Clinical outcome after dorso-ventral stabilization of the thoracolumbar and lumbar spine with vertebral body replacement and dorsal stabilization.

PURPOSE: Surgical stabilization of the spine by vertebral body replacement (VBR) is used for spinal disorders such as traumatic fractures to provide an anatomical re-adjustment of the spine to prevent late detrimental effects and pain [1-4]. This study addresses the clinical outcome after a ventral intervention with VBR and bisegmental fusion. METHODS: The study includes 76 patients (mean age: 59.34 ± 15.97; 34 females and 42 males) with fractures in the lower thoracic and lumbar spine. They were selected from patients of our hospital who received an anterolateral VBR surgery on the corresponding lower spine region over a nine-year period. Only patients were examined with X-rays and complete follow-up records. Exclusion criteria were changes due to degeneration and pathological fractures. Patients were divided into two groups, the thoracotomy group (Th10-L1) and the lumbotomy group (L2-5), respectively. Minimum one year after surgery, patients were asked about their well-being using a precasted questionnaire. RESULTS: No significant differences with respect to the subjective impression of the patients concerning their back pain, spinal functional impairment, their general functional status and their quality of life impairment. Unfortunately, however, only a rather modest but significant increase of the post-surgical life quality was reported. CONCLUSIONS: Patients who underwent VBR in the lower thoracic or lumbar spine show modest long-term well-being. The results suggest that injuries to the lower thoracic or lumbar spine requiring vertebral body replacement should be classified as severe injuries since they adversely affect the patients' long-term well-being. TRIAL REGISTRATION: Study of clinical outcome of patients after vertebral body replacement of the ventral thoracal and lumbal spine, DRKS00031452. Registered 10th March 2023 - Prospectively registered. Trial registration number DRKS00031452.

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats.

PURPOSE: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. METHODS: Eight-month-old male Sprague-Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. RESULTS: EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. CONCLUSION: The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation.

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

PURPOSE: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats. METHODS: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed. RESULTS: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone. CONCLUSIONS: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

[Complication rate after femoral shaft fractures in childhood and adolescence depending on patient factors and treatment measures]. / Die Komplikationsrate nach Femurschaftfrakturen im Kindes- und Jugendalter in Abhängigkeit von Patientenfaktoren und Behandlungsmaßnahmen.

BACKGROUND: The treatment of pediatric femoral shaft fractures has undergone an increasing change in recent years. The previously predominant treatment procedures were extensively replaced by minimally invasive techniques (e.g. elastic stable intramedullary nailing, ESIN). The aim of this study was the comparison of complication rates depending on patient factors as well as various treatment procedures. MATERIAL AND METHODS: This study involved a retrospective X­ray morphometric evaluation of data. The patient files and X­rays of 101 children who were treated at 2 level I trauma centers were analyzed. RESULTS: Conservative treatment was carried out in 19% of the cases. Among the surgical procedures the ESIN technique was predominant (n = 60). Complications that needed revision occurred in 10% of the children after conservative treatment. Revision surgery had to be carried out in more than 6% of the cases in children who were surgically treated. Among the surgical procedures ESIN stabilization demonstrated the lowest revision rate with only 3%. Children under three years and adolescents had a higher risk for developing complications. If the ESIN wires used were too thin in relation to the diameter of the medullary cavity there was an increased probability of complications of around 30%. CONCLUSION: This study revealed a moderate risk of complications in the treatment of femoral shaft fractures in children. The risk of complications after external fixation and conservative treatment was the highest in this study. Overall, the ESIN technique showed the lowest risk of complications. The results of this study could confirm the known limitations of the ESIN technique depending on age and body weight.

C-reactive protein in spinal surgery: more predictive than prehistoric.

