Comparing survival rates for clusters of depressive symptoms found by Network analysis' community detection algorithms: Results from a prospective population-based study among 9774 cancer survivors from the PROFILES-registry.

OBJECTIVES: Previous studies have shown that depression is associated with mortality in patients with cancer. Depression is however a heterogeneous construct and it may be more helpful to look at different (clusters) of depressive symptoms than to look at depression as a discrete condition. The aim of the present study is to investigate whether clusters of depressive symptoms can be identified using advanced statistics and to investigate how these symptom clusters are associated with all-cause mortality in a large group of patients with cancer. METHOD: Data from a large population-based cohort study (PROFILES) including various cancer types were used. Eligible patients completed self-report questionnaires (i.e. Fatigue assessment scale, Hospital anxiety and depression scale, EORTC QOL-C30) after diagnosis. Survival status was determined on 31 January 2022. RESULTS: In total, 9744 patients were included. Network analyses combining different community detection algorithms showed that clusters of depressive symptoms could be detected that correspond with motivational anhedonia, consummatory anhedonia and negative affect. Survival analyses using the variables that represented these clusters best showed that motivational and consummatory anhedonia were associated with survival. Even after controlling for clinical and sociodemographic variables items assessing motivational anhedonia were significantly associated with mortality over time. CONCLUSION: Separate clusters of symptoms that correspond with motivational and consummatory anhedonia and negative affect can be distinguished and anhedonia may be associated with mortality more than negative affect. Looking at particular (clusters of) depressive symptoms may be more informative and clinically relevant than using depression as a single construct (i.e. syndrome).

Modeling the migration of chemicals from food contact materials to food: The MERLIN-expo/VERMEER toolbox.

Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.

Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays.

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

Myocardial infarction patients referred to the primary care physician after 1­year treatment according to a guideline-based protocol have a good prognosis.

INTRODUCTION: Identifying ST-elevation myocardial infarction (STEMI) patients who can be referred back to the general practitioner (GP) can improve patient-tailored care. However, the long-term prognosis of patients who are returned to the care of their GP is unknown. Therefore, the aim of this study was to assess the long-term prognosis of patients referred back to the GP after treatment in accordance with a 1-year institutional guideline-based protocol. METHODS: All consecutive patients treated between February 2004 up to May 2013 who completed the 1­year institutional MISSION! Myocardial Infarction (MI) follow-up and who were referred to the GP were evaluated. After 1 year of protocolised monitoring, asymptomatic patients with a left ventricular ejection fraction >45% on echocardiography were referred to the GP. Long-term prognosis was assessed with Kaplan-Meier curves and Cox proportional hazards analysis was used to identify independent predictors for 5­year all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: In total, 922 STEMI patients were included in this study. Mean age was 61.6 ± 11.7 years and 74.4% were male. Median follow-up duration after the 1­year MISSION! MI follow-up was 4.55 years (interquartile range [IQR] 2.28-5.00). The event-free survival was 93.2%. After multivariable analysis, age, not using an angiotensin-converting enzyme (ACE) inhibitor/angiotensin-II (AT2) antagonist and impaired left ventricular function remained statistically significant predictors for 5­year all-cause mortality. Kaplan-Meier curves revealed that 80.3% remained event-free for MACE after 5 years. Multivariable predictors for MACE were current smoking and a mitral regurgitation grade ≥2. CONCLUSION: STEMI patients who are referred back to their GP have an excellent prognosis after being treated according to the 1­year institutional MISSION! MI protocol.

Identification and validation of two peptide markers for the recognition of Clostridioides difficile MLST-1 and MLST-11 by MALDI-MS.

