OBJECTIVE: To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro. METHODS: Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets. RESULTS: The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min. CONCLUSION CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.
Captopril ; Cytidine Triphosphate ; Drug Liberation ; Hydrochlorothiazide ; Printing, Three-Dimensional ; Tablets/chemistry* ; Technology, Pharmaceutical/methods*

OBJECTIVE: To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant. CONCLUSION The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.
Adult ; Diabetes Insipidus, Nephrogenic/genetics* ; Exons ; Female ; Frameshift Mutation ; Humans ; Hydrochlorothiazide/therapeutic use* ; Infant, Newborn ; Male ; Pedigree ; Receptors, Vasopressin/genetics*

BACKGROUND: The efficacy of combined diuretic treatment in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. METHODS: In a single-center, double-blinded, randomized controlled trial, we randomly assigned 51 adult CAPD patients to receive furosemide 1,000 mg/day, hydrochlorothiazide 100 mg/day, and spironolactone 50 mg/day (triple diuretics [TD] group) or furosemide 1,000 mg/day plus placebo (single diuretic [SD] group) for 6 months. The primary outcome was the difference in daily urine output at the 3rd and 6th month of the study compared to baseline (ΔUO) between the SD and TD group. Secondary outcomes were urinary sodium (UNa) and potassium (UK) excretion and overhydration (OH) measured by bioimpedance at 3 and 6 months compared to baseline (ΔUNa, ΔUK, and ΔOH, respectively) and daily glucose exposure (g/day). RESULTS: Forty-three of 51 patients completed the 6-month trial. The ΔUO at 3 and 6 months was significantly higher in the TD group compared to the SD group (386.32 ± 733.92 mL/day vs. −136.25 ± 629.08 mL/day, P < 0.001, at 3 months; 311.58 ± 640.31 mL/day vs. 120.00 ± 624.07 mL/day, P < 0.001, at 6 months) but there was no significant difference in ΔUNa and ΔUK excretion. Hydration status was significantly better in the TD group (ΔOH 1.84 ± 2.27 L vs. 0.44 ± 1.62 L, P = 0.03, at 3 months; 1.49 ± 2.82 L vs. −0.48 ± 2.61 L, P = 0.02, at 6 months). There was no serious adverse event in this study. CONCLUSION: For end-stage renal disease patients on CAPD, the combination of furosemide, hydrochlorothiazide, and spironolactone results in higher urine output and better volume control compared to furosemide alone.
Adult ; Diuretics ; Furosemide ; Glucose ; Humans ; Hydrochlorothiazide ; Kidney Failure, Chronic ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Potassium ; Sodium ; Spironolactone

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of STK39 gene with response to hydrochlorothiazide among ethnic Han Chinese patients with essential hypertension. METHODS: In total 118 patients with essential hypertension were recruited. All participants had received six weeks of treatment with hydrochlorothiazide 25 mg daily. Blood pressure (BP) and heart rate (HR) were measurement every 2 weeks. Genotypes of STK39 rs3754777 and rs6749447 were determined using a SNaPshot technique. RESULTS: A significant difference was found in ΔSBP between individuals with rs3754777 CC, CT and TT and those with rs3754777 CC and CT-TT (P<0.05). A significant difference was also detected in ΔDBP between those with rs3754777 CC and CT-TT (P<0.05). No significant difference was found in ΔSBP and ΔDBP between individuals with STK39 rs6749447 GG, GT and TT (all P>0.05). Relative risk analysis showed that STK39 rs3754777 was significantly associated with BP response to hydrochlorothiazide (OR=0.416, 95%CI=0.189-0.918, P<0.05). CONCLUSION Polymorphisms of STK39 rs3754777 may be associated with BP response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension.
Asian Continental Ancestry Group ; Essential Hypertension ; Genotype ; Humans ; Hydrochlorothiazide ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics

BACKGROUND/OBJECTIVE: This study was designed to investigate how a Portulaca oleracea L. extract (POE) stimulates insulin secretion in INS-1 pancreatic β-cells. MATERIALS/METHOD: INS-1 pancreatic β-cells were incubated in the presence of various glucose concentrations: 1.1 or 5.6, 16.7 mM glucose. The cells were treated with insulin secretagogues or insulin secretion inhibitor for insulin secretion assay using an insulin ELISA kit. In order to quantify intracellular influx of Ca2+ caused by POE treatment, the effect of POE on intracellular Ca2+ in INS-1 pancreatic β-cells was examined using Fluo-2 AM dye. RESULTS: POE at 10 to 200 µg/mL significantly increased insulin secretion dose-dependently as compared to the control. Experiments at three glucose concentrations (1.1, 5.6, and 16.7 mM) confirmed that POE significantly stimulated insulin secretion on its own as well as in a glucose-dependent manner. POE also exerted synergistic effects on insulin secretion with secretagogues, such as L-alanine, 3-isobutyl-1-methylxanthine, and especially tolbutamide, and at a depolarizing concentration of KCl. The insulin secretion caused by POE was significantly attenuated by treatment with diazoxide, an opener of the K+ ATP channel (blocking insulin secretion) and by verapamil (a Ca2+ channel blocker). The insulinotropic effect of POE was not observed under Ca2+-free conditions in INS-1 pancreatic β-cells. When the cells were preincubated with a Ca2+ fluorescent dye, Fluo-2 (acetoxymethyl ester), the cells treated with POE showed changes in fluorescence in red, green, and blue tones, indicating a significant increase in intracellular Ca2+, which closely correlated with increases in the levels of insulin secretion. CONCLUSIONS: These findings indicate that POE stimulates insulin secretion via a K+ ATP channel-dependent pathway in INS-1 pancreatic β-cells.
1-Methyl-3-isobutylxanthine ; Adenosine Triphosphate ; Alanine ; Calcium Channels ; Diabetes Mellitus ; Diazoxide ; Enzyme-Linked Immunosorbent Assay ; Fluorescence ; Glucose ; Insulin* ; Portulaca* ; Tolbutamide ; Verapamil

