Biomedical subjects

F Simón

Publications and source records attributed to F Simón.

At least 19 recordsLinked to original sources

PubMed2006

Immunopathology of Dirofilaria immitis infection.

Heartworm disease caused by Dirofilaria immitis affects canine and feline hosts, with infections occasionally being reported in humans. Studies have shown that both dirofilarial antigens and those derived from its bacterial endosymbiont Wolbachia, interact with the host organism during canine, feline and human infections and participate in the development of the pathology and in the regulation of the host's immune response. Both innate and acquired immune responses are observed and the development of the acquired response may depend on the host and, or on its parasitological status. This review aims at illustrating current research on the role of both D. immitis and Wolbachia, in the immunology and immunopathology of dirofilariosis.

Animals↗

PubMed2006

iNOs expression is stimulated by the major surface protein (rWSP) from Wolbachia bacterial endosymbiont of Dirofilaria immitis following subcutaneous injection in mice.

The bacterial endosymbiont Wolbachia of several species of filarial nematodes plays an important role in the inflammatory pathology of filariasis. Nitric oxide (NO) production has also been implicated in the immune response during filarial infections. Here we present data indicating that a recombinant Wolbachia surface protein (rWSP) induces iNOs mRNA expression and NO production, as well as IFN-gamma and a Th1-type antibody response, in inoculated BALB/c mice. This effect is not observed when mice are inoculated with a recombinant heat shock protein from Wolbachia (GroEL).

Animals↗

PubMed2006

Dogs with patent Dirofilaria immitis infection have higher expression of circulating IL-4, IL-10 and iNOS mRNA than those with occult infection.

Dirofilaria immitis is the agent of canine heartworm disease, in which adult worms reside in the pulmonary arteries, producing first stage larvae (microfilariae) that are released into the bloodstream. The present work describes the cytokine and iNOS mRNA expression in the peripheral blood of naturally infected dogs classified as either microfilariemic or amicrofilariemic. Results show that microfilariemic dogs had higher expression of IL-4 and iNOS mRNA than amicrofilariemic dogs. Furthermore, IL-10 mRNA expression was strongly expressed in dogs with circulating microfilariae, compared to only negligible expression in amicrofilariemic dogs. Finally, mf+ status was associated with a predominance in IgG1 production against worm antigens. These results would suggest that circulating mf may stimulate, like in other filarial infections, an immune bias towards unresponsiveness in D. immitis-infected dogs, consenting long-term adult worm survival.

Animals↗

PubMed2006

Ribosomal DNA second internal transcribed spacer sequence studies of Culicid vectors from an endemic area of Dirofilaria immitis in Spain.

Studies were performed in an endemic area of Dirofilaria immitis in Spain to genetically characterize the potential mosquito vector species present by means of DNA sequencing and elucidate which of these species may be involved in the transmission. The rDNA ITS-2 sequences of two Culex pipiens haplotypes, H1 and H2, Aedes (Aedimorphus) vexans, Fredwardsius vittatus, Ochlerotatus (Ochlerotatus) caspius, Anopheles (Anopheles) atroparvus, and Anopheles (Anopheles) plumbeus were obtained. F. vittatus and An. plumbeus were detected for the first time. Results on abundance, presence, and activity suggest that the month of August is the period of higher transmission risk, with C. pipiens, Ae. vexans, and An. atroparvus present simultaneously. Population studies indicate that C. pipiens may be considered the most important potential vector, while Ae. vexans, An. atroparvus, and O. caspius being involved in transmission only sporadically. The absence of larval dirofilarial infection agrees with the very low prevalences known in endemic areas.

Animals↗

PubMed2006

High levels of serum thromboxane B2 are generated during human pulmonary dirofilariosis.

The canine parasite Dirofilaria immitis can infect humans. Patients with pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than healthy individuals living in areas where dirofilariosis is endemic and in areas where dirofilariosis is not endemic. The possible role of Wolbachia bacteria in the appearance of this eicosanoid is discussed.

Animals↗

PubMed2005

What is happening outside North America regarding human dirofilariasis?

The etiologic agents of human dirofilariasis in the Old World are Dirofilaria immitis, which cause pulmonary and subcutaneous nodules, and Dirofilaria repens, which cause ocular lesions. Although reports of new cases of dirofilariasis are sporadic in other parts of the world, a considerable amount of information is generated in Europe regarding human dirofilariasis. Most cases have been detected in the Mediterranean countries, Ukraine, and Russia; however, isolated or short series of cases have been reported in the Balkan Republics and central and northern European countries. Seroepidemiologic studies have provided evidence that humans living in endemic areas present rates of infection similar to those of the autochthonous canine populations. Antibodies against endosymbiont Wolbachia bacteria have been demonstrated recently in human Dirofilaria infections. During D. immitis infections, preadult worms and third- and fourth-stage larvae are often destroyed by the host reaction, releasing a considerable amount of Wolbachia, and a Th1-type response against Wolbachia and/or filarial antigens is mounted. On the contrary, infections with D. repens, in which worms frequently remain intact, no Th1-type response has been observed. As humans are resistant hosts, the Th1-response could have a role in the resistance against parasites. The causes for the rise in the incidence of human dirofilariasis as well as the possible application of Wolbachia antigens in the serodiagnosis of human infections are discussed.

