In Vitro Study on Combined Effect of Drugs for Hyperphosphatemia on Phosphorus Adsorption Capacity.

Phosphorus binders are often used in combination to produce synergistic effects. However, the synergistic effect may be affected by the change in pH or concomitant drugs. Nonetheless, the data on the adsorption capacities of these binders when used in combination with other binders are limited. In this study, we evaluated the adsorption capacity of phosphorus binders when used in combination. Precipitated calcium carbonate (CC), ferric citrate hydrate (FC), lanthanum carbonate hydrate (LC), and sucroferric oxyhydroxide (SO) were used as phosphorus binders. SO showed high adsorption capacity in the 1st and 2nd fluid, and the adsorption capacity of SO in combination with other binders was stable. In contrast, the adsorption capacities of CC + FC and FC + LC decreased in the 1st and 2nd fluid compared with that when used alone because of the release of citrate ions that chelate calcium or lanthanum ions. These results suggest that SO is less affected by interactions with other phosphorus binders and changes in pH and may be suitable for patients receiving concomitant drugs.

Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis.

AIMS: The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS. METHODS AND RESULTS: We measured the serum HE4 levels of 55 participants (80.8 ± 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P = 0.003). CONCLUSIONS: We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.

Phosphate recovery from aqueous phase using novel zirconium-based adsorbent.

This study aims to document the phosphate ion (PO43-) adsorption capacity of a novel zirconium-based adsorbent. The physicochemical properties of the adsorbent are investigated using an array of methods and metrics such as electron microscopy, X-ray diffraction, thermal analysis, specific surface area, pore volume, pH point of zero charge (pHpzc), and surface hydroxyl groups. The batch method is used to elucidate PO43- adsorption capacity. Results suggested that the adsorption of PO43- was based on an internal diffusion and a monolayer adsorption. We also clarified that the pH of the solution significantly impacted the adsorption. Moreover, the adsorbent shows the ability to not only adsorb but also desorb PO43- for at least five cycles, based on an adsorption mechanism that we document. These findings indicate that this adsorbent could serve as a major industrial PO43- adsorbent.

Design of an Oral Tablet Containing Furosemide Nanoparticles with Elevated Bioavailability.

The solubility and permeability of the Biopharmaceutics Classification System (BCS) class IV drugs, such as furosemide (FUR), are low. Thus, the oral bioavailability of these drugs needs to be augmented. Here, we aimed to design orally disintegrating tablets containing FUR nanoparticles to improve bioavailability after oral administration. The FUR nanoparticles were generated by bead-milling in water containing 0.5% methylcellulose and 0.5% 2-hydroxypropyl-ß-cyclodextrin (w/w%). Particle size was approximately 47-350 nm (mean particle size, 188 nm). An orally disintegrating tablet (FUR-NP tablet) comprising FUR nanoparticles (1%) was successfully produced by employing suspensions outlined above that incorporated additives (4% D-mannitol, 0.4% polyvinylpyrrolidone, and 16% gum Arabic, w/w%), followed by freeze-drying. The FUR-NP tablet disaggregated after only 5 s in water, liberating nano-sized FUR particles (172 nm). Experiments using rats showed the absorption of the FUR-NP tablet was significantly improved by comparison with a FUR tablet containing microparticles. In summary, the orally disintegrating tablet containing FUR nanoparticles markedly enhanced the bioavailability of FUR. We anticipate this formulation will also improve the bioavailability of other BCS class IV drugs.

Effect of Concomitant Drugs on Sodium Zirconium Cyclosilicate Hydrate in Artificial Intestinal Juice.

To explore drug interactions involving sodium zirconium cyclosilicate hydrate (SZC) and concomitant drugs like calcium antagonists (amlodipine and nifedipine) and ß-blockers (carvedilol and bisoprolol), we investigate how these concomitant drugs influenced the administration of SZC in an artificial intestinal juice. Initially, we assessed the potassium ion adsorption capacity, ranking it as follows: calcium polystyrene sulfonate (CPS, 54.9 mg/g) < sodium polystyrene sulfonate (SPS, 62.1 mg/g) < SZC (90.8 mg/g). However, the adsorption equilibrium was achieved in the order of CPS ≒ SPS (within 1 min) < SZC (within 1 h). Subsequently, we determined the residual percentages of amlodipine, nifedipine, carvedilol, and bisoprolol, finding them to be 79.0-91.9% for SZC, 0.38-38.4% for SPS, and 0.57-29.0% for CPS. These results suggest the efficacy of SZC in managing hyperkalemia alongside concomitant drugs in an artificial intestinal juice, with particular emphasis on amlodipine (calcium antagonist) and carvedilol (ß-blocker). Additionally, we identified the presence of carbon, nitrogen, and oxygen components from both drugs on the SZC surface following interaction. We also evaluated how amlodipine, nifedipine, carvedilol, and bisoprolol affected the administration of SZC in the presence of potassium ions. Our results indicate that potassium ions and concomitant drugs did not interfere with each other in the artificial intestinal juice. These results offer valuable insights into the administration of SZC in conjunction with concomitant drugs. Lastly, the presented data shows qualitative results in this study.

