Researchers have found that Lansoprazole, an over-the-counter acid reflux drug that is often taken by pregnant women, may be a promising therapy to reduce preterm birth.
The study, published in the journal JCI Insight also identified 12 other USFDA-approved drugs that are deemed safe in pregnancy. While the drugs encompass a variety of modalities, the researchers said they all appear to act on biological pathways that affect the immune response, which is implicated in preterm birth.
“Inflammation clearly plays a role in initiating labour and preterm birth. Immune pathways are very significantly dysregulated in women who end up delivering preterm, and they’re also dysregulated in babies who are born early,” said said study senior author Marina Sirota from University of California.
“However, we have seen from our previous work that there is an interaction between the maternal and fetal immune systems and a breakdown in maternal-fetal tolerance,” Sirota added. To identify candidate drugs that might be effective in preventing preterm birth, the researchers first looked at which genes were up- or down-regulated in the blood cells of women who experienced spontaneous preterm birth to identify a gene expression “signature.”
Then they looked for the opposite signature in cells that had been exposed to 1,309 different drugs, reasoning that if a drug could correct the effects that preterm birth had on the women’s blood cells, the drugs might also prevent preterm birth itself.
The researchers identified 83 drug candidates, but when they excluded those found to have pregnancy risks in animal or human studies, they wound up with 13 drugs, ranked according to their “reversal score,” a measure of the extent to which they were able to reverse the gene expression signature of preterm birth.
The scientists chose lansoprazole for further testing because, in addition to its high reversal score, it is available over the counter, and they know from their previous work that it affects a stress-response protein, heme oxygenase-1, that has been linked with pregnancy disorders.
Lansoprazole, which is a proton-pump inhibitor marketed as Prevacid, had the second-highest reversal score of the 13 drugs identified as being safe and effective. Progesterone was further down the list. The researchers tested lansoprazole in pregnant mice that had been given a bacterial component to induce inflammation, which causes some fetuses to die in utero, where they are reabsorbed.
When these mice were given lansoprazole, they had more viable fetuses. Lansoprazole also worked better in these mice than progesterone. Although it is a good measure of how inflammation affects pregnancy in mice, the researhers said the fetal resorption mouse model is not an adequate model of human preterm birth.
They said more work, including studies in people, would need to be done before lansoprazole or any of the dozen other drugs they identified could be proven effective in pregnant women at risk for preterm birth.
“This, basically, is a proof of concept that this drug has anti-inflammatory properties, which are not the properties the drug was designed for, this is a short way to get to new therapeutics for known diseases,” said study author David K Stevenson. (IANS)
With all the havoc it’s wreaking across the globe, the coronavirus outbreak is naturally having an impact on couples and their relationships. Family therapists are conducting sessions remotely as patients are confined to their homes.
They say even the most subtle differences in temperament can be aggravated because of the outbreak’s stress. It’s a time when every domestic decision can seem to have impossibly high stakes, from going to the grocery store to deciding who gets quarantined together.
The 60-something husband works in the food industry and still insists upon leaving every day for work, saying he needs to keep his business afloat. His frightened wife desperately wants him to stay home.
For another couple, in the midst of a separation, the bitterly fought issue is the kids and whether they can safely see friends. One parent is allowing it in an effort to be the “fun parent”; the other bitterly opposes it.
And for still another couple, it’s simply about grocery shopping. She fills the cart, and he accuses her of hoarding unnecessarily. She argues that they need to be prepared.
Scenarios like these are playing out in urban high-rises, suburban homes and tiny rural communities across America as couples try to navigate what has abruptly become the “new normal” during the coronavirus outbreak. Described by therapists, lawyers or the couples themselves, they reveal how even the most subtle differences in temperament or coping strategy can be painfully exacerbated under the incredible stress and anxiety that the outbreak is causing.
It’s a time when every domestic decision can seem to have impossibly high stakes, says Catherine Lewis, therapist and faculty member at Ackerman Institute for the Family in New York, from the seemingly small — whether to go grocery shopping — to the fraught calculus of which family members should isolate together.
“This pandemic is making us all think about our relationships, because you really cannot do one thing without it impacting somebody else,,” says Lewis, who’s been conducting therapy sessions remotely. “It’s such a powerful example of how interconnected we all are.”
Added to that, Lewis notes, is the utter helplessness of having no idea how long the situation will last.
She does see some couples finding “that they have a wild capacity to be resilient, to just find a way to move through the day.” On the negative side, it’s clear that people are generally not at their best when under deep stress.
“Normal patterns are intensified,” she says. “There’s increased annoyance, people snapping.”
Alcohol can become a more frequent coping mechanism. Or worse.
“I’m worried about couples where there is intense aggression,” she says. In cases where there was already domestic abuse, advocates fear a dangerous escalation.
Jennifer Kouzi, a divorce lawyer and mediator, puts it bluntly: “We’re seeing a lot more bad behavior.”
In many cases, there may be no ramifications for bad behavior. One parent, for example, has refused to turn over a child to the other in accordance with their agreement, citing the virus crisis, even though the other parent is taking every precaution. Police have refused to enforce the custody order and recommended the parent go to court, but it’s unclear if judges will deem the case an emergency. In another case Kouzi is aware of involving a separated couple, one parent is allowing their kids to go see friends, “to be the fun parent, so the kids will want to stay there full-time instead of with the parent actually following recommendations and guidelines.” It’s not all grim.
“Some parents have actually risen to the occasion and are communicating better than normal, rearranging schedules and increasing FaceTime access and doing what makes sense” for their kids, she says.
Kouzi, who practices in both New York and in Westchester County, one of its suburbs, is telling her clients to try to use the time productively or to consider mediation.
“There will be such a backlog when courts open up again,” she says.
Some couples are experiencing only minor ripples, if any. Stephanie Pfeiffer, a business systems analyst in Boston, found herself annoyed with her husband when they went food shopping last week, and each time she put something into the cart — two pounds of butter, cans of tuna or tomato soup, a box of crackers — he questioned why.
“It’s been like most days,” she reported last week, “except that my husband is leaving dirty dishes and I get to clean up after him, too.” She joked that her spouse had made the mistake of coming down at one point to chat, “and I handed him a baby to put down for a nap. He hasn’t come down since!”
Adrienne Pattison, who lives in a rural area of Washington state, joined a Facebook group called “Parenting Under Quarantine” a week ago and wrote: “Is it just me or is anyone else totally frustrated with the husband/partner or whatever?? I’m about to go postal!” Her good-natured venting elicited more than 160 comments and anecdotes.
Maggie Hellman, the Bergenfield, New Jersey, mother who created the Facebook group for her friends to blow off their own steam — she never thought it would balloon to over 20,000 — notes that some couples are, of course, dealing with gravely serious challenges. Her brother, a pediatric intensive care physician, has to come home through a side door to discard dirty clothing and wash his hands to avoid infecting the family. His wife, a nurse, must be extremely careful as well.
Hellman, a social worker and stay-at-home mom, says it’s natural that couples with children are feeling intense stress.
“Children create stress in a marriage, period,” she says. “The relationship changes dramatically.” Under current conditions, she says, “you’re stuck at home all day with each other when perhaps there already were issues.” She imagines that single parents have it even worse, especially if they have only one child.
“They get no break, they have no one else to be with,” she says.