OBJECTIVES: Clostridioides difficile infection (CDI) has become the main cause of nosocomial infective diarrhoea. To survey and control the spread of different C. difficile strains, there is a need for suitable rapid tests. The aim of this study was to identify peptide/protein markers for the rapid recognition of C. difficile strains by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). METHODS: We analysed 44 well-characterized strains, belonging to eight different multi-locus sequence types (MLST), using ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS. The amino acid sequence of two peptide markers specific for MLST-1 and MLST-11 strains was elucidated by MALDI-TOF-MS/MS. The investigation of 2689 C. difficile genomes allowed the determination of the sensitivity and specificity of these markers. C18-solid-phased extraction was used to enrich the MLST-1 marker. RESULTS: Two peptide markers (m/z 4927.81 and m/z 5001.84) were identified and characterized for MLST-1 and MLST-11 strains, respectively. The MLST-1 marker was found in 786 genomes of which three did not belong to MLST-1. The MLST-11 marker was found in 319 genomes, of which 14 did not belong to MLST-11. Importantly, all MLST-1 and MLST-11 genomes were positive for their respective marker. Furthermore, a peptide marker (m/z 5015.86) specific for MLST-15 was found in 59 genomes. We translated our findings into a fast and simple method that allowed the unambiguous identification of the MLST-1 marker on a MALDI-TOF-MS platform. CONCLUSIONS: MALDI-FTICR MS-based peptide profiling resulted in the identification of peptide markers for C. difficile MLST-1 and MLST-11.

Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities.

OBJECTIVE: To investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m(2)), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI. RESULTS: Symptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185-0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197). CONCLUSIONS: Baker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment.

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium.

BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

Case-controlled identification of colorectal cancer based on proteomic profiles and the potential for screening.

AIM: Colorectal cancer (CRC) screening programmes detect early cancers but unfortunately have limited sensitivity and specificity. Mass spectrometry-based determination of serum peptide and protein profiles provides a new approach for improved screening. METHOD: Serum samples were obtained from 126 CRC patients before treatment and 277 control individuals. An additional group of samples from 50 CRC patients and 82 controls was used for validation. Peptide and protein enrichments were carried out using reverse-phase C18 and weak-cation exchange magnetic beads in an automated solid-phase extraction and spotting procedure. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight system. Discriminant rules using logistic regression were calibrated for the peptide and protein signatures separately, followed by combining the classifications to obtain double cross-validated predicted class probabilities. Results were validated on an identical patient set. RESULTS: A discriminative power was found for patients with CRC representative for all histopathological stages compared with controls with an area under the curve of 0.95 in the test set (0.93 for the validation set) and with a high specificity (94-95%). CONCLUSION: The study has shown that a serum peptide and protein biomarker signature can be used to distinguish CRC patients from healthy controls with high discriminative power. This relatively simple and cheap test is promising for CRC screening.

Acrylonitrile exposure in the general population following a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On Saturday May 4, 2013, a train transporting chemicals derailed in the village of Wetteren (Belgium) and caused a leak of acrylonitrile (ACN). OBJECTIVES: To assess the human exposure to acrylonitrile in the local population with the highest suspected exposure. METHODS: Between May 18-25, 242 residents participated in the study. N-2-cyanoethylvaline (CEV), a biomarker that is highly specific for ACN exposure, was measured in the blood. To account for potential influence by smoking, cotinine was determined in the urine. Participants also filled in a short questionnaire. RESULTS: In the evacuated zone, 37.3% of the non-smokers and 40.0% of the smokers had CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively, at the time of the train accident. Spatial mapping of the CEV concentrations depending on the residential address showed a distribution pattern following the sewage system. DISCUSSION AND CONCLUSION: The train derailment resulted in a highly atypical sequence-of-events. In addition to exposure in the direct vicinity of the site of the train derailment, exposure also occurred via the sewage system, into which acrylonitrile had entered shortly after the accident.

Acrylonitrile exposure assessment in the emergency responders of a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN. OBJECTIVES: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident. METHODS: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire. RESULTS: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function. DISCUSSION AND CONCLUSION: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population.

Investigation into the genotoxicity of water extracts from Hypoxis species and a commercially available Hypoxis preparation.

We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata) and a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.

Kinematics of a highly congruent mobile-bearing total knee prosthesis.

