Taurodeoxycholate, a GPCR19 agonist, ameliorates atopic dermatitis in Balb/c mice.

Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2X7R has not been feasible because of polymorphisms and ubiquitous expression of P2X7R. Here, we report that GPCR19 colocalizes with P2X7R, and a GPCR19 agonist (taurodeoxycholate [TDCA]) inhibits the activation of P2X7R. Noncistronically, TDCA inhibits NF-kB activation via the adenylate cyclase-PKA pathway and BzATP-mediated Ca++ mobilization. Cistronically, TDCA suppresses the expression of P2X7R and N3I components in keratinocytes. NLRP3 oligomerization and the production of mature IL-1ß and IL-18 was suppressed by TDCA treatment in keratinocytes. Topical TDCA treatment ameliorates proinflammatory features of AD in mice induced by DNCB, MC903, or oxazolone. Taken together, a GPCR19 agonist such as TDCA might inhibit P2X7R-mediated N3I activation of keratinocytes, which is crucial for the pathogenesis of AD.

Liver transplantation in Jehovah's Witnesses: two cases report.

Liver transplantation is especially challenging in patients who are Jehovah's Witnesses because their religious beliefs prohibit the receipt of blood products. We present two cases of living donor liver transplantation performed in adult Jehovah's Witnesses in South Korea without the use of blood products. In the first case, preoperative erythropoiesisstimulation therapy increased hemoglobin levels from 8.1 to 13.1 g/dl after 9 weeks. In the second case, hemoglobin levels increased from 7.4 to 10.8 g/dl after 6 months of erythropoiesis-stimulation therapy. With the combination of acute normovolemic hemodilution, intraoperative cell salvage, and use of transfusion alternatives, liver transplantation was successfully performed without transfusion of blood products.

The causes and treatment outcomes of 91 patients with adult nosocomial meningitis.

BACKGROUND/AIMS: Frequent pathogens of nosocomial meningitis were investigated and the adequacy of empiric antibiotic therapy was assessed. Outcomes of nosocomial meningitis were also evaluated. METHODS: Ninety-one patients, who were diagnosed and treated for nosocomial meningitis at a single tertiary hospital in Daegu, Korea for 10 years, were included. Medical record and electronic laboratory data on the causative pathogens, antibiotics used, and outcomes were retrospectively investigated. RESULTS: Coagulase-negative Staphylococcus (40.9%) was the most common pathogen, followed by Acinetobacter (32.5%). Both were cultured as a single organism in cerebrospinal fluid (CSF). Seventy-eight patients (85.7%) had infections related to external ventricular drains (EVD). The most common empirical antibiotics were extended-spectrum beta-lactam antibiotics plus vancomycin (35/91, 38.6%). Of the 27 patients who had cultured Acinetobacter in CSF, 10 (37%) were given the wrong empirical antibiotic treatment. Seven of the 27 patients (26.9%) with cultured Acinetobacter died, and overall mortality of the 91 patients was 16.5%. In the multivariate analysis, the presence of combined septic shock (p < 0.001) and a persistent EVD state (p = 0.021) were associated with a poor prognosis. CONCLUSIONS: Acinetobacter is one of the leading pathogens of nosocomial meningitis and may lead to inadequate coverage of empiric antibiotic therapy due to increasing resistance. An EVD should be removed early in cases of suspected nosocomial meningitis, and carbapenem might be required for the poor treatment response.

Causes and treatment outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in 82 adult patients.

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are predominantly known as medication-induced diseases. However, at our institution, we have experienced more cases of non-drug-related SJS and TEN than expected. Therefore, we studied the difference between non-drug-related and drug-related SJS and TEN in terms of clinical characteristics and prognoses. METHODS: The etiologies, clinical characteristics, and treatment outcomes for 82 adult patients with SJS and TEN were retrospectively reviewed. RESULTS: A total of 71 patients (86.6%) were classified as having SJS, and the other 11 patients (13.4%) were classified as having TEN. Drug-related cases were more common (43, 52.4%) than non-drug-related cases (39, 47.6%). Anticonvulsants (12/82, 14.6%) and antibiotics (9/82, 11%) were the most common causative medications. Anemia (p = 0.017) and C-reactive protein of ≥ 5 mg/dL (p = 0.026) were more common in the drug-related cases than in the non-drug-related cases. Intravenous steroid therapy was used as the main treatment regimen (70/82, 85.4%). Of the 82 patients, 8 (9.8%) died during the clinical course. A univariate analysis for mortality showed statistical significance for the following: kidney function abnormality, pneumonia, hemoglobin of < 10 g/dL, and combined underlying diseases. In a multivariate analysis, only pneumonia was statistically significant (odds ratio, 25.79; p = 0.009). CONCLUSIONS: Drugs were the most frequent cause of these diseases. However, non-drug-related causes also contributed to a significant proportion of cases. Physicians should keep this in mind when documenting patient history. In addition, early recognition and treatment may be important for better outcomes.