Allergy drug Chlorcyclizine could potentially treat erythropoietic protoporphyria, claims research

A common antihistamine may offer hope for patients with a rare genetic disease that can lead to severe liver damage and ultimately require transplantation, according to new research from Rutgers Health.

The study in Cellular and Molecular Gastroenterology and Hepatology found that chlorcyclizine, a decades-old allergy medication, could potentially treat erythropoietic protoporphyria (EPP), a condition that creates extreme skin light sensitivity and can produce toxic levels of protoporphyrin in the liver, bone marrow, red cells, and plasma.

“There is an unmet need for these patients,” said Bishr Omary, senior vice chancellor for academic affairs and research at Rutgers Health and senior author of the study. “The primary treatment for patients with severe liver damage is liver transplantation, which is a major and life-saving surgery that depends on available donor organs.”

EPP is a rare condition, affecting an estimated 4,000 people in the U.S. Of those, only a small percentage suffer enough liver damage to require transplantation. It is unlikely, therefore, that any company will develop a drug to treat the condition, which is why Omary and his colleagues tested existing medications.

The research team screened more than 2,500 compounds, including many FDA-approved drugs, in a zebrafish larvae EPP experimental system previously described by Omary’s lab. The tiny fish allow researchers to visualize the buildup of toxic compounds easily and test potential treatments.

“The zebrafish are transparent at their larval stage, and that allows us to quantify and visualize the porphyrin, which is fluorescent,” said Ning Kuo, the first author of the study who worked with Omary at the University of Michigan, then Rutgers before moving to the University of California, San Diego to pursue her PhD. “It was easy to evaluate each treatment under the microscope. If I saw glowing porphyrin, the treatment didn’t work. If I didn’t, the treatment had enabled the liver to excrete it into the fish culture medium.”

When the researchers tested chlorcyclizine in mice with EPP, they found that female mice, but not male mice, experienced reduced hepatic protoporphyrin accumulation and liver injury, decreased protoporphyrin in bone marrow and red cells and increased protoporphyrin excretion in stool. This sex-specific effect appears related to how quickly males metabolize the drug.

“In rats, chlorcyclizine is metabolized eight times higher in male versus female livers,” said Omary. “Fortunately, we’re not aware of similar chlorcyclizine metabolism differences in humans.”

The study team, which included one researcher from Michigan, replicated their findings using an independent toxin-induced EPP mouse model. They also showed in EPP liver cell culture models that the histamine pathway promotes porphyrin accumulation, which is blocked by the over-the-counter antihistamine drug classes that treat allergy (e.g., chlorcyclizine or fexofenadine) or that limit acid production (e.g., cimetidine or ranitidine).

Detailed analysis showed that chlorcyclizine appears to work through multiple mechanisms, including helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of mast cells, a type of immune cell that produces histamine.

For EPP patients, the findings could eventually lead to a much simpler treatment option than transplantation by preventing liver damage at a much earlier stage. The antihistamine allergy drugs have been used safely for decades, which could help speed the path to clinical trials for this new use.

The researchers hope to secure support for a clinical trial to test the effectiveness of chlorcyclizine in EPP patients for both liver and skin involvement. A phase 2 clinical trial is already underway, testing the antacid cimetidine for treating the skin manifestations of EPP. It is possible that the different antihistamines may act additively or synergistically.

“Given their well-established safety, we hope to fast-track trials of chlorcyclizine either alone or in combination with cimetidine,” Kuo said.

Reference:

Ning Kuo, Pei Li, Juliana Bragazzi Cunha, Lu Chen, Jordan A. Shavit, M. Bishr, The histamine pathway is a target to treat hepatic experimental erythropoietic protoporphyria, Cellular and Molecular Gastroenterology and Hepatology, DOI: https://doi.org/10.1016/j.jcmgh.2025.101463

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Long-Term Association Between Childhood Blood Pressure and Adult Hypertension: Insights from a Cohort Study

A recent groundbreaking study
revealed an interesting association between pediatric blood pressure and
hypertension. The study found that childhood normal blood pressure tends to be
maintained into adolescence but decreases from adolescence to young adulthood
as per the findings published in the journal JAMA Pediatrics.

