ABSTRACT
TTC7A mutations cause multiple neonatal intestinal atresias with early inflammatory bowel disease and severe combined immunodeficiency. There are no treatment protocols for this rare disease. Two new cases are described for which radical early treatment measures - total enterectomy, home parenteral nutrition, immunoglobulin therapy and intravenous antibiotic prophylaxis - have allowed both patients to develop optimally.
ABSTRACT
INTRODUCTION: All-inside posteromedial suture for lesions of the posterior horn of the medial meniscus in anterior cruciate ligament (ACL) repair provides effective freshening and good healing. HYPOTHESIS: The posteromedial portal provides satisfactory healing rates without increasing morbidity or complications rates. MATERIAL AND METHODS: Intra- and postoperative complications were collected for a consecutive single-center series of 132 patients undergoing posteromedial hook suture of the medial meniscus in ACL repair. Meniscal healing was assessed as the rate of recurrence of symptomatic medial meniscus lesions (Barret criteria) and on revision surgery, if any, in terms of the aspect and extent of the iterative lesion. The severity of any sensory disorder was assessed by questionnaire. RESULTS: The intraoperative complications rate was 1.5% (2 saphenous vein punctures). At a mean 31months (range, 28-35months), there was no loss to follow-up. Twelve patients (9%) showed symptomatic recurrence of the medial meniscus lesion, requiring 10 repeat surgeries. In 6 cases (4.5%), the iterative lesion involved a smaller, more central part of the meniscus anterior to the sutures, of "postage-stamp" effect, possibly implicating the suture hook and/or non-absorbable sutures. There were no cases of infection or fistula. Postoperative hematoma occurred in 7% of patients. In total, 1.8% reported dysesthesia areas equal to or greater than the size of a credit card (45cm2). DISCUSSION: Some retears, or "partial failures", may implicate a new lesion caused by the suture hook and possibly prolonged by non-resorbable sutures. Hematoma and sensory disorder rates were comparable to those reported in isolated ACL repair without posteromedial portal. CONCLUSION: The present results show that posteromedial arthroscopic hook suture in posterior medial meniscus tear provides good healing rates without increased morbidity due to the supplementary portal. LEVEL OF EVIDENCE: IV.
Subject(s)
Arthroscopy , Intraoperative Complications , Postoperative Complications , Suture Techniques/instrumentation , Tibial Meniscus Injuries/surgery , Adolescent , Adult , Anterior Cruciate Ligament Reconstruction , Child , Humans , Middle Aged , Prospective Studies , Recurrence , Reoperation/statistics & numerical data , Tendons/transplantation , Young AdultABSTRACT
BACKGROUND: Tibial spine avulsion fractures (TSAFs) occur chiefly in adolescents. Few published data are available on outcomes after arthroscopic surgical treatment of TSAFs in adults. OBJECTIVES: To evaluate outcomes of consecutive patients with TSAFs managed by arthroscopic bone suture followed by a standardised non-aggressive rehabilitation programme. HYPOTHESIS: Arthroscopic bone suture followed by non-aggressive rehabilitation therapy reliably produces satisfactory outcomes in adults with TSAF. METHODS: Thirteen adults were included. Outcomes were evaluated based on the Tegner score, International Knee Documentation Committee (IKDC) score, anterior-posterior knee laxity, passive and active motion ranges, and radiological appearance. RESULTS: After a mean follow-up of 41±27months (12-94months), all 13 patients had healed fractures without secondary displacement. No patient had knee instability. Post-operative stiffness was noted in 5 patients (2 with complex regional pain syndrome and 3 with extension lag), 1 of whom required surgical release. The mean IKDC score was 91.3±11.7. The mean Tegner score was 5.46±1.37 compared to 6.38±0.70 before surgery. Mean tibial translation (measured using the Rolimeter) was 1.09±1.22mm, compared to 5.9±1.85mm before surgery. CONCLUSION: The outcomes reported here support the reliability of arthroscopic bone suture for TSAF fixation. Nevertheless, a substantial proportion of patients experienced post-operative stiffness, whose contributory factors may include stunning of the quadriceps due to the short time from injury to surgery and the use of a gentle rehabilitation programme. LEVEL OF EVIDENCE: IV, retrospective study of treatment outcomes.
