作者: Du, Han ; Li, Xuanxuan ; Qi, Hui ; Zhang, Cheng ; Duan, Xuefeng ; Li, Jianxiong ; Rong, Wenwan ; Yuan, Manhua ; Bi, Yuhai ; Dai, Bo ; Zhang, Ning ; Ji, Tiannan ; Ma, Zhenghai ; Yang, Jing

ETHNOPHARMACOLOGICAL RELEVANCELianhuaqingwen (LH), a traditional Chinese medicine, presents a broad-spectrum antiviral effect and has been widely used to treat influenza. Given the potential rise of drug-resistant influenza viruses, it is necessary to develop new antiviral drugs and explore combination therapies involving LH in tandem with existing antivirals such as Oseltamivir acid (Osel) or Baloxavir (Bal). These multidrug combinations could help effectively control the seasonal influenza epidemics and reduce the disease burden.AIM OF THE STUDYThis study aimed to evaluate the antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses in vitro and in vivo models.MATERIALS AND METHODSThe antiviral efficacy of LH alone and LH in combination with Osel/Bal against seasonal influenza A viruses (IAVs) (H1N1 and H3N2 subtypes) and influenza B viruses (IBVs) (BV- and BY-lineages) was assessed in vitro using MDCK cells. The median effective concentration (EC₅₀) was determined, and the drug synergies were analyzed. Additionally, the antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated in vivo using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction.RESULTSIn vitro, LH alone and in combination with Osel/Bal exhibited antiviral activity against both IAVs and IBVs. The addition of LH to Osel/Bal improved the therapeutic efficacy compared to Osel/Bal alone. In vivo, LH monotherapy reduced body weight loss and increased the survival rates of H1N1-infected mice. LH in combination with Osel/Bal resulted in lower virus titers, more effective relief of pathological damage, and comparable low expression of inflammatory factors in the lungs of H1N1-infected mice compared to the use of Osel/Bal alone. Transcriptomic analysis of the lungs revealed that LH+Osel/Bal significantly increased the expression of genes associated with antiviral and anti-inflammatory effects.CONCLUSIONSThis study evaluated the antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses in vitro and in vivo models. The results suggest that combining LH with Osel or Bal could enhance the antiviral efficiency for influenza viruses compared to the monotherapy using any of these three drugs.

2024-11-01·Science of The Total Environment

Occurrence and environmental fate of anti-influenza drugs in a subcatchment of the Yodo River Basin, Japan

Article

作者: Hayashi, Tetsuya ; Hasei, Tomohiro ; Usui, Masaru ; Azuma, Takashi

Understanding the current situation and risk of environmental contamination by anti-influenza drugs in aquatic environments is key to prevent the unexpected emergence and spread of drug-resistant viruses. However, few reports have been focused on newer drugs that have recently been introduced in clinical settings. In this study, the behaviour of the prodrug baloxavir marboxil (BALM)-the active ingredient of Xofluza, an increasingly popular anti-influenza drug-and its pharmacologically active metabolite baloxavir (BAL) in the aquatic environment was evaluated. Additionally, their presence in urban rivers and a wastewater treatment plant (WWTP) in the Yodo River basin was investigated and compared with those of the major anti-influenza drugs used to date (favipiravir (FAV), peramivir (PER), laninamivir (LAN), and its active metabolite, laninamivir octanoate (LANO), oseltamivir (OSE), and its active metabolite, oseltamivir carboxylate (OSEC), and zanamivir (ZAN)) to comprehensively assess their environmental fate in the aquatic environment. The results clearly showed that BALM, FAV, and BAL were rapidly degraded through photolysis (2-h, 0.6-h, and 0.4-h half-lives, respectively), followed by LAN, which was gradually biodegraded (7-h half-life). In addition, BALM and BAL decreased by up to 47 % after 4 days and 34 % after 2 days of biodegradation in river water. However, the remaining conventional drugs, except for LANO (<1 % after 10 days), were persistent, being transported from the upstream to downstream sites. The LogK_d values for the rates of sorption of BALM (0.5-1.6) and BAL (1.8-3.1) on river sediment were higher than those of conventional drugs (-0.5 to 1.7). Notably, all anti-influenza drugs were effectively removed by ozonation (>90-99.9 % removal) after biological treatment at a WWTP. Thus, these findings suggest the importance of introducing ozonation to reduce pollution loads in rivers and the environmental risks associated with drug-resistant viruses in aquatic environments, thereby promoting safe river environments.

2024-10-01·Pediatrics

Severe Congenital Lead Poisoning in Siblings

Article

作者: Chhikara, Aditya ; Velagala, Suganthinie ; Haile, Jennifer

Congenital lead toxicity is rare. Lead freely crosses the placenta, therefore, placing the developing fetus at a higher risk for lead toxicity. This can lead to adverse consequences, such as spontaneous abortion, low birth weight, low IQ, and neurodevelopmental impairment. We present a rare case of siblings born to a mother with pica behaviors. Her venous lead level was 42 μg/dL at the time of disclosure. The repeat venous level at delivery 2 weeks later was 61 μg/dL. The infant’s venous level shortly after birth was 89 μg/dL. The neonate was transferred to the NICU, where he received 9 doses of intramuscular dimercaprol and 5 days of intravenous Ca2Na2EDTA. Seventy-two hours after completing chelation, the blood lead level rebounded to 46 μg/dL. A 19-day course of dimercaptosuccinic acid was then initiated. As of 12 months of age, he has not required additional chelation. Shortly after, the mother conceived another child, who was born prematurely at 29 weeks. Twelve days before delivery, the mother’s lead level was 30 ug/dL. The infant’s lead level was 32 ug/dL at the time of delivery. The infant’s lead trended down without requiring chelation. Both children have since demonstrated developmental delays and have needed early intervention services.

