Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Human Adipose Tissue-Derived Stem Cells Inhibit Coronary Artery Vasculitis in a Mouse Model of Kawasaki Disease.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ADSCs) are used for the treatment of various diseases because of their rapid proliferation and high anti-inflammatory and tissue repair properties. Kawasaki disease is a systemic vasculitis with coronary arteritis and aneurysms occurring in pediatric patients. In this study, we examined serologically and pathologically whether the administration of human ADSCs (hADSCs) to a mouse model of Kawasaki disease could suppress vasculitis. METHODS: Candida albicans water-soluble fractions were intraperitoneally injected into DBA/2 mice for 5 consecutive days to generate a mouse model of Kawasaki disease. The model mice were intravenously administered hADSCs or phosphate-buffered saline (PBS). Serum samples collected on days 15 and 29 were used to compare cytokine levels. Mouse hearts dissected on day 29 were subjected to hematoxylin and eosin and immunohistological staining using Galectin-1 (Gal-1), a protein involved in cardiovascular homeostasis, and CD44, a cell-surface marker of hADSCs. RESULTS: Comparison of inflammation-related cytokines showed a significant decrease in IL-1α expression at day 15 (P<0.05) and IL-6 expression at day 29 (P<0.01) in the hADSCs-treated group compared to the PBS group. Evaluation by hematoxylin and eosin staining showed decreased inflammatory cell infiltration and a tendency towards increased Gal-1 expression in the hADSCs group. CD44 expression was not observed in both the groups. The survival curve showed that the hADSCs group had a significantly longer survival time (P<0.05). CONCLUSIONS: The present experimental results indicate that hADSCs have an early anti-inflammatory effect, and that Gal-1 may be involved in preventing inflammation and reducing tissue damage.

Methylation of PLK-1 Potentially Drives Bendamustine Resistance in Leukemia Cells.

BACKGROUND: Drug resistance remains a significant impediment in leukemia treatment. While Bendamustine hydrochloride (BH) stands out as a promising therapeutic agent for non-Hodgkin' s lymphoma and mantle cell lymphoma, the mechanisms of resistance to BH are not yet fully understood. Our study focuses on elucidating the mechanisms behind bendamustine resistance in leukemia cells, with a specific emphasis on epigenetics. METHODS: Bendamustine-resistant cells were cultivated from human B cell lymphoblastic leukemia cell lines through systematic and sustained exposure to bendamustine, using the limiting dilution method. Gene expression was assessed via real-time polymerase chain reaction, while the expression of the multidrug resistance protein 1 (MDR1) was evaluated using flow cytometry. RESULTS: Bendamustine-resistant leukemia cells exhibited a decreased RNA expression level for Polo-like kinase-1 (PLK-1). Notably, after treatment with the demethylating agent 5-aza-2'-deoxycytidine, PLK-1 gene expression surged significantly, enhancing bendamustine's cytotoxicity in the resistant leukemia cells. However, MDR1 expression, as determined by flow cytometry, remained consistent between parental and bendamustine-resistant leukemia cells. CONCLUSIONS: Our findings indicate that the methylation of the PLK-1 gene plays a pivotal role in modulating PLK-1 expression and is central to the development of bendamustine resistance in leukemia cells.

A case of bacteremia and meningitis in a neonate infected with Group B Streptococcus via breastfeeding who survived without neurological sequelae: A case report.

Invasive neonatal infection with Group B Streptococcus (GBS) is a disease of concern that can lead to neurological sequelae. Guidelines for preventing mother-to-child transmission have been introduced to reduce the incidence of early-onset infection, but guidelines for controlling the late-onset form are lacking. Recently, the trans-breastfeeding route of transmission has been highlighted as an example of late-onset infection, but no consensus on how to manage such infections has been reached. In this report, we describe a case of late-onset bacteremia/meningitis in a neonate suspected to have been infected with GBS via breastfeeding. A vaginal culture test of the mother at 35 weeks' gestation was negative for GBS. Since she had symptoms of mastitis, breast milk and nipple cultures were also tested and found to be positive for the strain of GBS identified in the neonate on genetic analysis. Diagnosis of trans-mammary GBS infection is challenging because breastfeeding-related events are difficult to identify. In our case, the diagnosis was based on the mother's history of mastitis, and the patient was treated without escalation to sequelae. When a neonate develops a fever, physicians should consider GBS infection and examine the mother's medical history to facilitate accurate diagnosis, especially if the history includes mastitis. A breast milk culture should be performed if the mother has mastitis, especially in cases of infection in preterm infants and in recurrent cases.

A Case of Kawasaki Disease with Intussusception.

Kawasaki disease (KD) is a systemic vasculitis of unknown cause and is associated with various digestive disorders, although only a few cases of intussusception associated with KD have been reported. We describe a case of intussusception followed by KD in a 3-year-old boy. The patient was admitted to our hospital for evaluation of severe abdominal pain. Because the target sign was seen on ultrasonography, intussusception was diagnosed and hydrostatic reduction was performed. On the second day after admission, he developed a high fever (38°C) and an irregular rash over his whole body. On the fourth day after admission, the high fever continued, and bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, strawberry tongue, indurated edema of the dorsa of the hands and feet, and diffuse erythema of the palms and soles appeared, and KD was ultimately diagnosed. He was treated with intravenous immunoglobulin 2 g/kg, aspirin 30 mg/kg/day, and prednisolone 2 mg/kg/day. The high fever and other clinical symptoms resolved immediately after the start of treatment. There was no relapse of KD symptoms after initial treatment, and periungual desquamation was observed on the 10th day after admission. He was discharged on the 15th day, without abnormalities such as coronary dilatation, 3 months after the onset of KD symptoms. Patients with intussusception and KD were older (≥3 years vs <3 years) than those with intussusception alone. In addition, the site of intussusception in KD was mainly colonic rather than ileocolic. If intussusception precedes development of the characteristic clinical symptoms of KD, diagnosis of KD may be delayed. KD should be considered in children older than 3 years with intussusception at a colonic site.