Medical Treatment of Echinococcus multilocularis and New Horizons for Drug Discovery: Characterization of Mitochondrial Complex II as a Potential Drug Target

As an efficient drug for alveolar echinococcosis (AE) is still not available, new chemotherapy targets are necessary. The mitochondrial respiratory chain may be a good drug candidate because parasite respiratory chains are quite different from those of mammalian hosts. For example, Ascaris suum possesses an NADH‐fumarate reductase system (fumarate respiration) that is highly adapted to anaerobic environments such as the small intestine. It is composed of mitochondrial complex I (NADH‐ubiquinone reductase), complex II (succinate‐ubiquinone reductase), and rhodoquinone. We previously demonstrated that fumarate respiration is also essential in E. multilocularis. Quinazoline, a complex I inhibitor, inhibited growth of E. multilocularis larvae in vitro. These results indicate that fumarate respiration could be a target for E. multilocularis therapy. In the current chapter, we focused on complex II, which is another component of this system, because quinazoline exhibited strong toxicity to mammalian mitochondria. We evaluated the molecular and biochemical characterization of E. multilocularis complex II as a potential drug target. In addition, we found that ascofuranone, a trypanosome cyanide‐insensitive alternative oxidase inhibitor, inhibited E. multilocularis complex II at the nanomolar order. Our findings demonstrate the potential development of targeted therapy against Echinococcus complex II

Early Development of Larval \u3ci\u3eTaenia polyacantha\u3c/i\u3e in Experimental Intermediate Hosts

The early larval development and migration route of Taenia polyacantha were examined using oral inoculation of oncospheres into red-backed voles and Mongolian gerbils. The larvae were recovered in the wall of the small intestine and in the mesenteric lymph nodes by 5 days postinfection (PI) and from the peritoneal cavity after 6 days PI. These results suggest that the larval cestodes developed initially in the wall of the small intestine and the mesenteric lymph nodes, and later migrated to the peritoneal cavity. Although the development of the parasite was quite similar in the 2 host species, pathological changes were different. In Mongolian gerbils, these changes were slight, but in red-backed voles, they were marked and fatal. In addition to oral inoculation, hatched oncospheres were injected intraperitoneally and subcutaneously into red-backed voles, Mongolian gerbils, and AKRlJ mice. Larval development took place at the injection sites in gerbils and mice, but was delayed and abnormal. Some of the parasites in the injection site showed abnormal numerous budding. High pathogenicity was shown after subcutaneous and intraperitoneal injection as well as after oral inoculation

Increased Specific Antibody Titers Against Chlamydia pneumoniae in Patients with Age-related Macular Degeneration

We evaluated a possible association between Chlamydia pneumoniae (C. pneumoniae) infection and the occurrence of age-related macular degeneration (AMD). Specific antibody titers against C. pneumoniae were determined in the serum of 27 patients with AMD and 22 age-matched controls. Titers of IgA and IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA), and the levels were compared between the AMD patients and the control subjects. Titers of IgA and IgG serum antibodies were significantly higher in the AMD group (P < 0.05, MannWhitney); the mean ± standard deviation of the IgA index was 1.96 ± 0.80 in the AMD group and 1.39 ± 0.84 in the control group; that of the IgG index was 2.08 ± 0.95 in AMD and 1.32 ± 0.85 in the controls. The significantly higher IgA and IgG antibody titers against C. pneumoniae in patients with AMD than in age-matched controls suggest that C. pneumoniae infection may play a role in the pathogenesis of AM

Persistent Left Superior Vena Cava in Hematological Malignancy Requiring Central Venous Catheter Insertion for Intensive Chemotherapy

Persistent left superior vena cava is a congenital vascular anomaly, which is possibly arrhythmogenic and thrombogenic, rarely complicated with coronary sinus atresia. We treated a 42-year-old male with Hodgkin's lymphoma requiring central venous catheter placement for intensive chemotherapy. Persistent left superior vena cava was revealed after the insertion of the central venous catheter by the radiological finding of the catheter tip cannulated into the vena cava cavity. The relationship between coronary sinus atresia and persistent left superior vena cava induced by central venous catheterization remains unclear; however, the hematologist should pay attention to the malpositioning of the central venous catheter