Preoperative anthropomorphic radiographic measurements can predict postoperative pancreatic fistula formation following pancreatoduodenectomy.

BACKGROUND: Postoperative pancreatic fistulae (POPF) are a major contributing factor to pancreatoduodenectomy-associated morbidity. Established risk calculators mostly rely on subjective or intraoperative assessments. We hypothesized that various objective preoperatively determined computed tomography (CT) measurements could predict POPF as well as validated models and allow for more informed operative consent in high-risk patients. METHODS: Patients undergoing elective pancreatoduodenectomies between January 2013 and April 2018 were identified in a prospective database. Comparative statistical analyses and multivariable logistic regression models were generated to predict POPF development. Model performance was tested with receiver operating characteristics (ROC) curves. Pancreatic neck attenuation (Hounsfield units) was measured in triplicate by pancreatic protocol CT (venous phase, coronal plane) anterior to the portal vein. A pancreatic density index (PDI) was created to adjust for differences in contrast timing by dividing the mean of these measurements by the portal vein attenuation. Total areas of subcutaneous fat and skeletal muscle were calculated at the L3 vertebral level on axial CT. Pancreatic duct (PD) diameter was determined by CT. RESULTS: In the study period 220 patients had elective pancreatoduodenectomies with 35 (16%) developing a POPF of any grade. Multivariable regression analysis revealed that demographics (age, sex, and race) were not associated with POPF, yet patients resected for pancreatic adenocarcinoma or chronic pancreatitis were less likely to develop a POPF (10 vs. 24%; p = 0.004). ROC curves were created using various combinations of gland texture, body mass index, skeletal muscle index, sarcopenia, PDI, PD diameter, and subcutaneous fat area indexed for height (SFI). A model replacing gland texture with SFI and PDI (AUC 0.844) had similar predictive performance as the established model (p = 0.169). CONCLUSION: A combination of preoperative objective CT measurements can adequately predict POPF and is comparable to established models relying on subjective intraoperative variables. Validation in a larger dataset would allow for better preoperative stratification of high-risk patients and improve informed consent among this patient population.

Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice.

INTRODUCTION: It was the aim of the present experiments to examine potential antidiabetic effects of the Cimicifuga racemosa extract Ze 450. METHODS: Ze 450 and some of its components (23-epi-26-deoxyactein, protopine and cimiracemoside C) were investigated in vitro for their effects on AMP-activated protein kinase (AMPK) compared to metformin in HepaRG cells. Ze 450 (given orally (PO) and intraperitonally (IP)), metformin (PO) and controls were given over 7 days to 68 male ob/ob mice. Glucose and insulin concentrations were measured at baseline and during an oral glucose tolerance test (OGTT). RESULTS: Ze 450 and its components activated AMPK to the same extent as metformin. In mice, Ze 450 (PO/IP) decreased significantly average daily and cumulative weight gain, average daily food and water intake, while metformin had no effect. In contrast to metformin, PO Ze 450 virtually did not change maximum glucose levels during OGTT, however, prolonged elimination. Ze 450 administered PO and IP decreased significantly post-stimulated insulin, whereas metformin did not. HOMA-IR index of insulin resistance improved significantly after IP and PO Ze 450 and slightly after metformin. In summary, the results demonstrate that Ze 450 reduced significantly body weight, plasma glucose, improved glucose metabolism and insulin sensitivity in diabetic ob/ob mice. In vitro experiments suggest that part of the effects may be related to AMPK activation. CONCLUSIONS: Ze 450 may have utility in the treatment of type 2 diabetes. However, longer term studies in additional animal models or patients with disturbed glucose tolerance or diabetes may be of use to investigate this further.

Severely fibrotic pancreases from young patients with chronic pancreatitis: evidence for a ductal origin of islet neogenesis.