PURPOSE: Limited or absent axial rotation of the mobile insert of total knee prostheses could lead to high contact stresses and stresses at the bone-implant interface, which in turn might lead to implant loosening. The aim of this study was to assess knee kinematics and muscle activation and their possible change over time in patients with a highly congruent, mobile-bearing total knee prosthesis. METHODS: A prospective series of 11 rheumatoid arthritis patients was included to participate in this fluoroscopic and EMG study; only 7 patients completed the study. Kinematic evaluations took place 7 months, 1 and 2 years post-operatively. Repeated measurements ANOVA and linear mixed-effects model for longitudinal data were used to compare the differences between the follow-ups. RESULTS: There are no significant changes in axial rotations between follow-up moments for the femoral component as well as the mobile insert. The insert remained mobile and followed the femoral component from 0° until approximately 60° of knee flexion. Diverging and reversed axial rotations and translations were seen during the dynamic motions. CONCLUSIONS: Knee kinematics and muscle activation do not appear to change in the first 2 post-operative years. Reversed and divergent axial rotations with increasing knee flexion indicate that as soon as the congruency decreases, the femoral component is no longer forced in a certain position by the insert and moves to a self-imposed position. At lower knee flexion angles, the femoral component might be obstructed by the highly congruent insert and therefore might not be able to move freely. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

Clinical differentiation between acute appendicitis and acute mesenteric lymphadenitis in children.

INTRODUCTION: Acute mesenteric lymphadenitis in children has a clinical presentation very similar to that of acute appendicitis. The aim of this study was to evaluate whether it is possible to clinically differentiate between acute appendicitis and acute mesenteric lymphadenitis in children. METHODS: A prospective cohort analysis was performed for all children (<17 years) presenting to the emergency department of our institution with acute abdominal pain between June 2005 and July 2006. The relevant clinical parameters, clinical and radiological diagnoses and all management decisions were scored prospectively. Ultrasound was the primary imaging modality for the majority of patients. All patients were re-evaluated until a final diagnosis was attained. The Alvarado score was calculated retrospectively, and a logistic regression model was used to analyze the diagnostic potential of clinical parameters. RESULTS: 289 patients were eligible for analysis. 38 patients had acute mesenteric lymphadenitis, and 69 patients had acute appendicitis as a final diagnosis. The positive predictive values of the clinical diagnosis, the Alvarado score and the logistic regression model were 0.62, 0.81 and 0.79 respectively. Ultrasound had a positive predictive value of 96% for acute appendicitis. CONCLUSION: It is not possible to accurately distinguish acute mesenteric lymphadenitis from acute appendicitis in children using clinical evaluation alone. Ultrasound should be performed in equivocal cases.

Rehabilitation Programs for Cystic Fibrosis - View from a CF Center.

BACKGROUND: Rehabilitation programs are comprehensive interventions which effectively improve the health status and reduce costs in chronic respiratory illnesses. Because patients with cystic fibrosis have been discouraged to participate for concerns of microbial cross infection, the efficacy of systematic rehabilitation is unknown for this group. METHODS: We retrospectively studied 142 cystic fibrosis patients aged 2-46 years who participated in rehabilitation programs taking place in Germany/Switzerland and in Israel, focusing on changes in lung function and weight. RESULTS: During 172 stays in 97 patients in Israel and 68 stays in 45 patients rehabilitating in Germany/Switzerland, overall lung function and weight improved. Outcome did not differ between Israel and German/Swiss sites. Interestingly, lung function improved during the initial phase of the stay, whereas weight gain was sustained throughout. The study uncovered gaps in reporting sufficient individual outcome information back to the admitting centre. CONCLUSIONS: Rehabilitation programs specified for cystic fibrosis patients need to be assessed prospectively to optimize treatment of this life limiting condition.

Surgical treatment of sigmoid diverticulitis--analysis of predictive risk factors for postoperative infections, surgical complications, and mortality.