Adult Hypertension or adult blood
pressure (BP) is a risk factor for various cardiovascular diseases. Hence it is
necessary to identify and address these issues at the earliest. Pediatric blood
pressure has been associated with adverse cardiovascular outcomes. BP tracking and
its persistence across age, and the likelihood of an individual transitioning
between different BP categories over time has been discussed for a long time
but did not yield satisfactory results. There is ambiguity on the association between
maintaining normal BP in early life and the prevention of cardiovascular
diseases later in life. There is uncertainty about the effectiveness of
screening blood pressure in children and teenagers. The US Preventive Services
Task Force (USPSTF) has also highlighted the knowledge gap between the long-term
natural history of hypertension in children and the spontaneous resolution of
hypertension. Hence researchers conducted a trial to evaluate BP tracking from
childhood to midadulthood using the American Academy of Pediatrics (AAP)
thresholds and estimate transition probabilities among BP classifications over
time considering multiple time points.

Also Read: New AHA Guidelines Highlight Strategies to Prevent First Strokes: Emphasis on Lifestyle Changes, Screening

The analyses were carried
out in 2023 by utilizing data gathered from the longitudinal Cardiovascular
Risk in Young Finns Study. About 3,596 participants aged 3 to 18 years were
recruited and all the participants had BP examined 9 times over 38 years, from
childhood (aged 6-12 years) or adolescence (15-18 years) to young adulthood
(21-27 years), late young adulthood (30-37 years), and mid-adulthood (39-56
years). Three BP recordings were made at each visit and mean BP was taken. For
individuals less than 18 years old BP classifications (normal, elevated,
hypertension) were based on AAP guidelines, and for those 18 years or older the
2017 American College of Cardiology/American Heart Association guidelines were
taken. generalized estimated equations were used to track coefficients. Transition
probabilities among BP classifications were estimated using multistate Markov
models.

Findings:

  • This study included 2918 participants (mean [SD]
    baseline age, 10.7 [5.0] years; 1553 female [53.2%]).
  • Over 38 years, the tracking coefficient for
    maintaining elevated BP/hypertension was 2.16.
  • Males had a higher probability than females of
    progressing to and maintaining hypertension and a lower probability of
    reverting to normal BP from childhood to mid-adulthood.
  • For both sexes, the probability of transitioning
    from adolescent hypertension to normal BP in mid-adulthood was lower compared
    with childhood hypertension.
  • The probability of maintaining normal BP sharply
    decreased in the first 5 to 10 years, stabilizing thereafter.
  • Children with normal BP generally maintained
    this status into adolescence but decreased by young adulthood.
Also Read: New guideline: Preventing a first stroke may be possible with screening, lifestyle changes

Thus, the key takeaway from this
study is the long-lasting link between blood pressure (BP) levels in childhood
and adolescence and BP levels in adulthood. The BP levels in children and
adolescents are associated with BP levels later in life, from young adulthood
to mid-adulthood suggesting an early life high blood pressure can persist into
adulthood increasing the hypertension and cardiovascular risk. The researchers
also suggest early screening can help in early intervention.

Further reading: Meng Y, Sharman
JE, Iiskala F, et al. Tracking and Transition Probability of Blood
Pressure From Childhood to Midadulthood. JAMA Pediatr. Published
online November 04, 2024. doi:10.1001/jamapediatrics.2024.4368

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Women with severe pre-eclampsia or eclampsia more likely to have abnormal Cerebroplacental Ratio: Study

Hypertensive disorders of pregnancy (HDP) are known causes
of placental insufficiency leading to adverse perinatal outcomes—over half
(58.9%) of women with HDP at Mbarara Regional Referral Hospital have adverse
perinatal outcomes. The cerebroplacental ratio (CPR) is an important
noninvasive predictor of adverse perinatal outcomes because it considers both
the umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry
and provides valuable information about the hemodynamic status of the fetus. It
has a high diagnostic accuracy in the detection of abnormal fetal wellbeing and
can prevent approximately 30% of adverse perinatal outcomes. An abnormal CPR
reflects the redistribution of cardiac output to the cerebral circulation and
is predictive of adverse intrapartum and neonatal outcomes.

The cerebroplacental ratio (CPR) is an important predictor
and prevents approximately 30% of these adverse perinatal outcomes. Authors
determined the prevalence and factors associated with abnormal CPR among women
with HDP at MRRH.

Authors conducted a cross-sectional study from December 2022
to May 2023 at the high-risk obstetrics unit of MRRH. They consecutively
enrolled all women with hypertensive disorders and gestational ages ≥ 26 weeks
and performed obstetric Doppler studies to document the pulsatility index (PI)
of the umbilical artery (UA) and middle cerebral artery (MCA) and then
calculated the CPR as a ratio of the MCA-PI and UA-PI. The prevalence of women
with an abnormal CPR ≤ 1 0 was expressed as a percentage. They used robust
modified Poisson regression analysis to determine the factors associated with
abnormal CPR.