Subject(s)
Arthroscopy , Fractures, Avulsion/surgery , Knee Joint/physiopathology , Postoperative Complications/rehabilitation , Range of Motion, Articular/physiology , Sutures , Tibial Fractures/surgery , Adolescent , Adult , Female , Humans , Male , Middle Aged , Physical Therapy Modalities , Postoperative Complications/physiopathology , Prevalence , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Trochlear dysplasia is one of the main elements of patellofemoral instability. Although correction by trochleoplasty seems logical, the long-term outcome of this procedure is unknown and the progression to osteoarthritis has not been clarified. Thus, we performed a retrospective study of a series of sulcus deepening trochleoplasties with a 15-year follow-up whose goal was to (1) evaluate the long-term clinical outcome and radiological rate of osteoarthritis, and (2) define the results in relation to the type of instability and the grade of dysplasia. HYPOTHESIS: Sulcus deepening trochleoplasty is an effective procedure to stabilize the patellofemoral joint that does not increase the risk of osteoarthritis. PATIENTS AND METHODS: This retrospective study analyzed 34 sulcus deepening trochleoplasties based on clinical scores (IKS, Lille, Kujala and Oxford scores) and radiological results (stage of osteoarthritis according to the Iwano score) after a mean follow-up of 15 years (12-19 years). An Insall procedure was systematically associated with an anterior tibial tubercle transfer in 17 cases (7 prior tibial transfers). RESULTS: No recurrent objective instability was observed. Seven knees had additional surgery after a mean follow-up of 7 years (2-16): 7 underwent conversion to total knee arthroplasty because of progression of osteoarthritis and one knee had tibial tubercle transfer for pain and episodes of the knee giving way. The mean Lille, Kujala and IKS scores increased from 53.3 (30-92), 55 (13-75) and 127 (54-184) to 61.5 (25-93), 76 (51-94) and 152.4 (66-200) respectively between preoperative and follow-up assessment (P<0.05) (revisions included). Functional outcome was significantly better for dysplasia with supratrochlear spurs (IKS score 168 [127-200] versus 153 [98-198] and Kujula score 81.5 [51-98] versus 76 [51-94] [P<0.05]). Patients were satisfied in 65% of the cases and the total mean Oxford score was 24.1/60 (12-45 points). Occasional pain was present in 53% of the cases. The trochlear prominence decreased from 4.9 mm (3-9 mm) to -1.2mm (-7-4mm). Ten cases of preoperative patellofemoral osteoarthritis were identified, but none with>Iwano 2, while osteoarthritis was present in 33/34 cases at the final follow-up with 20 cases>Iwano 2 (65%). DISCUSSION: Sulcus deepening trochleoplasty corrects patellofemoral stability even in patients with severe dysplasia and the long-term functional outcome is better in this group. It does not prevent patellofemoral osteoarthritis. It should be limited to severe dysplasia with supratrochlear spurs and associated with procedures to realign the extensor apparatus.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Forecasting , Joint Instability/surgery , Knee Joint/surgery , Patellar Dislocation/surgery , Patellofemoral Joint/surgery , Adolescent , Adult , Disease Progression , Female , Femur/surgery , Follow-Up Studies , Humans , Joint Instability/diagnostic imaging , Joint Instability/physiopathology , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , Male , Middle Aged , Patellar Dislocation/diagnostic imaging , Patellar Dislocation/physiopathology , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/physiopathology , Radiography , Range of Motion, Articular , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Anterior knee pain (AKP) is a rare and difficult complication following anterior cruciate ligament (ACL) reconstruction. This disabling pain is persistent with conventional rehabilitation protocols. The aim of this work is to validate a new rehabilitation protocol that may improve the patients and allow return to daily activities including sports. MATERIALS AND METHODS: Forty-three patients identified