Gold(I) ion and the phosphine ligand are necessary for the anti-Toxoplasma gondii activity of auranofin.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

State selective enhanced production of excited fragments and ionic fragments of gaseous Si(CH3)2Cl2 and solid-state analogs following core-level excitation.

State-selective fragmentation dynamics for excited fragments and ionic fragments of gaseous and condensed Si(CH3)2Cl2 following Cl 2p and Si 2p core-level excitations have been characterized. The Cl 2p-->15a1* excitation of Si(CH3)2Cl2 induces significant enhancement of the Cl+ desorption yield in the condensed phase and the Si(CH3)+2 and SiCH+3 yields in the gaseous phase. The core-to-Rydberg excitations at both Si 2p and Cl 2p edges lead to enhanced production of the excited fragments. These complementary results provide deeper insight into the origin of state-selective fragmentation of molecules via core-level excitation.

Discovery and epidemiology of PCB poisoning in Taiwan: a four-year followup.

An outbreak of polychlorinated biphenyl (PCB) poisoning from the consumption of contaminated rice oil, covering four counties in central Taiwan, was investigated. There were 1843 cases by the end of 1980. The highest frequency of incidence occurred during the period from March to July 1979. The severity of clinical manifestations varied. Most patients showed symptoms of mild or moderate severity. The major age group affected was between 11 and 20 years old. Most of the victims were students and factory workers. The amount of PCB intake in each victim was estimated to be 0.7 to 1.84 g and the latent period from the time of intake to the onset of clinical manifestations was approximately 3 to 4 months. The patients' blood PCB concentrations ranged from 3 ppb to 1156 ppb; 44.27% of 613 patients had levels of 51 to 100 ppb and 27.6% PCB blood levels over 100 ppb. In the course of 3.5 years, 2061 persons were determined to be PCB poisoning victims. Now, except for a few severe cases, their skin symptoms are very much improved. Thirty-nine babies showing hyperpigmentation were born from PCB-poisoned mothers. The fatality rate was high: eight of them died. Another 24 deaths were reported among the PCB-poisoned group, almost half of them (12) from hepatoma, liver cirrhosis or liver diseases with hepatomegaly.

Discovery and epidemiology of PCB poisoning in Taiwan.

An outbreak of PCB poisoning through consumption of the contaminated rice Oil in Central Taiwan was investigated. It covered four counties and there were 1,843 cases by the end of 1980. The highest frequency of incidence occurred during the period from March to July 1979. Severity of clinical manifestations was graded, most patients exhibiting mild or moderate severity. The major age group of the outbreak was between 11 to 20 years old. Most of the victims were students and factory workers. The amount of PCB intake in each victim was estimated to be 0.7 to 1.84 gm and the latent period from the time of intake to the onset of clinical manifestations was approximately three to four months. The patients' blood PCB concentrations ranged from 3 to 1,156 ppb. In 613 patients, 44.37% (272 patients) had PCB levels of 51-100 ppb, and 27.51% (169 patients) had levels over 100 ppb.

Discovery and epidemiology of PCB poisoning in Taiwan.

An outbreak of PCB poisoning through consumption of the contaminated rice oil in Central Taiwan was investigated. It covered four counties and there were 1,843 cases by the end of 1980. The highest frequency of incidence occurred during the period from March to July 1979. Severity of clinical manifestations was graded, most patients exhibiting mild or moderate severity. The major age group of the outbreak was between 11 to 20 years old. Most of the victims were students and factory workers. The amount of PCB intake in each victim was estimated to be 0.7 to 1.84 gm and the latent period from the time of intake to the onset of clinical manifestations was approximately three to four months. The patients' blood PCB concentrations ranged from 3 to 1,156 ppb. In 613 patients, 44.37% (272 patients) had PCB levels of 51-100 ppb, and 27.57% (169 patients) had levels over 100 ppb.