Los prebióticos son definidos como ingredientes alimentarios no digeribles que producen efectos b... more Los prebióticos son definidos como ingredientes alimentarios no digeribles que producen efectos beneficiosos al huésped. En este trabajo se suplementó el alimento balanceado de pollos parrilleros con dos prebióticos diferentes: fructooligosacárido (FOS) y extracto seco de alcachofa (Cynara scolymus L) más cloruro de Colina (EA+Colina) a fin de evaluar sus efectos. Se trabajó con 198 pollos parrilleros recién nacidos de la línea cobb. Para los ensayos se separaron en 3 lotes, 2 experimentales y un control (L3). Un grupo experimental se suplementó con FOS (L1) y el otro con EA + Colina (L2). Se llevaron registros diarios de mortalidad. A los 7 y 14 días de crianza, 6 animales de cada grupo elegidos al azar fueron faenados. Los restantes animales se sacrificaron a los 45 días de edad. Se obtuvo el peso corporal (PC) individual antes de la faena. En las faenas de los 14 y 45 días, se extrajeron y pesaron la bolsa de Fabricio y el bazo. Durante la última faena, se seleccionaron al azar d...
<p>Mice were treated for ST (a,b,c) and LT (d,e,f) with vehicle solution (a&d), NFOH (b... more <p>Mice were treated for ST (a,b,c) and LT (d,e,f) with vehicle solution (a&d), NFOH (b&e) or BZL (c&f). (<b>A</b>) Liver deposition of lipids, an indicator of metabolic dysfunction, was determined by Oil Red O staining. Shown are the representative micrographs (magnification: 600×). (<b>B</b>) Tissue sections (3-sections/mouse, n>3/group) were scored for lipid deposition, as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003231#s2" target="_blank">Materials and Methods</a>.</p
<p>Mice were treated with vehicle solution (a&d), NFOH (b&e) or BZL (c&f) for a... more <p>Mice were treated with vehicle solution (a&d), NFOH (b&e) or BZL (c&f) for a short-term (a,b,c) and long-term (d,e,f). (<b>A</b>) Representative micrographs of liver tissue-sections stained with Masson's Trichome (magnification: 400×, scale bar: 100 µm) are shown. (<b>B</b>) Tissue sections (3-sections/mouse, n>3/group) were scored for fibrosis as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003231#s2" target="_blank">Materials and Methods</a>.</p
ABSTRACT Benznidazole and nifurtimox are the only drugs specifically approved for the treatment o... more ABSTRACT Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 4, 2018
To determine the course of serological tests in subjects with chronic T. cruzi infection treated ... more To determine the course of serological tests in subjects with chronic T. cruzi infection treated with antitrypanosomal drugs. We conducted a systematic review and meta-analysis using individual participant data. Survival analysis and Cox proportional hazards regression model with a random effect to adjust for covariates were applied. The protocol was registered at www.crd.york.ac.uk/PROSPERO (CRD42012002162). We included 27 studies (1296 subjects) conducted in eight countries. The risk of bias was low for all domains in 17 studies (63.0%). We assessed 913 subjects (149 seroreversion events, 83.7% censored data) for ELISA, 670 subjects (134 events, 80.0% censored) for IIF, and 548 subjects (99 events, 82.0% censored) for IHA. A higher probability of seroreversion was observed in subjects aged 1-19 years compared to adults at a shorter time span. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adju...
Serological tests are the main laboratory procedures used for diagnosis during the indeterminate ... more Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas' disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This w...
The American journal of tropical medicine and hygiene, 2004
We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population alo... more We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional inf...
