The renin angiotensin aldosterone system (RAS) regulates blood pressure and fluid balance by a cascade of angiotensin (Ang) peptides. Antihypertensive drug classes differentially modulate this cascade. This study examined how four mechanistically distinct antihypertensive drugs affect plasma concentrations of 10 Ang peptides and aldosterone in untreated hypertensive patients. In this randomized, open-label, parallel-group study, 88 patients received 4 weeks of monotherapy with angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), or hydrochlorothiazide (HCT). Equilibrium concentrations of 10 Ang peptides and aldosterone were quantified by LC-MS at baseline and after 4 weeks, both pre- and 4 h post-dose; drug exposure was confirmed by measured drug concentrations. Seventy-two participants completed the 4-week treatment (ACEi n = 18, ARB n = 17, CCB n = 20, HCT n = 17). The most prominent effects were seen for Ang I, Ang II, and aldosterone and were reflected in biomarkers for plasma renin activity (PRA-Q; Ang I+Ang II), ACE activity (ACE-Q; Ang II/Ang I), and the aldosterone/Ang II ratio (AA2-R). Downstream peptides showed minimal or no changes. Relative to baseline, ACEi increased Ang I and reduced ACE-Q. ARB increased Ang I and Ang II and lowered AA2-R without altering ACE-Q. CCB and HCT produced only minor changes. ACE-Q < 1.05 pM/pM identified ACEi use, and AA2-R < 0.85 pM/pM as well as Ang II > 175 pM identified ARB use. RAS-targeted monotherapy produces distinct peptide-level signatures that can be captured by Ang-derived biomarkers, supporting their potential utility for monitoring drug intake in personalized hypertension management.

The evaluation of arginine vasopressin resistance (AVP-R) and arginine vasopressin deficiency (AVP-D), respectively, previously referred to as nephrogenic and central diabetes insipidus, often includes brain magnetic resonance imaging (MRI). Its purpose is to assess pituitary structural changes and identify the physiological T1 hyperintensity of the posterior pituitary, present in most individuals. This hyperintensity reflects vasopressin storage, which shortens the T1 relaxation time. Its absence supports a diagnosis of AVP-D over AVP-R. A 13-year-old boy was referred to endocrinology in his second year of life for polyuria and polydipsia. Brain MRI revealed normal pituitary morphology and a spontaneous T1 hyperintensity of the posterior pituitary. The AVP-R was confirmed by a hemizygous AVPR2 gene mutation. Treatment with hydrochlorothiazide, potassium supplementation, and dietary sodium restriction achieved good clinical control. During school age, progressive growth deceleration led to short stature and delayed puberty. At 13 years, repeated MRI showed a smaller pituitary gland and loss of the posterior pituitary T1 hyperintensity. Loss of posterior pituitary T1 hyperintensity is rare in AVP-R, and late disappearance has not been previously described in genetically confirmed cases. This case underscores the importance of integrating clinical, genetic, and imaging findings.

The current study aimed to improve the dissolution rate and physical stability of two antihypertensive drugs, hydrochlorothiazide, and valsartan, through the development of a co-amorphous system. A co-amorphous system was successfully prepared at molar ratios of 1:1, 1:2, and 1:6 employing rotary evaporation technique. Characterization of the formulations was performed using powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Powder X-ray diffraction confirmed the amorphous nature of all samples, which remained physically stable under ambient dry conditions for at least 8 months. Differential scanning calorimetry confirmed the formation of a single-phase system. The experimental glass transition temperature values revealed a negative deviation from those calculated by the Gordon-Taylor equation, indicating nonideal mixing and intermolecular interactions. Fourier transform infrared spectroscopy spectra supported these findings, showing peak broadening in regions corresponding to the functional groups of the parent drugs. The thermogravimetric analysis demonstrated that the samples were thermally stable, with no degradation observed up to 100°C. Dissolution studies performed in phosphate buffer (pH 6.8, 25°C) revealed significant enhancements in the dissolution rates of both hydrochlorothiazide and valsartan from the co-amorphous formulations compared to their unprocessed forms and corresponding physical mixtures. A validated high-performance liquid chromatography method was developed for the simultaneous analysis of hydrochlorothiazide and valsartan using a Shimadzu LC-2030C 3D Plus system with a photodiode array detector. Separation was achieved on a Waters C18 column (250 × 4.6 mm, 5 μm) using a mobile phase of acetonitrile, methanol, and ammonium acetate buffer (20:50:30, v/v) at a flow rate of 0.70 mL/min. Detection wavelengths were set at 271 nm for hydrochlorothiazide and 249 nm for valsartan. The method showed good linearity in the range from 0.0033 to 0.0670 mM (3.3-67.0 μM), precision (RSD < 2%), and reproducibility, with hydrochlorothiazide and valsartan eluting at 3.5 and 7.2 min, respectively. At the first minute, hydrochlorothiazide release increased by approximately 8.5-, 8.7-, and 7.1-fold from the 1:1, 1:2, and 1:6 co-amorphous systems relative to the unprocessed drug, and by 4.5-, 4.8-, and 2.4-fold, respectively, compared to the corresponding physical mixtures. For valsartan, the co-amorphous systems showed 2.9-, 2.6-, and 1.9-fold improvements over the unprocessed drug, and 1.5-, 1.8-, and 1.5-fold improvements over the matching physical mixtures at the same molar ratios. Calcium carbonate was physically mixed with all samples to minimize gelation upon aqueous exposure. These results suggest that co-amorphous formulation is a promising strategy for enhancing the dissolution rate and physical stability of hydrochlorothiazide and valsartan.

