Locking Nail versus Plate Fixation in Calcaneal Fractures: Brief report on a Retrospective Analysis of Treatment Characteristics and Radiographic Correction Potential.

PURPOSE OF THE STUDY Minimal and limited access techniques are gaining increasing interest for the treatment of displaced intra-articular calcaneal fractures. The ideal treatment method is however still debated and largely based on individual case factors and surgeon experience. Aim of this study was thus to compare the treatment characteristics and radiographic correction potential of a locking nail system with a sinus tarsi approach to plate fixation via an extended lateral approach. MATERIAL AND METHODS We retrospectively reviewed 39 cases of patients with calcaneal fractures that received primary fracture treatment for displaced intra-articular calcaneal fractures between July 2017 and March 2020. Patient characteristics, time to surgery, time to discharge, OR time and the correction achieved were analyzed and comparative statistics performed. RESULTS In total 19 patients treated with the locking nail and 20 patients treated with plate fixation were analyzed. Patient age and fracture severity according to the Sanders classification were comparable between the groups. Overall surgical time, as well as the achieved reduction was equal between both groups. Time to surgery, as well as time from surgery to discharge was significantly shorter in the locking nail group. 2 additional soft tissue procedures were necessary in the extended lateral approach group. DISCUSSION AND CONCLUSIONS The results with the locking calcaneus nail and sinus tarsi approach suggest, that similar treatment results can be achieved as with plate osteosynthesis and an extended lateral approach. Soft tissue management, as well as pre- and postoperative timing and discharge management can be improved with the nail. Further controlled trials comparing the longterm outcome between the treatment options are needed. Key words: calcaneus fracture, sinus tarsi approach, calcaneal nail, C-Nail.

Weight-Bearing Restrictions after Acetabular Fracture, Necessity or False Hope? A Brief Observational Study.

PURPOSE OF THE STUDY Most common postoperative treatment recommendations after acetabulum fractures suggest at least 6 weeks of postoperative partial or non weight-bearing. To protect the osteosynthetic construct this surgically set weight-bearing limit is trained by physical therapy. Aim of our analysis was to determine the free field patient compliance to these weight-bearing restrictions and observe their influence on the early postoperative radiographic imaging. MATERIAL AND METHODS Patients after surgical treatment of an acetabulum fracture were included in our analysis. Every patient was instructed to maintain a 20 kg weight-bearing limit for 6 weeks. Postoperative weight-bearing was continuously monitored during this time with a pressure measuring insole. Maximum weight-bearing per day was recorded and maintenance of reduction assessed after this time. RESULTS In total 10 patients were included into the study. Only 1 patient stayed within the weight-bearing limit during the analysis. Maximum weight-bearing as high as 110 kg was recorded. All patients maintained postoperative reduction at the 6 week timepoint. DISCUSSION AND CONCLUSIONS Despite regular physical therapy training compliance to the generally accepted weight-bearing limits was low. Regardless of the non-compliance the radiographic outcome remained unchanged. Further analysis on the use of permissive weightbearing aftercare regimes are warranted. Key words: weight-bearing, acetabulum fracture, compliance.

The effect of an infra-acetabular screw for anatomically shaped three-dimensional plate or standard plate designs in acetabulum fractures: a biomechanical analysis.

BACKGROUND: Various plate shapes and implant configurations are used for stabilization of acetabulum fractures via anterior approaches. Little is known about the biomechanical stability of a two-dimensionally shaped "conventional" plate ("J-Plate"-JP) in comparison to three-dimensionally shaped plate configurations (3DP). In addition, the augmentary effect of an infra-acetabular lag-screw (IACS) fixation for anterior column and posterior hemi-transverse acetabulum fractures has not been clarified in comparison of JP and 3DP constructs. This study analyzed the difference between the biomechanical stability of JP compared to 3DP and the role of an IACS in a standardized acetabular fracture model in a single-leg stance loading configuration. METHODS: In an artificial bone substitute pelvis model (Synbone© Malans, Switzerland), a typical and standardized fracture pattern (anterior column and posterior hemi-transverse) was created with osteotomy jigs. After anatomic reduction the stabilization was performed using JP or 3DP. Eight pelvises per group were axially loaded in a single-leg stance model up to 400 N. After the load cycle, an additional infra-acetabular screw was placed and the measurement repeated. Fragment displacement was recorded by an optical tracking system (Optitrack Prime 13®, Corvallis, USA). RESULTS: In the pure placement, 3DP provided significantly superior stability when compared to JP. Augmentation of JP by IACS increased the stability significantly, up to the level of 3DP alone, whereas augmentation of the 3DP did not result in further increase of overall stability. CONCLUSION: The anatomically shaped plate alone provides a superior biomechanical stability in fixation of an anterior column and posterior hemi-transverse fracture model. In a JP fixation the augmentation by IACS provides similar strength as the anatomically shaped 3DP. By use of the anatomically shaped 3DP the need of a clinically risky application of IACS might be avoidable. LEVEL OF EVIDENCE: IV, Experimental study.