Trypanosoma cruzi, the causative agent of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Trypanosoma cruzi, the causative agent of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease, is transmitted mainly by insect vectors, but congenital and transfusion-borne infections occasionally occur. The factors that are involved in transmission from mother to offspring are not well understood. The objective of this study was to study the presence of T cruzi infection in children who were born to infected mothers and in the children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s siblings to evaluate the epidemiologic risk factors associated with congenital transmission of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease. Congenital T cruzi infection was studied in 340 children who were born to chronically infected mothers in Salta, Argentina. Infection was detected in 31 children, who were selected for additional study as infected index cases (IIC). Of the 309 noninfected children, 31 were taken as noninfected index cases (NIIC). We compared the prevalence of congenital T cruzi transmission in the remaining siblings of the IIC and NIIC. Data and blood samples were collected in house-to-house visits. Diagnosis of infection was established mainly by serologic methods, indirect hemmagglutination, and enzyme-linked immunosorbent assay. The prevalence was 31.4% (32 of 102 children) for IIC siblings, whereas no infected siblings were found in families with NIIC (0 of 112). Clustering of congenital infection was found in 14 families, in which &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 child was infected. Second-generation congenital transmission (from grandmother to mother to newborn) was established in 4 families. The association among low weight at birth, prematurity, and congenital transmission was highly significant. An important observation was the absence of pathologic findings in a high proportion of infected children. The detection of asymptomatic infections was a consequence of population screening, as opposed to hospital-based diagnosis, for which symptomatic cases predominate. Congenital transmission was associated with the geographic origin of mothers: women from areas where insect vectors proliferate were less likely to give birth to infected offspring than women from areas under active vector control. Siblings of an infant infected with T cruzi are at high risk for infection themselves and, even in the absence of symptoms, should also be screened for infection. The findings of family clustering of infection and of second-generation congenital infection in vector-free areas suggest that new modalities of transmission, other than classic vector-borne spread, may occur both in endemic and in nonendemic areas.
Trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis ... more Trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis of different genetic markers. Identifying lineages circulating among humans in different areas is essential to understand the molecular epidemiology of Chagas disease. In the present study, 18 T. cruzi isolates from congenitally infected newborns in the northwestern province of Salta-Argentina were studied by multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD). All isolates were typed by MLEE and RAPD as belonging to T. cruzi IId. Analysis of minor variants of TcIId using probes hybridizing with hypervariable domains of kDNA minicircles, detected three variants with a similar distribution among the isolates. Our findings confirm the presence of T. cruzi IId among congenitally infected newborns in northwestern Argentina and support the assumption that human infection by T. cruzi in the Southern Cone countries of Latin America is due principally to T. cruzi II.
Serological tests are the main laboratory procedures used for diagnosis during the indeterminate ... more Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas’ disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This was observed at serum dilutions of 1/320 and occurred between the 6th and the 30th months posttreatment. The immune response and the interval for a serological regression to negativity were different for each patient. For some of the recombinant antigens, only 50% (9/18) of the patients reached the serological regression to negativity. Recombinant antigen 13 might be a good marker of treatment effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (Pç=0.002).
Los prebióticos son definidos como ingredientes alimentarios no digeribles que producen efectos b... more Los prebióticos son definidos como ingredientes alimentarios no digeribles que producen efectos beneficiosos al huésped. En este trabajo se suplementó el alimento balanceado de pollos parrilleros con dos prebióticos diferentes: fructooligosacárido (FOS) y extracto seco de alcachofa (Cynara scolymus L) más cloruro de Colina (EA+Colina) a fin de evaluar sus efectos. Se trabajó con 198 pollos parrilleros recién nacidos de la línea cobb. Para los ensayos se separaron en 3 lotes, 2 experimentales y un control (L3). Un grupo experimental se suplementó con FOS (L1) y el otro con EA + Colina (L2). Se llevaron registros diarios de mortalidad. A los 7 y 14 días de crianza, 6 animales de cada grupo elegidos al azar fueron faenados. Los restantes animales se sacrificaron a los 45 días de edad. Se obtuvo el peso corporal (PC) individual antes de la faena. En las faenas de los 14 y 45 días, se extrajeron y pesaron la bolsa de Fabricio y el bazo. Durante la última faena, se seleccionaron al azar d...
<p>Mice were treated for ST (a,b,c) and LT (d,e,f) with vehicle solution (a&d), NFOH (b... more <p>Mice were treated for ST (a,b,c) and LT (d,e,f) with vehicle solution (a&d), NFOH (b&e) or BZL (c&f). (<b>A</b>) Liver deposition of lipids, an indicator of metabolic dysfunction, was determined by Oil Red O staining. Shown are the representative micrographs (magnification: 600×). (<b>B</b>) Tissue sections (3-sections/mouse, n>3/group) were scored for lipid deposition, as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003231#s2" target="_blank">Materials and Methods</a>.</p
<p>Mice were treated with vehicle solution (a&d), NFOH (b&e) or BZL (c&f) for a... more <p>Mice were treated with vehicle solution (a&d), NFOH (b&e) or BZL (c&f) for a short-term (a,b,c) and long-term (d,e,f). (<b>A</b>) Representative micrographs of liver tissue-sections stained with Masson's Trichome (magnification: 400×, scale bar: 100 µm) are shown. (<b>B</b>) Tissue sections (3-sections/mouse, n>3/group) were scored for fibrosis as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003231#s2" target="_blank">Materials and Methods</a>.</p
ABSTRACT Benznidazole and nifurtimox are the only drugs specifically approved for the treatment o... more ABSTRACT Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 4, 2018
To determine the course of serological tests in subjects with chronic T. cruzi infection treated ... more To determine the course of serological tests in subjects with chronic T. cruzi infection treated with antitrypanosomal drugs. We conducted a systematic review and meta-analysis using individual participant data. Survival analysis and Cox proportional hazards regression model with a random effect to adjust for covariates were applied. The protocol was registered at www.crd.york.ac.uk/PROSPERO (CRD42012002162). We included 27 studies (1296 subjects) conducted in eight countries. The risk of bias was low for all domains in 17 studies (63.0%). We assessed 913 subjects (149 seroreversion events, 83.7% censored data) for ELISA, 670 subjects (134 events, 80.0% censored) for IIF, and 548 subjects (99 events, 82.0% censored) for IHA. A higher probability of seroreversion was observed in subjects aged 1-19 years compared to adults at a shorter time span. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adju...