While it is known that islet cell mass increases considerably after birth, general uncertainty surrounds the source of new beta cells in humans. Chronic pancreatitis (CP) presents a natural injury model for studying postnatal beta-cell regeneration in the human pancreas. In this report, we present histological evidence from human CP pancreases to support the theory that islet neogenesis can occur from ductal precursor cells after birth. Three young patients (ages 16, 12, and 28 years) underwent total pancreatectomy for the management of CP followed by islet isolation and autologous transplantation to prevent or minimize postsurgical diabetes. In all cases, the pancreases had extensive fibrosis, a rock-like consistency, and calcifications in the ducts. During islet isolations, we observed the unusual release of islets with many ductal fragments. In histopathological evaluation of these pancreases, solid cords of cells sometimes formed islet like structures intraductally or extending from ductal structures. Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon, and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both ß-cells and α-cells. Labeling for Ki67 to demonstrate mitotic activity showed frequent labeling of duct epithelial cells and of some periductal cells. Using insulin and wide-spectrum cytokeratin double immunofluorescent labeling, we found insulin-positive cells to be present within the ductal lumens, among the cytokeratin-positive ductal epithelium, and extending from the ductal epithelium into surrounding connective tissues, providing evidence for a ductal origin of islet neogenesis.

Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic ß-cell mass in a streptozotocin-induced mouse model of type 2 diabetes.

AIMS: We examined the effects of the oral dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin on glycaemic control and pancreatic ß-cell mass and morphology in a mouse model of type 2 diabetes mellitus (T2DM). METHODS: Male C57BL/6 mice (n = 12/group) aged 4 to 6 weeks and weighing >15 g received a high-fat diet throughout this 45-day study. After a 7-day handling period, baseline levels of plasma glucose, plasma insulin and glycated haemoglobin (HbA1c) were assessed. Animals were allocated to one of six groups: compound vehicle control, intraperitoneal streptozotocin (STZ, 50 mg/kg)-treated control and saxagliptin (10 mg/kg) or sitagliptin (10 mg/kg, positive control) initiated 7 days before or 1 day after STZ administration. Endpoints included changes in body weight, food and water consumption, glucose tolerance (approximately 3 weeks post-STZ), fasting glucose and HbA1c and immunohistochemical analyses of the pancreas. RESULTS: Body weight, weight gain and food intake were reduced in STZ versus control mice. DPP-4 inhibitor treatment did not affect these changes, but the increase in water intake observed post-STZ administration was significantly attenuated with DPP-4 inhibitors whether initiated before or after STZ injury. Small but significant improvements in glycaemic control were observed with DPP-4 inhibitors versus the STZ control. Improved ß-cell mass and morphology were observed with saxagliptin given pre- or post-STZ and sitagliptin given post-STZ. CONCLUSIONS: Saxagliptin mitigated damage to ß-cells and improved glycaemic control in this mouse model of T2DM.

Molecular targeted approaches for treatment of pancreatic cancer.

Human pancreatic cancer remains a highly malignant disease with almost similar incidence and mortality despite extensive research. Many targeted therapies are under development. However, clinical investigation showed that single targeted therapies and most combined therapies were not able to improve the prognosis of this disease, even though some of these therapies had excellent anti-tumor effects in pre-clinical models. Cross-talk between cell proliferation signaling pathways may be an important phenomenon in pancreatic cancer, which may result in cancer cell survival even though some pathways are blocked by targeted therapy. Pancreatic cancer may possess different characteristics and targets in different stages of pathogenesis, maintenance and metastasis. Sensitivity to therapy may also vary for cancer cells at different stages. The unique pancreatic cancer structure with abundant stroma creates a tumor microenvironment with hypoxia and low blood perfusion rate, which prevents drug delivery to cancer cells. In this review, the most commonly investigated targeted therapies in pancreatic cancer treatment are discussed. However, how to combine these targeted therapies and/or combine them with chemotherapy to improve the survival rate of pancreatic cancer is still a challenge. Genomic and proteomic studies using pancreatic cancer samples obtained from either biopsy or surgery are recommended to individualize tumor characters and to perform drug sensitivity study in order to design a tailored therapy with minimal side effects. These studies may help to further investigate tumor pathogenesis, maintenance and metastasis to create cellular expression profiles at different stages. Integration of the information obtained needs to be performed from multiple levels and dimensions in order to develop a successful targeted therapy.

Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway.

Pancreatic cancer is the fourth leading cause of cancer related deaths and is a disease with poor prognosis. It is refractory to standard chemotherapeutic drugs or to novel treatment modalities, making it imperative to find new treatments. In this study, using both primary and metastatic pancreatic cancer cell lines, we have demonstrated that the flavonoid myricetin induced pancreatic cancer cell death in vitro via apoptosis, and caused a decrease in PI3 kinase activity. In vivo, treatment of orthotopic pancreatic tumors with myricetin resulted in tumor regression and decreased metastatic spread. Importantly, myricetin was non-toxic, both in vitro and in vivo, underscoring its use as a therapeutic agent against pancreatic cancer.