Amlodipine accelerates bone healing in a stable closed femoral fracture model in mice.

Calcium channel blockers (CCBs), which are widely used in the treatment of hypertension, have been shown to influence bone metabolism. However, there is little information on whether CCBs also influence the process of fracture healing. Therefore, the effect of the CCB amlodipine on bone healing was studied in a stable closed fracture model in mice using intramedullary screw fixation. Bone healing was investigated by radiology, biomechanics, histomorphometry and Western blot analysis 2 and 5 weeks after fracture healing. Animals were treated daily (post operatively) per os using a gavage with amlodipine low dose (1 mg/ kg body weight, n = 20), amlodipine high dose (3 mg/kg body weight, n = 20) or vehicle (NaCl) (control, n = 20) serving as a negative control. At 2 and 5 weeks, histomorphometric analysis revealed a significantly larger amount of bone tissue within the callus of amlodipine low-dose- and high-dose-treated animals when compared to controls. This was associated with a smaller amount of cartilaginous and fibrous tissue, indicating an acceleration of fracture healing. Biomechanics showed a slightly, but not significantly, higher bending stiffness in amlodipine low-dose- and high-dose-treated animals. Western blot analysis revealed a significantly increased expression of bone morphogenetic protein (BMP)-2 and vascular endothelial growth factor (VEGF). Moreover, the analysis showed a 5-fold higher expression of osteoprotegerin (OPG) and a 10-fold elevated expression of the receptor activator of NF-κB ligand (RANKL), indicating an increased bone turnover. These findings demonstrated that amlodipine accelerated fracture healing by stimulating bone formation, callus remodelling and osteoclast activity.

Erythropoietin does not improve fracture healing in aged mice.

Fracture healing in the elderly is associated with a declined healing potential caused by multiple factors including a delay of vascularization. Erythropoietin (EPO) has been demonstrated to improve vascularization and fracture healing in adult mice. We, therefore, hypothesized that EPO in aged mice also improves fracture healing. For this purpose, EPO was given daily in a femoral fracture model in aged mice and compared to vehicle-treated controls using radiological, biomechanical, histomorphometric and Western blot techniques. Blood analyses revealed significantly higher concentrations of hemoglobin and a higher hematocrit in EPO-treated animals at 14 and 35 days after fracture. Micro-computed tomography (µCT) indicated that the fraction of bone volume/tissue volume within the callus did not differ between the two groups. However, µCT showed a 3-fold increased tissue mineral density (TMD) in the callus of EPO-treated animals compared to controls. The callus TMD of the EPO-treated animals was also 2-fold higher when compared to the TMD of the unfractured contralateral femur. Interestingly, biomechanical analyses revealed a reduced bending stiffness in femurs of EPO-treated animals at day 35. The histomorphometrically analyzed callus size and callus composition did not show significant differences between the study groups. However, Western blot analyses exhibited an increased expression of osteoprotegerin (OPG), but in particular of receptor activator of NF-κB ligand (RANKL) in the callus of the EPO-treated animals. Further histological analyses of the callus tissue showed that this was associated with an increased number of newly formed blood vessels and a higher number of tartrate-resistant acid phosphatase (TRAP)+ cells. Conclusion: In fracture healing of aged mice EPO treatment increases callus TMD as well as OPG and RANKL expression, indicating an accelerated bone turnover when compared to controls. However, EPO does not improve fracture healing in aged mice. The process of fracture healing may be altered by EPO due to a deterioration of the microcirculation caused by the worsened rheological properties of the blood and due to an increased bone fragility caused by the accelerated bone turnover. Thus, EPO may not be used to improve fracture healing in the elderly.

Determination of Green's function for three-dimensional traction force reconstruction based on geometry and boundary conditions of cell culture matrices.