Vascular Ehlers-Danlos syndrome (vEDS), caused by likely pathogenic COL3A1 variants, carries a high risk of arterial dissection or rupture, intestinal perforation and uterine rupture, and a median survival near 51 years. It is often recognized only at a catastrophe, and its acute management is deliberately counter-intuitive. The therapeutic landscape changed in 2025 with the first randomized evidence for an angiotensin-receptor blocker. We provide a clinical, practice-oriented review for internists and the multidisciplinary team. As is appropriate for a rare disease, case-level evidence was considered alongside cohorts and trials. Suspicion is the rate-limiting step, and we set out speciality-specific red flags. Diagnosis requires molecular confirmation, with differentiation from other heritable arteriopathies. Genotype is a probabilistic predisposition, not a deterministic predictor: there is ascertainment bias, reduced penetrance and intrafamilial variability temper inference. Emergency care is harm-avoidant-catheter angiography, elective endoscopy and unnecessary surgery should be avoided, and endovascular and tissue-sparing techniques preferred. Pharmacological prevention rests on celiprolol, with randomized evidence now supporting irbesartan added to background celiprolol, and expert-centred consideration of angiotensin-receptor blockade when celiprolol is not tolerated. Surveillance should be individualized along the European Reference Network on Rare Multisystemic Vascular Diseases logic. Pregnancy, psychosocial care and cascade testing complete lifelong management. In vEDS, earlier recognition and the avoidance of iatrogenic harm-not new molecules-offer the largest near-term gains in survival and quality of life.

Translating adsorption performance from batch experiments to continuous-flow operation is a key step toward practical water-treatment applications. In this study, a laboratory-scale continuous adsorption system based on a water-insoluble β-cyclodextrin-epichlorohydrin (β-CD-EPI) polymer was validated from hydrodynamic, adsorptive, and operational perspectives. Downflow operation caused progressive bed compaction and excessive pressure development, whereas a 90 mm column operated in upflow mobile-bed mode, with visually observed bed expansion, showed comparatively stable pressure-drop behavior at superficial linear velocities below approximately 12 m h[-1]. Under these controlled high-loading conditions, removal was strongly contaminant-dependent: cyproconazole exceeded 90%, acetaminophen reached 72-77%, hydrochlorothiazide reached 40-65%, ciprofloxacin reached 24-50%, and furosemide remained below 30%. The relative performance for furosemide and hydrochlorothiazide differed from that predicted by previous batch-derived adsorption parameters, demonstrating that batch results cannot be directly extrapolated to dynamic operation. Competitive adsorption in binary and ternary mixtures reduced contaminant removal, while cyproconazole removal decreased from >90% in tap water to 48-55% in secondary-treated wastewater, demonstrating the relevance of the aqueous matrix under the tested continuous-flow conditions. Operational screening tests showed that desorption with 220 mM acetate buffer at pH 4.0 recovered >80% of the retained cyproconazole within 10 min in the tested sequence, followed by a two-stage rinse that restored the operational pH. These preliminary conditions require confirmation through replicated adsorption-desorption cycles under continuous-flow operation. These results identify laboratory-scale hydrodynamic, adsorption, matrix, and regeneration considerations that require confirmation through fixed-condition, long-term testing during subsequent process development.

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerotic cardio-cerebrovascular disease. The role of impaired mitochondrial dynamics in the pathophysiological process of aging-related diseases is being actively researched. We discovered that targeting proteins related to mitochondrial dynamics, especially those involved in fission and fusion, may offer new treatment strategies for these diseases. Various approaches, including aerobic interval and treadmill training and the use of drugs such as the antidiabetic agents metformin and dapagliflozin, the antihypertensive agent irbesartan, and certain traditional Chinese medicine components, have shown potential in alleviating imbalances in mitochondrial dynamics in aging-related cardio-cerebrovascular diseases. In this review, we systematically summarize recent research on alterations in mitochondrial dynamics in age-related cardio-cerebral diseases and explore therapeutic strategies targeting these alterations, which may offer new directions for improving cardiac and brain health and guiding clinical practice.