Real-time evaluation of nitric oxide (NO) levels in cortical and hippocampal areas with a nanopore-based electrochemical NO sensor

Nitric oxide (NO) is an important biomolecule for regulating various brain functions, such as the control of neurovascular tone. NO, however, cannot be stored inside cells where NO is produced and immediately diffuses through the cellular membrane and decays rapidly, which makes the detection of NO extremely hard in an in vivo setting. We constructed an amperometric NO nanosensor and utilized it to directly measure NO release in the living brain. The NO nanosensor uses nanopores (pores with an opening radii <500 nm) in which NO is oxidized at the porous platinum surface. The nanopore-based sensor was inserted vertically into the brains of anesthetized mice up to the end of the hippocampal CA 3 region, or to a depth of about 3 mm. The sensor was slowly advanced in the brain in 0.5 μm increments and in 0.05 s temporal steps. Different levels of NO release were monitored by the nanopore NO sensor during the course of the penetration. The hippocampal CA3 region had the highest level of NO release, which was followed by CA2 and CA1 of the hippocampus and the cortex. The levels of NO release were not uniformly distributed within the cortical and hippocampal areas of living brain. In sum, the nanopore-based NO sensor was able to grossly measure NO contents within living brain in real time and with high sensitivity. This study may provide good insights about the relationship between the distributions of NOS-immunoreactive neurons and the directly measured levels of NO release in brain.     

Targeting Nitric Oxide With Drug Therapy

Increasing knowledge of the role of nitric oxide (NO) in physiology and disease has stimulated efforts to target the NO pathway pharmacologically. These therapeutic strategies include NO donors that directly or indirectly release NO and agents that increase NO bioactivity. Traditional organic nitrates such as nitroglycerin, which indirectly release NO, were believed to have limited long-term efficacy and tolerability, chiefly because of nitrate tolerance. Recent studies, however, suggest more effective ways of using these agents and new applications for them. Nicorandil, a hybrid organic nitrate that also activates potassium channels, has demonstrated significant benefits in acute coronary syndromes. Other nitrates are being investigated for use in neurodegenerative diseases. Direct NO donors include NO gas, which is useful in respiratory disorders, and the more recent classes of diazeniumdiolates, sydnonimines, and S-nitrosothiols. Preliminary data suggest that these agents may be effective as anti-atherosclerotic agents as well as in other disease states. In addition, hybrid agents that consist of an NO donor coupled with a parent anti-inflammatory drug, including nonsteroidal anti-inflammatory drugs, have demonstrated enhanced efficacy and tolerability compared with the anti-inflammatory parent drug alone in diverse experimental models. Established drugs that enhance NO bioactivity include antihypertensive agents, particularly angiotensin-converting enzyme inhibitors, calcium channel blockers, and newer vasodilating β-blockers. In addition, 3-methylglutaryl coenzyme A reductase inhibitors (statins) promote NO bioactivity, both through and independent of lipid lowering. The NO-promoting actions of these established drugs provide some insight into their known benefits and suggest possible therapeutic potential.     

Cryptococcal fungemia and probable histoplasmosis in a patient infected with HIV. Case report

Background

Those infected by human immunodeficiency virus (HIV) have a higher risk of opportunistic infections. The risk is related to the level of immunosuppression. We report a case of a young male with the unusual scenario of three opportunistic infections occurring simultaneously: Cryptococcosis, Histoplasmosis and Cryptosporidiosis. Histoplasmosis and cryptococcosis are major causes of morbimortality in immunocompromised patients due to HIV infection.

Case presentation

We report the case of a patient with HIV infection with a CD4 T lymphocyte cell (CD4) count of 2 cells/mm3, who presented with 6?months of diarrhea, non-productive dry cough, nocturnal diaphoresis, fever, weight loss, and a maculopapular rash. He had a concurrent infection with three opportunistic microorganisms: fungemia by cryptococcosis, disseminated histoplasmosis confirmed by detection of the antigen in urine and chronic diarrhea by cryptosporidiosis confirmed by direct observation in feces by modified Ziehl–Neelsen stain. The patient received antifungal treatment with a satisfactory outcome.