BACKGROUND AND AIMS: Sigmoid diverticular disease has great clinical importance due to its increasing incidence in the Western world and a broad spectrum of clinical features with potential fatal complications after surgery. The definition of risk factors associated with postoperative infections, surgical complications and mortality could be helpful in clinical decision-making and optimizing perioperative treatment. MATERIALS AND METHODS: Based on a prospective database, 168 consecutive patients undergoing surgery for sigmoid diverticulitis were included in this study. The association of different potential risk factors such as age, Hinchey classification, type and duration of operation, surgeons' experience, blood loss, comorbidities, and hospital course with perioperative complications and mortality were tested by univariate and multivariate analysis. RESULTS: Of the 168 patients enrolled in this study, there were 84 male and 84 female. A third of patients were operated as emergency cases (within 24 h after surgical evaluation); 62% underwent open surgery, 35% were treated laparoscopically with a conversion rate of 3%. A blood transfusion received 14% of patients, a surgical infection occurred in 20%, surgical complications appeared in 24% with a necessity for re-exploration in 9.5%. Leakage of the primary anastomosis was seen in 3.3%, whereas a leakage of the Hartmann's stump occurred in 4.3%. Overall in-hospital mortality was 4.1%. Multivariate analysis demonstrated Hinchey classification and intraoperative blood transfusion to be independently associated with postoperative infections, complications and mortality. CONCLUSION: Hinchey classification and intraoperative blood transfusion are independently associated with a worse perioperative outcome in patients undergoing surgery for sigmoid diverticular disease. While Hinchey classification cannot be influenced per se by the surgeon, outcome might be influenced by reducing the need for intraoperative blood transfusion.

Surgery groups differed in adverse outcome probabilities and can be used to adjust hospital comparisons.

BACKGROUND AND OBJECTIVE: In the Netherlands, all procedures in general surgery are categorized into 12 surgery groups by the Association of Surgeons of the Netherlands. The purpose of this study was to assess whether surgery groups differ in adverse outcome probabilities, to decide whether hospital comparisons on adverse outcomes should be adjusted for differences in surgery groups. METHODS: All surgical patients in one hospital discharged in 1997-1999 were included. Only the first operation during admission was included, with the assumption that successive operations were treatment of adverse outcomes. To avoid bias, only operations with procedures from the same surgery group were included. A total of 6,025 admissions were included and analyzed by a two-step multilevel analysis. RESULTS: Four surgery groups had fewer admissions with adverse outcomes than expected, and two groups had more. After adjustment for patient and operation characteristics, the remaining variance between surgery groups is still large. Similar results were found when differences in mortality were analyzed. CONCLUSION: Surgery group can therefore be used to adjust hospital comparisons for differences in surgical procedure mix.

Flt-3 ligand, in combination with bovine granulocyte-macrophage colony-stimulating factor and interleukin-4, promotes the growth of bovine bone marrow derived dendritic cells.

Culture of bone marrow precursor cells with cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and the tyrosine kinase receptor binding proteins Flt-3 ligand (Flt-3L) and stem-cell factor (SCF), has previously been shown, in both mouse and human, to result in the generation of large numbers of dendritic cells. We extend these findings to bovine dendritic cells. Culture of bovine bone marrow cells with GM-CSF, IL-4 and either Flt-3L or SCF enhanced the generation of low buoyant-density dendritic cells. However, only the addition of Flt-3L to cells cultured with GM-CSF and IL-4 was shown to increase the number of dendritic cells and induce the differentiation of dendritic cells with potent capacity to stimulate allogeneic T cells and resting CD4+ memory T cells. The effective ability to stimulate T cells was associated with the expression of major histocompatibility complex (MHC) class II molecules and CD80/86 by dendritic cells. Bovine bone marrow derived dendritic cells appeared to be exclusively of myeloid origin because they expressed the myeloid-related antigens CD14, MyD-1 and CD11b.

Immune response of cattle infected with African trypanosomes.

