Orphenadrine Hydrochloride

This study presents the first investigation into the occurrence, spatial distribution, and ecological risk of pharmaceuticals and personal care products (PPCPs) in the coastal zone of Ubatuba, a tourist hotspot with significant ecological value located on the southeastern coast of Brazil. Sampling was conducted immediately after the New Year holidays, over two consecutive years (January 2019 and 2020), in two areas with distinct physiographic and oceanographic characteristics and different levels of anthropogenic impact: Flamengo Inlet and Ubatuba Bay. Quantitative analysis using high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) detected 15 of the 22 target compounds, including antihypertensives, anti-inflammatory/analgesics, β-blockers, caffeine, cocaine, and its human metabolite, benzoylecgonine. Concentrations ranged from 0.024 ng L^-1 (carbamazepine) to 3500 ng L^-1 (caffeine). The occurrence of caffeine, cocaine, diclofenac, and propanolol at outer stations in Flamengo Inlet suggests that lateral advection by coastal currents may transport these contaminants along the inner shelf, far from their original sources. Ecological risk assessment indicated that caffeine and diclofenac pose a high risk in both study areas, with phytoplankton being the most sensitive to these contaminants. Notably, concentrations of some target compounds in Ubatuba Bay were comparable to or exceeded those reported in highly urbanized coastal regions globally. Our findings complement earlier studies and contradict the assumption that PPCPs contamination are mainly connected with highly anthropized areas. This also highlights the need to investigate the impact of domestic sewage and touristic pollution on ecologically sensitive coastal habitats to obtain a more comprehensive view of PPCPs pollution and its implication for conservation goals and public health.

Tauopathies are neurodegenerative diseases that manifest with intracellular accumulation and aggregation of tau protein. These include Pick’s disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease, where tau is believed to be the primary disease driver, as well as secondary tauopathies, such as Alzheimer’s disease. There is a need to develop effective pharmacological therapies. Here we tested >1,400 clinically approved compounds using transgenic zebrafish tauopathy models. This revealed that carbonic anhydrase (CA) inhibitors protected against tau toxicity. CRISPR experiments confirmed that CA depletion mimicked the effects of these drugs. CA inhibition promoted faster clearance of human tau by promoting lysosomal exocytosis. Importantly, methazolamide, a CA inhibitor used in the clinic, also reduced total and phosphorylated tau levels, increased neuronal survival and ameliorated neurodegeneration in mouse tauopathy models at concentrations similar to those seen in people. These data underscore the feasibility of in vivo drug screens using zebrafish models and suggest serious consideration of CA inhibitors for treating tauopathies.