CYP19A1 gene expression in the peripheral blood of Brazilian women with breast cancer relapse.

BACKGROUND: The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer. METHODS: In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher's exact test (p <  0.05). RESULTS: There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p <  0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p <  0.0001). CONCLUSIONS: The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.

Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene.

An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.

Feline Leishmaniasis: Evidence-based Treatments and Challenges to be Solved.

Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats' resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.

Risk Profiles for Leishmania infantum Infection in Brazil.

The aim of this study was to characterize risk profiles for Leishmania infantum infection in a population living in an area endemic for visceral leishmaniasis. A cohort study was conducted between January 2004 and December 2006 with the participation of 430 individuals living in the city of Teresina, northeast Brazil, who were initially negative for the Montenegro test. Data analysis was performed using the classification and regression tree method. The cumulative incidence (CI) of Montenegro's test conversion was 35% at 18-month follow-up. Eight different risk profiles for L. infantum infection were identified. The profile with the highest risk (CI = 75%) comprised individuals with less than 4 years of education who had never lived outside Teresina. The profile with the lowest risk (CI = 5%) included highly educated subjects who had owned a dog for 5 years or more and lived in areas that received some type of intervention. These results show that there is a high degree of complexity involved in the risk for L. infantum infection and point out the need of developing new studies to perform a comprehensive analysis focused on investigating the interrelation between risk factors rather than their isolated roles on the determination of infection levels in urban areas.

Leishmania infantum Genetic Diversity and Lutzomyia longipalpis Mitochondrial Haplotypes in Brazil.

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in the Americas with domestic dogs being its major reservoir hosts. The main VL vector is the sandfly Lutzomyia longipalpis, while other Lutzomyia species may play a role in disease transmission. Although the genetic structure of L. infantum populations has been widely evaluated, only a few studies have addressed this subject coupled to the genetic structure of the respective sandfly vectors. In this study, we analyzed the population structure of L. infantum in three major VL endemic areas in Brazil and associated it with Lutzomyia longipalpis geographic structure.

Effectiveness of insecticide spraying and culling of dogs on the incidence of Leishmania infantum infection in humans: a cluster randomized trial in Teresina, Brazil.

BACKGROUND: To evaluate the effect of insecticide spraying for vector control and elimination of infected dogs on the incidence of human infection with L. infantum, a randomized community intervention trial was carried out in the city of Teresina, Brazil. METHODS/PRINCIPAL FINDINGS: Within each of ten localities in the city, four blocks were selected and randomized to 4 interventions: 1) spraying houses and animal pens with insecticide; 2) eliminating infected dogs; 3) combination of spraying and eliminating dogs, and 4) nothing. The main outcome is the incidence of infection assessed by the conversion of the Montenegro skin test (MST) after 18 months of follow-up in residents aged ≥ 1 year with no previous history of visceral leishmaniasis (VL). Reactions were measured at 48-72 h, induration of ≥ 5 mm considered positive. Interventions were executed after the baseline interview and repeated 6 and 12 months later. The effects of each type of intervention scheme on the incidence of infection were assessed by calculating relative risks and 95% confidence intervals using Poisson population-averaged regression models with robust variance. Among the 1105 participants, 408 (37%) were MST positive at baseline. Of the 697 negatives, only 423 (61%) were reexamined at the end of the follow-up; 151 (36%) of them converted to a positive MST. Only dog culling had some statistically significant effect on reducing the incidence of infection, with estimates of effectiveness varying between 27% and 52%, depending on the type of analysis performed. CONCLUSIONS/SIGNIFICANCE: In light of the continuous spread of VL in Brazil despite the large scale deployment of insecticide spraying and dog culling, the relatively low to moderate effectiveness of dog culling and the non-significant effect of insecticide spraying on the incidence of human infection, we conclude that there is an urgent need for revision of the Brazilian VL control program.