propranolol

Efficient Propranolol Delivery Enabled by Manganese-Based Bioactive Metal-Organic Frameworks With High Loading Capacity.

Borhanipasvisheh Hanieh H, Deghani Siyahaki Soheil S, Gholamhosseinzadeh Elham E

A green and efficient method was developed for propranolol delivery utilizing manganese-based bioactive metal-organic frameworks (MOFs) as biocompatible drug carriers. Mn-based bioactive MOFs with a high aspect ratio were synthesized and characterized for size (average, 17 µm), morphology, stability, elemental composition, crystallinity, functionality, charge character, and biocompatibility (a protein adsorption capacity of 0.03 µg µg-1 (5 h) and a hemolysis ratio of < 0.5%). Afterward, the MOFs were utilized for drug loading via an encapsulation method, and the drug release studies were also performed. The drug loading was confirmed using the zeta potential, CHN analysis, and thermogravimetric analysis (TGA) measurements. An encapsulation efficiency of 96% (0.5 W/W (drug/MOFs)) and a maximal capacity (Qmax) of 0.526 mg mg-1 were obtained. The drug release showed that 93.72% of the loaded drug was released after 10 h for a composite of 0.25 W/W (drug/MOFs), while for 0.5 W/W (drug/MOFs), the drug release reached a plateau after 3 h. The kinetic studies showed longer release times and higher release rates for higher drug loading efficiency. Overall, herein, a bioactive platform for efficient delivery of propranolol was developed to improve the therapeutic efficacy by enhancing the drug loading and achieving controlled drug release.

Case Report: Early-onset portal hypertension revealing pediatric ADPKD with a truncating PKD1 variant.

Minota Idarraga Ana Katerin AK, Llanos Arango Ivan Mauricio IM

Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic ciliopathy whose clinical spectrum extends into childhood. Although hepatic cysts are the most common extrarenal manifestation, early portal hypertension associated with congenital hepatic fibrosis (CHF)-like features is uncommon and likely underrecognized. We report a 10-year-old girl with no known family history of ADPKD who presented at 9 years of age with upper gastrointestinal bleeding secondary to grade III esophageal varices. The diagnostic evaluation established non-cirrhotic portal hypertension, and she underwent endoscopic variceal ligation followed by secondary prophylaxis with propranolol. Imaging demonstrated hepatosplenomegaly, patent portal and splenic veins, and no hepatic cysts. Liver biopsy showed mild portal fibrosis (METAVIR F1), while liver stiffness measured 6.4 kPa, consistent with mild fibrosis. Renal imaging revealed multiple bilateral cortical cysts, and whole-exome sequencing identified a heterozygous truncating PKD1 variant (p.Glu1633Ter), classified as pathogenic according to ACMG criteria. The patient remains clinically stable without recurrent bleeding during multidisciplinary follow-up. This case expands the phenotypic spectrum of pediatric ADPKD by illustrating clinically significant portal hypertension despite only mild hepatic fibrosis. It also highlights the importance of integrating histopathology, non-invasive liver assessment, imaging, and molecular testing when evaluating children with unexplained non-cirrhotic portal hypertension. ADPKD should be considered in the differential diagnosis of pediatric non-cirrhotic portal hypertension, even in the absence of hepatic cysts. Early genetic testing may facilitate accurate diagnosis and appropriate multidisciplinary management.

Steroid Rescue for Vision-Threatening Segmental Periocular Infantile Haemangioma in PHACE Syndrome When Propranolol Escalation Was Limited.

Dixit Ishana I, Webster Richard R, Gooi Alex A, Smith James J et al.

Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation.

Lee Kyeongho K, Cho Hana H, Kim June Yeon JY, Hwang Hyun H et al.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive therapy, yet no reliable circulating biomarker exists for risk stratification. Using an unbiased serum proteomics approach in a multicentre framework, we identified dopamine β-hydroxylase (DBH) as a differentially expressed protein with significantly lower levels in patients with MRONJ. This finding was validated in an independent clinical cohort and further supported in the UK Biobank population. Circulating DBH levels were positively associated with blood-pressure traits, consistent with its role as a surrogate marker of sympathetic nervous system activity, and suggesting that reduced DBH levels in MRONJ may reflect altered sympathetic regulation. In a mouse model, pharmacological sympathetic inhibition with propranolol exacerbated jaw osteonecrosis and further suppressed osteoclast activity in the presence of zoledronic acid. Osteoblast-osteoclast co-culture experiments demonstrated additive inhibitory effects on osteoclast differentiation under β-adrenergic blockade. Together, these findings support an association between reduced circulating DBH levels and MRONJ and suggest that sympathetic dysregulation may contribute to disease pathogenesis. Circulating DBH may serve as a candidate biomarker for risk assessment and disease monitoring in patients receiving antiresorptive therapy.