with functional AKP after ACL reconstruction was enrolled in the rehabilitation protocol between 2009 and 2011. The series included twenty-six patients with hamstring grafting and seventeen patients with patellar tendon transplant. This study compares the functional outcomes and pain scores before and after the isokinetic protocol until the last follow-up at an average of 25.7 months after surgery. The evaluation was performed according to the International Knee Documentation Committee (IKDC) and included a pain assessment using the visual analog scale. Statistical analysis used Student's t-test for unpaired data and the Pearson correlation test for the variables. The IKDC scores were compared by the Wilcoxon test. RESULTS: Functional outcomes and pain are significantly improved (p<0.0001). The average IKDC score improved with 28 points and the pain improved with 3.2 points on the visual analog scale (VAS). The results are correlated with the follow-up time (p=0.008) but not correlated with the delay between the surgery and the beginning of the isokinetic protocol. DISCUSSION: Isokinetic rehabilitation provides a significant improvement in the knee function as measured by the IKDC score and by the VAS, regardless of the painful period preceding the program. The function improvement continues after the end of the protocol, but the pain may not completely disappear. The isokinetic rehabilitation program may resume functional AKP related to muscular deficit and may be used as the starter of other physical therapy protocols. LEVEL OF EVIDENCE: IV.
Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction/adverse effects , Arthralgia/rehabilitation , Exercise Therapy/methods , Knee Joint , Adult , Anterior Cruciate Ligament Reconstruction/rehabilitation , Arthralgia/etiology , Humans , Male , Muscle Strength/physiology , Muscle Strength Dynamometer , Pain, Postoperative/etiology , Pain, Postoperative/rehabilitation , Quadriceps Muscle/physiology , Retrospective StudiesABSTRACT
Intraoperative spinal cord monitoring consists in a subcontinuous evaluation of spinal cord sensory-motor functions and allows the reduction the incidence of neurological complications resulting from spinal surgery. A combination of techniques is used: somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), neurogenic motor evoked potentials (NMEP), D waves, and pedicular screw testing. In absence of intraoperative neurophysiological testing, the intraoperative wake-up test is a true form of monitoring even if its latency long and its precision variable. A 2011 survey of 117 French spinal surgeons showed that only 36% had neurophysiological monitoring available (public healthcare facilities, 42%; private facilities, 27%). Monitoring can be performed by a neurophysiologist in the operating room, remotely using a network, or directly by the surgeon. Intraoperative alerts allow real-time diagnosis of impending neurological injury. Use of spinal electrodes, moved along the medullary canal, can determine the lesion level (NMEP, D waves). The response to a monitoring alert should take into account the phase of the surgical intervention and does not systematically lead to interruption of the intervention. Multimodal intraoperative monitoring, in presence of a neurophysiologist, in collaboration with the anesthesiologist, is the most reliable technique available. However, no monitoring technique can predict a delayed-onset paraplegia that appears after the end of surgery. In cases of preexisting neurological deficit, monitoring contributes little. Monitoring of the L1-L4 spinal roots also shows low reliability. Therefore, monitoring has no indication in discal and degenerative surgery of the spinal surgery. However, testing pedicular screws can be useful. All in all, thoracic and thoracolumbar vertebral deviations, with normal preoperative neurological examination are currently the essential indication for spinal cord monitoring. Its absence in this indication is a lost opportunity for the patient. If neurophysiological means are not available, intraoperative wake-up test is a minimal obligation.