Cell migration plays a particular important role in the initiation and progression of many physical processes and pathological conditions such as tumor invasion and metastasis. Three-dimensional traction force microscopy (TFM) of high resolution and high accuracy is being developed in an effort to unveil the underlying mechanical process of cell migration in a vivo-like environment. Linear elasticity-based TFM (LETM) as a mainstream approach relies on the Green's function (that relates traction forces to matrix deformation), of which the inherent boundary conditions and geometry of the matrix could remarkably affect the result as suggested by previous 2D studies. In this study, we investigated this close linkage in 3D environment, via modeling of a cell sensing a close-by fixed boundary of a 3D matrix surrounding it, and comparing the reconstructed traction forces from three different solutions of the Green's function, including a fully matching solution derived using the adapted Mindlin's approach. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function in a non-conventional way to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. A single case experimental study was conducted for a multi-cellular structure of endothelial cells that just penetrated into the gel at the early stage of angiogenesis. STATEMENT OF SIGNIFICANCE: This study focused on the fundamental issue regarding extension of linear elasticity-based TFM to deal with physically realistic matrices (where cells are encapsulated), which concerns determination of the Green's function matching their geometry and boundary conditions. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. The proposed approach to adapting the Green's function for the specific 3D cell culture situation was examined in a single case experimental study of endothelial cells in sprouting angiogenesis.

[A new continuous gait analysis system for ankle fracture aftercare]. / Ein neues, kontinuierliches Ganganalysesystem zur Nachbehandlung von Sprunggelenkfrakturen.

BACKGROUND: Correct aftercare following lower extremity fractures remains a controversial issue. Reliable, clinically applicable weight-bearing recommendations have not yet been defined. The aim of the current study was to establish a new gait analysis insole during physical therapy aftercare of ankle fractures to test patients' continuous, long-term compliance to partial weight-bearing restrictions and investigate whether patients can estimate their weight-bearing compliance. MATERIALS AND METHODS: The postoperative gait of 14 patients after operative treatment of Weber B-type ankle fractures was monitored continuously for six weeks (OpenGO, Moticon GmbH, Munich). All patients were instructed and trained by physical therapists on how to maintain partial weight-bearing for this time. Discontinuous (three, six and twelve weeks) clinical (patient questionnaire, visual analogue pain score [VAS]) and radiographic controls were performed. RESULTS: Despite the set weight-bearing limits, individual ranges for overall weight-bearing (range 5-107% of the contralateral side) and patient activity (range 0-366 min/day) could be shown. A good correlation between weight-bearing and pain was seen (rs = -0.68; p = <0.0001). Patients significantly underestimated their weight-bearing time over the set limit (2.3 ± 1.4 min/day vs. real: 12.6 ± 5.9 min/day; p < 0.01). CONCLUSIONS: Standardized aftercare protocols and repeated training alone cannot ensure compliance to postoperative partial weight-bearing. Patients unconsciously increased weight-bearing based on their pain level. This study shows that new, individual and possibly technology-assisted weight-bearing regimes are needed. The introduced measuring device is feasible to monitor and steer patient weight-bearing during future studies.

[Periprosthetic acetabular fractures in geriatric patients]. / Die periprothetische Azetabulumfraktur des geriatrischen Patienten.

Periprosthetic acetabular fractures in geriatric patients are rare injuries; however, the incidence is increasing because of the current demographic developments. For diagnosis of periprosthetic acetabular fractures, conventional X­ray images are regularly complemented by computed tomography (CT). For exclusion of loosening of the prosthesis more advanced techniques, such as single photon emission CT (SPECT/CT) are applied. In addition to classification of periprosthetic acetabular fractures by the traditional system of Letournel there are several other classification systems, which take into account the etiology of the fracture and the stability of the prosthesis. While, under certain circumstances conservative treatment of periprosthetic acetabular fractures is possible, operative treatment often requires extensive surgical procedures to restore the stability of the acetabulum as a support for the cup of the prosthesis. Besides the traditional techniques of acetabular osteosynthesis, special revision systems, augmentations and allografts are used for the reconstruction of periprosthetic acetabular fractures. To determine a therapeutic regimen patient-specific preconditions as well as fracture pattern and type of prosthesis need to be taken into account. In the literature there are several algorithms, which are aimed at supporting the attending physician in making the correct decision for the treatment of periprosthetic acetabular fractures. In cases of periprosthetic acetabular fractures even experienced surgeons are faced with great challenges. Thus, treatment should be carried out in specialized centers.

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors.