Trypanosomosis is the most economically important disease constraint to livestock productivity in sub-Saharan Africa and has significant negative impact in other parts of the world. Livestock are an integral component of farming systems and thus contribute significantly to food and economic security in developing countries. Current methods of control for trypanosomosis are inadequate to prevent the enormous socioeconomic losses resulting from this disease. A vaccine has been viewed as the most desirable control option. However, the complexity of the parasite's antigenic repertoire made development of a vaccine based on the variable surface glycoprotein coat unlikely. As a result, research is now focused on identifying invariant trypanosome components as potential targets for interrupting infection or infection-mediated disease. Immunosuppression appears to be a nearly universal feature of infection with African trypanosomes and thus may represent an essential element of the host-parasite relationship, possibly by reducing the host's ability to mount a protective immune response. Antibody, T cell and macrophage/monocyte responses of infected cattle are depressed in both trypanosusceptible and trypanotolerant breeds of cattle. This review describes the specific T cell and monocyte/macrophage functions that are altered in trypanosome-infected cattle and compares these disorders with those that have been described in the murine model of trypanosomosis. The identification of parasite factors that induce immunosuppression and the mechanisms that mediate depressed immune responses might suggest novel disease intervention strategies.

Cytokine mRNA profiles in trypanotolerant and trypanosusceptible cattle infected with the protozoan parasite Trypanosoma congolense: protective role for interleukin-4?

African trypanosomes are important pathogens of both humans and livestock. We investigated the association of cytokine responses with disease susceptibility in Trypanosoma congolense-infected cattle. Changes in interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-12 p40, tumor necrosis factor-alpha (TFN-alpha), CD40L, and transforming growth factor-beta (TGF-beta) gene expression were compared in peripheral blood mononuclear cells of infected trypanotolerant N'Dama (Bos taurus) and trypanosusceptible Boran (Bos indicus) cattle. Results revealed that IL-2 transcription was decreased in both breeds of cattle at 21 days after infection. IL-12 p40 mRNA expression was increased in N'Dama cattle at 21 days after infection and at a later time in Boran cattle. The highest IL-4 mRNA expression was observed at 32 days after infection in N'Dama cattle. IL-6 mRNA expression increased in Boran cattle at 11 days after infection and was elevated at 21 and 32 days after infection in both breeds. Transcripts for IL-5 were barely detectable throughout the experimental period in both Boran and N'Dama cattle. Expression of TNF-alpha, IL-1beta, and TGF-beta mRNA did not change notably during the course of infection. In summary, differences in the expression of IL-4 and IL-6 mRNA were identified between the two breeds of cattle during infection with T. congolense, suggesting a possible protective role for IL-4 and a disease-promoting role for IL-6 in bovine trypanosomosis.

Trypanosoma congolense infection of trypanotolerant N'Dama (Bos taurus) cattle is associated with decreased secretion of nitric oxide by interferon-gamma-activated monocytes and increased transcription of interleukin-10.

The mechanisms whereby trypanotolerant N'Dama cattle control infection with Trypanosoma congolense are unknown. Previous studies have suggested that the monocytes of N'Dama cattle are more highly activated during infection than those of trypanosusceptible Boran cattle. However, we have recently reported that the monocytes of Boran cattle have a reduced capacity to secrete nitric oxide during trypanosome infection. We therefore evaluated the production of nitric oxide by monocytes of trypanotolerant N'Dama cattle infected with T. congolense in response to interferon-gamma, bacterial lipopolysaccharide or trypanosome antigens. Interferon-gamma-induced nitric oxide production was decreased between days 25 and 76 of infection, while lipopolysaccharide-induced secretion of nitric oxide was increased at days 13 and again at day 76 post-infection. Trypanosome antigens did not elicit nitric oxide production. Analysis of interleukin-10 mRNA transcription in peripheral blood leucocytes revealed an increase at time points that coincided with decreased interferon-gamma-induced nitric oxide synthesis. In contrast, interferon-gamma mRNA expression was not changed during infection while tumour necrosis factor-alpha was slightly reduced at day 32 post-infection. Recombinant interleukin-10 suppressed interferon-gamma-induced nitric oxide and tumour necrosis factor-alpha secretion, but not lipopolysaccharide-induced nitric oxide secretion in cultures of peripheral blood mononuclear cells and monocytes of uninfected cattle. These results suggest that the nitric oxide response of monocytes to IFN-gamma but not lipopolysaccharide, is suppressed during infection. The kinetics of the upregulation of interleukin-10 and its biological activity indicate a possible association with the depression of nitric oxide production and control of tumour necrosis factor-alpha.