Subject(s)
Intraoperative Neurophysiological Monitoring/methods , Spinal Cord Diseases/surgery , Spinal Cord/physiopathology , France , Humans , Reproducibility of Results , Spinal Cord/surgery , Spinal Cord Diseases/physiopathologyABSTRACT
Acute hamstring strains are a common athletic injury, which may be treated non-operatively with a satisfactory outcome. A complete proximal hamstring avulsion is a rare and potentially career ending injury to an elite athlete. For these high demand patients, surgical reattachment should be immediately undertaken to shorten return to sport and to improve functional outcome. This report describes the occurrence of a complete avulsion of the proximal hamstrings in a professional footballer during an international match. We highlight the clinical presentation, the appropriate diagnostic investigations, the surgical technique and the rehabilitation protocol for this injury. The successful surgical reattachment of the common hamstring tendon was confirmed by magnetic resonance imaging done 5 months after repair and allowed the player a full return to competition at 6 months after surgery. Hamstrings isokinetic peak torque was 80% at 6 months and 106% at 11 months after repair comparing with the uninjured side.
Subject(s)
Soccer/injuries , Tendon Injuries/surgery , Humans , Leg , Male , Orthopedic Procedures/methods , Young AdultABSTRACT
During arthroscopic ACL reconstruction, intra-articular visualization can be compromised by the interposition of the infrapatellar fat pad (IPFP) between the scope and the notch. In this technical note, we describe our technique of using lateral higher arthroscopic portal, starting arthroscopy with the resection of the ligamentum mucosum and performing the tibial tunnel in 40° of knee flexion to optimise the intra-articular view without IPFP debridement. This technique was performed in 112 consecutive arthroscopic ACL reconstructions and compared to that in the previous 112 cases in which a conventional method was used. The use of this technique was associated with a shorter operative time and no increase in the difficulty in performing associated meniscal procedures.
Subject(s)
Adipose Tissue/transplantation , Anterior Cruciate Ligament/surgery , Arthroscopes , Arthroscopy/methods , Knee Injuries/surgery , Patella/surgery , Plastic Surgery Procedures/methods , Anterior Cruciate Ligament Injuries , Equipment Design , HumansABSTRACT
It has been suggested that an increased posterior tibial slope (PTS) and a narrow notch width index (NWI) increase the risk of anterior cruciate ligament (ACL) injury. The aim of this study was to establish why there are conflicting reports on their significance. A total of fifty patients with a ruptured ACL and 50 patients with an intact ACL were included in the study. The group with ACL rupture had a statistically significantly increased PTS (p < 0.001) and a smaller NWI (p < 0.001) than the control group. When a high PTS and/or a narrow NWI were defined as risk factors for an ACL rupture, 80% of patients had at least one risk factor present; only 24% had both factors present. In both groups the PTS was negatively correlated to the NWI (correlation coefficient = -0.28, p = 0.0052). Using a univariate model, PTS and NWI appear to be correlated to rupture of the ACL. Using a logistic regression model, the PTS (p = 0.006) and the NWI (p < 0.0001) remain significant risk factors. From these results, either a steep PTS or a narrow NWI predisposes an individual to ACL injury. Future studies should consider these factors in combination rather than in isolation.
Subject(s)
Anterior Cruciate Ligament Injuries , Knee Injuries/pathology , Knee Joint/pathology , Tibia/pathology , Adolescent , Adult , Anterior Cruciate Ligament/pathology , Epidemiologic Methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Rupture/etiology , Rupture/pathology , Young AdultABSTRACT
Diffusion is one of the most frequently used assumptions to explain dispersal. Diffusion models and in particular reaction-diffusion equations usually lead to solutions moving at constant speeds, too slow compared to observations. As early as 1899, Reid had found that the rate of spread of tree species migrating to northern environments at the beginning of the Holocene was too fast to be explained by diffusive dispersal. Rapid spreading is generally explained using long distance dispersal events, modelled through integro-differential equations (IDEs) with exponentially unbounded (EU) kernels, i.e. decaying slower than any exponential. We show here that classical reaction-diffusion models of the Fisher-Kolmogorov-Petrovsky-Piskunov type can produce patterns of colonisation very similar to those of IDEs, if the initial population is EU at the beginning of the considered colonisation event. Many similarities between reaction-diffusion models with EU initial data and IDEs with EU kernels are found; in particular comparable accelerating rates of spread and flattening of the solutions. There was previously no systematic mathematical theory for such reaction-diffusion models with EU initial data. Yet, EU initial data can easily be understood as consequences of colonisation-retraction events and lead to fast spreading and accelerating rates of spread without the long distance hypothesis.
