Antibiofilm Property and Biocompatibility of Siloxane-Based Polymer Coatings Applied to Biomaterials.

Biofilm infections sometimes occur on biomaterials inserted into the body because biomaterials can block the attack of immune cells such as macrophages, promoting biofilm formation by invading bacteria. Owing to their use in antifouling applications, including biofilm formation, siloxane-based polymer coatings are considered a promising method to prevent biofilm formation on the surface of biomaterials. In this study, we explored the antibiofilm property and biocompatibility of siloxane-based polymer coatings. Biofilm formation and cytotoxicity tests were performed using Escherichia coli and Staphylococcus epidermidis to quantify the biofilms while U937 cells were used to measure the time course of viable cell concentration and viability, respectively. In both the biofilm formation and cytotoxicity tests, stainless steel SUS316L plates and titanium plates coated with the siloxane-based polymer and sterilized in an autoclave were used as the biomaterials. The amount of biofilm formed on the polymer-coated titanium plate was substantially higher than that on a noncoated titanium plate in the case of S. epidermidis. The viable cell concentration and viability of U937 cultured on the polymer-coated titanium plate were lower than those of U937 cultured on the noncoated titanium plate. The same trend was observed between polymer-coated and noncoated SUS316L plates. These results indicate that the siloxane-based polymer coatings need additional treatment to achieve a satisfactory antibiofilm property and that they are sensitive to autoclave treatment, resulting in cytotoxicity.

Clinical characteristics of hyponatremia in patients receiving nutrition support†:†A cross-sectional study evaluated by bioelectrical impedance analysis.

Background & aims : We investigated the contributing factors of hyponatremia in patients on nutrition support using bioelectrical impedance analysis (BIA). Methods : Thirty patients administered enteral or parenteral nutrition support for at least 72 hours were studied. We collected nutritional and electrolyte intake, serum biochemical parameters, and body composition measured by BIA. Patients were classified into two groups according to their serum sodium levels : (1) Normanatremia group, 135-145 mEq / L (n = 18) and (2) Hyponatremia group, less than 135 mEq / L (n = 12), and their characteristics were analyzed. Results : There were no significant differences between the Normonatremia and Hyponatremia groups in terms of energy, protein, and sodium intake. Serum biochemical parameters other than serum sodium and chloride levels were comparable between the two groups. On the other hand, the ratio of extracellular water to total body water (ECW / TBW) obtained by BIA was significantly higher in the Hyponatremia group than in the Normonatremia group. Further, an elevated ECW / TBW significantly and negatively correlated with serum albumin level. Conclusions : Regardless of sodium intake, higher ECW / TBW was associated with hyponatremia in patients on nutrition support. ECW / TBW may be an important clinical parameter relevant to the nutritional care of hyponatremia. J. Med. Invest. 68 : 112-118, February, 2021.

Essential roles of nucleotide-switch and metal-coordinating residues for chaperone function of diol dehydratase-reactivase.

Diol dehydratase-reactivase (DD-R) is a molecular chaperone that reactivates inactivated holodiol dehydratase (DD) by cofactor exchange. Its ADP-bound and ATP-bound forms are high-affinity and low-affinity forms for DD, respectively. Among DD-Rs mutated at the nucleotide-binding site, neither the Dα8N nor Dα413N mutant was effective as a reactivase. Although Dα413N showed ATPase activity, it did not mediate cyanocobalamin (CN-Cbl) release from the DD·CN-Cbl complex in the presence of ATP or ADP and formed a tight complex with apoDD even in the presence of ATP, suggesting the involvement of Aspα413 in the nucleotide switch. In contrast, Dα8N showed very low ATPase activity and did not mediate CN-Cbl release from the complex in the presence of ATP, but it did cause about 50% release in the presence of ADP. The complex formation of this mutant with DD was partially reversed by ATP, suggesting that Aspα8 is involved in the ATPase activity but only partially in the nucleotide switch. Among DD-Rs mutated at the Mg(2+)-binding site, only Eß31Q was about 30% as active as wild-type DD-R and formed a tight complex with apoDD, indicating that the DD-R ß subunit is not absolutely required for reactivation. If subunit swapping occurs between the DD-R ß and DD ß subunits, Gluß97 of DD would coordinate to Mg(2+). The complex of Eß97Q DD with CN-Cbl was not activated by wild-type DD-R. No complex was formed between this mutant and wild-type DD-R, indicating that the coordination of Gluß97 to Mg(2+) is essential for subunit swapping and therefore for (re)activation.

Suppression of primary aldosteronism and resistant hypertension by the peroxisome proliferator-activated receptor gamma agonist pioglitazone.

The peroxisome proliferator-activated receptor gamma (PPAR γ) agonists have been reported to have antiproliferative and tumor-suppressive effects. We report a case of 55-year-old man with primary aldosteronism (PA) whose hyperaldosteronism was suppressed with the PPAR γ agonist pioglitazone. He had drug-resistant hypertension, hypokalemia, and diabetes mellitus. The diagnosis of PA was confirmed by the oral sodium loading test (20.5 µg/d of urinary aldosterone) and Captopril challenge test (19.5 ng/dL of plasma aldosterone). Computed tomography imaging revealed no apparent adrenal mass. The result of the posture stimulation test was consistent with the diagnosis of idiopathic adrenal hyperplasia. On administration of pioglitazone (30 mg/d) and nifedipine (40 mg/d), hypertension and hypokalemia improved and plasma aldosterone decreased for more than 6 months. The sodium loading test done after 6 months of the administration revealed the near normal results (11.2 ng/dL of plasma aldosterone and 13.1 µg/d of urinary aldosterone). The findings indicated that pioglitazone suppressed PA.

Butyrate enhancement of inteleukin-1ß production via activation of oxidative stress pathways in lipopolysaccharide-stimulated THP-1 cells.