Therapeutic Effects of Hydrogel Formulations Incorporating Troxipide Nanoparticles on Oral Mucositis in Hamsters.

Purpose: Medical therapies, such as the use of anti-inflammatory agents, are commonly used for the treatment of oral mucositis (OM). However, these treatments have limited efficacy in treating severe cases of OM. In this study, we aimed to develop a carbopol gel incorporating troxipide (TRO) nanoparticles and methylcellulose (TRO-NP gel) and demonstrate its efficacy in accelerating wound healing in a hamster model of OM (OM model) induced by acetic acid injection. Methods: TRO nanoparticles were prepared using bead milling. The crystalline form was determined by powder X-ray diffraction, and the particle size was measured using a NanoSight LM10 instrument. The drug release was determined using a Franz diffusion cell, and the hamsters injected with acetic acid were selected to evaluate the therapeutic effect of OM. Results: After preparing TRO nanoparticles, we observed a mixture of crystals and amorphous TRO, and the particle size of TRO in the TRO-NP gel ranged from 50 to 280 nm. The TRO-NP gel exhibited a more uniform TRO distribution and viscosity compared to the Carbopol gel containing TRO microparticles (TRO-MP gel). However, the solubility of TRO was comparable in both TRO-MP and TRO-NP gels. The TRO-NP gel released a higher amount of TRO than that from the TRO-MP gel, with detectable release of TRO nanoparticles. TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were higher than those treated with TRO-MP gel. The increased TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were attenuated by treatment with 40 µM dynasore, an inhibitor of clathrin-dependent endocytosis (CME). Moreover, the therapeutic effect of the TRO-NP gel was superior to that of the TRO-MP gel in the hamster model of OM. Conclusion: We have designed a TRO-NP gel, and this gel showed excellent TRO delivery into the cheek pouch tissue through the CME pathway. Moreover, the TRO-NP gel treatment enhanced wound healing after acetic acid injection.

Nasal Absorption Enhancement of Mometasone Furoate Nanocrystal Dispersions.

Purpose: We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local absorption compared to traditional nasal MF formulations (CA-MF). Methods: MF nanocrystal dispersions (MF-NPs) were prepared by bead milling MF microcrystal dispersions (MF-MPs) consisting of MF, 2-hydroxypropyl-ß-cyclodextrin, methylcellulose, and purified water. Pluronic F-127 combined with methylcellulose, Pluronic F-68, or carbopol was used as a base for in situ gelation (thickener). MF concentrations were measured using high-performance liquid chromatography, and nasal absorption of MF was evaluated in 6 week-old male Institute of Cancer Research (ICR) mice. Results: The particle size range of MF prepared with the bead mill treatment was 80-200 nm, and the nanoparticles increased the local absorption of MF, which was higher than that of CA-MF and MF-MPs. In addition, unlike the results obtained in the small intestine and corneal tissue, the high absorption of nanocrystalline MF in the nasal mucosa was related to a pathway that was not derived from energy-dependent endocytosis. Moreover, the application of the in situ gelling system attenuated the local absorption of MF-NPs, owing to a decrease in drug diffusion in the dispersions. Conclusion: We found that nanoparticulation of MF enhances local intranasal absorption, and nasal bioavailability is higher than that of CA-MF. In addition, we demonstrate that viscosity regulation is an important factor in the design of nasal formulations based on MF nanocrystals. These findings provide insights for the design of novel nanomedicines with enhanced nasal bioavailability.

Potential Interaction between Sodium Polystyrene Sulfonate and Prescription Drugs in Artificial Intestinal Juice.