Study enrolled 128 women with hypertensive disorders in
pregnancy, with a mean age of 28 8±6 3 years. Of these, 67 (52.3%) had abnormal
CPR. The factors associated with abnormal CPR were severe pre-eclampsia (adjusted
prevalence ratio (aPR): 5.0, 95% CI: 1.28, 29.14) and eclampsia (aPR: 5.27, 95%
CI: 1.11, 34.27).

This cross-sectional study determined the prevalence and
factors associated with abnormal CPR among pregnant women with hypertensive
disorders at a tertiary hospital in a low-resource setting in southwestern
Uganda. Authors found that more than half (52.3%) of the women with HDP had
abnormal CPR. Additionally, severe pre-eclampsia and eclampsia were
independently associated with abnormal CPR by fivefold compared to gestational
hypertension. Taken together, these findings build on prior studies in the
setting that have documented high rates of adverse perinatal outcomes among
women with HDP and highlight the need to implement routine obstetric Doppler
studies with CPR assessment among women with HDP. These findings could guide
the management of women with these conditions and aid in interventions to
optimize perinatal outcomes.

This study highlights a high prevalence of abnormal CPR
among women with HDP. Pregnant women with severe pre-eclampsia and eclampsia
are more likely to have abnormal CPR. Obstetric Doppler studies with CPR maybe
considered for the assessment of pregnant women with HDP, prioritizing those
with severe pre-eclampsia and eclampsia. Authors recommend further research to
assess perinatal outcomes among those with and without abnormal CPR to profile
women with HDP at increased risk of adverse perinatal outcomes, which could aid
in early intervention to improve outcomes. A matched case-control study with
participants matched especially in terms of gestational age may also be
considered to show an association between pre-eclampsia and abnormal CPR.

Source: Suada Suleiman Ibrahim, Yarine Fajardo
Tornes, Musa Kayondo; Wiley Journal of Pregnancy Volume 2024, Article ID
8895971, 8 pages https://doi.org/10.1155/2024

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Lupin’s Generic Entresto Approved by USFDA, Set to Rival Novartis’ Bestseller

Mumbai: In a fresh challenge to Novartis’ blockbuster heart failure drug Entresto, Indian generics maker Lupin has received approval from the U.S. Food and Drug Administration (FDA) for its generic version of Sacubitril and Valsartan Tablets. This comes amid an ongoing legal tussle between Novartis and generics manufacturers, including MSN Pharmaceuticals.

Announcing the approval, Lupin confirmed that its Abbreviated New Drug Application (ANDA) for Sacubitril and Valsartan Tablets has been cleared by the FDA. These tablets are indicated for reducing the risk of cardiovascular death and hospitalization in adult patients with chronic heart failure and reduced ejection fraction, as well as for treating symptomatic heart failure in pediatric patients aged one year and older.

Also Read: Lupin receives USFDA approval for heart failure drug

Entresto remains one of Novartis’ top-selling drugs, according to a recent media report in ET, generating over USD 6 billion in the U.S. drug market in 2023. However, the Swiss pharmaceutical giant has been aggressively defending its patent, leading to multiple lawsuits against generics manufacturers.

In 2022, Novartis sued MSN Pharmaceuticals and other companies in a Delaware federal court, alleging patent infringement over their generic versions of Entresto. It also took legal action against the FDA, arguing that the agency’s approval of MSN’s generic was “unlawful.”

Also Read: US Appeals Court decision favors MSN Pharma in Novartis heart drug Entresto generic dispute

Despite these efforts, Novartis faced setbacks. In August 2023, U.S. District Judge Richard Andrews denied the company’s request for a preliminary injunction, stating that Novartis was unlikely to succeed in its infringement claims. However, MSN’s generic launch was temporarily paused as Novartis pursued an appeal.

Most recently, a Washington, D.C. federal judge rejected Novartis’ last-minute attempt to block MSN’s generic launch, paving the way for the first U.S. generic version of Entresto.

With Lupin now securing FDA approval, Novartis is set to face yet another challenge to its multibillion-dollar heart failure drug in the generics market.

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No significant relationship between effect of maternal diet quality indices on neonatal thyroid function: Study

Thyroid hormones regulate the growth of fetal and
differentiation of several tissues, such as brain, adipose tissue, and bone.
The physiology of thyroid significantly changes during pregnancy and provides
adequate hormones for the mother and fetus. During early pregnancy, the growth
and development of fetus depend on the maternal thyroxine because the fetal
thyroid gland is entirely mature after 20 weeks of gestation. Several factors
including maternal thyroid diseases, some drugs, type of delivery, dietary
pattern, and birth conditions are associated with changes in the neonatal
thyroidstimulating hormone (TSH) concentration.

