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.

Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries.

Spinal cord injury (SCI) represents a severe trauma to the nervous system, leading to significant neurological damage, chronic inflammation, and persistent neuropathic pain. Current treatments, including pharmacotherapy, immobilization, physical therapy, and surgical interventions, often fall short in fully addressing the underlying pathophysiology and resultant disabilities. Emerging research in the field of regenerative medicine has introduced innovative approaches such as autologous orthobiologic therapies, with bone marrow aspirate (BMA) being particularly notable for its regenerative and anti-inflammatory properties. This review focuses on the potential of BMA to modulate inflammatory pathways, enhance tissue regeneration, and restore neurological function disrupted by SCI. We hypothesize that BMA's bioactive components may stimulate reparative processes at the cellular level, particularly when applied at strategic sites like the sacral hiatus to influence lumbar centers and higher neurological structures. By exploring the mechanisms through which BMA influences spinal repair, this review aims to establish a foundation for its application in clinical settings, potentially offering a transformative approach to SCI management that extends beyond symptomatic relief to promoting functional recovery.

Bone Marrow Aspirate Concentrate Improves Outcomes in Adults With Osteochondral Dissecans of the Talus and Achilles Rupture.

PURPOSE: The objective of this systematic literature review was to investigate the effects of the clinical application of bone marrow aspirate (BMA) and/or bone marrow aspirate concentrate (BMAC) in tendon and cartilage injuries in the foot and ankle. METHODS: A search of the Embase, MEDLINE/PubMed, CINAHL, and Cochrane databases was performed in January 2021. The risk of bias of the studies was assessed using the tool "A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies." The outcomes analyzed included pain reduction and functional improvement with the use of BMA/BMAC in patients with tendon and cartilage injuries in the foot and ankle. RESULTS: Eleven studies met the inclusion criteria for analysis, involving a total of 527 subjects with osteochondral lesions (OCLs) of the talus, cartilage lesions of the talus, and acute Achilles tendon rupture. BMAC was applied alone in 4 studies, and in 7 studies, it was compared with other techniques such as matrix-induced autologous chondrocyte implantation, particulate juvenile articular cartilage, or microfracture. Interventions demonstrated improved function and reduced foot and ankle pain and showed no serious adverse effects. CONCLUSIONS: Evidence indicates that BMAC provides good clinical results, with improved function and reduced pain in adults with OCL and cartilage lesions of the talus and acute Achilles tendon rupture. LEVEL OF EVIDENCE: Level IV, systematic review of level II to IV studies.

Entomological survey of phlebotominae sand flies (diptera: psychodidae) and vector species in the tegumentary leishmaniasis endemic area in eastern brazilian Amazon, Amapá state / Levantamento entomológico de flebotomíneos (Diptera: Psychodidae) e espécies vetoras na área endêmica de leishmaniose tegumentar na Amazônia oriental brasileira, Estado do Amapá

American tegumentary leishmaniasis is an endemic that has increased considerably in recent decades in the Amazon region, sand flies are the vectors of the transmission of the protozoan that causes leishmaniasis, so the objective of this study was to carry out a survey of the diversity of species and the presence of Leishmania DNA in vectors circulating in three endemic counties for tegumentary leishmaniasis in the eastern Brazilian Amazon (Amapá state, Brazil). Using CDC light traps, a total of 10,773 specimens were collected between February 2019 and February 2020, representing 64 species in 15 genera. The vector specie Nyssomyia umbratilis Ward and Frahia, 1977 was the predominant species (13.20% of the total), being collected in all three counties, followed by Trichopygomyia trichopyga Floch & Abonnenc, 1945 (11.41%), Trichophoromyia ubiquitalis Mangabeira,1942 (9.47%) and Nyssomyia anduzei Rozeboom, 1942 (7.61%). For the identification of Leishmania DNA, 775 pools of unengorged females were used, of which 5 tested positive, 2 of Nyssomya umbratilis Ward & Fraiha,1977, 1 of Nyssomyia anduzei and 2 of Psychodopygus davisi Root,1934, demonstrating a natural total infection rate of 0.64%. This study increases the knowledge of vector diversity, as well as identifying Leishmania spp. in circulation in the eastern region of the Amazon.