PURPOSE: In spinal surgery, surgical site infections (SSI) after dorsal spondylodesis lead to severe short- and long-term complications. Despite various clinical and serological evidence, the detection of a postoperative SSI remains crucial. In this retrospective cohort study, we determined the prognostic value of C-reactive protein (CRP) kinetics after open reduction and dorsal spondylodesis in the development of a SSI. METHODS: We retrospectively analyzed 192 patients from 2016 to 2018 undergoing open reduction and dorsal spondylodesis with and without SSI for 20 days at a level-I trauma center and assessed their serological and clinical characteristics. RESULTS: On day 7 and 8 after surgery, patients who developed a SSI displayed significantly higher CRP levels. A second peak after the initial maximum of CRP and a restricted failure to decline as well as a maximum CRP of more than 225 mg/l predict an infectious complication with a sensitivity of 92.9%, and a specificity of 78.2%. A binary logistic regression leads to 85.7% and 69.7%, respectively. A one-phase decay exponential regression can predict 75.6% of the variance after the initial peak of CRP. CONCLUSION: Our study demonstrates a high value of postoperative CRP kinetics in SSI detection after dorsal spondylodesis. Moreover, we observed typical CRP levels with a specific course as indicative predictors that may facilitate an early SSI detection in clinical practice.

[Laparoscopic resection of a giant colon diverticulum : Case report and review of the literature]. / Laparoskopische Resektion eines Riesenkolondivertikels : Fallbericht und Literaturübersicht.

BACKGROUND: Giant diverticula are rare complications of diverticular disease. Current opinion regards operative therapy as the method of choice for the treatment of symptomatic giant diverticula; however, there is neither consensus about the technique nor about the necessary extent of resection. Based on a non-systematic review of the literature, an overview of giant diverticula in terms of epidemiology, pathology and classification is given. The current case is considered with respect to appropriate diagnostic procedures and possible therapeutic options. CASE PRESENTATION: An 80-year-old female patient presented to the emergency department with abdominal pain and dyspnea. A computed tomography scan showed a large gas-filled structure in the upper left abdomen adjacent to the left colon. A giant colonic diverticulum was suspected and laparoscopy was performed. Intraoperatively, the diagnosis of a giant colon diverticulum located at the splenic flexure was confirmed. An unremarkable diverticulosis only was found in the descending colon. The giant diverticulum was treated by an atypical colon wedge resection and the postoperative course was uneventful. DISCUSSION: This case report describes a laparoscopic atypical colon wedge resection as treatment of a giant colon diverticulum. Only four laparoscopic bowel resections in terms of sigmoid resections or hemicolectomy with primary anastomosis have been reported. Minimally invasive surgery can be a valuable alternative to open procedures. In the current case a laparoscopic atypical colon wedge resection was safely performed. This option might be considered as an alternative to extended resections of giant diverticula. Localization of the giant diverticulum and the simultaneous existence of diverticular disease are the main criteria for the decision between the different operative approaches.

Small fields output factors measurements and correction factors determination for several detectors for a CyberKnife® and linear accelerators equipped with microMLC and circular cones.

PURPOSE: The use of small photon fields is now an established practice in stereotactic radiosurgery and radiotherapy. However, due to a lack of lateral electron equilibrium and high dose gradients, it is difficult to accurately measure the dosimetric quantities required for the commissioning of such systems. Moreover, there is still no metrological dosimetric reference for this kind of beam today. In this context, the first objective of this work was to determine and to compare small fields output factors (OF) measured with different types of active detectors and passive dosimeters for three types of facilities: a CyberKnife(®) system, a dedicated medical linear accelerator (Novalis) equipped with m3 microMLC and circular cones, and an adaptive medical linear accelerator (Clinac 2100) equipped with an additional m3 microMLC. The second one was to determine the kQclin,Qmsr (fclin,fmsr) correction factors introduced in a recently proposed small field dosimetry formalism for different active detectors. METHODS: Small field sizes were defined either by microMLC down to 6 × 6 mm(2) or by circular cones down to 4 mm in diameter. OF measurements were performed with several commercially available active detectors dedicated to measurements in small fields (high resolution diodes: IBA SFD, Sun Nuclear EDGE, PTW 60016, PTW 60017; ionizing chambers: PTW 31014 PinPoint chamber, PTW 31018 microLion liquid chamber, and PTW 60003 natural diamond). Two types of passive dosimeters were used: LiF microcubes and EBT2 radiochromic films. RESULTS: Significant differences between the results obtained by several dosimetric systems were observed, particularly for the smallest field size for which the difference in the measured OF reaches more than 20%. For passive dosimeters, an excellent agreement was observed (better than 2%) between EBT2 and LiF microcubes for all OF measurements. Moreover, it has been shown that these passive dosimeters do not require correction factors and can then be used as reference dosimeters. Correction factors for the active detectors have then been determined from the mean experimental OF measured by the passive dosimeters. CONCLUSIONS: Four sets of correction factors needed to apply the new small field dosimetry formalism are provided for several active detectors. A protocol for small photon beams OF determination based on passive dosimeters measurements has been recently proposed to French radiotherapy treatment centers.