A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer.

PURPOSE: (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment. METHODS: Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. RESULTS: Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. CONCLUSIONS: Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.

The role of heat shock proteins in gastrointestinal diseases.

Heat shock proteins (HSPs) are a highly conserved family of proteins which inhabit almost all subcellular locations and cellular membranes. Depending on their location, these proteins perform a variety of chaperoning functions including folding of newly synthesised polypeptides. HSPs also play a major role in the protection of cells against stressful and injury-inciting stimuli. By virtue of this protective function, HSPs have been shown to prevent acinar cell injury in acute pancreatitis. Also, the levels of HSPs have been shown to be markedly elevated in various forms of cancers when compared with non-transformed cells. Further, inhibition of HSPs has been shown to induce apoptotic cell death in cancer cells suggesting that inhibition of HSPs has a potential to emerge as novel anti-cancer therapy, either as monotherapy or in combination with other chemotherapeutic agents. Several studies have suggested that HSPs can interact with and inhibit both intrinsic and extrinsic pathways of apoptosis at multiple sites. Besides the anti-apoptotic role of HSPs, recent studies suggest that they play a role in the generation of anti-cancer immunity, and attempts have been made to utilise this property of HSPs in the generation of anti-cancer vaccines. The anti-apoptotic function and mechanism of various subtypes of HSPs as well as the current status of anti-HSP therapy are discussed in this review.

The effects of glycosaminoglycan content on the compressive modulus of cartilage engineered in type II collagen scaffolds.

OBJECTIVE: The current study determined the unconfined compressive modulus of tissue-engineered constructs with varying sulfated glycosaminoglycan (GAG) density produced by goat articular chondrocytes in type II collagen scaffolds prepared with a range of cross-link densities and various times in culture. The purpose of this work is to establish a basis for future studies employing constructs of selected maturity (e.g., 25%, 50%, or 75% normal GAG content) for cartilage repair in vivo. METHODS: Porous scaffolds (8 mm diameter by 2 mm thick) were fabricated from porcine type II collagen by freeze-drying, followed by dehydrothermal treatment and carbodiimide cross-linking. In a pilot study, passage 3 adult caprine articular chondrocytes isolated from one goat were grown in scaffolds with six cross-link densities for 2, 3, 4, and 6 weeks (n=3). The goal was to select scaffold cross-link densities and times in culture that would produce constructs with approximately 25%, 50% and 75% the GAG density of native articular cartilage. Based on the results of the pilot study, chondrocytes from three goats were grown in scaffolds with two cross-link densities for three time periods: 3, 5, and 9 weeks (n=6; one of the cross-link groups was run in quadruplicate). The equilibrium modulus from unconfined compression testing of these samples was correlated with GAG content. RESULTS: There was a notable increase in GAG density with decreasing cross-link density. Histological analysis verified a chondrogenic phenotype and revealed various amounts of GAG and type II collagen-containing cartilage. The correlation between modulus and GAG density had a linear coefficient of determination of 0.60. One group with a mean GAG density of 22 microg/mm(3), which was 140% the GAG density of normal caprine articular cartilage, averaged a compressive modulus of 31.5 kPa, which was 10% of caprine articular cartilage tested in this study. CONCLUSIONS: The GAG density and modulus of tissue-engineered constructs can be controlled by the degree of cross-linking of type II collagen scaffolds and time in culture.

Genetically designing a more potent antipancreatic cancer agent by simultaneously co-targeting human IL13 and EGF receptors in a mouse xenograft model.