A leishmaniose tegumentar americana é uma endemia que aumentou consideravelmente nas últimas décadas na região amazônica, os flebotomíneos são os vetores da transmissão do protozoário causador da leishmaniose, portanto o objetivo deste estudo foi realizar um levantamento da diversidade de espécies e a presença de DNA de Leishmania em vetores que circulam em três municípios endêmicos de leishmaniose tegumentar na Amazônia oriental brasileira (Amapá, Brasil). Usando armadilhas luminosas do tipo CDC, um total de 10.773 espécimes foram coletados entre fevereiro de 2019 e fevereiro de 2020, representando 64 espécies em 15 gêneros. As espécie vetoras - singular Nyssomyia umbratilis Ward e Frahia 1977 foram as espécies predominantes (13,20% do total), sendo coletadas nos três municípios, seguido por Trichopygomyia trichopyga Floch & Abonnenc, 1945 (11,41%), Trichophoromyia ubiquitalis Mangabeira, 1942 (9,47%) e Nyssomyia anduzei Rozeboom, 1942 (7,61%). Para a identificação do DNA de Leishmania, foram utilizados 775 pools de fêmeas não ingurgitadas, dos quais 5 foram positivos, 2 de Nyssomya umbratilis Ward & Fraiha, 1977, 1 de Nyssomyia anduzei e 2 de Psychodopygus davisi Root, 1934, demonstrando uma taxa de infecção total de 0,64%. Este estudo aumenta o conhecimento da diversidade de vetores, bem como a identificação das espécies de Leishmania spp. em circulação na região oriental da Amazônia.

Human platelet lysate - A potent (and overlooked) orthobiologic.

The knowledge of the essential role of platelets in tissue healing is gradually increasing and as regenerative medicine prompts new solutions, platelet-derived bioproducts have been proposed as a potential tool in this field. In orthopaedics and sports medicine, the use of PRP has been rapidly increasing in popularity as patients seek novel non-surgical approaches to acute and chronic musculoskeletal conditions. The concept of having platelets as a secretory organ other than a mere sponge-like coagulation component opens up new frontiers for the use of the platelet secretome. Platelet lysate is a solution saturated by growth factors, proteins, cytokines, and chemokines involved in crucial healing processes and is administered to treat different diseases such as alopecia, oral mucositis, radicular pain, osteoarthritis, and cartilage and tendon disorders. For this purpose, the abundant presence of growth factors and chemokines stored in platelet granules can be naturally released by different strategies, mostly through lyophilization, thrombin activation or ultrasound baths (ultrasonication). As a result, human platelet lysate can be produced and applied as a pure orthobiologic. This review outlines the current knowledge about human platelet lysate as a powerful adjuvant in the orthobiological use for the treatment of musculoskeletal injuries, without however failing to raise some of its most applicable basic science.

The regenerative mechanisms of platelet-rich plasma: A review.

Orthobiologics continue to gain popularity in many areas of medical science, especially in the field of regenerative medicine. Platelet-rich plasma derivatives are orthobiologic tools of particular interest. These biologic products can be obtained via centrifugation of a patient's whole blood and the components can then be subsequently isolated, concentrated and ultimately administered into injured tissues, particularly in areas where standard healing is disrupted. The elevated concentration of platelets above the basal value enables accelerated growth of various tissues with minimal side effects. The application of autologous orthobiologics is a relatively new biotechnology undergoing expansion which continues to reveal optimistic results in the stimulation and enhanced healing of various sorts of tissue injuries. The local release of growth factors and cytokines contained in platelet alpha granules accelerates and ameliorates tissue repair processes, mimicking and supporting standard wound healing. This effect is greatly enhanced upon combination with the fibrinolytic system, which are essential for complete regeneration. Fibrinolytic reactions can dictate proper cellular recruitment of certain cell populations such as mesenchymal stem cells and other immunomodulatory agents. Additionally, these reactions also control proteolytic activity in areas of wound healing and regenerative processes of mesodermal tissues including bone, cartilage, and muscle, which makes it particularly valuable for musculoskeletal health, for instance. Although many investigations have demonstrated significant results with platelet-rich plasma derivatives, further studies are still warranted.