Diet is one of the lifestyle factors that influence the risk
of thyroid disorders. The neonatal thyroid is very sensitive to variations in
maternal dietary intake. Neonatal TSH levels could show the intake of some
nutrients including iodine during pregnancy. A healthy diet includes fruits,
vegetables, nuts, and fish and contains useful micronutrients that are important
for thyroid function. These findings showed the importance of maternal diet
during pregnancy on neonatal TSH levels. Proper nutrition and healthy dietary
pattern may improve maternal thyroid function.

The thyroid health of neonates has a significant effect on
brain development. Maternal and infant factors affect infant TSH and thyroid
hormone levels. However, conflicting findings have been reported. Authors
hypothesized that since maternal nutrition affects birth weight and offspring
growth, it may also impact endocrine patterns in offspring. There is some
evidence related to single nutrients and thyroid function. However, there is
few evidence related to specific dietary patterns and thyroid function. In
fact, no studies have yet assessed the possible impact of maternal DPI on
neonatal thyroid function. Thus, this study aimed at investigating the
association between maternal DPI on neonatal cord blood thyroid hormone levels.

This cross-sectional study is a substudy of a birth cohort.
Overall, 216 mothers, aged 16–45 years, were recruited in their first trimester
of pregnancy. To calculate DPI, the daily energy percentage of
phytochemical-rich foods was divided by the total daily energy intake. At delivery
time, TSH and free thyroxine (FT4) levels were measured in cord blood samples
using chemiluminescence immunoassay. Results: The mean (standard deviation
(SD)) age of mothers was 29.56 (5.50) years, and 47% of newborns were girls.
The mean (SD) of DPI in the first, second, third, and fourth quartiles was 25
03 ± 4 67, 33 87 ± 2 18, 40 64 ± 2 10, and 51 17 ± 4 98, respectively. There
was not any significant correlation between DPI score with cord serum TSH and
FT4 levels in crude and adjusted analysis.

In the present study, the DPI score was not associated with
neonatal TSH and FT4 levels. So, no significant association between neonatal
thyroid function and maternal diet quality index was shown in the present
study. In previous studies, no association was observed between diet and weight
gain during pregnancy with cord blood TSH levels.

The present study reports no significant relationship
between maternal DPI with neonatal TSH and FT4 levels. The amount of foods rich
in phytochemical compound consumption can be important, and their beneficial
effects may be shown with high consumption. There is little information about
the impact of maternal DPI on fetal and neonatal thyroid function. It
highlights the need for further studies to investigate the impacts of maternal
quality of diet on neonatal thyroid dysfunction.

Source: Vida Hashemi Dehkordi, Mehri Khoshhali, Motahar
Heidari-Beni; Wiley Journal of Pregnancy Volume 2024, Article ID 9558023, 6
pages

https://doi.org/10.1155/2024/9558023

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Maternal medications lower the protein and fat levels in breast milk: JAMA

A recent study published in the Journal of American Medical Association highlighted the potential impact of maternal medications on the macronutrient composition of human milk. This cross-sectional study examined breast milk samples from mothers in the US and Canada who were either on long-term medications, untreated but with the same underlying health conditions, or completely healthy.

The study by Essi Whaites Heinonen and at the University of California, San Diego analyzed milk samples collected from October 2014 to January 2024 as part of the Mommy’s Milk Human Milk Research Biorepository. This research compared macronutrient levels (protein, fat, carbohydrates, and total energy) in milk samples from 310 mothers on medications, 151 untreated mothers with similar health conditions (disease-matched controls , or DMCs), and 73 healthy untreated mothers. The medications studied included selective serotonin reuptake inhibitors (SSRIs), monoclonal antibodies (MABs), systemic steroids, and other anti-inflammatory drugs (ADs).

After excluding samples with multiple medication exposures or extreme outliers, a total of 384 samples remained for analysis. The team adjusted their findings for several variables, including maternal and infant age, maternal body mass index, breastfeeding practices and other relevant factors. The study found that breast milk from mothers taking certain medications showed significantly lower levels of protein and fat when compared to healthy mothers.

The samples from mothers using SSRIs and systemic steroids showed a 15% to 21% reduction in protein levels when compared to healthy mothers. For instance, milk from mothers on SSRIs contained 0.92 g/100 mL of protein on average when compared to 1.08 g/100 mL in samples from healthy mothers. These differences were statistically significant (P = 0.04 for SSRIs and P = 0.03 for steroids).