Subject(s)
Models, Theoretical , DiffusionABSTRACT
The endogenous or exogenous origin of Staphylococcus aureus, responsible for orthopaedic surgical-site infections (SSI), remains debated. We conducted a multicentre prospective cohort study to analyse the respective part of exogenous contamination and endogenous self-inoculation by S. aureus during elective orthopaedic surgery. The nose of each consecutive patient was sampled before surgery. Strains of S. aureus isolated from the nose and the wound, in the case of SSI, were compared by antibiotypes or pulsed-field gel electrophoresis (PFGE). A total of 3,908 consecutive patients undergoing orthopaedic surgery were included. Seventy-seven patients developed an SSI (2%), including 22 related to S. aureus (0.6%). S. aureus was isolated from the nose of 790 patients (20.2%) at the time of surgery. In the multivariate analysis, S. aureus nasal carriage was found to be a risk factor for S. aureus SSI in orthopaedic surgery. However, only nine subjects exhibiting S. aureus SSI had been found to be carriers before surgery: when compared, three pairs of strains were considered to be different and six similar. In most cases of S. aureus SSI, either an endogenous origin could not be demonstrated or pre-operative nasal colonisation retrieved a strain that was different from the one recovered from the surgical site.
Subject(s)
Carrier State/epidemiology , Carrier State/microbiology , Staphylococcal Infections/transmission , Staphylococcus aureus/classification , Surgical Wound Infection/epidemiology , Surgical Wound Infection/microbiology , Aged , Bacterial Typing Techniques , DNA Fingerprinting , Electrophoresis, Gel, Pulsed-Field , Female , Genotype , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Molecular Epidemiology , Prospective Studies , Risk Factors , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purificationABSTRACT
There is an increasing recognition that long distance dispersal (LDD) plays a key role in establishing spatial genetic structure during colonization. Recent works, focused on short distance dispersal, demonstrated that a neutral mutation arising at the colonization front can either 'surf' with the wave front and reach high frequencies or stay near its place of origin at low frequencies. Here, we examine how LDD, and more generally the shape of the dispersal kernel, modifies this phenomenon and how the width of the colonization corridor affects the fate of the mutation. We demonstrate that when LDD events are more frequent, the 'surfing phenomenon' is less frequent, probably because any alleles can get far ahead from the colonization front and preclude the invasion by others alleles, thus leading to an attenuation of the diversity loss. We also demonstrate that the width of the colonization corridor influences the fate of the mutation, wide spaces decreasing the probability of invasion. Overall, the genetic structure of diversity resulted not only from LDD but also particularly from the shape of the dispersal kernel.
Subject(s)
Gene Flow , Models, Genetic , Alleles , Computer Simulation , Genetic Variation , Population DynamicsABSTRACT
Evolution in a single environment is expected to erode genetic variability, thereby precluding adaptation to novel environments. To test this, a large population of spider mites kept on cucumber for approximately 300 generations was used to establish populations on novel host plants (tomato or pepper), and changes in traits associated to adaptation were measured after 15 generations. Using a half-sib design, we investigated whether trait changes were related to genetic variation in the base population. Juvenile survival and fecundity exhibited genetic variation and increased in experimental populations on novel hosts. Conversely, no variation was detected for host choice and developmental time and these traits did not evolve. Longevity remained unchanged on novel hosts despite the presence of genetic variation, suggesting weak selection for this trait. Hence, patterns of evolutionary changes generally matched those of genetic variation, and changes in some traits were not hindered by long-term evolution in a constant environment.
