An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection. These profiles were then associated with symptoms, revealing important aspects of the immunopathophysiology of ZIKV infection. The levels of some cytokines/chemokines were significantly higher in acute ZIKV-infected individuals compared to healthy donors, including interferon (IFN) gamma-induced protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), IFN-γ, interleukin (IL)-9, IL-7, IL-5, and IL-1ra, including some with predominantly immunoregulatory activity. Of note, we found that higher levels of IP-10 and IL-5 in ZIKV-infected individuals were strongly associated with exanthema and headache, respectively. Also, higher levels of IL-1ra were associated with subjects with arthralgia, whereas those with fever showed lower levels of granulocyte-colony stimulating factor (G-CSF). No correlation was observed between the number of symptoms and ZIKV viral load. Interestingly, only IP-10 showed significantly decreased levels in the recovery phase. In conclusion, our results indicate that acute ZIKV infection in a larger cohort resident to an endemic area displays a modest systemic immune activation profile, involving both proinflammatory and immunoregulatory cytokines and chemokines that could participate of virus control. In addition, we showed that differential cytokine/chemokine levels are related to specific clinical symptoms, suggesting their participation in underlying mechanisms.

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Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease that affects motor neurons and promotes progressive muscle atrophy. It has a multifactorial etiology, where environmental conditions playing a remarkable role through the increase of oxidative stress. Genetic polymorphisms in cell detoxification genes, such as Glutathione S-Transferase Pi 1 (GSTP1) can contribute to excessive oxidative stress, and therefore may be a risk factor to ALS. Thus, this study aimed to investigate the role of the GSTP1 rs1695 polymorphism in ALS susceptibility in different genetic inheritance models and evaluate the association of the genotypes with risk factors, clinical and demographic characteristics of ALS patients from the Brazilian central population. This case-control study was conducted with 101 patients with ALS and 101 healthy controls. GSTP1 rs1695 polymorphism genotyping was performed with Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP). The statistical analysis was carried out using the SPSS statistical package and SNPStats software. Analysis of genetic inheritance models was performed by logistic regression, which was used to determine the Odds Ratio. The results of this first study in the Brazilian population demonstrated that there was no risk association between the development of ALS and the GSTP1 rs1695 polymorphism in any genetic inheritance model (codominant, dominant, recessive, overdominant, and logarithmic); and that the polymorphic variants were not associated with the clinical and demographic characteristics of ALS patients. No association of the GSTP1 rs1695 polymorphism and ALS development in the Brazilian central population was found. These findings may be justified by the multifactorial character of the disease.

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O gene DMD localiza-se no cromossomo X e codifica a distrofina, uma proteína do citoesqueleto responsável pela manutenção da integridade e da função contrátil das fibras musculares. Alterações moleculares no gene DMD interferem na produção da distrofina, resultando no desenvolvimento de uma doença degenerativa conhecida como Distrofia Muscular de Duchenne (DMD). A DMD é uma doença de herança recessiva ligada ao cromossomo X, causada por mutações, principalmente deleçõesno gene DMD. A doença acomete, em sua maioria, homens e caracteriza-se por fraqueza muscular progressiva detectada nos primeiros anos de vida.

A Fibrose Cística (FC), também conhecida por mucoviscidose, é uma doença genética de herança autossômica recessiva causada por mutações no gene CFTR (do inglês Cystic Fibrosis Transmembrane Conductance Regulator). Esse gene codifica uma proteína transmembranar de mesmo nome, inserida na membrana apical de células epiteliais, que transporta cloreto (Cl-) e bicarbonato (HCO3-). Diversas mutações nesse gene estão relacionadas com o desenvolvimento da doença, sendo a F508del (c.1522_1524del ou p.Phe508del, de acordo com as normas do HGVS) a mais frequente, acarretando na degradação proteica. A ausência dessa proteína desencadeia um desequilíbrio hidrossalino e alteração do pH do fluido superficial das células epiteliais, afetando órgãos como pulmão, pâncreas e glândulas do trato gastrointestinal. Essas alterações levam ao acúmulo de muco espesso na superfície epitelial, especialmente nos pulmões, que torna o indivíduo suscetível a infecções pulmonares recorrentes, uma das principais características da doença e a maior causa de morte prematura na FC.

Glutathione S-transferases (GSTs) are enzymes that act in the cellular detoxification of harmful compounds. Due to the role of the GSTP1 isoenzyme in the brain, the presence of the single nucleotide polymorphism (SNP) rs1695 in the GSTP1 gene may play an important role in the development of neurodegenerative diseases through oxidative stress, one of the main pathogenic mechanisms associated with the degeneration and death of motor neurons.Thus, this protocol provides a standardized methodology for genotyping the rs1695 polymorphism in the GSTP1 gene through polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP). This polymorphism consists of the exchange of adenine for guanine at position 313 (codon 105), which causes the substitution of amino acid isoleucine (Ile) for valine (Val), resulting in a decreased Pi enzyme activity. Polymorphism genotyping techniques have been of great interest in determining the genetic association of several polymorphisms with different diseases, and therefore this protocol may facilitate future genetic studies.