Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer.

Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Th1/Th2 balance in the liver and hepatic lymph nodes of vaccinated and unvaccinated sheep during acute stages of infection with Fasciola hepatica.

The expression of IFNγ and IL4 was quantified using q-PCR in the liver and hepatic lymph nodes (HLN) of sheep during early stages of infection with Fasciola hepatica (1, 3, 9 and 18days post-infection, dpi). A group of animals (Group 1) were vaccinated with Fasciola hepatica recombinant cathepsin L1 (FhCL1) in montanide 70 VG prior to infection, a second group (group 2) was used as infected control and a third (group 3) was used as uninfected control. To study vaccine efficacy three additional groups were sacrificed 19 weeks post-infection (group 4 immunized with CL1, group 5 with the adjuvant and group 6 was used as infected control). The vaccinated group did not show significant fluke reduction compared to the adjuvant group and infected control group. IL4 expression was observed to increase at 9 dpi and was further elevated at 18 dpi in the liver and HLN of vaccinated and infected control groups compared to the uninfected group. IFNγ expression exhibited different dynamics in the liver and HLN compared to IL4; thus, in the liver this cytokine increased at 9 dpi in the vaccinated and at 18 dpi in vaccinated and infected control groups, while in the HLN it decreased gradually and significantly from 1 dpi onwards. These results suggest that a marked Th2 polarization is present from 9 dpi in HLN and from 18 dpi in the liver. The increase of IFNγ in the liver may correspond with tissue damage response with granuloma formation. The FhCL1 vaccine did not alter the Th1/Th2 balance when compared to unvaccinated and infected sheep. The study of IFNγ and IL4 in the various tissue compartments in sheep could facilitate selection of new adjuvants inducing a strong Th1 response for a more rationale vaccine formulation.

Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep.

The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection.

Role of thymic epithelial cells in lymphoid depletion after experimental infection with the noncytopathogenic BVDV1 strain 7443.

Thymic epithelial cells could play an important role in lymphoid depletion during bovine viral diarrhea virus (BVDV) infection. To evaluate this hypothesis, we examined proliferation of lymphocytes, expression of cytokeratins by thymic epithelial cells, and ultrastructural features at sequential time points after experimental infection of colostrum-deprived calves with the noncytopathogenic BVDV1 strain 7443. Ten clinically healthy Friesian calves were used. Eight were inoculated with the virus, and 2 were used as uninfected controls. Calves were sedated and euthanized in batches between 3 and 14 days postinoculation. At necropsy, thymus samples were collected for structural, immunohistochemical, and ultrastructural study. Thymic lymphoid depletion was accompanied by a decrease in lymphocyte proliferation and immunohistochemical and ultrastructural changes in thymic epithelial cells. Immunohistochemical and ultrastructural results reflect a disturbance of the thymic epithelial cell network, which may explain the decrease in lymphocyte proliferation by defective thymocyte-epithelial cell interactions.

Pathology of African swine fever: the role of monocyte-macrophage.

African swine fever (ASF) is a viral hemorrhagic disease with different clinical and lesional changes depending of virulence of strains/isolates and immunological status of pigs. In acute and subacute forms of ASF, severe vascular changes are present, with hemorrhages in different organs (mainly melena, epistaxis, erythema, renal petechiaes and diffuse hemorrhages in lymph nodes), pulmonary edema, disseminate intravascular coagulation and thrombocytopenia. Lymphopenia and monocytopenia are developed during acute and subacute ASF. Lymphopenia is associated with lymphoid depletion in primary and secondary lymphoid organs, which is caused by apoptosis. All these lesions are not related to viral replication in endothelial cells or lymphocytes. Monocytes-macrophages show viral replication and cytophatic effect, including hemadsorption. The more significant changes in these cells are increased number and secretory activation (increased levels of proinflammatory cytokines) in targets organs. Proinflammatory activation is the initial cause of clinical and lesional pictures in ASF, including fever and changes in levels of acute phase proteins. Levels of IFN-ß and -γ are increased from initial phase of acute ASF. Anti-inflammatory response, represented by increased level of IL-10, is observed also, although in the final phase of acute ASF only.

Virus distribution and role of thymic macrophages during experimental infection with noncytopathogenic bovine viral diarrhea virus type 1.