Subject(s)
Adaptation, Biological , Biological Evolution , Cucumis sativus/parasitology , Tetranychidae/physiology , Animals , Genetic Variation , Host-Parasite Interactions , Tetranychidae/geneticsABSTRACT
Pancreatic phospholipase A2 (PLA(2)-I) stimulates U(III) cells proliferation, a rat uterine cell line, after binding to membrane receptors, internalization and translocation. Here, we demonstrate that during these steps of internalization, PLA(2)-I retains its hydrolytic activity and thus could exert its proliferative effect via nuclear phospholipids hydrolysis. Since fatty acids and eicosanoids released by such activity are known to be ligands of PPAR, we study the expression of these nuclear receptors and demonstrate that, in the experimental conditions where PLA(2)-I stimulates U(III) cells proliferation, PLA(2)-I also regulates PPAR expression indicating a possible mechanism of its proliferative effect.
Subject(s)
Cell Nucleus/metabolism , Phospholipases A/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Transcription Factors/metabolism , Animals , Cell Division , Cell Line , Eicosanoids/metabolism , Enzyme Activation , Female , Group II Phospholipases A2 , Hydrolysis , Microscopy, Fluorescence , Phospholipases A2 , Phospholipids/metabolism , Rats , Time Factors , Transduction, Genetic , Uterus/metabolismABSTRACT
The mechanisms underlying arachidonic acid (AA) release by uterine stromal (U(III)) cells were studied. Stimulation of AA release by calcium ionophore and PMA are inhibited by various PKC inhibitors and by calcium deprivation. These results suggest the involvement of an AA-specific cPLA2 as the release of docosahexaenoic acid (DHA) from prelabelled cells is much lower than the release of AA. The results also show a more original stimulation of AA and DHA release induced by PKC inhibitors, which is insensitive to calcium deprivation. This stimulation is not due to acyltransferase inhibition, suggesting the participation of a Ca2+-independent PLA2 (iPLA2). However, iPLA2 activity measured in U(III) cells is inhibited by the specific iPLA2 inhibitor, BEL, and is not stimulated by PKC inhibitors, in contrast with the AA and DHA release. It seems therefore that this iPLA2 cannot be involved in this mechanism. The participation of another iPLA2, BEL-insensitive, is discussed.
Subject(s)
Arachidonic Acid/metabolism , Calcium/physiology , Docosahexaenoic Acids/metabolism , Enzyme Inhibitors/pharmacology , Protein Kinase C/antagonists & inhibitors , Signal Transduction/drug effects , Uterus/cytology , Acyltransferases/physiology , Animals , Calcimycin/pharmacology , Female , Phospholipases A/drug effects , Phospholipases A/metabolism , Phospholipases A2 , Phospholipids/metabolism , Rats , Signal Transduction/physiology , Stromal Cells/cytology , Stromal Cells/drug effects , Stromal Cells/metabolism , TritiumABSTRACT
We have previously demonstrated that pancreatic PLA2 (PLA2-I) stimulates the proliferation of UIII cells, a stromal cell line derived from normal rat uterus. In order to gain further insight into the mechanism of action of PLA2-I, we have investigated the intracellular processing of PLA2-I. Either highly proliferative or growth arrested UIII cells were analyzed. Growth arrested cells were obtained from a contact inhibited monolayer or from aristolochic acid-treated cultures. Using cellular fractionation, western blotting, immunocytochemistry and confocal microscopy, we demonstrate that endogenous PLA2-I was mainly located in the nucleus in highly proliferative cells whereas its location was cytoplasmic in non proliferative cells. When non confluent UIII cells were incubated with nanomolar amounts of exogenous PLA2-I, the enzyme was internalized and, in the majority of cells, appeared within the nucleus. Both internalization and nuclear location of exogenous PLA2-I were suppressed by the addition of aristolochic acid to the culture medium. Binding experiments performed on purified nuclear preparations showed the presence of specific cooperative binding sites for PLA2-I. Collectively our data suggest that the proliferative effect exerted by pancreatic PLA2 in UIII cells is mediated by a direct interaction of the enzyme at the nuclear level. Putative mechanisms and targets are discussed.
