Pfizer CEO says there will be no generic Paxlovid for China

 Pfizer Inc is not in talks with Chinese authorities to license a generic version of its COVID-19 treatment Paxlovid for use there, but is in discussions about a price for the branded product, Chief Executive Albert Bourla said on Monday.

Reuters reported on Friday that China was in talks with Pfizer to secure a license that will allow domestic drugmakers to manufacture and distribute a generic version of the U.S. firm's COVID-19 antiviral drug Paxlovid in China.

Referring to that report, Bourla speaking at J.P. Morgan's healthcare conference in San Francisco, said "We are not in discussions. We have an agreement already for local manufacturing of Paxlovid in China. So we have a local partner that will make Paxlovid for us, and then we will sell it to the Chinese market."

Bourla said the company had shipped thousands of courses of the treatment in 2022 to China and in the past couple of weeks, had increased that to millions.

On Sunday, China's Healthcare Security Administration (NHSA) said that the country would not include Paxlovid in an update to its list of medicines covered by basic medical insurance schemes as the U.S. firm quoted a high price for the COVID-19 drug.

Bourla said that talks with China on future pricing for the treatment had broken off after China had asked for a lower price than Pfizer is charging for most lower middle income countries.

"They are the second highest economy in the world and I don't think that they should pay less than El Salvador," Bourla said.

Still, Bourla said the removal from the list would not have an effect on the company's business there until April. He said the company had shipped millions of courses of the drug to China in recent weeks.

The company could end up selling only to the private market in China, he said. 

https://www.yahoo.com/now/1-pfizer-ceo-says-no-005654058.html

Bolsonaro Is Hospitalized in US With Abdominal Pain

 Brazil’s ex-President Jair Bolsonaro has been admitted to a US hospital with abdominal pain a day after his supporters stormed Brasilia demanding military intervention against his loss in the October election, according to his wife.

The conservative leader, who traveled to the US on Dec. 30 to skip the inauguration of his successor Luiz Inacio Lula da Silva, is being treated at the AdventHealth Celebration, a hospital near Orlando, O Globo newspaper reported earlier, without revealing how it obtained the information.

Bolsonaro’s wife confirmed he’s hospitalized though she didn’t say where. A former aide to Bolsonaro, who requested anonymity to discuss his heath, said he was being treated for possible intestinal obstruction. The ex-president has undergone several surgeries after being stabbed in the abdomen while campaigning in 2018.

Emails and calls to the US hospital went unanswered.

While Lula has alleged that Bolsonaro had been encouraging the riots in Brasilia, US National Security Adviser Jake Sullivan said Monday the Biden administration hasn’t received any requests from Brazil to extradite the former president.

Bolsonaro published on social media on Sunday, speaking out against the depredation of public buildings carried out by his supporters in Brasilia, and again on Monday, touting his government’s achievements.

https://www.yahoo.com/news/bolsonaro-hospitalized-us-brasilia-riots-172738012.html

Another step toward an insulin tablet

 For the millions of people living with diabetes, insulin is a life-saving drug. Unlike many other medicines, though, insulin cannot be easily delivered by swallowing a pill -- it needs to be injected under the skin with a syringe or pump. Researchers have been making steps toward an insulin pill, and now, a team reports in ACS Nano that they've delivered insulin to the colons of rats using an orally administered tablet powered by chemical "micromotors."

Patients with diabetes have trouble regulating their blood glucose levels because they produce little or no insulin. Synthetic insulin has existed for over a hundred years, but it is often administered with an injection or an implanted pump. People affected by diabetes often take insulin multiple times per day, so frequent injections can be painful, and as a result, some patients do not take the recommended dose at the correct times.

An oral form of the drug would be ideal, but the harsh environment of the stomach breaks down and neutralizes the hormone before it can be absorbed by the intestines and get into the bloodstream. Previous attempts at oral administration protected the hormone from stomach acids with micro- or nanocarriers but relied on insulin to passively diffuse into the cells that line the colon, which isn't very efficient. A better approach could be actively moving the medicine around the body instead, such as with a recently reported robo-capsule that delivers its cargo by drilling itself into the thick, mucosal layer of the small intestine. Yingfeng Tu, Fei Peng, Kun Liu and colleagues wanted to achieve a similar effect with their an insulin-loaded mini-tablets, which featured tiny, chemical "micromotors" that could deliver insulin to the colon safely and effectively.

To make these tablets, the researchers covered magnesium microparticles with a layer of an insulin-containing solution and a layer of liposomes. They then mixed these particles with baking soda, pressed them into mini-tablets that were about 3 mm long then covered them with an esterified starch solution. The starch protected the tablets from stomach acid, allowing them to reach the colon intact. As they broke down, the magnesium microparticles reacted with water to generate a stream of hydrogen gas bubbles, which acted as micromotors that propelled insulin toward the colon's lining to be absorbed. The team also tested their mini-tablets in rats and found that they could significantly reduce the animals' blood glucose levels for over five hours. In fact, they could maintain a glucose level almost as low as injection-delivered insulin. Though more work is needed, the researchers say that this is a concrete step toward creating more oral formulations of traditionally injection-only medications.