Thymic depletion, presence of viral antigen, and changes in distribution and cytokine production of thymic macrophages were investigated in calves experimentally infected with a noncytopathogenic bovine viral diarrhea virus type (BVDV) 1 strain. Ten clinically healthy colostrum-deprived calves were used. Eight calves were inoculated with the virus and two were used as uninfected controls. Calves were sedated and euthanized in batches between 3 and 14 days postinoculation. At necropsy, thymus samples were collected for structural, immunohistochemical, and ultrastructural study and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling). From 6 days postinoculation, the thymic cortex was multifocally depleted with increased frequency of pyknosis and karyorrhexis, suggestive of apoptosis and confirmed by the TUNEL technique. Although the onset of lymphoid depletion was coincident with the detection of viral antigen by immunohistochemistry, the number of infected lymphocytes was very low through the experiment. There was an increase in number of macrophages in cortex and medulla, accompanied by ultrastructural changes indicative of phagocyte activation, and a decrease in cells expressing tumor necrosis factor-alpha (TNF-α) and IL-1α. These results suggest that the increase in number of these cells could be related to phagocytosis of cell debris and apoptotic lymphocytes. Furthermore, the results imply that, in contrast to the situation with classical swine fever virus, the lymphocyte apoptosis resulting from bovine viral diarrhea virus infection is not mediated by TNF-α or interleukin-1 alpha (IL-1α) production by virus-infected macrophages. This is the first study that describes this decrease in the number of thymic cells expressing TNF-α and IL-1α in cattle experimentally infected with bovine viral diarrhea virus type 1.

Concurrent pulmonary adenocarcinoma and silicate pneumoconiosis in a red-legged partridge (Alectoris rufa).

An adult red-legged partridge (Alectoris rufa) presented with concurrent pulmonary carcinoma and severe silicosis. The animal was submitted to the Veterinary Teaching Hospital of the University of Córdoba (Spain) because of respiratory signs, and it died during clinical examination. At postmortem examination, numerous firm, whitish to yellowish nodules involving the lungs, mainly the right lobe, were found. The histopathologic study revealed numerous peribronchiolar large granulomatous lesions composed of macrophages, which showed abundant cytoplasm containing numerous birefringent crystals identified as silicates by transmission electron microscopy. An epithelial neoplasm showing papillary, acinar, and solid patterns occupied large areas of the pulmonary parenchyma. The histopathologic and immunohistochemical features were consistent with a pulmonary carcinoma. Small tumor nests were often located close to the granulomatous lesions. This is the first report of concurrent pneumoconiosis and pulmonary carcinoma in a nonhuman species.

[Analysis of the effectiveness of an antiemetic protocol used in an oncology division]. / Análisis de la efectividad de un protocolo de antiemesis implantado en la Unidad de Oncología.

OBJECTIVE: To analyse the effectiveness of an antiemetic protocol in patients receiving chemotherapy treatment. METHOD: Prospective study in patients with solid tumours receiving chemotherapy in an oncology day hospital between January 2006 and 2007. We conducted a literature review and an evaluation of the recommendations of different clinical practice guidelines. The emetogenic potential was calculated according to the Hesketh level (HL), and the antiemetic premedication was determined for each regimen. We evaluated the effectiveness of an antiemetic protocol by using a survey as a method for measuring emetic episodes and nausea in the acute and delayed phases. RESULTS: 172 patients completed the survey. 13.4% vomited in the acute phase and 16.9% in the delayed phase; the median number of times was 2 (1-8) and 1 (1-5) for each respective phase. With treatment regimens classed as HL 4-5, 18.5% experienced vomiting in the acute phase and 20.2% in the delayed phase, with 46% experiencing nausea in the acute phase and 38.4% in the delayed phase. Control of vomiting in patients with treatment regimens classed as HL 1-3 was 100% in acute phase and 91.7% in the delayed phase; nausea was reported by 27% in the acute phase and 31% in the delayed phase. The factors that contributed the most to the presence of vomiting and nausea were the emetogenic potential of the treatment regimen (p<0.05), vomiting in the previous cycle (p<0.05) and age younger than 50 years (p<0.002). DISCUSSION: The proposed antiemetic protocol is effective for controlling vomiting in chemotherapy regimens with an HL of 1-3. For highly emetogenic regimens, the antiemetic protocol is also effective, but protection is not complete. This protocol seems less effective for controlling nausea, although this is a subjective symptom which is difficult to assess and not routinely measured in clinical trials.

[Treatment with cetuximab in metastatic colorectal cancer patients who do not express the epidermal growth factor receptor]. / Tratamiento con cetuximab en pacientes con cáncer colorrectal metastásico que no expresan el receptor del factor de crecimiento epidérmico.

