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.

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.

Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) widely used in human heart failure and has demonstrated potential cardiorenal and neurohormonal effects in experimental canine studies. Hydrochlorothiazide is a thiazide diuretic that acts at a more distal segment of the nephron than furosemide. Its addition to loop diuretic therapy may enhance sodium and fluid excretion through sequential nephron blockade and thereby improve the diuretic response in cases of refractory congestion. However, information regarding the combination of these two drugs in cats with congestive heart failure is lacking. This report describes the long-term clinical outcome of a cat with recurrent cardiogenic pleural effusion treated with sacubitril/valsartan and hydrochlorothiazide. A 14-year-old spayed female Persian-cross cat was referred for severe respiratory distress caused by recurrent pleural effusion. Echocardiography identified advanced cardiomyopathy with a nonspecific phenotype and overlapping hypertrophic and restrictive features, including focal basal septal hypertrophy, biatrial enlargement, atrial fibrillation and spontaneous echocardiographic contrast. Despite conventional treatment, which included pimobendan, torasemide, and antithrombotic medications, the cat experienced multiple episodes of pleural effusion over the following months, requiring repeated thoracocentesis. Consequently, the treatment regimen was expanded to include sacubitril/valsartan and hydrochlorothiazide. According to the owner, all other cardiac medications were discontinued approximately one week later without veterinary consultation. At long-term follow-up approximately two years after sacubitril/valsartan and hydrochlorothiazide therapy initiation, the cat remained clinically stable, with no further episodes of respiratory distress. Echocardiography revealed persistent severe structural heart disease, although improved left ventricular systolic indices were observed. This case report describes prolonged clinical stabilization in a cat with advanced cardiomyopathy and recurrent congestive heart failure following the administration of sacubitril/valsartan and hydrochlorothiazide over a two-year period. Whether this outcome reflects a specific effect of sacubitril/valsartan, the addition of hydrochlorothiazide, or a combination of both cannot be determined from a single observation. Nonetheless, the duration and completeness of the response observed here warrant prospective evaluation of combination of ARNI therapy and hydrochlorothiazide in cats with refractory congestive heart failure. Further studies are needed to assess the safety and effectiveness of this approach in feline cardiomyopathy.

We investigated seasonal variation in the office and ambulatory blood pressure control in hypertensive patients treated with two single-pill dual-combination antihypertensive therapies. The study participants (n = 560) were hypertensive patients enrolled in a 24-week therapeutic study. Antihypertensive treatment was initiated with amlodipine/benazepril 5/10 mg/day or benazepril/hydrochlorothiazide 10/12.5 mg/day, with the possible up-titration to 10/20 mg/day or 20/25 mg/day during follow-up, respectively. Office blood pressure was measured at each clinic visit, and ambulatory blood pressure monitoring was performed at baseline and 24-week follow-up. At 24 weeks of follow-up, in patients who continued antihypertensive treatment (n = 511), the proportion of up-titration to higher dosages was significantly different across seasons of treatment commencement in the benazepril/hydrochlorothiazide group (P = 0.002), but not in the amlodipine/benazepril group (P = 0.84). The between-group difference was significantly different in 134 patients who commenced treatment in winter (18.9% vs. 5.0%, P = 0.02), but not in 377 patients who commenced treatment in the other seasons (P ≥ 0.33). The control rate of office blood pressure (<140/90 mmHg) was significantly different across seasons of treatment commencement in the amlodipine/benazepril group (P = 0.01), but not in the benazepril/hydrochlorothiazide group (P = 0.16). The mean changes from baseline to 24-week follow-up tended to be smaller in the benazepril/hydrochlorothiazide than amlodipine/benazepril group in 24-h (mean between-group difference, -2.8 mmHg) and daytime diastolic blood pressure (mean between-group difference, -3.2 mmHg) in patients who commenced treatment in winter, though statistical significance was not achieved (P ≥ 0.07). In conclusion, there was seasonality in the clinic and ambulatory blood pressure-lowering effect of antihypertensive drug combinations, with a marginally significant difference in treatment intensity and blood pressure control between treatment with amlodipine or hydrochlorothiazide in combination with benazepril.