French diagnostic reference levels in diagnostic radiology, computed tomography and nuclear medicine: 2004-2008 review.

After 5 y of collecting data on diagnostic reference levels (DRLs), the Nuclear Safety and Radiation Protection French Institute (IRSN) presents the analyses of this data. The analyses of the collected data for radiology, computed tomography (CT) and nuclear medicine allow IRSN to estimate the level of regulatory application by health professionals and the representativeness of current DRL in terms of relevant examinations, dosimetric quantities, numerical values and patient morphologies. Since 2004, the involvement of professionals has highly increased, especially in nuclear medicine, followed by CT and then by radiology. Analyses show some discordance between regulatory examinations and clinical practice. Some of the dosimetric quantities used for the DRL setting are insufficient or not relevant enough, and some numerical values should also be reviewed. On the basis of these findings, IRSN formulates recommendations to update regulatory DRL with current and relevant examination lists, dosimetric quantities and numerical values.

Functional and molecular immune response of Mediterranean mussel (Mytilus galloprovincialis) haemocytes against pathogen-associated molecular patterns and bacteria.

The effect of live bacteria (Micrococcus lysodeikticus and Vibrio anguillarum), and PAMPs (poly I:C, zymosan, LPS, LTA and CpG) on the production of intermediate toxic radicals (respiratory burst activity and production of nitric oxide) and mytilin B, myticin C and lysozyme gene expression was studied in vivo and in vitro. In vitro, bacteria were able to modulate the haemocytes' respiratory burst activity, being significantly increased after 6 h of incubation. The effect of pathogen-associated molecular patterns (PAMPs) was also studied. Zymosan produced an increase of the PMA-mediated response but an inhibition of the zymosan-mediated response. A significant increase of nitric oxide production was found at all the sampled time points (1, 3 and 6 h) in comparison with controls on both, the Gram-positive and Gram-negative bacteria. The in vivo responses measured on haemocytes after M. lysodeikticus injection were faster than those induced by V. anguillarum. However, V. anguillarum induced stronger in vitro effects. Mytilin B, myticin C and lysozyme in vitro gene expression, occurred at short times after infection. The maximum in vitro expression was detected 3 h post-infection. The differences between M. lysodeikticus and V. anguillarum in different measured parameters may suggest that different signalling pathways might be involved. Moreover, among all assayed PAMPs, LPS elicited the highest response.

Partial susceptibility of the SSN-1 fish cell line to a crustacean virus: a defective replication study.

This study evaluated the possible use of the fish SSN-1 cell line to investigate the development of Macrobrachium rosenbergii nodavirus (MrNV). Cells were incubated with viral particles and cytopathic effects were observed. De novo synthesis of viral capsid proteins was shown by immuno-fluorescence labelling and a sandwich ELISA test. Viral genomic replication was demonstrated by RT-PCR using primers specific to RNA-1 as well as by quantitative RT-PCR (RT-qPCR). Using electron microscopy, only a few empty particles were observed and attempts to isolate complete infectious particles or to re-infect healthy cells (second passage) were unsuccessful. As complete viral particles were rarely observed, it appeared that defaults in MrNV virogenesis might arise resulting in the formation of scarce and non-infectious particles. SSN-1 cells were found to be partially permissive to MrNV infection that induced cell lysis, but key elements for viral infection were lacking such as regulatory factors for gene replication or post-translational modifications.

Application of voxel phantoms in whole-body counting for the validation of calibration phantoms and the assessment of uncertainties.