OBJECTIVE: To evaluate the response to cetuximab, in terms of time passed until disease progression and overall survival, in patients with colorectal cancer (CRC) in which the epidermal growth factor receptor (EGFR) is undetectable. METHOD: Nine EGFR-negative patients (confirmed by an immunohistochemistry study), who were being treated with cetuximab, were selected. Variables collected: demographic data, diagnosis, previous treatments, time since first metastasis to start of treatment with cetuximab, adverse events and tumour markers. The response was monitored using tumour markers and disease progression. Well-being was assessed using the Karnofsky performance status (KPS) or that of the Eastern Cooperative Oncology Group (ECOG). RESULTS: 22% men (2/9) with a median age of 48 (31-63). The median time from being diagnosed with the metastatic disease to the start of treatment with cetuximab was 19 months (12-48). All patients had failed an irinotecan-based regime, 77.77% (7/9) had also failed one which included oxaliplatin. The median number of cycles with cetuximab was 14 (6-32). The main adverse event was the appearance of an acneiform rash in 100% of the cases. The median time until disease progression was 7 months (3-16) and 10.2 months (4-24) for overall survival. The results for well-being showed a KPS of between 80-100% and an ECOG of < 2. The results obtained in the present study for overall survival and time until disease progression are higher than those in the pivotal study (10.2 compared to 8.6 months and 7 compared to 4.1 months respectively). CONCLUSIONS: According to the results obtained, the use of assessing the EGFR expression (by the immunohistochemistry technique at least), as a means of predicting response to treatment with cetuximab may be questioned. This suggests that selecting patients using the routine assessment of this receptor is inappropriate, since it excludes patients who may potentially benefit from the treatment. However, more clinical trials are required in this area in order to confirm these conclusions.

Atoxoplasma spp. infection in captive canaries (Serinus canaria).

Clinical signs, histopathological and ultrastructural findings associated with Atoxoplasma spp. natural infection in captive canaries (Serinus canaria) are described. Intracytoplasmic Atoxoplasma-like protozoa were found in the liver and lung. In the liver, protozoa were found in hepatocytes and Kupffer's cells and were associated with granulomatous hepatitis and a marked bile duct hyperplasia. An usual finding was the presence of infected mononuclear cells adhered to the endothelium of the blood vessels in lung. The diagnosis was confirmed by ultrastructural examination of reprocessed paraffin-embedded tissues.

An immunohistochemical study of the tonsils in pigs with acute African swine fever virus infection.

An immunohistochemical study of the tonsils was carried out to gain further insight in the pathogenesis of acute African swine fever (ASF). Twenty-one pigs were inoculated by intramuscular route with a highly virulent isolate of ASF virus and painlessly killed at 1-7dpi. Viral antigen was highly distributed in the tonsil from 3 to 4dpi and an increase in the number of monocyte-macrophages was very evident at the same days post inoculation. This phenomenon was observed together with an increase of the expression of proinflammatory cytokines (Tumour necrosis factor alpha and Interleukin-1 alpha) and the apoptosis of lymphocytes studied by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) technique and haemorrhages. With these results, we can conclude that the tonsil is suffering similar lesions than those observed in other lymphoid organs in acute African swine fever, even when the route of inoculation is the intramuscular and not oral-nasal.

African swine fever and classical swine fever: a review of the pathogenesis.

This paper describes major pathogenetic mechanisms of African and Classical Swine Fever virus infections. The interactions between both viruses and the monocyte-macrophage-system result in the release of mediator molecules, which are important for the further progression of the diseases. The causes of the thrombocytopenia and the mechanisms of the haemorrhages, which are characteristic in both infections, are described. Apoptotic cell death is regarded as the predominant cause of lymphopenia in both virus infections.

Pathology of AA amyloidosis in domestic sheep and goats.

We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.

Classical Swine Fever: pathology of bone marrow.

Twenty pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (CSF) virus to determine the chronological development of lesions in bone marrow. Histopathologic, ultrastructural and immunohistochemical (detection of viral antigen gp55, myeloid-histiocyte antigen, CD3 antigen, and FVIII-rag), and morphometric techniques were employed. Viral antigen was detected from 2 days postinfection (dpi) in stromal and haematopoitic cells, and severe atrophy related to apoptosis of haematopoitic cells was observed. Megakaryocytes (MKs) did not show significant changes in number, but there were important qualitative changes including 1) increased numbers of cloud-nuclei MKs, microMKs, apoptotic MKs, and atypical nucleated MKs and 2) decreased number of typical nucleated MKs. Morphometric study of these cells showed a decrease in cytoplasmic area. MK infection was detected from 2 dpi, but in a small percentage of cells. Myeloid cells showed quantitative changes, with an increase in granulocyte numbers. Apoptosis of lymphocytes and viral infection of erythroblasts were also observed. The main changes in stroma were depletion of T lymphocytes in the middle phase of the experiment and macrophages. Viral infection was also observed in these cells. MK lesions suggest dysmegakaryocytopoiesis, which would aggravate the thrombocytopenia already present and could be responsible for it. Granulocyte changes would lead to the appearance of circulating immature forms, whereas lymphocyte apoptosis in bone marrow would contribute to lymphopenia.

Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever.