Animals↗

PubMed2005

Is Wolbachia complicating the pathological effects of Dirofilaria immitis infections?

Human and animal parasitic filarial nematodes, which often are the cause of severe disease, harbor intracellular bacteria of the genus Wolbachia (Rickettsiaceae). It is thought that these bacteria play an important role in the pathogenesis and immune response to filarial infection. In order to determine the possible role of Wolbachia in heartworm disease, dogs naturally infected with Dirofilaria immitis were studied for specific antibody response to Wolbachia surface protein (WSP). Antibody subclasses were analyzed to determine immune response polarization. Dogs that died from heartworm disease were necropsied, and various organs were studied by immunohistochemistry to determine whether Wolbachia-derived molecules were present in tissue from infected dogs. Humoral response to the WSP was present in all infected dogs and appeared to be predominantly of the Th1-type. Several organs, including lung, liver, and kidney, contained positive-staining cells for WSP, confirming that the canine host does come into contact with Wolbachia-derived molecules.

Animals↗

PubMed2005

Immune response to and tissue localization of the Wolbachia surface protein (WSP) in dogs with natural heartworm (Dirofilaria immitis) infection.

Human and animal parasitic filarial nematodes, including the agent of canine and feline heartworm disease Dirofilaria immitis, harbour intracellular bacteria of the genus Wolbachia (Rickettsiaies). It is thought that these bacteria play an important role in the pathogenesis and immune response to filarial infection. Immunoglobulin G (total IgG, IgG1, IgG2) production against and immunohistochemical staining of tissues for the Wolbachia surface protein (WSP) from dogs with natural heartworm infection were evaluated. All infected dogs had significant total anti-WSP IgG levels compared to healthy controls. Interestingly, WSP was recognized by the IgG2 subclass in both microfilariemic dogs and in dogs with no circulating microfilariae (occult infection). However, microfilariemic dogs also produced gG1 antibodies. Positive staining for WSP was observed in lungs, liver and kidneys, in particular in glomerular capillaries of naturally infected dogs who had died from heartworm disease. Our results show for the first time that Wolbachia is recognized specifically by D. immitis--infected dogs and that the bacteria is released into host tissue. Furthermore, microfilariemic status appears to effect immune responses to this endosymbiont.

Animals↗

PubMed2005

A coprological and serological survey for the prevalence of Ascaridia spp. in laying hens.

Ascaridia galli is a common nematode found in the intestine of domesticated chickens. The objectives of the study were to conduct a coprological and serological survey on the prevalence of ascaridiosis in laying hens of commercial farms. The farms recently adopted a breeding programme, where the hens have access to outdoor pens. Different amounts of Ascaridia eggs were detected in five of seven studied farms, while the other two farms were found to be free from the parasite. Serological tests revealed a seroprevalence of 21.8% (range 7.6-95%). No positive serum samples were detected in the same farms with previous negative coprological analysis. Western blot analyses confirmed the results obtained by the enzyme-linked immunosorbent assay (ELISA) test. In four experimentally infected hens, a progressive increase of the IgG antibody levels was observed, surpassing the cut-off point established for ELISA test 6 weeks post-infection. Serological tests are able to detect the infection before the eggs of the parasite appear in the faeces of infected hens, providing a useful tool to detect infections with Ascaridia spp. in avian farms.

Animals↗

PubMed2005

Mortality in Spain during the heat waves of summer 2003.

The effect of the elevated temperatures on mortality experienced in Europe during the summer of 2003 was observed in several countries. This study, carried out in Spain, describes mortality between 1 June and 31 August and evaluates the effect of the heat wave on mortality. Observed deaths were obtained from official death registers from 50 provincial capitals. Observed deaths were compared with the expected number, estimated by applying a Poisson regression model to historical mortality series and adjusting for the upward trend and seasonality observed. Meteorological information was provided by the Instituto Nacional de Meteorologia (National Institute of Meteorology). Spain experienced three heat waves in 2003. The total associated excess deaths were 8% (43 212 observed deaths compared with 40 046 expected deaths). Excess deaths were only observed in those aged 75 years and over (15% more deaths than expected for the age group 75 to 84 and 29% for those aged 85 or over). This phenomenon (heat-associated excess mortality) is an emerging public health problem because of its increasing attributable risk, the aging of the Spanish population and its forecasted increasing frequency due to global warming. The implementation of alert and response systems based on monitoring of climate-related risks, emergency room activity and mortality, and strengthening the response capacity of the social and health services should be considered.