OBJECTIVE: Investigators are currently interested in the epidermal growth factor receptor (EGFR) and interleukin 13 receptor (IL13R) as potential targets in the development of new biologicals for pancreatic cancer. Attempts to develop successful agents have met with difficulty. The novel approach used here was to target these receptors simultaneously with EGF and IL13 cloned on the same bispecific single-chain molecule with truncated diphtheria toxin (DT(390)) to determine if co-targeting with DTEGF13 had any advantages. DESIGN: Proliferation experiments were performed to measure the potency and selectivity of bispecific DTEGF13 and its monospecific counterparts against pancreatic cancer cell lines PANC-1 and MiaPaCa-2 in vitro. DTEGF13 was then administered intratumourally to nude mice with MiaPaCa-2 flank tumours to measure efficacy and toxicity (weight loss). RESULTS: In vitro, bispecific DTEGF13 was 2800-fold more toxic than monospecific DTEGF or DTIL13 against PANC-1. A similar enhancement was observed in vitro when MiaPaCa-2 pancreatic cancer cells or H2981-T3 lung adenocarcinoma cells were studied. DTEGF13 activity was blockable with recombinant EGF13. DTEGF13 was potent (IC(50) = 0.00017 nM) against MiaPaCa-2, receptor specific and significantly inhibited MiaPaCa-2 tumours in nude mice (p<0.008). CONCLUSIONS: In vitro studies show that the presence of both ligands on the same bispecific molecule is responsible for the superior activity of DTEGF13. Intratumoural administration showed that DTEGF13 was highly effective in checking aggressive tumour progression in mice. Lack of weight loss in these mice indicated that the drug was tolerated and a therapeutic index exists in an "on target" model in which DTEGF13 is cross-reactive with native mouse receptors.

The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats.

INTRODUCTION: Treatment with some antipsychotic drugs may result in excessive body weight gain which can have detrimental effects on patient compliance, morbidity and mortality. The aim of the present study was to investigate the effect of atypical antipsychotic drugs on dietary macronutrient selection, body weight, body composition and biochemical parameters related to obesity in female rats. MATERIALS AND METHODS: Forty pair-housed, adult female hooded-Lister rats (250 +/- 5 g) were habituated to three diets containing principally protein, fat, or carbohydrate in a home cage self-selection paradigm. Olanzapine (2 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), or vehicle was injected intraperitoneally once daily for 22 days; food selection, water intake, and body weight were recorded daily, while body composition and plasma hormones (insulin, glucose, nonesterified free fatty acid, total cholesterol, glycerol, triacylglycerol, leptin, and prolactin) were analyzed at the end of the study. RESULTS: Only olanzapine significantly increased body weight and food intake. Macronutrient selection was significantly altered after olanzapine and risperidone treatment (increased protein and decreased fat preference). Only olanzapine increased carcass fat content. Locomotor activity was significantly reduced in all treatment groups. Both olanzapine and risperidone significantly increased plasma prolactin. Olanzapine was without effect on any other biochemical parameter measured. Ziprasidone significantly reduced plasma leptin and nonsignificantly reduced NEFA, while risperidone significantly reduced fasting plasma glucose. CONCLUSION: This study supports our previous work demonstrating weight gain and increased feeding behavior induced by olanzapine and could have important implications for enhancing our understanding of the mechanisms by which olanzapine and other atypical antipsychotics induce weight gain in the clinic.

Tinted contact lenses as an alternative management for photophobia in stationary cone dystrophies in children.

BACKGROUND: Intense photophobia is a debilitating symptom of the stationary cone dystrophies. The dark-tinted glasses with side-shields and floppy hats used to manage this are very conspicuous and can cause marked psychological morbidity to the children and their families. We assess the use of tinted contact lenses as an alternative management for the photophobia. METHODS: Three children, aged 5 to 13, with cone dystrophies, all with markedly reduced visual acuity, color vision, and profound photophobia were fitted with Lunelle ES70 Solaire 70% brown contact lenses. The child's parents completed two Children's Visual Function Questionnaires, the first pertaining to the period when the child wore tinted glasses; the second pertaining to the period of tinted contact lens wear. RESULTS: Subjectively, two of the children and their parents described a striking improvement in their quality of life, with improved confidence, interactions with other children, and cessation of name-calling and bullying. The Children's Visual Function Questionnaires gave objective evidence for this improvement in one child and was not significantly different in the other. The third child was reluctant to wear the contact lenses despite her parents' active encouragement. CONCLUSION: Tinted contact lenses offer an alternative management of the photophobia associated with stationary cone dystrophies in children. Marked improvements in their quality of life were observed in this case series.

Contamination of disposable tonometer prisms during tonometry.