In vivo vaccination studies are conventionally conducted in a single mouse strain with results, only reflecting responses to a single immunogenetic background. We decided to examine the immune response to an HIV transgene (gag, pol and nef fusion protein) in 3 strains of mice (CBA, C57BL/6 and BALB/c) to determine the spectrum of responses and in addition to determine whether the serotype of the adenoviral vector used (ChAd3 and ChAd63) impacted the outcome of response. Our results demonstrated that all three strains of mice responded to the transgene and that the magnitude of responses were different between the strains. The C57BL/6 strain showed the lowest range of responses compared to the other strains and, very few responses were seen to the same peptide pool in all three strains of mice. In CBA and BALB/c mice there were significant differences in IFNγ production dependent on the adenoviral vector used. Our results suggest that employing a single strain of mouse may underestimate the efficacy and efficiency of vaccine products.

[Influence of the pelvic trauma registry of the DGU on treatment of pelvic ring fractures]. / Einfluss des Beckenregisters der DGU auf die Versorgung von Beckenringfrakturen.

Fractures of the pelvic ring are comparatively rare with an incidence of 2-8 % of all fractures depending on the study in question. The severity of pelvic ring fractures can be very different ranging from simple and mostly "harmless" type A fractures up to life-threatening complex type C fractures. Although it was previously postulated that high-energy trauma was necessary to induce a pelvic ring fracture, over the past decades it became more and more evident, not least from data in the pelvic trauma registry of the German Society for Trauma Surgery (DGU), that low-energy minor trauma can also cause pelvic ring fractures of osteoporotic bone and in a rapidly increasing population of geriatric patients insufficiency fractures of the pelvic ring are nowadays observed with no preceding trauma.Even in large trauma centers the number of patients with pelvic ring fractures is mostly insufficient to perform valid and sufficiently powerful monocentric studies on epidemiological, diagnostic or therapeutic issues. For this reason, in 1991 the first and still the only registry worldwide for the documentation and evaluation of pelvic ring fractures was introduced by the Working Group Pelvis (AG Becken) of the DGU. Originally, the main objectives of the documentation were epidemiological and diagnostic issues; however, in the course of time it developed into an increasingly expanding dataset with comprehensive parameters on injury patterns, operative and conservative therapy regimens and short-term and long-term outcome of patients. Originally starting with 10 institutions, in the meantime more than 30 hospitals in Germany and other European countries participate in the documentation of data. In the third phase of the registry alone, which was started in 2004, data from approximately 15,000 patients with pelvic ring and acetabular fractures were documented. In addition to the scientific impact of the pelvic trauma registry, which is reflected in the numerous national and international publications, the dramatically changing epidemiology of pelvic ring fractures, further developments in diagnostics and the changes in operative procedures over time could be demonstrated. Last but not least the now well-established diagnostic and therapeutic algorithms for pelvic ring fractures, which could be derived from the information collated in registry studies, reflect the clinical impact of the registry.

Effect of Stabilization on the Healing Process of Femur Fractures in Aged Mice.

BACKGROUND: The influence of mechanical stability on fracture healing has previously been studied in adult mice, but is poorly understood in aged animals. Therefore, we herein studied the effect of stabilization on the healing process of femur fractures in aged mice. METHODS: Twenty-four 18-month-old CD-1 mice were stabilized after midshaft fracture of the femur with an intramedullary screw. In another 24 18-month-old mice, the femur fractures were left unstabilized. Bone healing was studied by radiological, biomechanical, histomorphometric, and protein expression analyses. RESULTS: After 2 and 5 weeks of healing, the callus of nonstabilized fractures compared to stabilized fractures was significantly larger, containing a significantly smaller amount of osseous tissue and a higher amount of cartilaginous tissue. This was associated with a significantly lower biomechanical stiffness during the early phase of healing. However, during the late phase of fracture healing both nonstabilized and stabilized fractures showed a biomechanical stiffness of ∼40%. Of interest, Western blot analyses of callus tissue demonstrated that the expression of proteins related to angiogenesis, bone formation and remodeling, i.e. VEGF, CYR61, BMP-2, BMP-4, Col-2, Col-10, RANKL, OPG, did not differ between nonstabilized and stabilized fractures. CONCLUSION: Nonstabilized fractures in aged mice show delayed healing and remodeling. This is not caused by an altered protein expression in the callus but rather by the excessive interfragmentary movements.

Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag-pol-nef antigen.

Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene.

[Penetrating injury of two body cavities with a 20 cm long dagger-like sliver after falling into a glass door]. / Penetrierende 2-Höhlen-Verletzung mit einer 20 cm langen dolchartigen Scherbe nach Sturz in eine Glastür.