This study evaluated the interaction between sodium polystyrene sulfonate (SPS) and several commonly used concomitant drugs, such as carvedilol, bisoprolol, imidapril, atorvastatin and azilsartan. The residual rate of adsorption 6 h after starting the experiment followed the order carvedilol (0.36%) < bisoprolol (19.7%) < imidapril (81.2%) < atorvastatin (86.5%) < azilsartan (87.9%) in artificial intestinal juice (pH 6.8). In addition, the pKa of carvedilol and bisoprolol was 8.0 and 9.6 and that of atorvastatin, azilsartan, and imidapril was 4.5, 6.1, and 2.4, respectively. These results indicate that the form (ionic or uncharged) of each drug is important to its reaction with SPS. Moreover, we demonstrated the effect of potassium ions (concentration of 1000 or 2000 mg/L) on the adsorption of concomitant drugs onto SPS in artificial intestinal juice. Our results show that the residual rate of adsorption of carvedilol and bisoprolol increases with increasing concentration of potassium ions whereas adsorption of potassium ions onto SPS was unaffected by carvedilol and bisoprolol under our experimental conditions. Finally, the obtained results revealed that interactions between SPS and carvedilol or bisoprolol readily occur in artificial intestinal juice.

Evaluation of the Mechanism of Phosphate Removal Using Oyster Shell Powder in Aqueous Environments.

Eutrophication is caused by the inflow of nutrients, such as phosphorus and nitrogen, into closed waterbodies from wastewater. Calcination of oyster shells greatly increases their capacity for phosphate removal; however, information available on this mechanism and the capacity for phosphate removal under different initial pH values and temperatures is less. Herein, we investigated the utilization of oyster shells for phosphate removal under different pH and temperature conditions. Oyster shell powder (OSP) was calcined in a muffle furnace at temperature ranges of 200-1000 °C. Each OSP sample was added to a phosphate solution and the suspension was shaken under different pH and temperature conditions. The main component of OSP changed from CaCO3 to CaO after calcination at approx. 800 °C. The amount of phosphate removal by the calcined OSPs at 800 and 1000 °C was higher than that removal by the other OSPs. Further, the amount of calcium elution from the OSPs calcined at 800 and 1000 °C was higher than that elution from the other OSPs. This was because the solubility of CaO was higher than that of CaCO3. The amount of phosphate removal by the OSP and calcined OSPs at 200-600 °C was the highest at pH 5-7, and increased with increasing reaction temperature. These findings suggested that the mechanism of phosphate removal may involve adsorption in the OSP and OSPs calcined at 200-600 °C, whereas it is associated with coagulation settling and adsorption in the OSPs calcined at 800 and 1000 °C.

Application of Granulated Nickel-Aluminum-Zirconium Complex Hydroxide in the Flow Method for Recovery of Chromium(VI) Ions.

A colloidal silicate granulated nickel-aluminum-zirconium (CSG-NAZ) was prepared, and the chromium(VI) (Cr(VI)) ions recovery capacity was evaluated using a sodium sulfate solution in a column experiment. The amount adsorbed and breakthrough time were enhanced by decreasing the flow rate (flow rate is in the order of 3.0 > 2.0 > 0.5 mL). The breakthrough curves and model parameters were estimated using the Thomas and Yoon-Nelson models. The obtained data confirmed to fit both the Yoon-Nelson model (0.858-0.906) and the Thomas model (0.813-0.906). Additionally, Cr(VI) ions that adsorbed onto CSG-NAZ could be desorbed using a sodium sulfate solution in a column experiment. The total recovery percentage of Cr(VI) ions was 80.9% after six repetitions of adsorption/desorption. Finally, the obtained results revealed that CSG-NAZ was a candidate adsorbent for the recovery of Cr(VI) ions owing to its applicability toward a continuous system.

Skin absorption of felbinac solid nanoparticles in gel formulation containing l-menthol and carboxypolymethylene.