This article is dedicated to the application of voxel phantoms in whole-body counting calibration. The first study was performed to validate this approach using IGOR, a physical phantom dedicated to fission and activation product (FAP) measurement, and a graphical user interface, developed at the IRSN internal dose assessment laboratory, called OEDIPE (French acronym for the tool for personalised internal dose assessment) associated with the Monte Carlo code MCNP. The method was validated by comparing the results of real measurements and simulations using voxel phantoms obtained from CT scan images of IGOR. To take this application further, two studies were carried out and are presented in this article. First, a comparison was made between the IGOR voxel based phantom (IGOVOX) and a voxel human body (Zubal Phantom) to confirm whether IGOR could be considered as a realistic representation of a human. Second, the errors made when considering sources homogeneously distributed in the body were assessed against real contamination by taking into account the biokinetic behaviour of the radioactive material for two modes of exposure: the ingestion of 137Cs in soluble form and the inhalation of insoluble 60Co several days after acute incorporation.

Estrone and estradiol C-16 derivatives as inhibitors of type 1 17beta-hydroxysteroid dehydrogenase.

Three series of steroid derivatives, enones 1, enols 2 and saturated alcohols 3, were easily synthesized from estrone according to a sequence of three reactions: an aldol condensation with an aromatic aldehyde (R(a-g)CHO) to afford 1, the carbonyl reduction of 1 to obtain the enol 2, and the double bond reduction of 2 to give 3 with the R(a-g) group 16beta-oriented. All compounds were tested as inhibitors of type 1 17beta-HSD. The inhibitory potency increases in the following order 1<2<3, suggesting that the presence of a flexible 16beta-methylene group allows a better positioning of the aryl moiety. With an IC50 of 0.8 microM, the 16beta-benzyl-E2 (3a) is the best inhibitor in this series.

Estradiol-adenosine hybrid compounds designed to inhibit type 1 17beta-hydroxysteroid dehydrogenase.

The steroidogenic enzyme type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is involved in the synthesis of estradiol (E(2)), a hormone well-known to stimulate the growth of estrogen-sensitive tumors. To obtain compounds able to control E(2) formation, two moieties were linked with a methylene side chain: an adenosine moiety for interacting with the cofactor-binding site and an E(2) moiety for interacting with the substrate-binding site. When tested as inhibitors of type 1 17beta-HSD, the hybrid compounds inhibited the reductive activity (E(1) into E(2)) with IC(50) values ranging from 52 to 1,000 nM. The optimal side-chain length was determined to be eight methylene groups for a 16 beta-orientation. The presence of two components (E(2) and adenosine) is essential for good inhibition, since 16 beta-nonyl-E(2) and 5-nonanoyl-O-adenosine, two compounds having only one of the components, did not inhibit the enzyme. Moreover, the 3D-structure analysis of EM-1,745 complexed with type 1 17beta-HSD showed key interactions with both substrate- and cofactor-binding sites.

Inhibitors of type 1 17beta-hydroxysteroid dehydrogenase with reduced estrogenic activity: modifications of the positions 3 and 6 of estradiol.

Breast cancer is the second most frequent cancer affecting women. Among all endocrine therapies for the treatment of breast cancer, inhibition of estrogen biosynthesis is becoming an interesting complementary approach to the use of antiestrogens. The enzyme type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD) plays a critical role in the biosynthesis of estradiol catalyzing preferentially the reduction of estrone into estradiol, the most active estrogen. Consequently, this enzyme is an interesting biological target for designing drugs for the treatment of estrogen-sensitive diseases such as breast cancer. Our group has reported the synthesis and the biological evaluation of N-methyl, N-butyl 6beta-(thiaheptamamide)estradiol as a potent reversible inhibitor of type 1 17beta-HSD. Unfortunately, this inhibitor has shown an estrogen effect, thus reducing its possible therapeutic interest. Herein three strategies to modify the biological profile (estrogenicity and inhibitory potency) of the initial lead compound were reported. In a first approach, the thioether bond was replaced with a more stable ether bond. Secondly, the hydroxyl group at position 3, which is responsible for a tight binding with the estrogen receptor, was removed. Finally, the amide group of the side-chain was changed to a methyl group. Moreover, the relationship between the inhibitory potency and the configuration of the side-chain at position 6 was investigated. The present study confirmed that the 6beta-configuration of the side chain led to a much better inhibition than the 6alpha-configuration. The replacement of the 3-OH by a hydrogen atom as well as that of the amide group by a methyl was clearly unfavorable for the inhibition of type 1 17beta-HSD. Changing the thioether for an ether bond decreased by 10-fold the estrogenic profile of the lead compound while the inhibitory potency on type 1 17beta-HSD was only decreased by 5-fold. This study contributes to the knowledge required for the development of compounds with the desired profile, that is, a potent inhibitor of type 1 17beta-HSD without estrogen-like effects.