In Germany the numbers of penetrating thoracic injuries are rare compared to Anglo-American countries; however, the number of cases has increased in recent years due to an increase in violent incidents. This article reports the case of a patient who suffered such a penetrating thoracic injury after a domestic accident. Operative treatment was performed according to the well-established standard treatment algorithms. Contrary to the initial assessment of the emergency doctor, substantially more severe injuries were found.

[Fractures of the acetabulum: complications and joint replacement]. / Azetabulumfrakturen: Komplikationen und Endoprothetik.

Acetabular fractures assume a special role amongst the fractures of the pelvis, because they involve a major weight-bearing joint. As those fractures mostly result from exposure to great force, and because of their location in an anatomically complex region, a high rate of complications has to be anticipated. Besides general and perioperative complications long-term consequences, especially post-traumatic arthrosis, are relevant problems when it comes to treating fractures of the acetabulum. The primary reconstruction of the acetabulum, as well as a possibly necessary prosthetic replacement of the hip joint, makes high demands on the diagnostic and operative capabilities of the attending physician. Exact knowledge of the specific risks and pitfalls for each type of fracture and for the specific surgical techniques is crucial for a successful treatment. Due to the much worse long-term outcome when compared to primary total hip replacement in patients with osteoarthritis, acetabular fractures should, regardless of the patient's age, whenever possible be treated by operative reconstruction.

Artificially disordered birefringent optical fibers.

We develop and experimentally verify a theory of evolution of polarization in artificially-disordered multi-mode optical fibers. Starting with a microscopic model of photo-induced index change, we obtain the first and second order statistics of the dielectric tensor in a Ge-doped fiber, where a volume disorder is intentionally inscribed via UV radiation transmitted through a diffuser. A hybrid coupled-power & coupled-mode theory is developed to describe the transient process of de-polarization of light launched into such a fiber. After certain characteristic distance, the power is predicted to be equally distributed over all co-propagating modes of the fiber regardless of their polarization. Polarization-resolved experiments, confirm the predicted evolution of the state of polarization. Complete mode mixing in a segment of fiber as short as ∼ 10cm after 3.6dB insertion loss is experimentally observed. Equal excitation of all modes in such a multi-mode fiber creates the conditions to maximize the information capacity of the system under e.g. multiple-input-multiple-output (MIMO) transmission setup.

Markers of the uterine innate immune response of the mare.

Reproductive efficiency in mares is low and persistent mating-induced endometritis (PMIE) is an important cause of subfertility. Mating-induced endometritis (MIE) an obligate precursor to PMIE, is a ubiquitous, transient inflammatory response to the presence of sperm, seminal components and pathogens. However, the specific inflammatory pathways that derive from MIE and that may also be precursors to PMIE are not clear. The ability to identify and measure robust, repeatable markers of inflammation integral to MIE may be key to understanding the progression to PMIE. The aim of the study was to (i) refine a protocol for inducing MIE and in doing so test a range of cellular and molecular parameters as valid markers of MIE to facilitate future studies of mares susceptible to PMIE (ii) concurrently identify those parameters with potential as inflammatory indicators during MIE to inform and enhance early treatment regimens in practice. Mating-induced endometritis was induced in pony mares using a stringent protocol; mares were treated intrauterine with frozen/thawed semen (n = 5; FTS) or frozen/thawed extender (n = 6: FTEx). The parameters tested were measured before treatment were compared to samples collected at strategic time points after treatment: uterine cytology using cytological (at 8, 16, 24, 48 and 72 h after treatment) or histological analysis (at 24 and 72 h); uterine bacteriology (at 24 and 72 h); secretion of prostaglandin F(2alpha) (PGF(2alpha); at 8, 16, 24, 48 and 72 h); peripheral concentrations of serum amyloid A (SAA; at 24h); endometrial mRNA gene expression, focussing upon IL8 and TLR4, as examples of genes pertinent to inflammation (at 24 h). Uterine neutrophil cell numbers in both treatment groups increased at 8 (P < 0.001), 16 (P < 0.01) and 24 (P < 0.01) h after insemination, indicative of MIE and distinguished between different treatments because neutrophil numbers were greater from FTS mares than FTEx mares 8h after challenge. Uterine neutrophil cell numbers, assessed by histology, increased (P < 0.001) 24 and 72 h after treatment. Prostaglandin F(2alpha) concentrations increased (P < 0.05) 16 h after treatments, while SAA concentrations and bacterial growth scores were not significantly different after treatment. Endometrium from pony mares expressed mRNA for IL8 and TLR4 but expression was not altered after insemination. The protocol induced MIE, as confirmed by uterine cytology and maybe used hereafter as a repeatable and robust method for studying immune mechanisms that underlie MIE and so may aid the understanding of progression to persistent inflammation. It can be concluded that of the range of parameters tested, neutrophil cell numbers by cytological analysis and PGF(2alpha) were regarded as the most accurate markers of inflammation during MIE and important for use in practice.

