Tetratricopeptide Repeat Protein-Associated Proteins Contribute to the Virulence of Porphyromonas gingivalis▿ †

Porphyromonas gingivalis is one of the most etiologically important microorganisms in periodontal disease. We found in a previous study that PG1385 (TprA) protein, a tetratricopeptide repeat (TPR) protein, was upregulated in P. gingivalis wild-type cells placed in a mouse subcutaneous chamber and that a tprA mutant was clearly less virulent in the mouse subcutaneous abscess model (M. Yoshimura et al., Oral Microbiol. Immunol. 23:413-418, 2008). In the present study, we investigated the gene expression profile of tprA mutant cells placed in a mouse subcutaneous chamber and found that 9 genes, including PG2102 (tapA), PG2101 (tapB), and PG2100 (tapC) genes, were downregulated in the tprA mutant compared with those in the wild type. Expression of a cluster of tapA, tapB, and tapC genes of the mutant was also downregulated in an in vitro culture with enriched brain heart infusion medium. The TprA protein has three TPR motifs known as a protein-protein interaction module. Yeast two-hybrid system analysis and in vitro protein binding assays with immunoprecipitation and surface plasmon resonance detection revealed that the TprA protein could bind to TapA and TapB proteins. TprA and TapB proteins were located in the periplasmic space, whereas TapA, which appeared to be one of the C-terminal domain family proteins, was located at the outer membrane. We constructed tapA, tapB, and tapC single mutants and a tapA-tapB-tapC deletion mutant. In the mouse subcutaneous infection experiment, all of the mutants were less virulent than the wild type. These results suggest that TprA, TapA, TapB, and TapC are cooperatively involved in P. gingivalis virulence

Relapsing Peritoneal Dialysis-Associated Peritonitis due to Kocuria rhizophila: A Case Report

Introduction: The Kocuria genus, encompassing gram-positive coccoid actinobacteria belonging to the Micrococcaceae family, has recently been discovered residing on the human skin and oral flora. Reports of Kocuria-associated infections in humans have been scarce. Herein, we present the first case of relapsing peritoneal dialysis (PD)-associated peritonitis caused by Kocuria rhizophila. Case Presentation: The patient, a 78-year-old male, presented with turbid effluent PD fluid, accompanied by an elevated white blood cell count of 253 cells/μL, of which 59% were neutrophils. A diagnosis of PD-associated peritonitis was established, leading to the initiation of intraperitoneal administration of ceftazidime and vancomycin. Subsequently, Kocuria rhizophila was identified through the bacterial culture of the dialysate. On the seventh day of initial treatment, the antibiotic regimen was changed to penicillin G, and the patient underwent a 3-week course of antibiotics. However, 1 week after discharge, the patient’s dialysis fluid became cloudy once again, with subsequent detection of Kocuria rhizophila in the fluid culture. Ultimately, the decision was made to remove the patient’s PD catheter and transition to hemodialysis. Conclusion: PD-associated peritonitis attributed to Kocuria species may be considered a potential risk for recurrence

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites

Biopsy-proven vancomycin-induced acute kidney injury: a case report and literature review

Abstract Background Vancomycin is the first-line antibiotic for methicillin-resistant Staphylococcus aureus and coagulase-negative strains. The risk of vancomycin-induced acute kidney injury increases with plasma vancomycin levels. Vancomycin-induced acute kidney injury is histologically characterized by acute interstitial nephritis and/or acute tubular necrosis. However, only 12 biopsy-proven cases of vancomycin-induced acute kidney injury have been reported so far, as renal biopsy is rarely performed for such cases. Current recommendations for the prevention or treatment of vancomycin-induced acute kidney injury are drug monitoring of plasma vancomycin levels using trough level and drug withdrawal. Oral prednisone and high-flux haemodialysis have led to the successful recovery of renal function in some biopsy-proven cases. Case presentation We present the case of a 41-year-old man with type 1 diabetes mellitus, who developed vancomycin-induced acute kidney injury during treatment for Fournier gangrene. His serum creatinine level increased to 1020.1 μmol/L from a baseline of 79.6 μmol/L, and his plasma trough level of vancomycin peaked at 80.48 μg/mL. Vancomycin discontinuation and frequent haemodialysis with high-flux membrane were immediately performed following diagnosis. Renal biopsy showed acute tubular necrosis and focal acute interstitial nephritis, mainly in the medullary rays (medullary ray injury). There was no sign of glomerulonephritis, but mild diabetic changes were detected. He was discharged without continuing haemodialysis (serum creatinine level, 145.0 μmol/L) 49 days after initial vancomycin administration. Conclusions This case suggests that frequent haemodialysis and renal biopsy could be useful for the treatment and assessment of vancomycin-induced acute kidney injury, particularly in high-risk cases or patients with other renal disorders

iBTA-Induced Biotube® Blood Vessels: 2020 Update

Blood access is a lifeline for dialysis patients. However, serious problems such as stenosis or obstruction of access blood vessels, which are life-threatening conditions in daily clinical practice, still remain. One of the most promising candidates for solving these problems may be Biotube blood vessels. More than 20 years have passed since the development of in-body tissue architecture (iBTA), a technology for preparing tissues for autologous implantation in patients. The tissues obtained by iBTA do not elicit immunological rejection, which is one of the ultimate goals of regenerative medical engineering; however, their practical applications were quite challenging. The seemingly unorthodox iBTA concepts that do not follow the current pre-established medical system may not be readily accepted in general medicine. In contrast, there are many diseases that cannot be adequately addressed even with the latest and most advanced medical technology. However, iBTA may be able to save patients with serious diseases. It is natural that the development of high-risk medical devices that do not fit the corporate logic would be avoided. In order to actively treat such largely unattached diseases, we started Biotube Co., Ltd. with an aim to contribute to society. Biotubes induced by iBTA are collagenous tubular tissues prepared in the patient’s body for autologous implantation. The application of Biotubes as tissues for vascular implantation has been studied for many years. Biotubes may have excellent potential as small-diameter artificial blood vessels, one of the most difficult to clinically achieve. Their possibility is currently being confirmed in preclinical tests. Biotubes may save hundreds of thousands of patients worldwide annually from amputation. In addition, we aim to eliminate the recuring access vascular problems in millions of dialysis patients. This study provides an update on the current development status and future possibilities of Biotubes and their preparation molds, Biotube Makers