New method of voxel phantom creation: application for whole-body counting calibration and perspectives in individual internal dose assessment.

The purpose of this work is to present an innovative approach for the creation and application of voxel phantoms associated with the Monte Carlo calculation (MCNP) for the calibration of whole-body counting systems dedicated to the measurement of fission and activation products. The new method is based on a graphical user interface called 'OEDIPE' that allows to simulate a whole measurement process using all measurement parameters, the final goal being to approach a numerical calibration of the facilities. The creation of voxel phantoms and validation of the method are presented in this paper using the IGOR phantom. Finally, the efficiency of the method is discussed, in particular, with the perspective of validating IGOR as a suitable human-equivalent phantom and for the assessment of uncertainties in dose estimation due to the inhomogeneous distribution of activity in the body, correlated to the bio-kinetic behaviour of the radionuclides.

3Beta-sulfamate derivatives of C19 and C21 steroids bearing a t-butylbenzyl or a benzyl group: synthesis and evaluation as non-estrogenic and non-androgenic steroid sulfatase inhibitors.

A series of C19 and C21 steroids bearing one or two inhibiting groups (3beta-sulfamate and 17alpha- or 20(S)-t-butylbenzyl or benzyl) were synthesized and tested for inhibition of steroid sulfatase activity. When only a sulfamate group was added to dehydroepiandrosterone, androst-5-ene-3beta,17beta-diol, pregnenolone and 20-hydroxy-pregnenolone, no significant inhibition of steroid sulfatase occurred at concentrations of 0.3 and 3 microM. With only a t-butylbenzyl or a benzyl group, a stronger steroid sulfatase inhibition was obtained in the androst-5-ene than in the pregn-5-ene series. Comparative results from the screening tests and the IC50 values have shown that the effect of a sulfamate moiety as a second inhibiting group can be combined to the t-butylbenzyl or benzyl effect in the C19 and C21 steroid series. The 3beta-sulfamoyloxy-17alpha-t-butylbenzyl-5-androsten-17beta-ol (10) was thus found to be the most active compound with IC50 values of 46 +/- 8 and 14 +/- 1 nM, respectively for the transformations of E1S to E1 and DHEAS to DHEA. The IC50 values of compound 10 are similar to that of 17alpha-t-butylbenzyl-estradiol, which was previously reported by our group as a good steroid sulfatase reversible inhibitor, but remains higher than that of the potent inactivators estrone-3-O-sulfamate (EMATE) and 17alpha-t-butylbenzyl-EMATE. However, contrary to these two latter inhibitors, compound 10 did not induce any proliferative effect on estrogen-sensitive ZR-75-1 cells nor on androgen-sensitive Shionogi cells at concentrations tested, suggesting that this steroid sulfatase inhibitor is non estrogenic and non androgenic.

Protease inhibitors and haemagglutinins associated with resistance to the protozoan parasite, Perkinsus marinus, in the Pacific oyster, Crassostrea gigas.

Perkinsus marinus is a protozoan responsible for dramatic mortality in the Eastern oyster, Crassostrea virginica, but not in the Pacific oyster, C. gigas. To understand the host-parasite relationship, we inoculated P. marinus trophozoites into the shell cavity of C. gigas and measured, over 2 months, (i) intensity of infection, (ii) protease inhibitory activities against P. marinus proteases and against bovine z-chymotrypsin, (iii) plasma haemagglutinin titre, (iv) plasma protein concentration, (v) plasma lysozyme activity and (vi) total haemocyte count. We observed that the highest protease inhibitory activities and haemagglutinin titres (3-10 days post-challenge) preceded parasite elimination (initiated 7 days post-challenge). In contrast, plasma protein concentration, lysozyme activity and total haemocyte count showed no significant modification following the challenge. It is hypothesized that the capacity of C. gigas to increase its protease inhibitors represents the key event in resistance to parasite infection by neutralizing the proteases secreted by P. marinus, thus preserving the oyster haemagglutinins from degradation. Such haemagglutinins will be ready to act as opsonins stimulating phagocytosis of parasites.