Endometrial explant culture to study the response of equine endometrium to insemination.

Mating-induced endometritis (MIE) is ubiquitous in the horse after natural mating and artificial insemination with frozen/thawed semen causing the most aggressive response. The majority of mares eliminate MIE 24-48 h after insemination. An endometrial explant culture was tested as a potential in vitro exemplar for sperm-induced MIE. Endometrial prostaglandin F(2alpha) (PGF(2alpha)) secretion and expression of interleukin-8 (IL-8) were used as markers of inflammation. Endometrial explants were cultured from uteri collected from follicular phase mares. Explants were challenged with 1 or 10 x 10(6) sperm/ml frozen/thawed semen, chilled semen, washed sperm or seminal plasma. Medium was collected 24 and 72 h after challenge and assayed for PGF(2alpha) by radioimmunoassay. Treatment of endometrial explants with frozen/thawed, chilled semen or washed sperm did not change the secretion of PGF(2alpha) compared with untreated controls. However, 24 h after challenge cultured explants expressed IL-8. The in vitro endometrial explant system did not represent the in vivo response to semen when PGF(2alpha) was used as a marker of inflammation, yet the use of gene expression as an inflammatory marker warrants further investigation.

Effect of Escherichia coli infection of the bovine uterus from the whole animal to the cell.

Following parturition, contamination of the uterine lumen by bacteria is ubiquitous, and uterine health is impaired in cattle because infection persists in 10% to 15% of animals as endometritis. Endometritis causes infertility for the duration of infection, and subfertility persists even after apparent successful resolution of the disease. Escherichia coli is the pathogenic bacterium most frequently isolated from the post partum uterus, and is associated with increased concentrations of peripheral plasma acute phase proteins and fetid vaginal mucus. The presence of E. coli is also associated with slower growth of the first post partum dominant follicle and perturbed oestradiol secretion. Furthermore, in animals that ovulate the first dominant follicle, the corpus luteum is smaller and secretes less progesterone. The endotoxin lipopolysaccharide (LPS), which is released from E.coli, can pass from the uterine lumen to the peripheral circulation and LPS concentrations are increased in cows with uterine infection. Infusion of E. coli LPS into the uterine lumen suppresses the pre-ovulatory luteinising hormone surge and disrupts ovulation in heifers. In vitro, endometrial explants produce prostaglandins in response to LPS. Addition of LPS or E. coli to stromal or epithelial cells increases cyclooxygenase-2 mRNA expression, and stimulates the production of prostaglandin E2 and prostaglandin F2α . Furthermore, uterine and ovarian cells express mRNA of the molecules required for recognition of LPS, Toll-like receptor-4 and CD14. In summary, E. coli is a common cause of infertility involving the perturbation of the hypothalamus, pituitary and ovary in dairy cows.

The effects of Arcanobacterium pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo.

Uterine bacterial infection after parturition causes endometritis, perturbs ovarian function and leads to infertility in cattle. Although endometritis is caused by mixed infections, endometrial pathology is associated with the presence of Arcanobacterium pyogenes. The aims of the present study were to determine the effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Heat-killed A. pyogenes did not affect the production of prostaglandin F2alpha (PGF) or prostaglandin E(2) (PGE) from endometrial explants, or purified populations of endometrial epithelial or stromal cells. However, the explants produced more PGF and PGE than controls when treated with a bacteria-free filtrate (BFF) cultured from A. pyogenes. Similarly, BFF stimulated PGF and PGE production by epithelial and stromal cells, respectively. So, BFF or control PBS was infused into the uterus of heifers (n=7 per group) for 8 days, starting the day after estrus. Emergence of the follicle wave, dominant follicle or corpus luteum diameter, and peripheral plasma FSH, LH, estradiol, progesterone, PGFM, or acute phase protein concentrations were unaffected by the BFF infusion. In the live animal it is likely that the intact uterine mucosa limits the exposure of the endometrial cells to the exotoxin of A. pyogenes, whereas the cells are readily exposed to the toxin in vitro.