The authors acknowledge funding from the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation and the Key Research and Development Project of Lishui.

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Story Source:

Materials provided by American Chemical Society. Note: Content may be edited for style and length.

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Journal Reference:

1. Kun Liu, Qiuyue Liu, Jiarong Yang, Chen Xie, Shuanghu Wang, Fei Tong, Junbin Gao, Lu Liu, Yicheng Ye, Bin Chen, Xiaoying Cai, Zhendong Liu, Zeqi Li, Fei Peng, Yingfeng Tu. Micromotor Based Mini-Tablet for Oral Delivery of Insulin. ACS Nano, 2022; DOI: 10.1021/acsnano.2c07953

https://www.sciencedaily.com/releases/2023/01/230109112742.htm

Why obesity is more dangerous for men

 A newly published study from York University sheds light on the biological underpinnings in sex differences in obesity-related disease, with researchers observing "striking" differences in the cells that build blood vessels in the fatty tissue of male versus female mice.

Men are more likely than women to develop conditions associated with obesity such as cardiovascular disease, insulin resistance and diabetes, says York Professor Tara Haas with the Faculty of Health's School of Kinesiology and Health Science.

"People have used rodent models to study obesity, and the diseases that are associated with obesity—like diabetes—but they've typically always studied male rodents, because females are resistant to developing the same kinds of diseases," says Haas, lead on the study. "We were really interested in exploring that difference because, to us, it spoke of something really fascinating happening in females that protects them."

Haas and her team observed in a 2018 study in Frontiers in Physiology that when mice become obese, females grow a lot of new blood vessels to supply the expanding fat tissue with oxygen and nutrients, whereas males grow a lot less.

In this latest study published in iScience, Haas and her co-authors, including York Ph.D. student Alexandra Pislaru, Faculty of Health Assistant Professor Emilie Roudier, and former York post-doctorate student Martina Rudnicki, focused on differences in the endothelial cells that make up the building blocks of these blood vessels in fat tissue.

The team used software to help sift through thousands of genes to zero in on the ones that would be associated with blood vessel growth. They discovered that processes associated with the proliferation of new blood vessels were high in the female mice, whereas the males had a high level of processes associated with inflammation.

"It was very striking the extent of inflammation-associated processes that were prevalent in the males," Haas recalls. "Other studies have shown that when endothelial cells have that kind of inflammatory response, they're very dysfunctional, and they don't respond to stimuli properly."

"It is exciting to observe the continuing resilience that female endothelial cells display even when stressed by a long-term high-fat diet," Pislaru says. "The findings from our study can help researchers to get a better understanding of why obesity manifests differently in men and women."

The researchers also examined the behavior of the endothelial cells when they were taken out of the body and studied in petri dishes.

"Even when we take them out of the body where they don't have the circulating sex hormones or other kinds of factors, male and female endothelial cells still behave very differently from each other," Haas explains.

Female endothelial cells replicated faster, while male endothelial cells displayed greater sensitivity to an inflammatory stimulus. By comparing with previously published data sets, the researchers found endothelial cells from aged male mice also displayed a more inflammatory profile compared to female cells.

"You can't make the assumption that both sexes are going to respond to the same series of events the same way," says Haas. "This isn't just an obesity related issue—I think it's a much broader conceptual problem that also encompasses healthy aging. One implication of our findings is that there will be situations where the treatment that is ideal for men is not going to be ideal for women and vice-versa."

While humans and mice have different genes that may be turned up or down, Haas believes the general findings would likely apply and is interested studying the same cells in humans in future research.

More information: Martina Rudnicki et al, Transcriptomic profiling reveals sex-specific molecular signatures of adipose endothelial cells under obesogenic conditions, iScience (2022). DOI: 10.1016/j.isci.2022.105811

Martina Rudnicki et al, Female Mice Have Higher Angiogenesis in Perigonadal Adipose Tissue Than Males in Response to High-Fat Diet, Frontiers in Physiology (2018). DOI: 10.3389/fphys.2018.01452

https://medicalxpress.com/news/2023-01-obesity-dangerous-men.html

COVID: On the lookout for new antibodies

 A team of researchers at FAU and Universitätsklinikum Erlangen has gained new insights into the maturation of SARS-CoV-specific antibodies after multiple vaccinations with the Comirnaty mRNA vaccine. They have now published their work in the journal Science Immunology.

Antibody response is essential for protection against viral infectious diseases, since only neutralizing antibodies can prevent the initial penetration of a pathogen effectively. These antibodies block the binding sites in the surface protein of the virus that are required for docking onto the cellular receptor and thus for uptake into the cell. In addition, antibodies can limit the spread of the virus in the body via additional functions. These functions depend, to a very high extent, on the relevant subclass of the antibody molecule.