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.
Adult ; Alkalosis ; Arthritis, Rheumatoid* ; Fatigue ; Furosemide ; Genetic Testing ; Gitelman Syndrome* ; Hand ; Humans ; Hypesthesia ; Hypokalemia ; Muscle Cramp ; Paralysis ; Solute Carrier Family 12, Member 3 ; Thiazides ; Tremor

Management of congenital hyperinsulinemia of infancy (CHI) is challenging. A 4-month-old female infant with persistent hypoglycemia and elevated insulin levels was diagnosed with CHI. Gallium-68 DOTANOC positron emission tomography/computed tomography (PET/CT) scan (⁶⁸Ga-labeled [1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid]-1-NaI3-octreotide) demonstrated focal disease in the body of the pancreas. Genetic studies indicated paternal inheritance, making focal disease likely. She was started on diazoxide therapy with partial improvement in blood glucose levels. Due to a suboptimal response to diazoxide and the likelihood of focal disease amenable to surgery, a laparoscopic subtotal pancreatectomy with preservation of the head of the pancreas was performed. The biopsy demonstrated diffuse hyperplastic pancreatic islet cells on immunohistochemistry, indicative of diffuse rather than focal disease. Paternal inheritance is a recognized indicator of focal disease. Gallium-68 DOTANOC PET/CT scan is the only available imaging modality in South India as ¹⁸F-L-dihydroxyphenylalanine (DOPA) PET/CT scan is not available at present. A laparoscopic approach reduces the postoperative recovery time and morbidity in such patients. The absence of ¹⁸F-L-DOPA PET/CT scan and the limited supply of diazoxide makes the management of this complex condition more challenging in developing countries.
Biopsy ; Blood Glucose ; Congenital Hyperinsulinism* ; Developing Countries* ; Diazoxide ; Electrons ; Female ; Head ; Humans ; Hyperinsulinism ; Hypoglycemia ; Immunohistochemistry ; India ; Infant ; Insulin ; Islets of Langerhans ; Pancreas ; Pancreatectomy ; Positron-Emission Tomography and Computed Tomography ; Wills

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.
Cross-Over Studies ; Diuretics ; Edema ; Furosemide ; Humans ; Hydrochlorothiazide* ; Kidney Failure, Chronic* ; Proteinuria ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.
Adult ; Alkalosis ; Arthritis, Rheumatoid ; Fatigue ; Furosemide ; Genetic Testing ; Gitelman Syndrome ; Hand ; Humans ; Hypesthesia ; Hypokalemia ; Muscle Cramp ; Paralysis ; Solute Carrier Family 12, Member 3 ; Thiazides ; Tremor

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease. The prevalence of hypertension in the Western Pacific Region is 37% of adults older than 24, while in the Philippines it is 25% of adults 21 years old and above. Several guidelines have been developed for the management of hypertension. All these guidelines have recommendations for assessment and treatment.
OBJECTIVES: The overall objective of the development and implementation of this clinical pathway is to improve outcomes of patients with hypertension seen in family and community practice.
METHODS: The PAFP Clinical Pathways Group reviewed published medical literature to identify, summarize, and operationalize the clinical content of diagnostics, interventions and clinical indicators or outcomes to develop an evidence-based clinical pathway in family medicine practice. The group developed a time-related representation of recommendations on patient care processes, in terms of history and physical examination, laboratory tests, pharmacologic and non-pharmacologic interventions as well as social and community strategies to treat hypertension and prevent complications.
RECOMMENDATIONS: Recommendations were made based on the number of visits. During the first visit, all adult patients consulting at the clinic should be screened for hypertension with appropriate BP measurement. A thorough history focusing on symptoms, family history using genogram, smoking and other lifestyle and co-existing chronic disease and a thorough physical examination focusing on the weight/BMI, waist/hip ration, funduscopy, neurological, cardiac, renal and peripheral arteries should be done. For the laboratory, request for 12-lead ECG, urinalysis, FBS, creatinine, serum K and lipid profile to determine co-morbidities and baseline values. If the patient is already diagnosed hypertensive, start/continue medications with either or a combination of thiazide-type diuretic, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blocker depending on co-morbidities or side effects. But if there is a need for further confirmation, no medication is warranted. Educate the patient about hypertension, risk factors and complications. If medications were prescribed, explain the dose, frequency, intended effect, possible side effects and importance of medication adherence. Lifestyle modifications focusing on weight control, exercise and smoking cessation should be advised. During the first first visit is expected that the patient is aware of the diagnosis of hypertension, its risks factors and complications to encourage compliance.
IMPLEMENTATION: Education, training and audit are recommended strategies to implement the clinical pathway.

Human ; Angiotensin-converting Enzyme Inhibitors ; Smoking Cessation ; Medication Adherence ; Sodium Chloride Symporter Inhibitors ; Hypertension ; Chronic Disease ; Lipids ; Thiazides ; Arteries