Aged↗

PubMed2004

Specific IgG antibody response against antigens of Dirofilaria immitis and its Wolbachia endosymbiont bacterium in cats with natural and experimental infections.

Sera from three groups of cats under different experimental conditions were studied by ELISA to assess the host's immune response against synthetic peptides derived from Dirofilaria immitis (Dipp) and against the surface protein of its endosymbiont, Wolbachia (WSPr). In experimentally infected cats (Group 1), an increase of IgG antibody against both Dipp and WSPr was observed from 2 months post-infection until the end of the study, 6 months post-infection. In experimentally infected cats, treated against infective larvae (Group 2), anti-Dipp IgG decreased dramatically from 4 months post-infection (3 months post treatment), showing very low values till the end of the study (6.5 months from infection, 5.5 months from treatment), while anti-WSP IgG increased constantly till the end of the study. Of 49 outdoor, asymptomatic cats exposed to a high risk of natural infection (Group 3), 9 were positive for anti-Dipp IgG and for a validated, in-clinic commercial antibody diagnostic kit for cats. Two cats were also found positive for circulating antigens of adult female worm. Anti-WSPr IgG were found in five of nine anti-Dipp IgG-positive sera and from eight ELISADipp-negative sera. Our results confirm the strong IgG response in heartworm infected cats and demonstrate the involvement of the Wolbachia endosymbiont in the immune reaction to the parasite both in experimentally infected cats and in cats exposed to a high risk of natural infection.

Animals↗

PubMed2003

Th1 response in BALB/c mice immunized with Dirofilaria immitis soluble antigens: a possible role for Wolbachia?

The immune response to filarial infection has been shown to be of both the Th1 and Th2 types. Studies aimed at developing immunization strategies against Dirofilaria immitis infection in dogs have shown that protection against larval challenge is of the Th2 type and that several proteins are recognized by immunized or infected animals. The bacterial endosymbiont Wolbachia, harbored by many filarial species including D. immitis, has recently been shown to interact with the host immune system. Specific antibodies to the Wolbachia recombinant surface protein (WSPr) have been observed in cats infected with D. immitis. In this work the authors have determined cytokine production and antibody response in BALB/c mice inoculated with soluble antigens from third stage larvae or from adult worms of D. immitis. Inoculated mice first produced IFN-gamma followed by a peak in IL-4. Specific antibodies to the Wolbachia protein WSPr were exclusively IgG2a, while antibodies against peptides derived from antigens of D. immitis were in the IgG1 and IgE subclasses. The cytokine response is thus similar to that reported for other filarial infection, where Th1 response shifts towards Th2. Antibody response indicates that Wolbachia may induce preferentially a Th1 response during filarial infection, while nematode antigens may be involved in Th2 response. There is thus an overall agreement with current opinions on the role of bacterial versus nematode molecules in driving the response towards the different directions.

Animals↗

PubMed2003

Immunoglobulin G antibodies against the endosymbionts of filarial nematodes (Wolbachia) in patients with pulmonary dirofilariasis.

The dog parasite Dirofilaria immitis can infect humans. Patients with pulmonary dirofilariasis were tested for immunoglobulin G (IgG) antibodies against the surface protein of Wolbachia, the bacterial endosymbiont of D. immitis. These patients showed significantly higher IgG titers than healthy individuals from areas in which D. immitis was endemic as well as areas in which it was not endemic. Titration of anti-Wolbachia surface protein IgG could become useful for diagnostic applications.

Animals↗

PubMed2002

Feline dirofilariosis: antibody response to antigenic fractions containing specific 20 to 30 kDa polypeptides from the adult Dirofilaria immitis somatic antigen.

Fractions from the adult somatic antigen (SA) Dirofilaria immitis complex, containing polypeptides from 20 to 30kDa, previously identified as molecular markers of feline dirofilariosis are isolated by sequential application of gel filtration and anion exchange chromatography. Indirect enzyme-linked immunosorbent assays, employing these fractions (20-26kDa/ELISAF1 and 30kDa/ELISAF7) show multivalent diagnostic capacities: they were able to detect pre-patent infections 2 months after infection, infections in clinical phase, and the fall of antibodies after the worms were removed from the heart, or the application of a ivermectin treatment. The results obtained by the two tests correlated well, in spite of the fact that ELISAF1 was most useful to detect antibodies in sera from cats in the clinical phase, while ELISAF7 has more sensitivity for the early detection of the infections. Both ELISAs were useful in the detection of the decrease of antibodies after the worms were removed by surgery or pharmacological treatment.

Animals↗

PubMed2000

Canine dirofilariosis in two cities of southeastern Spain.