AIM: Due to the theoretical possibility of prion transmission in applanation tonometry, many ophthalmological units in the United Kingdom now use disposable tonometer prisms. We have investigated the potential for bacterial and viral transmission from the health practitioner to the patient via disposable prisms. METHODS: All staff who perform applanation tonometry at the Sussex Eye Hospital (SEH) received a questionnaire to evaluate if the applanating face of the prism is touched during tonometry and the ease of use of the disposable prism compared to the reusable prisms that were previously used. We then cultured prisms handled by a random sample of staff members for common bacteria. Finally, we constructed a model to investigate the possibility of interpatient adenoviral transmission via disposable tonometer prisms. RESULTS: The questionnaire revealed that almost 50% of the staff admit to touching the applanating face of the tonometer prism prior to applanation. Cultures of the prisms grew a range of bacteria including Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus species. The viral model suggested that adenovirus could be transmitted by applanation tonometry. CONCLUSION: The use of disposable prisms for applanation tonometry may reduce the risk of prion transmission but is not bacteriologically or virologically aseptic. This is a potential infection risk to patients.

Synthesis and biological evaluation of novel hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines as potent and selective 5-HT(2C) receptor agonists.

Further lead optimization efforts on previously described 1,2,3,4,10,10a-hexahydro-1H-pyrazino[1,2-a]indoles led to the new class of 5,5a,6,7,8,9-hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines culminating in the discovery of (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3', 2':4,5]pyrrolo[1,2-a]pyrazine 18 as a potent, full 5-HT(2C) receptor agonist with an outstanding selectivity profile and excellent hERG and phospholipidosis properties.

Water-soluble upper GI based on clinical findings is reliable to detect anastomotic leaks after laparoscopic gastric bypass.

Anastomotic leak after laparoscopic Roux-en-Y gastric bypass (LGB) is a major complication that must be recognized and treated early for best results. There is controversy in the literature regarding the reliability of upper GI series (UGI) in diagnosing leaks. LGB was performed in patients meeting NIH criteria for the surgical treatment of morbid obesity. All leaks identified at the time of surgery were repaired with suture and retested. Drains were placed at the surgeon's discretion. Postoperatively, UGI was performed by an experienced radiologist if there was a clinical suspicion of leak. From September 2001 until October 2004, a total of 553 patients (age 40.4 +/- 9.2 years, BMI 48.6 +/- 7.2) underwent LGB at UAB. Seventy-eight per cent (431 of 553) of patients had no clinical evidence suggesting anastomotic leak and were managed expectantly. Twenty-two per cent (122 of 553) of patients met at least one inclusion criteria for leak and underwent UGI. Four of 122 patients (3.2%) had a leak, two from anastomosis and two from the perforation of the stapled end of the Roux limb. No patient returned to the operating room without a positive UGI. High clinical suspicion and selectively performed UGI based on clinical evidence is reliable in detecting leaks.

Identification of 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT2C receptor agonists.

Synthesis and evaluation of the activity of new 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT(2C) receptor agonists are described. Appropriately substituted, several analogs displayed selectivity against the other 5-HT(2) receptor subtypes of 1 order of magnitude or more. Selectivity was improved for several compounds versus the lead 1, increasing the therapeutic interest in this series of 5-HT(2C) receptor agonists.

Cannabinoids and the regulation of ingestive behaviour.

Over past centuries, Cannabis sativa (Delta(9)-tetrahydrocannabinol being the principal active ingredient) has been used extensively for both medicinal and recreational uses, and one widely reported effect is the onset of a ravenous appetite and eating behaviour. The pharmacological properties of such exogenous cannabinoids are mediated through the activation of two receptor subtypes, the CB(1) and CB(2) receptors. A number of endogenous ligands for these receptors, the endocannabinoids, have now also been identified allowing their effects on ingestive behaviour to be determined. In a number of species, including man, the administration of exogenous and endogenous cannabinoids leads to robust increases in food intake and can promote body weight gain. These effects are believed to be mediated through activation of the CB(1) receptor. Conversely, experiments with selective CB(1) receptor antagonists have demonstrated reductions in food intake and body weight with repeated compound administration. These reductions in body weight appear to be greater in obese animals and may be the result of a dual effect on both food intake and metabolic processes. Such findings have led to a number of pharmaceutical companies developing selective CB(1) receptor antagonists for the treatment of obesity. The most advanced compound is Sanofi-Synthelabo's inverse agonist, rimonabant (Acomplia; SR-141716), and early Phase III results have recently demonstrated significant reductions in body weight, waist circumference and improvement of lipid and glucose metabolism in overweight and obese humans. Accordingly, the cannabinoid system appears to have an important role in the regulation of ingestive behaviour in man and animals.

Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium.

Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells.