The interface at eroded dentin appeared very prone to degradation as was shown by the increased amount of adhesive failures and by the silver infiltration detected by TEM.

Conclusions and clinical relevance

Although a minimally invasive approach should clinically always be strived for, superficial preparation (or minimal roughening) with a diamond bur is recommendable for long-term bonding to eroded dentin.