项与二巯丙醇相关的新闻（医药）

2023-11-27

·Medical Design and Outsourcing

Researchers develop therapy for metal poisoning from implants

Researchers say they found a way to protect people from heavy metal poisoning as a result of toxicity from cobalt implants. Cobalt was widely used for hip and knee joint replacements due to strength and durability, but this led to cases of heavy metal poisoning. Toxicity can arise from cobalt and other metals if they accumulate in body tissues at high levels. After years of implant wear and tear, metal particles can build up around the joint and cause pain, inflammation and dark discoloration. Teams at the University of Connecticut School of Medicine and Carnegie Mellon say they can protect people from this toxicity, called metallosis. They say implant removal represents “the obvious solution.” However, invasive revision joint surgery brings risk with it. According to the team, traditional chelation therapy is another option. In this therapy, a drug binds the heavy metal and allows the body to excrete it. However, this has a difficult time penetrating joints and surrounding tissues. Researchers found that injecting a material made of traditional chelator combined with a molecule naturally found in the fluid surrounding the joints makes an effective, less invasive therapy to clear out cobalt. They used a chelator called British anti-Lewisite (BAL). This treatment originally helped soldiers poisoned with arsenic-containing Lewisite during World War II. The teams attached the BAL to hyaluronic acid and injected it into the hip joints of rats with cobalt metallosis. Within hours, they say the acid cleared a great deal of cobalt into the bloodstream and kidneys so the rats could excrete it. “This unique approached developed by teams at The Cato T. Laurencin Institute and the department of chemistry at Carnegie Mellon University offer a possible breakthrough treatment for metal ion disease after joint replacement,” said Dr. Cato Laurencin, CEO of the Cato T. Laurencin Institute for Regenerative Engineering. “Now that we know it works in animals, our hope is to eventually bring this type of therapy to humans,” he says.

2023-07-27

·EndPoints

Akorn’s bankruptcy, recalls bring a drug to treat lead poisoning into shortage

A drug used to treat lead poisoning is now in short supply after Akorn Pharmaceuticals filed for bankruptcy and many of its products were recalled this spring. Dimercaprol is on the FDA’s drug shortages list , with no date for resolution listed. It’s “very frustrating” not to have an essential antidote available, as another injectable product that can be used to treat lead poisoning is also not readily available, according to Erin Fox, an expert on drug shortages and an adjunct professor at the College of Pharmacy at the University of Utah. Unlock this article instantly, along with access to limited free monthly articles and our suite of newsletters

2023-03-20

·Outsourcing Pharma

EDSA outlines supply danger to 100 medicines after manufacturer bankruptcy

The End Drug Shortages Alliance (EDSA), a collaboration between healthcare industry stakeholders, has called attention to the risk of drug shortages by publishing a report outlining what treatments could be at risk. The decision to publish the report arrived after Akorn Pharmaceuticals filed for bankruptcy on February 23, 2023, and ceased all manufacturing operations in the US. Prior to the company closing its doors, it possessed a portfolio of over 100 medications. According to EDSA, Akorn was the sole manufacturer for various acute care injectables, including products that are currently in shortage. This includes products such as physostigmine injection, dimercaprol injection, and calcitriol injection. There is currently a mitigation strategy in place for some of the products most at risk, but in the cases where Akorn had less than 100% of the market share for a particular product, such as sufentanil injection, this is not true. “Transparency regarding drug shortages is important to ensure patient care remains uninterrupted,” said Mittal Sutaria, SVP, Vizient pharmacy contract and program services and EDSA board member. “The healthcare system needs time so that pharmaceutical companies can increase manufacturing when possible and providers can develop mitigation strategies to alleviate any potential disruption in supply when a manufacturer exits the market.” EDSA stated that due to the potential for drug shortages, clinicians will need to develop strategies to mitigate the issue, and encouraged them to exercise a ‘stewardship mindset’ when ordering, prescribing and administering medication affected by supply constraints. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Further, the organization advised manufacturers of impacted products to evaluate their ability to maintain or increase product availability for the marketplace. Akorn bankruptcy The problems that Akorn had faced had been ongoing for a number of years. In 2018, the company had attempted to merge with Fresenius Kabi, but the deal had fallen through after the latter company cited operational problems at the former. Following this period, the company looked to sell itself, but could only manage the sale of individual products and brands. Earlier this year , Herald & Review published a letter from Akorn’s then CEO, Douglas Boothe, to employees of the company, announcing that it would file for bankruptcy, As a result of the decision, the company closed all US sites and engaged in a company-wide lay-off of employees.

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