BACKGROUND: It is important to design an effective formulation to enhance the skin penetration, and nanotechnologies have been used in dermal and transdermal drug delivery. In this study, we prepared formulations (gels) containing l-menthol and felbinac (FEL) solid nanoparticles (FEL-NP gel) for topical application, and investigated the local and systemic absorption of the prepared FEL-NP gel. METHODS: FEL solid nanoparticles were obtained by bead milling of FEL powder (microparticles), and a topical formulation (FEL-NP gel) consisting of 1.5% FEL solid nanoparticles), 2% carboxypolymethylene, 2% l-menthol, 0.5% methylcellulose, and 5% 2-hydroxypropyl-ß-cyclodextrin (w/w %) were prepared. RESULTS: The particle size of FEL nanoparticles was 20-200 nm. The released FEL concentration from FEL-NP gel was significantly higher than that from FEL gel without bead mill treatment (carboxypolymethylene gel in which FEL microparticles (MPs) instead of FEL nanoparticles were incorporated, FEL-MP gel), and FEL was released as nanoparticles from the gel. Moreover, both transdermal penetration and percutaneous absorption of FEL-NP gel were significantly increased compared with those of FEL-MP gel, and the area under the FEL concentration-time curve (AUC) of FEL-NP gels was 1.52- and 1.38-fold of commercially available FEL ointment and FEL-MP gel, respectively. In addition, after 24 h of treatment, the FEL content in rat skin treated with FEL-NP gels was 1.38- and 2.54-fold higher than that when treated with commercially available FEL ointment and FEL-MP gel, respectively. Moreover, the enhanced skin penetration of FEL-NP gels was significantly attenuated by inhibition of energy-dependent endocytosis, such as clathrin-mediated endocytosis. CONCLUSIONS: We successfully prepared a topically applied carboxypolymethylene gel containing FEL nanoparticles. In addition, we observed that the endocytosis pathway was mainly related to the high skin penetration of FEL nanoparticles, and FEL-NP gel application resulted in high local tissue concentration and systemic absorption of FEL. These findings provide useful information for the design of topically applied nanoformulations against inflammation by providing local and systemic effects.

Effect of Ointment Base on the Skin Wound-Healing Deficits in Streptozotocin-Induced Diabetic Rat.

Wound-healing deficits of the skin, one of the most common complications in patients with diabetes, delay wound healing, significantly reducing the patient's QOL. Therefore, the topical treatment of wound areas with drug-containing ointments and dressings is important. In this study, we investigated the effect of various ointment bases on skin wound healing in normal and streptozotocin-induced diabetic rats (STZ rats). Three ointment bases were used: white ointment (oil-based), absorbent cream (emulsion-based, w/o), and macrogol ointment (water-based). Skin wound healing in STZ rats was delayed compared with that in normal rats. Each of the three ointment bases was applied to the skin wound area in normal rats, and there was no difference in the therapeutic effect. The therapeutic effect of both white ointment and absorbent cream was higher in the STZ rats group than that in the non-treated group, and delayed wound healing was observed in STZ rats treated with macrogol ointment. In conclusion, skin wound healing in STZ rats is affected by the properties of the ointment base, and it is important to use an ointment base that controls the drying of the wound area in STZ rats. These findings provide information for the selection of ointment bases useful for application to skin wounds in patients with diabetes.

Orally disintegrating tablets containing famotidine nanoparticles provide high intestinal absorbability via the energy-dependent endocytosis pathway.

The permeability of the Biopharmaceutics Classification System (BCS) class III drugs are low, and their oral bioavailability needs to be improved. In this study, we attempted to design oral formulations containing famotidine (FAM) nanoparticles to overcome the limitations of BCS class III drugs. Dispersions containing FAM nanoparticles with a particle size of approximately 50-220 nm were produced by the bead-milling treatment. Moreover, we succeeded in preparing an orally disintegrating tablet containing FAM nanoparticles using the dispersions described above, additives (D-mannitol, polyvinylpyrrolidone, and gum arabic), and freeze-dry treatment (FAM-NP tablet). The FAM-NP tablet was disaggregated 3.5 s after addition to purified water, and the FAM particles in the redispersion of the FAM-NP tablet stored for 3 months were nano-sized (141 ± 6.6 nm). The ex-vivo intestinal penetration and in vivo absorption of FAM in rats applied with the FAM-NP tablet were significantly higher than those in rats applied with the FAM tablet containing microparticles. In addition, enhanced intestinal penetration of the FAM-NP tablet was attenuated by an inhibitor of clathrin-mediated endocytosis. In conclusion, the orally disintegrating tablet containing FAM nanoparticles improved low mucosal permeability and low oral bioavailability and overcame these issues of BCS class III drugs as oral formulations.

Potential of waste mangosteen shell in the removal of cadmium ions: Effects of pH, contact time, and temperature.