The fat levels in milk from mothers on other anti-inflammatory drugs were 10% to 22% lower than the milk from healthy and DMC mothers. Milk from mothers on these medications contained an average of 3.40 g/100 mL of fat, when compared to 3.85 g/100 mL in healthy mothers and 4.38 g/100 mL in DMCs. Also, the energy levels were reduced with treated the milk of mothers in averaging 69.56 kcal/100 mL, versus 77.16 kcal/100 mL in healthy mothers. The difference in fat content compared to DMCs was particularly significant (P = 0.01).

These findings suggest that certain maternal medications may affect the nutritional quality of breast milk, potentially posing risks to the growth and development of infants. The outcomes emphasize the need for further research to identify other contributing factors and fully understand the clinical implications.

Source:

Whaites Heinonen, E., Bertrand, K., & Chambers, C. (2025). Macronutrients in Human Milk Exposed to Antidepressant and Anti-Inflammatory Medications. In JAMA Network Open (Vol. 8, Issue 1, p. e2453332). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.53332

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Pune Businessman Duped of Rs 40 Lakh in MBBS Admission Fraud

Pune- A recent case of fraud in medical admission has come to light in Pune, Maharashtra. A businessman seeking admission for his daughter in an MBBS course was cheated of Rs 40 lakh. In the complaint lodged with the police, the man said that he was promised admission of his daughter to a medical college in exchange for the amount.

According to the News18 Media news report, a 49-year-old businessman living in the Magarpatta area of ​​Hadapsar in Pune was cheated of Rs 40 lakh in the name of getting admission for his daughter in the MBBS course.

Also Read: Pune man duped of Rs 70 lakh in medical admission fraud

The businessman came in contact with the fraudsters through an acquaintance in August last year. He was promised admission for his daughter into a private medical college in Pune. The accused used have been identified as Sunil Kumar (45), Saurabh Gupta (40), Vikas Gupta (28), Randhir Singh (30) and Priyanka Mishra (25).

The five fraudsters assured the victim that they had the necessary connections and guaranteed admission. Believing their claims, the businessman agreed to pay Rs 60 lakh to secure his daughter’s admission.

The accused took the amount through cash payment and online transfer. However, despite the promise, the businessman’s daughter did not get admission from anywhere. After this, when he asked for the money back from the accused, they returned only Rs 20 lakh, reports News18.

After realizing that he had been cheated of the remaining Rs 40 lakh, the businessman lodged a complaint with the police about being scammed. Currently, the police have also started an investigation, in which Assistant Inspector Deepak Barge is investigating under the guidance of Senior Police Inspector Sanjay Mogle.

Also Read: PG seat scam: Udupi doctor duped of Rs 8.5 lakh over promise of MPH seat in UK, 3 held

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NMC explains why NEET 2025 will stick to Pen-and-Paper format

Explaining why the National Eligibility-cum-Entrance Test exam is being conducted in pen-and-paper mode, a top official at the National Medical Commission (NMC) informed Education Times that before switching to the Computer-Based Test mode, the students must be it is necessary to ensure that proper infrastructure is in place, students are prepared mentally for the new format and to ease the pressure on the students.

As per the Chairman of the National Medical Commission (NMC) Dr BN Gangadhar, in the CBT mode, the exam will be conducted in multiple shifts and multiple question papers, which could result in logistical issues. Further, lakhs of computers will be required and the candidates, especially those belonging to rural and remote areas will need to get comfortable with the new pattern.

For more information, click on the link below:

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CAG urges Himachal Pradesh Medical Council to maintain data on Doctors’ license renewal

Altogether 2,779 doctors in Himachal Pradesh failed to renew their registration as of September 2022 and despite this, they did not face any action by the State Medical Council (SMC), revealed a recent report on the healthcare system by the Comptroller and Auditor General (CAG).

The report highlighted that even though the Himachal Pradesh Medical Council Act, 2003 requires doctors practicing modern medicine to mandatorily register with the Council, not all the employed doctors in the State were registered with the Council. It also noted that no mechanism was adopted by the Council to track such non-registered employed/non-employed doctors.

For more information, click on the link below:

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NEET PG Aspirants seek justice over delayed MP round 2 counselling, seat allotment issues

Pointing out how the NEET PG 2024 Round 2 State Counselling has not been concluded yet in Madhya Pradesh, the NEET PG aspirants across the country have claimed that this is giving an undue advantage to the Madhya Pradesh students where people can choose between State Round 2 and AIQ Round 3 seats.

Apart from this, the candidates have also claimed that there was a huge negative shift in the seat allotment and upgradation of seats and institutes, compared to last year.

For more information, click on the link below:

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