During their research, the team led by Prof. Dr. Matthias Tenbusch, Institute of Clinical and Molecular Virology at Universitätsklinikum Erlangen; Prof. Dr. Thomas Winkler, FAU Professorship for Genetics; and PD Dr. Kilian Schober, Institute of Clinical and Molecular Virology at Universitätsklinikum Erlangen, was able to demonstrate that an increased number of antibodies of the IgG4 subclass form after repeated vaccinations with the Comirnaty mRNA vaccine.

Up to now, only a small amount of research in the context of viral infectious diseases has been carried out on these antibodies, which tend to be considered as non-inflammatory, because they are quite rare. This exciting discovery in the field of immunology thus raises new questions about antibody maturation.

The ability of IgG4 antibodies to successfully neutralize the SARS-CoV-2 virus and its variant remains unchanged—an ability that does not differentiate this class of antibodies from the subclass IgG1, which are most frequently formed. The vaccination continues to be effective and it offers very good protection from serious cases as proven in clinical trials. In addition, there is no evidence of adverse effects to the clinical course of an infection with SARS-CoV-2 after several mRNA vaccinations.

However, in the context of the potential of mRNA vaccines for use in infectious diseases as well as for tumors and auto-immune diseases, it is all the more important that the triggered immune responses are fully understood. Further studies are required to find out which immunological mechanisms are responsible for the unusual IgG4 antibody production. During these studies, it will be interesting to investigate whether this type of antibody is formed with other mRNA vaccinations and whether they could be significant for the progression of viral infections.

More information: Pascal Irrgang et al, Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination, Science Immunology (2022). DOI: 10.1126/sciimmunol.ade2798

https://medicalxpress.com/news/2023-01-covid-lookout-antibodies.html

GE HealthCare to Acquire IMACTIS

 

• Acquisition expected to provide significant future expansion opportunity for the IMACTIS CT-Navigation system through GE HealthCare’s large installed base and global scale

• IMACTIS CT-Navigation enables intuitive pre-planning, continuous control, and navigation throughout a range of minimally invasive percutaneous procedures

• This acquisition is the latest example demonstrating that GE HealthCare is executing on its strategy to enable precision care and drive growth

GE HealthCare (Nasdaq: GEHC) today announced it has entered into an agreement to acquire IMACTIS, an innovator in the rapidly growing field of computed tomography (CT) interventional guidance across an array of care areas. IMACTIS is a France-based company that was founded in 2009 by Stephane Lavallee and Lionel Carrat, who created CT-Navigation™, an ergonomic universal solution that provides stereotactic needle guidance, enabling intuitive pre-planning and continuous control throughout a wide range of procedures, from diagnosis to treatment.

https://finance.yahoo.com/news/ge-healthcare-announces-agreement-acquire-213800451.html

UMMS refused to perform gender-affirming surgery; federal court ruled discrimination

 The Baltimore-based University of Maryland Medical System scheduled a gender-affirming surgery for a transgender man, but canceled it the night before the procedure was set to take place. That was a violation of the Affordable Care Act, a federal court ruled Jan. 6. 

In late 2019, a transgender man named Jesse Hammons visited St. Joseph Medical Center in Towson, Md. A physician at the hospital scheduled Mr. Hammons for a hysterectomy to treat his gender dysphoria, The Baltimore Banner reported Jan. 7. 

Gail Cunningham, MD, the hospital's chief medical officer, ordered the procedure to be canceled in accordance with National Catholic Bioethics Standards, which prohibit Catholic hospitals like St. Joseph's from performing gender confirmation surgeries. The physician called Mr. Hammons and canceled the night before the surgery. 

In a statement, UMMS said the "surgeon mistakenly [scheduled] a procedure that could not be performed at the hospital." Additionally, the health system said it offered the surgery to Mr. Hammons at a different hospital, which he refused. 

When UMMS purchased St. Joseph Medical Center in 2012, it agreed to continue operating the hospital under Catholic directives, according to the Banner. But the hospital receives federal Medicaid and Medicare funding, and under Section 1557 of the Affordable Care Act, it can not descriminate on the basis of sexual orientation, gender identity or sex characteristics. 

District Court Judge Deborah Chasanow ruled that UMMS violated the ACA by denying Mr. Hammons a procedure it performs for other patients, simply because he is transgender, The Hill reported Jan. 6. She ruled in favor of a summary judgment, and no damages have been determined. 

"Although our offer to perform gender affirming surgery at a different location was declined by Mr. Hammons, the University of Maryland Medical System remains committed to meeting the unique medical needs of transgender individuals and patients who are routinely scheduled by physicians for appointments and procedures at UMMS member organizations," a spokesperson for the health system told The Hill. The spokesperson said UMMS is "carefully reviewing" the judge's decision, which it largely disagrees with. 

"This is a great win for myself and all transgender people denied equal treatment because of who they are," Jesse Hammons said in a Jan. 6 news release from the ACLU. "All I wanted was for UMMS to treat my health care like anyone else's, and I'm glad the court recognized how unfair it was to turn me away." 

https://www.beckershospitalreview.com/legal-regulatory-issues/umms-refused-to-perform-gender-affirming-surgery-federal-court-ruled-discrimination.html