In inflammatory bowel diseases, interleukin-1ß production is accelerated. Butyrate, a short chain fatty acid, plays an important role in inflammatory bowel diseases. We investigated the effect of butyrate on interleukin-1ß production in macrophage and elucidated its underlying mechanism. We stimulated THP-1 cells, a human premonocytic cell line, by lipopolysaccharide alone and by butyrate with lipopolysaccharide. Butyrate with lipopolysaccharide increased interleukin-1ß production more than lipopolysaccharide alone. Butyrate with lipopolysaccharide increased caspase-1 activity more than lipopolysaccharide alone. As for the phosphorylation pathway, PD98059 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor) decreased caspase-1 activity and interleukin-1ß production to approximately 50% of the controls. Pertussis toxin (G protein-coupled signal transduction pathway inhibitor) also reduced interleukin-1ß production to approximately 50%. Butyrate with lipopolysaccharide increased reactive oxygen species levels more than lipopolysaccharide alone. The addition of N-acetyl L-cysteine reduced reactive oxygen species levels to a level similar to that of lipopolysaccharide alone. Butyrate with lipopolysaccharide increased nitric oxide production more than lipopolysaccharide alone, and the addition of N-acetyl L-cysteine reduced the elevated amount of nitric oxide. In conclusions, butyrate enhances interleukin-1ß production by activating caspase-1, via reactive oxygen species, the phosphorylation of MAPK, and G protein mediated pathways in lipopolysaccharide stimulated THP-1 cells.

A case of rheumatoid arthritis improved from Steinbrocker classification class IV to class II after multi-joint surgery.

We report the case of a patient with rheumatoid arthritis (RA) who showed a reduction in disease severity (from class IV to class II) after multi-joint surgery. The patient was a 61-year-old man with a history of RA, type-2 diabetes, chronic obstructive pulmonary disease, and nephrotic syndrome. He had been undergoing treatment for RA for the past 10 years, but his condition could not be appropriately controlled. In addition to generalized edema, marked destruction of the left elbow joint and knees was observed, and he was unable to move in bed (Steinbrocker classification: stage IV, class IV). In March 2009, he developed suppurative arthritis of the left elbow (methicillin-sensitive Staphylococcus aureus [MSSA] infection) and was referred to our institution, where the infection subsided after cleaning of the wound and administration of antibiotics. In March 2010, he underwent artificial joint replacement arthroplasty of the left elbow, followed by replacement arthroplasty of the right knee in July that year and of the left knee in November. As of December 2011, the patient showed no signs of inflammatory reactions and was able to walk using crutches (Steinbrocker classification: stage IV, class II). Recent advancements in pharmacotherapy have made it possible to control the advancement of joint destruction in RA. However, in this patient, because of the advanced stage of joint destruction, surgical methods were required to aid the patient in recovering his ability to walk.

The suppressive effects of dietary protein restriction on the progression of renal impairment in OLETF rats.

BACKGROUND: The suppressive effect of dietary protein restriction on the progression of diabetic nephropathy remains controversial. We investigated the effects of protein and energy restrictions on both albuminuria and morphology using diabetic-prone Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: In this study, male OLETF rats were divided into two groups according to their energy intake. They were then further divided into three subgroups based on their amount of dietary protein, which ranged between 10% and 30% of their total intake. Urinary albumin excretion (UAE) was used as a marker of renal impairment, and body weight fasting (F) and postchallenge (P), blood glucose (BG) levels, and systolic blood pressure (SBP) were all measured during various experimental periods up to 28 weeks of age. RESULTS: The OLETF rats fed with the high-calorie diet started to gain weight at 12 weeks, and their FBG and PBG were elevated at 22 weeks, while SBP did not differ between the two groups. In addition, UAE increased significantly in the rats fed with the high-calorie diet. However, the increasing rates of UAE with age were higher in the rats with a higher protein diet within the same energy groups. UAE correlated well with the amounts of dietary energy and protein at 16 and 28 weeks of age, while it correlated with both the FBG and PBG at only 28 weeks of age. A linear regression analysis, using the data obtained at 28 weeks, showed that the amount of protein intake and FBG explained 63.4% and 23.9% of the variation in UAE, respectively. Histological studies revealed that protein and energy restriction markedly reduced the sclerotic changes of the glomeruli. CONCLUSION: Dietary protein restriction starting very early in the life of OLETF rats, in combination with energy restriction, clearly suppressed UAE and the typical morphological changes that otherwise occurred at around 16 weeks of age. This method also seemed to be more effective than energy restriction alone in slowing down any increase in UAE. The influence of BG levels on UAE was lower at an early age, while it became an increasingly important factor at later ages in the experimental rat model.

Effect of filtration leukocytapheresis therapy: modulation of white blood cell enzyme activities in patients with rheumatoid arthritis.

We treated 12 patients with rheumatoid arthritis by filtration leukocytapheresis (FLCP) and evaluated its effect on leukocyte enzyme activities. We calculated the number of leukocytes removed and assessed the clinical response. We also evaluated the cellular enzyme activities of elastase and dipeptidylpeptidase IV (DPP IV). Out of 12 patients, 7 patients achieved 20% improvement for 4 weeks following FLCP. The FLCP treatment resulted in removal of 96% of granulocytes, 98% of monocytes, and 61% of lymphocytes. Granulocytes and monocytes with high elastase activity were effectively removed by FLCP. The elastase activity of granulocytes was increased 4 weeks after the last FLCP only in responders. On the other hand, the DPP IV activity of lymphocytes was low at 4 weeks after the last FLCP in responders. Modulation of leukocyte enzyme activities is one of the main effects of FLCP therapy and alteration of granulocytes, monocytes, and lymphocytes.