Several cases of human subcutaneous/ocular dirofilariosis caused by Dirofilaria repens from an area in the southeastern Spain where previous epidemiological studies have shown a very low prevalence of this species in dogs, have been studied in our laboratory. Since the prevalence of this species in dogs did not correspond to the incidence of human cases in the zone studied, a preliminary epidemiological survey was carried out on 114 dog blood samples from two kennels and one veterinary clinic. Knott, polymerase chain reaction (PCR) with specific primers for Dirofilaria immitis and D. repens, and ELISA with adult E/S D. immitis and adult somatic D. repens antigens for the detection of specific IgG, were used. Fifty-three out of the 114 samples analyzed were positive for Knott and/or PCR to D. immitis or to D. repens. D. repens was the species with the highest prevalence, 84.6 and 37.1%, respectively, in each kennel. IgG antibodies against D. immitis and D. repens, were detected in 11 samples which gave negative results to both Knott and PCR. These results demonstrate a very high prevalence of D. repens that could be associated with the increasing incidence of human subcutaneous/ocular cases recently detected in this zone.

Adult↗

PubMed2000

Human antibody response to a 56-kDa purified excretory/secretory product of Dirofilaria immitis.

Canine dirofilariasis is widespread in urban areas of central and northern Colombia. Previously we detected specific antibodies against complex antigens from Dirofilaria immitis adult worms in individuals from an isolated Tikuna Indian community in the Colombian Amazon. In this study a 56 kDa polypeptide from the adult D. immitis excretory/secretory (E/S) products is identified by Western blot, isolated by elution from polyacrilamide gels and applied in an ELISA-based test for the detection of specific IgG. Eleven of 74 serum samples analysed were positive by ELISADi56. Positive individuals came from five different areas of Colombia. The highest number of positives was found in the Amazon (4), followed by Bogotà (3). The physicians of the area must be alerted regarding the existence of human D. immitis infections and include dirofilariasis in the differential diagnosis of pulmonary nodules.

Animals↗

PubMed1999

Utility of adult antigens of Dirofilaria immitis for the early detection of dirofilariosis and for the evaluation of chemoprophylactic treatment in experimentally infected cats.

Early detection of feline dirofilariosis was achieved by ELISA testing using adult somatic (SA) and excretory/secretory (E/S) antigens. Sera from experimentally infected cats showed significantly higher IgG levels at 2 months post-infection (p.i.) when compared to sera obtained prior to infection. This difference was apparent at all serum dilutions (1:100 to 1:800) in ELISA(SA) and at all dilutions except 1:800 when tested with ELISA(E/S). Changes in specific anti-SA and anti-E/S IgG levels were found in infected cats treated with the macrolid parasiticide. ELISA(E/S) was able to detect a significant decrease in IgG levels in ivermectin treated cats at 3 months post-treatment (p.t.), compared to infected, untreated controls. However, testing with ELISA(SA) showed a significant decrease in antibody levels in treated cats only at 4 months after treatment. Sera from untreated cats recognized previously identified specific markers for feline dirofilariosis on SA (22, 26, 30 and 40 kDa) and on E/S (22 and 25 kDa) in Western blot analysis. Sera from treated cats, on the other hand, gave only weak bands or none at all, indicating a decrease in antibody concentration. These results suggest that serologic testing with ELISA is useful in the early detection of Dirofilaria immitis infection and, together with Western blot analysis, can assist in the evaluation of response to chemoprophylactic treatment of feline dirofilariosis, two aspects of prime importance in the prevention of this disease in cats.

Animals↗

PubMed1999

Trimetazidine prevents cochlear lesions induced by intraperitoneal and perilymphatic administration of kainic acid.

The protective activity of trimetazidine (TMZ) against cochlear neurotoxicity induced by intraperitoneal and intracochlear administration of kainic acid (KA) has been analyzed. The amplitude of the CAP N1 wave was significantly higher in KA rats pretreated with TMZ, independently of the administration route, than in those only treated with KA. However, CAP N1 amplitude of both TMZ pretreated and non-pretreated animals was always lesser than the N1 wave amplitude observed in the control group. The CAP N1 latency did not show any significant difference between KA and TMZ+KA groups except at high intensities of 8 and 12 kHz. As a complementary control, we have demonstrated that the intraperitoneal administration of TMZ (5 mg/kg) alone did not affect either the electrophysiological activity or the morphology of the auditory nerve. Morphological results fit well with electrophysiology. Some isolated swollen afferent fibers were observed in TMZ+KA cochleae, the swollen dendrites being sparser than in the KA only treated animals. In TMZ+KA animals, the cochlear apical coils were less affected than the basal coils. Our results are in agreement with recent clinical studies and suggest that TMZ could be an active drug on cochlear impairment linked to hypoxic-ischaemic syndromes.

Animals↗