Nebulized Glutathione as a Key Antioxidant for the Treatment of Oxidative Stress in Neurodegenerative Conditions.

Glutathione (GSH), a tripeptide synthesized intracellularly, serves as a pivotal antioxidant, neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) while maintaining redox homeostasis and detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), thus aiding in detoxification processes and mitigating oxidative damage and inflammation. Mitochondria, being primary sources of reactive oxygen species, benefit significantly from GSH, which regulates metal homeostasis and supports autophagy, apoptosis, and ferroptosis, playing a fundamental role in neuroprotection. The vulnerability of the brain to oxidative stress underscores the importance of GSH in neurological disorders and regenerative medicine. Nebulization of glutathione presents a novel and promising approach to delivering this antioxidant directly to the central nervous system (CNS), potentially enhancing its bioavailability and therapeutic efficacy. This method may offer significant advantages in mitigating neurodegeneration by enhancing nuclear factor erythroid 2-related factor 2 (NRF2) pathway signaling and mitochondrial function, thereby providing direct neuroprotection. By addressing oxidative stress and its detrimental effects on neuronal health, nebulized GSH could play a crucial role in managing and potentially ameliorating conditions such as Parkinson's Disease (PD) and Alzheimer's Disease (AD). Further clinical research is warranted to elucidate the therapeutic potential of nebulized GSH in preserving mitochondrial health, enhancing CNS function, and combating neurodegenerative conditions, aiming to improve outcomes for individuals affected by brain diseases characterized by oxidative stress and neuroinflammation.

Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy.

Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success.

Alterações motoras e funcionais em diferentes estágios da doença de Alzheimer / Motor and functional changes in different stages of Alzheimer's disease

CONTEXTO: A doença de Alzheimer (DA) é a demência de maior prevalência e está associada a alterações cognitivas, comportamentais e funcionais. Entretanto, faz-se necessário esclarecer a influência do agravamento da doença no declínio dessas funções.OBJETIVO: Comparar funções cognitivas específicas, funções motoras e atividades de vida diária (AVD) de pacientes com DA em diferentes estágios da doença.MÉTODOS: Foram avaliadas as funções cognitivas, as funções motoras e as AVD de 74 pacientes com doença de Alzheimer (35 pacientes CDR1; 20 pacientes CDR2; 19 pacientes CDR3).RESULTADOS: A função motora e a independência das AVD apresentam declínio não linear. Enquanto a função motora apresenta maior declínio na fase leve para moderada, as AVD básicas sofrem maior declínio na fase grave da doença.CONCLUSÃO: O declínio motor é mais importante nas fases moderada e grave, associado a valores de perda de capacidade física e risco de quedas. Verifica-se que a perda de independência para realização das AVD instrumentais dos pacientes é muito maior do que o declínio físico e cognitivo avaliado objetivamente nas três fases da doença.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent dementia, being associated with cognitive, behavioral, and functional alterations. However, clarifying the influence of the disease worsening in the decline of these functions is of major relevance. OBJECTIVE: Compare specific cognitive functions, motor functions and activities of daily living (ADL) of AD patients in different stages of the disease. METHODS: Cognitive and motor functions, as well as ADL of 74 AD patients (35 patients CDR1; 20 patients CDR2; 19 patients CDR3) were evaluated. RESULTS: Motor function and independency in the ADL have presented a non-linear decline. While motor function shows a greater decline from the mild to the moderate phase, ADL present a greater decline in the severe stage of the disease. DISCUSSION: Motor function decline is more evident in both moderate and severe stages of AD, associated with losses in physical capacity and increases in risk of falls. The patients' loss of independency to perform instrumental ADL occurs in a non-linear pattern and it is much greater than both physical and cognitive declines when these parameters are objectively evaluated in the three phases of the disease.

Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil.

The positivities of two methods for the diagnosis of localised cutaneous leishmaniasis (CL) were estimated in 280 patients enrolled in a clinical trial. The trial was conducted in an endemic area of Leishmania (Viannia) braziliensis and trial participants were patients with skin ulcers and positive leishmanin skin tests. Patients underwent aspirative skin punctures of the ulcerated lesions and lymph nodes for in vitro cultures, which were processed under field conditions at the local health centre. Skin lesion biopsies were tested at a reference laboratory using kinetoplastid DNA (kDNA)-PCR to detect DNA. The median time required to obtain a positive culture from the skin samples was seven days and the contamination rate of the samples was 1.8%. The positivities of the cultures from skin lesions, kDNA-PCR and the combination of the two methods were 78.2% (95% CI: 73-82.6%), 89.3% (95% CI: 85.1-92.4%) and 97.1% (95% CI: 94.5-98.5%). We conclude that parasite culture is a feasible method for the detection of Leishmania in field conditions and that the combination of culture and PCR has a potential role for the diagnosis of CL in candidates for clinical trials.

Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil

The positivities of two methods for the diagnosis of localised cutaneous leishmaniasis (CL) were estimated in 280 patients enrolled in a clinical trial. The trial was conducted in an endemic area of Leishmania (Viannia) braziliensis and trial participants were patients with skin ulcers and positive leishmanin skin tests. Patients underwent aspirative skin punctures of the ulcerated lesions and lymph nodes for in vitro cultures, which were processed under field conditions at the local health centre. Skin lesion biopsies were tested at a reference laboratory using kinetoplastid DNA (kDNA)-PCR to detect DNA. The median time required to obtain a positive culture from the skin samples was seven days and the contamination rate of the samples was 1.8 percent. The positivities of the cultures from skin lesions, kDNA-PCR and the combination of the two methods were 78.2 percent (95 percent CI: 73-82.6 percent), 89.3 percent (95 percent CI: 85.1-92.4 percent) and 97.1 percent (95 percent CI: 94.5-98.5 percent). We conclude that parasite culture is a feasible method for the detection of Leishmania in field conditions and that the combination of culture and PCR has a potential role for the diagnosis of CL in candidates for clinical trials.

Esofagoplastia torácica com retalho de pericárdio em gatos / Thoracic esophagoplasty with pericardial flap in cats

Com o objetivo de testar a eficiência do retalho de pericárdio autógeno pediculado como alternativa para reparar defeitos esofágicos torácicos em felinos, foram estudados doze animais adultos, sendo seis avaliados até 30 dias de pós-operatório. Todos os animais foram submetidos à ressecçäo esofágica e posterior reparo com pericárdio pediculado. As análises constaram de exames clínicos diários e, ao final do período estabelecido, os animais foram submetidos à eutanasia e necropsiados para avaliaçäo macroscópica e microscópica dos esôfagos. Observou-se proliferaçäo da mucosa esofágica sobre o pericárdio pediculado.