Ecological aspects and molecular detection of Leishmania DNA (Kinetoplastida: Trypanosomatidae) in phlebotomine sand flies (Diptera: Psychodidae) from a rural settlement in the Eastern Amazon, Brazil

ABSTRACT Notifications concerning American tegumentary leishmaniasis (ATL) are increasing in the northern areas of Brazil, particularly due to the ongoing increase in human settlements inside the Amazon Forest. Notwithstanding the economical and sanitary importance of the ATL, the ecological aspects of its potential vectors, the Phlebotomine sand flies (Diptera: Psychodidae), remains largely neglected. This study aimed to investigate the diversity of the phlebotomine fauna as well as the detection of Leishmania DNA in these insects in the rural settlement Perimetral Norte, in the state of Amapá, eastern region of the Amazon, endemic region for tegumentary leishmaniasis. Sand flies were collected bimonthly from February 2018 to February 2019, using CDC light traps exposed for three consecutive nights in 10 houses of settlement residents. DNA extraction and multiplex PCR were performed to detect trypanosomatids. A total of 3,946 sandflies belonging to 37 species were collected. The most abundant species were Ty. trichopyga (Floch & Abonnenc, 1945) (21.9%) and Mi. rorotaensis (Floch & Abonnenc, 1944) (16.9%). A total of 36 positive pools were found with Leishmania DNA (Kinetoplastida: Trypanosomatidae), representing 17.9% of the total pools tested (201), those with the highest Minimum infection rates were Mg. migonei (França, 1920) and Lu. gomezi (Nitzulescu, 1931), Leishmania DNA was also detected in Bi. flaviscutellata (Mangabeira, 1942), Ny. umbratilis (Ward & Fraiha, 1977), Ny. anduzei (Roseboom, 1942) and Ny. antunesi (Coutinho, 1939). These data confirm the probable participation of these four species in the tegumentary leishmaniasis cycle in the eastern Amazon.

Bone marrow-derived products: A classification proposal - bone marrow aspirate, bone marrow aspirate concentrate or hybrid?

Degenerative musculoskeletal disorders are one of the top causes of pain and disability in the adult population. Current available alternatives to mitigate symptoms include conservative treatments such as the administration of pharmacological agents and an educative approach towards lifestyle modification. The use of certain analgesics, such as opiates and corticosteroids, delivers short term results but do not address the etiological source of pain and disability. Also, prolonged use of such medications may cause additional complications. Therefore, the demand for musculoskeletal tissue regeneration has led to an alternative approach referred to as "orthobiologics". This alternative is based on cellular and molecular components capable of inducing and promoting tissue repair. Bone marrow (BM) aspirate (BMA) and concentrate are well-known orthobiologics used to treat musculoskeletal conditions. Orthobiologics derived from the BM have been discussed in the literature; however, the lack of standardization regarding collection and processing protocols presents a challenge for generalization of study outcomes and determination of efficacy. Since BM-derived orthobiologics have not yet been classified, to our knowledge, this manuscript proposes the ACH classification system, which speaks to BMA (A), BMA and concentrate (C) and hybrid (H), which combines A and C. This classification proposes and describes 8 parameters that are relevant for the quality of biological products. The more parameters used would imply greater characterization and complexity of the evaluation of the biological product used. The ACH classification envisages a necessary contribution to the comprehension of both clinical procedures and research outcomes, ultimately ushering in a standardization of best practice.