Atrophy of the thymic cortex and loss of thymocytes were studied in 32 pigs inoculated with the virulent strain "Alfort" of classical swine fever (CSF) virus and killed at intervals from 2 to 15 days after infection. Immunohistochemical, ultrastructural, ELISA and TUNEL methods were used. The results suggested that direct action of CSF virus on thymocytes played no more than a minor role. The massive lymphoid depletion observed in the thymus, may, however, have been associated with the numerical increase in monocytes-macrophages in this organ, and their secretory activation, leading to synthesis and release of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha and C1q complement component as main chemical mediators, and IL-1beta and IL-6 as minor mediators. These cytokines (TNF-alpha and IL-1alpha) may have played a role in the apoptosis of thymocytes, demonstrated by TUNEL and ultrastructural methods. The pathogenetic mechanism outlined may contribute to the lymphoid depletion observed in others organs in CSF and may explain the lymphopenia characteristic of the disease.

Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines.

To gain further insight into the pathogenesis of African swine fever (ASF), the cytokine expression by macrophages in spleen and lymph nodes were examined. Twenty-one piglets were inoculated with the highly virulent isolate Spain-70 of ASF virus and killed in groups at 1-7 post-inoculation days (pid). An increase in the immunohistochemical detection of proinflammatory monokines in spleen and renal and gastrohepatic lymph nodes is reported, along with an increase in the serum levels of TNF-alpha and IL-1 beta. The expression of these cytokines is detected simultaneously in time and space with the viral protein 73 (vp 73) of the ASF virus detection. Our results demonstrate that mononuclear phagocyte system cell activation results in the release of several cytokines that could induce apoptosis of lymphocytes and haemodynamic changes.

Immunohistochemical characterization of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic tumors of Duroc and Iberian swine.

The immunophenotype of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic lesions (29 melanocytomas, two malignant melanomas, and 23 residual lesions) from 54 adult Iberian and Iberian x Duroc pigs were examined using a panel of nine antibodies. All neoplastic cells were vimentin+, cytokeratin-, and alpha-1-antitrypsin- and the majority were S100+, whereas all pigmented macrophages were vimentin+, cytokeratin-, and S100- and most expressed alpha-1-antitrypsin. Regressing tumors were characterized by zones with low density of neoplastic cells accompanied by heavy infiltration of CD3+ T lymphocytes, whereas zones with high density of neoplastic cells showed very low numbers of CD3+ T lymphocytes. The infiltrate of CD79a+ B cells and IgG, IgM, and IgA plasma cells was low. The majority of lymphocytes of the peri- and intratumoral infiltrate were major histocompatibility complex class II+, but neoplastic cells did not express class II antigen. The 17 residual lesions examined were composed of macrophages containing abundant melanin pigment and low to moderate numbers of CD3+ T lymphocytes. The results of the present study suggest that the local cellular immune response plays a crucial role in the host response that induces regression of cutaneous melanomas and melanocytomas of the Iberian and crossbred Iberian x Duroc pigs.

Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever.

Classical swine fever (CSF) was induced in 20 pigs by inoculation with a virulent strain of CSF virus to determine sequential changes (2, 4, 7, 10 and 14 days post-inoculation) in the number and morphology of splenic macrophages (red pulp and lymphoid marginal zone) and thus to assess the role of these cells in the pathogenesis of the disease. The first splenic cells to be infected with CSF virus were macrophages in the marginal zone followed by other macrophage populations. The initial phase of CSF was associated with an increase in splenic macrophage numbers in the marginal zone and a decrease in the red pulp. Subsequently, the numbers in the red pulp increased. The study suggested that infection, mobilization and apoptosis of splenic macrophages play an important role in the spread of CSF virus in vivo. Moreover, the secretory changes that occurred in macrophages in the initial phase of the infection suggested that macrophages release chemical mediators capable of modulating pathogenesis.

Classical swine fever: pathogenesis of glomerular damage and immunocharacterization of immunocomplex deposits.

Twenty-six pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (hog cholera) virus to determine the chronological development of lesions in the renal glomeruli and the pathogenesis of glomerular damage and immunocomplex deposition. The study included the use of histopathological, ultrastructural and immunohistochemical (detection of viral antigen gp55, myeloid-histiocyte antigen, IgM, IgG and C1q) techniques. The main changes in glomerular structure were observed from 7 days post-inoculation (dpi) onwards, at which time the glomeruli showed macrophage infiltrations in the mesangium, and viral infection in circulating cells, glomerular endothelial cells and podocytes. Moreover, significant subcellular changes were detected in podocytes, which appeared swollen, with fusion of foot processes. Immunocomplex deposits immunoreactive for IgM, IgG and C1q were detected in mesangial, subepithelial and subendothelial areas from 10 dpi, but viral antigen was not detected as a component of these deposits; fusion of foot processes had increased in severity, especially near immunocomplex deposits. All these changes had increased still further in the final phase of the experiment (14 dpi), with neutrophil infiltrations in the mesangium.