Imatinib mesylate ameliorates the dystrophic phenotype in exercised mdx mice.

Myofiber degeneration, inflammation, and fibrosis are remarkable features of Duchenne muscular dystrophy. We hypothesized that the administration of imatinib mesylate, an inhibitor of tyrosine kinase and TGF-beta pro-fibrogenic activity, could improve the muscular conditions in mdx mice. Four-week old mdx mice were treated and exercised for 6 weeks. Gastrocnemius and diaphragm histopathology, strength, creatine kinase, and cytokine levels were evaluated. The treated group presented increased muscular strength and decreased CK levels, injured myofibers, and inflammatory infiltrates. Pro-inflammatory cytokines and TGF-beta were also reduced, while IL-10 was increased, suggesting an immunomodulatory effect of imatinib, which can ameliorate the dystrophic phenotype in mdx mice.

HTLV-2 horizontal and vertical transmission in a family from a Brazilian urban area: seroepidemiological, clinical and molecular study.

Human T cell lymphotropic virus type 2 (HTLV-2) has been shown to be endemic in Brazilian Indians and among intravenous drug users in urban areas, but transmission of this infection seems to be infrequent in the general population living in urban areas in Brazil. Six persons in three generations of a Brazilian family were evaluated to assess HTLV-2 transmission and its molecular features in the positive cases. The index was detected during screening (HTLV EIA) of donated blood in Fundação Hemominas, Belo Horizonte, Brazil. Confirmatory serological test and viral typing were performed by Western blotting and polymerase chain reaction. The family consisted of husband, wife (index case), three daughters, and the mother of the index case. The husband and one daughter were found positive, thus pointing to horizontal and vertical transmission. The husband was a truck driver, who reported casual sex during frequent traveling. The positive daughter was breast-fed for 3 months, as opposed to the remaining two (seronegative), who breast-fed for 1 month. The index case's mother was negative. To identify HTLV-2 subtype(s), phylogenetic analysis of the noncoding long terminal repeat region and part of the env and tax coding regions was performed. These new isolates from Belo Horizonte are related to subtype IIa but present a molecular variant with extended tax, previously reported in subtype IIc. Analyzing both LTR and env regions, the family's sequences clustered with isolates of Brazilian intravenous drug users and transfusion transmitted virus.

Globin haplotypes of human T-cell lymphotropic virus type I-infected individuals in Salvador, Bahia, Brazil, suggest a post-Columbian African origin of this virus.

The city of Salvador, Bahia, Brazil, has sociodemographic characteristics similar to some African cities. Up to now, it has had the highest prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection (1.74%) in the country. To investigate which strains of HTLV-I are circulating in Salvador, we studied isolates from 82 patients infected with HTLV-I: 19 from the general population, 21 from pregnant women, 16 from intravenous drug users, and 26 from patients and their family attending a neurologic clinic. Phylogenetic analysis from part of the LTR fragments showed that most of these isolates belonged to the Transcontinental subgroup of the Cosmopolitan subtype (HTLV-Ia). Only one sample from a pregnant woman was closely related to the Japanese subgroup, suggesting recent introduction of a Japanese HTLV-I lineage into Salvador. betaA-Globin haplotypes were examined in 34 infected individuals and found to be atypical, confirming the racial heterogeneity of this population. A total of 20 chromosomes were characterized as Central African Republic (CAR) haplotype (29.4%), 31 (45.6%) were characterized as Benin (BEN) haplotype, and 17 (25%) were characterized as Senegal (SEN) haplotype. Five patients' genotypes (14.7%) were CAR/CAR; 10 (29,4%), BEN/BEN; 9 (26.5%), CAR/BEN; 2 (5.9%), BEN/SEN; and 7 (20.6%), SEN/SEN. One patient's genotype (2.9%) was CAR/SEN. The betaA-globin haplotype distribution in Salvador is unusual compared with other Brazilian states. Our data support the hypothesis of multiple post-Columbian introductions of African HTLV-Ia strains in Salvador, Bahia, Brazil.