In this study, waste biomass adsorbents produced from mangosteen shells (MGS) were prepared (denoted as MGS500 and MGS1000). The physical and chemical characteristics, such as scanning electron microscopy, thermogravimetric-differential thermal analysis, specific surface area, pore volumes, surface functional groups, and point of zero charge of the prepared MGS samples were determined, and the adsorption capacity of cadmium ions from aqueous media was assessed. The effects of pH, adsorption time, temperature, and coexistence on adsorption were carefully assessed using an inductively coupled plasma optical emission spectrometer under several experimental conditions. The adsorption capacity decreased in the order, MGS < MGS500 < MGS1000. The optimal pH for cadmium ion removal was 5.0. The amount of cadmium ions adsorbed gradually increased with time, and adsorption equilibrium was achieved within 24 h after adsorption. Additionally, the amount of adsorbed cadmium ions increased with increasing adsorption temperature. To elucidate the adsorption mechanism in detail, the elemental distribution and X-ray photoelectron spectra of the prepared adsorbents were analyzed. Finally, desorption solutions such as HNO3, H2O, and NaOH were used to desorb the absorbed cadmium ions from MGS1000. Under our experimental conditions, the desorption percentage of cadmium ions was approximately 98.8% using HNO3. In conclusion, MGS1000 exhibited a good adsorption capacity of 12.0 mg/g for adsorbing cadmium ions from aqueous media and desorption capacity with HNO3 at 1000 mmol/L.

Relationship of masked obesity to self-reported lifestyle habits, ideal body image, and anthropometric measures in Japanese university students: A cross-sectional study.

INTRODUCTION: Masked obesity (MO) is defined as a normal body mass index (BMI) with a high body fat percentage (%BF), and is associated with the onset of lifestyle-related diseases. However, little is known about the current status of MO. Therefore, we investigated the relationship of MO to physical characteristics and lifestyle habits among Japanese university students. METHODS: Between 2011 and 2019, we conducted a survey of 10,168 males and 4,954 females with BMI within the normal range (18.5 ≤ BMI < 25 kg/m2). MO was defined as %BF ≥ 20% in males and %BF ≥ 30% in females. Students completed a questionnaire containing items about lifestyle habits. Systolic and diastolic blood pressures were measured, and hypertension was defined as systolic above 140 mmHg and/or diastolic blood pressure above 90 mmHg. A multivariate logistic regression analysis was performed to evaluate the relationships as follows: the relationship of masked obesity to self-reported lifestyle habits, ideal body image, and anthropometric measures; the relationship between hypertension and body indices. RESULTS: The proportion of students with MO in 2019 was 13.4% in males and 25.8% in females, and the proportion of females increased over time. MO was associated with desire for weight loss (odds ratio, 95% confidence interval: 1.76, 1.53-2.02), intake of five macronutrients (0.79, 0.67-0.93), rice and wheat intakes (1.22, 1.01-1.47), sleep duration of < 7hr (0.85, 0.74-0.98), and exercise habit (0.71, 0.63-0.81) in males; and with balanced diet intake (0.79, 0.64-0.99) and exercise habit (0.65, 0.51-0.82) in females. There was a significant association of MO with hypertension in males (1.29, 1.09-1.53). CONCLUSION: The percentage of female students with MO increased during the study period, and in males, MO may be a risk factor for hypertension. These results suggest that intervention for MO is needed in Japanese university students.

Design of a Transdermal Sustained Release Formulation Based on Water-Soluble Ointment Incorporating Tulobuterol Nanoparticles.

We aimed to investigate which base was suitable for preparing transdermal formulations incorporating tulobuterol (TUL) nanoparticles (30-180 nm) in this study. Three bases (water-soluble, absorptive, and aqueous ionic cream) were selected to prepare the transdermal formulations, and TUL nanoparticles were prepared with a bead-milling treatment. In the drug release study, the TUL release from the water-soluble ointment was higher than that from the other two ointments. Moreover, the addition of l-menthol enhanced TUL nanoparticle release from the ointment, and the rat skin penetration of the TUL water-soluble ointment was also significantly higher than that of the other two ointments. In addition, the drug penetration of the TUL water-soluble ointment with l-menthol sustained zero-order release over 24 h, and the skin permeability of TUL increased with TUL content in the ointment. On the other hand, this penetration was significantly inhibited by treatment with a caveolae-mediated endocytosis inhibitor (nystatin). In conclusion, we found that the water-soluble base incorporating TUL nanoparticles and l-menthol was the best among those assessed in this study. Furthermore, the pathway using caveolae-mediated endocytosis was related to the skin penetration of TUL nanoparticles in the TUL water-soluble ointment with l-menthol. These findings are useful for the design of a transdermal sustained-release formulation based on TUL nanoparticles.

Fundamental Investigation of Adsorption Behavior onto Sodium Polystyrene Sulfonate to Potassium Ions and Its Concomitant Drugs in the Digestive Tract.