Subject(s)
Cell Nucleus/enzymology , Phospholipases A/metabolism , Animals , Binding Sites , Cell Division , Cell Line , Cell Nucleus/metabolism , Cell Nucleus/ultrastructure , Enzyme Activation , Female , Isoenzymes/metabolism , Phospholipases A2 , Protein Binding , Rats , Stromal Cells , Subcellular Fractions/enzymology , Subcellular Fractions/metabolism , Subcellular Fractions/ultrastructure , UterusABSTRACT
It is well known that arachidonic acid, as a substrate of prostaglandin G/H synthase (PGHS), is converted into prostaglandins of the two-series. In this work, we attempted to determine whether arachidonic acid and prostaglandin E2 might regulate the expression of PGHS and the pancreatic-type phospholipase A2 (PLA2I), which may be involved in the liberation of arachidonic acid from membrane phospholipids. For this purpose, we used the uterine stromal cell line UIII, which produces prostaglandin E2 and expresses both the constitutive and inducible PGHS enzymes (PGHS1 and PGHS2) and PLA2 I. The results show that PGHS1, which is expressed at a high level in UIII cells, was not modified by arachidonic acid. The expression of PGHS2 and PLA2 I was up-regulated by increasing arachidonate concentrations (1-10 microM). The maximal response was obtained at 24 h, reaching a 2.3-fold and 2.6-fold increase for PGHS2 and PLA2 I expression, respectively, compared to the control level. To discriminate between the effect of arachidonic acid and that of prostaglandins, which are highly increased in the presence of exogenous arachidonic acid, we treated the cells with two inhibitors of PGHS activity, aspirin and meclofenamic acid. Both inhibitors failed to suppress the arachidonate-induced increase of PLA2 I and PGHS2 expression and even enhanced it either in the presence or absence of arachidonic acid. In contrast, the addition of prostaglandin E2 to the culture medium decreased the expression of both enzymes in a dose-dependent manner, the maximal response being reached at 1 microM. We conclude that arachidonic acid up-regulates the expression of PLA2 I and PGHS2 in the uterine stromal cells, independently of prostanoids, and that prostaglandin E2 is capable of down-regulating enzyme expression.
Subject(s)
Arachidonic Acid/pharmacology , Cyclooxygenase Inhibitors/metabolism , Dinoprostone/pharmacology , Oxytocics/pharmacology , Phospholipases A/metabolism , Up-Regulation , Uterus/metabolism , Animals , Aspirin/pharmacology , Cells, Cultured , Cyclooxygenase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Enzymologic , Meclofenamic Acid/pharmacology , Phospholipases A2 , Rats , Stromal Cells/cytology , Stromal Cells/drug effects , Stromal Cells/enzymology , Stromal Cells/metabolism , Uterus/cytology , Uterus/drug effects , Uterus/enzymologyABSTRACT
Uterine stromal cells produce and release PGE2, both processes being regulated by hormonal factors. In this study, we examined the effect of PRL on the PGE2 production and release measured by radioimmunoassay. For this purpose, we used a rat uterine stromal cell line, UIII cells, which produce PGE2 and contain PRL receptors. The expression of sPLA2I and PGHS (PGHS1 and PGHS2), enzymes required for PGE2 production, was also estimated by immunocytochemistry and 'Western blotting' in response to PRL. PRL (10 to 60 ng/ml) significantly increased the PGE2 release (up to 6-fold) and production, in a dose-dependent manner. Results show that PGHS1 and PGHS2 are both expressed constitutively in the uterine UIII cells, although PGHS2 is expressed at a low level. PRL did not increase PGHS1 expression, but stimulated the expression of sPLA2I and PGHS2 by 3.5- and 2.5-fold, respectively. These data show for the first time a regulation of sPLA2I and PGHS2 expression by PRL and may indicate that, in uterine cells, PRL enhances the PGE2 release and production by increasing the expression of both sPLA2I and PGHS2.