Conclusions

There are still regions where HIV detection programs are deficient thus facilitating occurrence of HIV infection cases in advanced stages of immunosuppression. A high level of suspicion of systemic mycoses and concurrent infection by several opportunistic pathogens is required in severely immunocompromised patients.

     

Subacute Thyroiditis After Receiving the mRNA COVID-19 Vaccine (Moderna): The First Case Report and Literature Review in Korea

Subacute thyroiditis (SAT) is a painful thyroiditis that often requires steroid therapy. Here, we report the first case of severe SAT in a patient who received the first dose of mRNA coronavirus disease 2019 (COVID-19) vaccination. A 34-year-old man without a viral prodrome felt a lump when swallowing 5 days after his first dose of mRNA-1273 (Moderna) vaccination. Ten days after vaccination, the patient visited the hospital and was advised to rest and take nonsteroidal anti-inflammatory drugs. He revisited the hospital 10 days later as symptoms aggravated with anterior neck pain, headache, fatigue, muscle weakness, and weight loss. Thyroid hormone levels and inflammatory markers were consistent with thyrotoxicosis. A thyroid ultrasound scan revealed typical SAT findings. His symptoms rapidly improved after receiving prednisone. A week later, the patient successfully completed his second dose of the vaccine. The thyroid function test results were nearly normal 1 month after the completion of the vaccination. We report this case to raise awareness of the occurrence of SAT after COVID-19 vaccination. As the risk of COVID-19 outweighs the minor risks of the vaccine, managing the side effects of the first vaccine dose is crucial to complete COVID-19 vaccination.     

Implementation of isoniazid preventive therapy in southern Lima,Peru: an analysis of health center characteristics

Background::Tuberculosis (TB) prevention through the use of preventive treatment is a critical activity in the elimination of TB. In multiple settings, limited ...     

Bonghan System as Mesenchymal Stem Cell Niches and Pathways of Macrophages in Adipose Tissues

A new technique for visualizing Bonghan ducts (BHDs) and Bonghan corpuscles (BHCs) was developed by using a vivi-staining dye, Trypan blue. The dye stains BHDs and BHCs preferentially to adipocytes so that tracking a BHD and a BHC, even inside adipose tissues, is possible. Concerning the functions of the BHD and the BHC in adipose tissues, we propose conjectures: the Bonghan system may be niches for mesenchymal stem cells, which can differentiate into adipocytes, and pathways for macrophages involved in adipogenesis.     

Flavonoids and aromatic compounds from the rhizomes of<Emphasis Type="Italic">Zingiber zerumbet</Emphasis>

Repeated column chromatography of the CHCl3-soluble fraction of Zingiber zerumbet led to the isolation and identification of two aromatic compounds, p-hydroxybenzaldehyde (1) and vanillin (2), and six kaempferol derivatives, kaempferol-3,4',7-O-trimethylether (3), kaempferol-3-O-methylether (4), kaempferol-3,4'-O-dimethylether (5), 4'-O-acetylafzelin (6), kaempferol-3-O-(4-O-acetyl-alpha-L-rhamnopyranoside)], 2',4'-O-diacetylafzelin (7), kaempferol-3-O-(2,4-O-diacetyl-alpha-L-rhamnopyranoside)], and 3',4'-O-diacetylafzelin (8), kaempferol-3-O-(3,4-O-diacetyl-alpha-L-rhamnopyranoside)]. The structures of 1-8 were identified by analysis of spectroscopic data as well as by comparison with published values. This is the first report on the isolation of compounds 1-3 from this plant.     

Specific erythrocyte binding capacity and biological activity of Plasmodium falciparum-derived rhoptry-associated protein 1 peptides

Rhoptry-associated protein 1 (RAP1) is a merozoite antigen within Plasmodium falciparum rhoptries as yet having no specific function described for it. Synthetic peptides spanning the RAP1 sequence were tested in erythrocyte binding assays to identify possible RAP1 functional regions. Five high activity binding peptides (HABPs) were identified; 26201, 26202, 26203 and 26204 spanned residues 461C-K540 within RAP1 Cys region, whilst 26188 (201T-Y220) was located in p67 amino terminal. The results showed that peptide binding was saturable, some HABPs inhibited in vitro merozoite invasion and specifically bound to a 72 kDa protein in red blood cell membrane. HABP possible function in merozoite invasion of erythrocytes is also discussed.