To verify the interaction between sodium polystyrene sulfonate (SPS) and its concomitant drugs, we elucidated the capability of potassium ions and concomitant drugs to adsorb onto SPS and the effect of their coexistence on the amount adsorbed. We identified 14 drugs used concomitantly with SPS from 2017-2019 in our investigation, and 5 drug preparations used in the clinical setting were used for the experiments. In the artificial intestinal juice, SPS adsorbed 39.05-69.77 mEq/g of potassium ions. Amlodipine besylate and nifedipine were well-adsorbed, while azosemide and febuxostat were did not adsorb well onto SPS. Our results and the results of a previous study suggest that additives in drug preparations affect the adsorption of drugs onto SPS. The adsorption kinetics onto SPS of drugs conformed to the pseudo-second order model. However, the adsorption of amlodipine besylate completely may not be fitted to the pseudo-second order model. The amount of amlodipine besylate adsorbed under the coexistence of potassium ions decreased compared to when potassium ions were absent. The amount of nifedipine and potassium ions adsorbed remained constant, regardless of whether potassium ions were present or not. These results might be due to the differences in their mechanisms of adsorption onto SPS and to the characteristics of the drugs. In a clinical setting, SPS is used concomitantly with various oral drugs. The interaction between SPS and its other concomitant drugs need to be elucidated more to obtain enough evidence for pharmacists to propose the appropriate prescription.

Pharmaceutical Incompatibility of Lubricating Gel Formulation Reduces Antibacterial Activity of Chlorhexidine Gluconate: In Vitro Study in Northern Thailand.

Chlorhexidine gluconate (CHG) is a cationic disinfectant. The positive charge of CHG molecules binds to phospholipid's negative charge in bacterial cell walls, causing membrane disruption. The in vitro kinetic physical, chemical and biological incompatibilities of nine lubricating gels with 1% w/v CHG were investigated. Five containing anionic thickener, two containing nonionic thickener, and two containing cationic thickener were collected from hospitals in northern Thailand. All the anionic and nonionic lubricating gels significantly reduced (p < 0.05) the CHG amount after 5 min of exposure time from 12.54% to 54.99%, respectively. In contrast, the amount of CHG exposed with cationic lubricating gels was maintained. Antibacterial activity was significantly reduced to a 1.17-4.33 log10 reduction for Staphylococcus aureus ATCC25923 and a 1.07-3.52 log10 reduction for Escherichia coli ATCC25922 after 5 min exposure to all anionic and nonionic lubricating gels. In contrast, the two cationic lubricating gels maintained the antibacterial activity of the CHG solution (5.69 ± 0.14 and 5.45 ± 0.17 log10 reduction). The results suggest that anionic and nonionic thickeners in lubricating gel formulations may neutralize the positive charge and reduce the antibacterial activity of CHG, reducing its effectiveness as a disinfectant.

Adverse event profiles of microscopic colitis in the Japanese Adverse Drug Event Report (JADER) database.

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. "Colitis microscopic" (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.

Recovery of Chromium(VI) Ions Using a Nickel-Aluminum-Zirconium Complex Hydroxide Based on Adsorption and Desorption Treatment.

In this study, we evaluate the desorption or recovery capacity of chromium(VI) ions using desorption solutions containing sodium hydroxide (NaOH) or sodium sulfate (Na2SO4). A complex hydroxide of nickel-aluminum-zirconium (NAZ) was prepared as the adsorbent for the removal of chromium(VI) ions. The results from repeated adsorption/desorption experiments on chromium(VI) ions using NAZ complex hydroxide were evaluated. The desorption percentage of chromium(VI) ions increased with the increase in the concentration of NaOH or Na2SO4 in the desorption solution. The determined optimal concentration of NaOH or Na2SO4 in the desorption solution was 10 mmol/L under the used experimental conditions. After three adsorption-desorption cycles, the recovery percentages of chromium(VI) ions using NaOH and Na2SO4 were 60% (total amounts adsorbed and desorbed were 102 and 61 mg/g, respectively) and 75% (total amounts adsorbed and desorbed were 96 and 72 mg/g, respectively), respectively. Additionally, we confirmed the existence of chromium on the surface of the NAZ complex hydroxide. After three adsorption/desorption cycles, the crystal structure of the NAZ complex hydroxide was maintained. These results indicated the potential of the NAZ complex hydroxide using a desorption solution containing NaOH or Na2SO4 for the recovery of chromium(VI) ions.