Serological tests are the main laboratory procedures used for diagnosis during the indeterminate ... more Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas' disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This w...
The American journal of tropical medicine and hygiene, 2004
We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population alo... more We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional inf...
Trypanosoma cruzi, the causative agent of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Trypanosoma cruzi, the causative agent of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease, is transmitted mainly by insect vectors, but congenital and transfusion-borne infections occasionally occur. The factors that are involved in transmission from mother to offspring are not well understood. The objective of this study was to study the presence of T cruzi infection in children who were born to infected mothers and in the children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s siblings to evaluate the epidemiologic risk factors associated with congenital transmission of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease. Congenital T cruzi infection was studied in 340 children who were born to chronically infected mothers in Salta, Argentina. Infection was detected in 31 children, who were selected for additional study as infected index cases (IIC). Of the 309 noninfected children, 31 were taken as noninfected index cases (NIIC). We compared the prevalence of congenital T cruzi transmission in the remaining siblings of the IIC and NIIC. Data and blood samples were collected in house-to-house visits. Diagnosis of infection was established mainly by serologic methods, indirect hemmagglutination, and enzyme-linked immunosorbent assay. The prevalence was 31.4% (32 of 102 children) for IIC siblings, whereas no infected siblings were found in families with NIIC (0 of 112). Clustering of congenital infection was found in 14 families, in which &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 child was infected. Second-generation congenital transmission (from grandmother to mother to newborn) was established in 4 families. The association among low weight at birth, prematurity, and congenital transmission was highly significant. An important observation was the absence of pathologic findings in a high proportion of infected children. The detection of asymptomatic infections was a consequence of population screening, as opposed to hospital-based diagnosis, for which symptomatic cases predominate. Congenital transmission was associated with the geographic origin of mothers: women from areas where insect vectors proliferate were less likely to give birth to infected offspring than women from areas under active vector control. Siblings of an infant infected with T cruzi are at high risk for infection themselves and, even in the absence of symptoms, should also be screened for infection. The findings of family clustering of infection and of second-generation congenital infection in vector-free areas suggest that new modalities of transmission, other than classic vector-borne spread, may occur both in endemic and in nonendemic areas.
Trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis ... more Trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis of different genetic markers. Identifying lineages circulating among humans in different areas is essential to understand the molecular epidemiology of Chagas disease. In the present study, 18 T. cruzi isolates from congenitally infected newborns in the northwestern province of Salta-Argentina were studied by multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD). All isolates were typed by MLEE and RAPD as belonging to T. cruzi IId. Analysis of minor variants of TcIId using probes hybridizing with hypervariable domains of kDNA minicircles, detected three variants with a similar distribution among the isolates. Our findings confirm the presence of T. cruzi IId among congenitally infected newborns in northwestern Argentina and support the assumption that human infection by T. cruzi in the Southern Cone countries of Latin America is due principally to T. cruzi II.
Serological tests are the main laboratory procedures used for diagnosis during the indeterminate ... more Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas’ disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This was observed at serum dilutions of 1/320 and occurred between the 6th and the 30th months posttreatment. The immune response and the interval for a serological regression to negativity were different for each patient. For some of the recombinant antigens, only 50% (9/18) of the patients reached the serological regression to negativity. Recombinant antigen 13 might be a good marker of treatment effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (Pç=0.002).
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effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (Pç=0.002).
effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (Pç=0.002).