Immunological analysis in xenogeneic fetal porcine liver transplantation into a beagle

BACKGROUND/AIMS: While allogeneic organ transplantation has been performed safely, a major barrier in xenogeneic transplantation is how to inhibit hyperacute rejection. METHODOLOGY: We challenged xenogeneic fetal liver transplantation from pig to dog. The graft was investigated by immunohistochemical analysis on recipient's IgG, IgM and C3. RESULTS: In 1 of 4 cases, the graft escaped hyperacute rejection for about 4 hours after transplantation, however, the recipient died next day due to hemorrhage from the torn capsule of the liver due to the arterial blood pressure of the recipient. Histologically, the parenchyma showed good countenance and no congestion nor hemorrhage was shown in the vessels. On immunohistochemical analysis, canine IgG, IgM and C3 were deposited on the sinusoidal epithelium of the fetal liver more moderately than that of adult control. Fetal porcine liver showed less expression of major histocompatability complex class I antigen than that of the adult one. CONCLUSIONS: We consider that the hyperacute rejection occurred more slowly in xenogeneic fetal liver transplantation than in the adult one due to not only less expression of major histocompatability complex class I, but also lower expression of the epitope recognized by a natural antibody of the recipient.     

Continuous in vitro culture of Plasmodium falciparum using microaerophilic gas generators and portable incubator

AnaeroPack Malaria Culture System (SUGIYAMA-GEN Co., Ltd.) using AnaeroPack.plas (5% O2, 5% CO2) and AnaeroPack.CO2 (15% O2, 6% CO2) was evaluated by comparing with the standard laboratory in vitro continuous culture technique. Two culture-adapted strains of Plasmodium falciparum, SGE-1 (chloroquine sensitive strain) and K1 (chloroquine resistant strain), were continuously cultured for 26 days in vitro under the 3 systems. The parasite proliferation curves under the different set systems were paralleled in both strains, which demonstrate that this AnaeroPack Malaria Culture System is useful for the culture-adapted strains of P. falciparum. Although further test using isolates from falciparum malaria patients should be carried out, the AnaeroPack Malaria Culture System seems promising for the culture in the field studies.     

Prevalence and the long-term prognosis of functional mitral regurgitation in Japanese patients with symptomatic heart failure

Functional mitral regurgitation (FMR) is a common and critical condition in patients with heart failure (HF); however, the prevalence and clinical outcome of FMR in Japanese real-world clinical practice remain unclear. Within a single hospital-based cohort in the Shinken Database 2004–2011, which comprised all new patients (n = 17,517) who visited the Cardiovascular Institute, we followed symptomatic HF patients. A total of 1,701 patients were included: 104 FMR patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia, but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York Heart Association functional class III/IV. FMR patients had higher levels of brain natriuretic peptide and lower left ventricular function. Use of cardiovascular drugs was more common among FMR patients. Kaplan–Meier curves revealed that the incidences of all-cause death, cardiovascular death, and admission for HF were significantly higher in FMR patients. The adjusted Cox regression analysis showed that significant FMR was associated with higher incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval (CI) 1.266–3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157–4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133–2.920; P = 0.013). FMR was common in Japanese symptomatic HF patients and was associated with adverse long-term outcomes. Establishing optimal therapeutic strategies for FMR is warranted.     

Direct exposure of non-equilibrium atmospheric pressure plasma confers simultaneous oxidative and ultraviolet modifications in biomolecules

Thermal plasmas and lasers are used in medicine to cut and ablate tissues and for coagulation. Non-equilibrium atmospheric pressure plasma (NEAPP) is a recently developed, non-thermal technique with possible biomedical applications. Although NEAPP reportedly generates reactive oxygen/nitrogen species, electrons, positive ions, and ultraviolet radiation, little research has been done into the use of this technique for conventional free radical biology. Recently, we developed a NEAPP device with high electron density. Electron spin resonance spin-trapping revealed ^•OH as a major product. To obtain evidence of NEAPP-induced oxidative modifications in biomolecules and standardize them, we evaluated lipid peroxidation and DNA modifications in various in vitro and ex vivo experiments. Conjugated dienes increased after exposure to linoleic and α-linolenic acids. An increase in 2-thiobarbituric acid-reactive substances was also observed after exposure to phosphatidylcholine, liposomes or liver homogenate. Direct exposure to rat liver in saline produced immunohistochemical evidence of 4-hydroxy-2-nonenal- and acrolein-modified proteins. Exposure to plasmid DNA induced dose-dependent single/double strand breaks and increased the amounts of 8-hydroxy-2''-deoxyguanosine and cyclobutane pyrimidine dimers. These results indicate that oxidative biomolecular damage by NEAPP is dose-dependent and thus can be controlled in a site-specific manner. Simultaneous oxidative and UV-specific DNA damage may be useful in cancer treatment.     

Simulation to Locate Burr Hole Sites in a Patient for Deep Brain Stimulation Surgery and Clipping of Intracranial Aneurysm

Background and Objective: Deep brain stimulation (DBS) candidates with neurologic diseases such as unruptured aneurysm present additional challenges to neurosurgeons when craniotomy must precede DBS surgery. Such craniotomy may potentially overlap with intended burr hole sites for the later insertion of DBS electrodes, and the skin incision for craniotomy may lie very close to or intersect with that for the burr holes. We report here a case of forehead craniotomy prior to DBS surgery in which we employed a neuronavigation system to simulate locations for the craniotomy and burr holes. Method: A 62‐year‐old male patient with Parkinson's disease was a candidate for DBS. He also had an aneurysm and was planned first to undergo frontal craniotomy for clipping before the DBS surgery. The locations of the craniotomy, burr holes, and skin incisions were therefore simulated using a neuronavigation system during craniotomy. Results: Two weeks after the craniotomy, the patient underwent DBS surgery. Planning software confirmed the absence of cortical veins beneath the entry points of tentative burr holes and aided trajectory planning. The DBS surgery was performed without the interference of the burr holes and head pins and the craniotomy. Conclusion: Simulation of the locations of craniotomy and burr holes using a neuronavigation system proved valuable in the present case of frontal craniotomy before DBS surgery.