Anaerobic NADH-fumarate reductase system is predominant in the respiratory chain of Echinococcus multilocularis, providing a novel target for the chemotherapy of alveolar echinococcosis

Alveolar echinococcosis, which is due to the massive growth of larval Echinococcus multilocularis, is a life-threatening parasitic zoonosis distributed widely across the northern hemisphere. Commercially available chemotherapeutic compounds have parasitostatic but not parasitocidal effects. Parasitic organisms use various energy metabolic pathways that differ greatly from those of their hosts and therefore could be promising targets for chemotherapy. The aim of this study was to characterize the mitochondrial respiratory chain of E. multilocularis, with the eventual goal of developing novel antiechinococcal compounds. Enzymatic analyses using enriched mitochondrial fractions from E. multilocularis protoscoleces revealed that the mitochondria exhibited NADH-fumarate reductase activity as the predominant enzyme activity, suggesting that the mitochondrial respiratory system of the parasite is highly adapted to anaerobic environments. High-performance liquid chromatography-mass spectrometry revealed that the primary quinone of the parasite mitochondria was rhodoquinone-10, which is commonly used as an electron mediator in anaerobic respiration by the NADH-fumarate reductase system of other eukaryotes. This also suggests that the mitochondria of E. multilocularis protoscoleces possess an anaerobic respiratory chain in which complex II of the parasite functions as a rhodoquinol-fumarate reductase. Furthermore, in vitro treatment assays using respiratory chain inhibitors against the NADH-quinone reductase activity of mitochondrial complex I demonstrated that they had a potent ability to kill protoscoleces. These results suggest that the mitochondrial respiratory chain of the parasite is a promising target for chemotherapy of alveolar echinococcosis.     

HIV prevention risks for Black women in Canada

The future availability of HIV vaccines can increase options available to Canadian Black women for risk reduction. However, current conceptual frameworks do not adequately address barriers to HIV prevention for this population, and may be inadequate to address challenges with vaccines. This study explored knowledge and attitudes regarding HIV vaccines and associated prevention methods to inform appropriate conceptual frameworks for their dissemination to Canadian Black women. We completed four 90-min focus groups with women (n=26) of African or Caribbean origins, and six interviews with key informants providing health and social services in the Black communities of Toronto. The participants suggested that there were significant risks associated with seeking prevention information and attempting to reduce exposure to HIV infection. They described individual, familial, community and institutional domains of risk and predicted the same spectrum of risk for HIV vaccines. Participants advocated for education, empowerment and institutional change to create a supportive environment for vaccines and other HIV prevention methods. They further indicated that preparation for vaccine dissemination will need to prioritize building trust between women of the Black communities and institutions in the research, health and government sectors.     

A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis

ObjectiveStudies suggest that synbiotic therapy could prove more effective in the treatment of ulcerative colitis (UC) than therapies limited to probiotics or prebiotics. This study compared the effect of each of these therapies in the treatment of UC.MethodsOne hundred twenty outpatients with UC were randomly sorted into three groups of 40 patients each for probiotic, prebiotic, or synbiotic therapy. The probiotic group ingested one daily capsule consisting of Bifidobacterium longum 2 × 10⁹ colony-forming units and the prebiotic group ingested daily 8.0-g doses of psyllium. The synbiotic group underwent both treatments. All patients completed Inflammatory Bowel Disease Questionnaires (IBDQs) at the onset of the trial, at the 2-wk midpoint, and at the 4-wk end of the trial. Blood variables were also evaluated in a subset of 32 patients randomly selected from all groups and values were compared with IBDQ scores.ResultsThirty-one patients in the probiotic group, 31 in the prebiotic group, and 32 in the synbiotic group qualified for analyses. The remaining 26 patients had incomplete questionnaires. Total IBDQ scores improved within groups by the end of the trial (probiotics 162 to 169, NS; prebiotics 174 to 182, NS; synbiotics 168 to 176, P = 0.03). Individual scores improved as follows: probiotics, emotional function (P = 0.03); prebiotics, bowel function (P = 0.04); and synbiotics, systemic and social functions (P = 0.008 and P = 0.02). C-reactive protein decreased significantly only with synbiotic therapy (from 0.59 to 0.14 mg/dL, P = 0.04). There were no adverse events.ConclusionPatients with UC on synbiotic therapy experienced greater quality-of-life changes than patients on probiotic or prebiotic treatment. These data suggest that synbiotic therapy may have a synergistic effect in the treatment of UC.     

Expression,localization and possible actions of 25-Dx,a membraneassociated putative progesterone-binding protein,in the developing Purkinje cell of the cerebellum: A new insight into the biosynthesis,metabolism and multiple actions of progesterone as a neurosteroid

Neurosteroids are now known to be steroids that are synthesized de novo from cholesterol in the central and peripheral nervous systems of vertebrates through mechanisms at least partly independent of peripheral steroidogenic glands, such as the adrenal and gonads. A series of our studies have demonstrated that the rat Purkinje cell, a cerebellar neuron, actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and synaptogenesis via its nuclear receptor in this neuron. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to genomic neurosteroid actions. Recently, we have further found that Purkinje cells express the putative membrane progesterone receptor, 25-Dx in rats. By immunocytochemistry, the expression of 25-Dx was localized in the Purkinje cell and external granule cell layer. RT-PCR and Western immunoblot analyses revealed the expressions of 25-Dx and its mRNA in the rat cerebellum, which increased during neonatal life. Therefore, progesterone would promote dendritic growth, spinogenesis and synaptogenesis via 25-Dx as well as its nuclear receptor in the Purkinje cell in the neonate. Because the subcellular localization of 25-Dx was associated with membrane structures of the endoplasmic reticulum and Golgi, 25-Dx may also play a role in the regulation of neurosteroidogenesis in the developing Purkinje cell. Here we summarize the advances made in our understanding of the expression, localization and its possible actions of 25-Dx in the developing Purkinje cell.     

Two cases of ampulla (takotsubo-shaped) cardiomyopathy associated with hemophagocytic lymphohistiocytosis

There have been many reports of patients with ampulla cardiomyopathy described as takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique cardiomyopathy is characterized by transient apical ballooning and hypokinesis of the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular dysfunction suddenly occurred during the active phase of HLH. In each case, the findings on ECG, echocardiogram and left ventriculogram were compatible with ampulla cardiomyopathy. To our knowledge, this communication is the first to report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.     

Effect of varicocelectomy on patients with unobstructive azoospermia and severe oligospermia

OBJECTIVES

To assess the treatment outcome and benefits after varicocelectomy in men with unobstructive azoospermia (UOA) and severe oligospermia (SO).

PATIENTS AND METHODS

The records were retrospectively evaluated for six patients with UOA and 54 with SO who had microsurgical inguinal varicocele ligation (mean age 33.3 years, sd 5.3). Fifty‐one (85%) had a unilateral left‐sided procedure (five of six with UOA, 46 of 54 with SO), and nine (15%) had a bilateral procedure.

RESULTS

After ligation, spermatogenesis was induced in two of the six men with UOA; the mean (sd ) sperm concentration increased from 2.3 (1.6) to 9.2 (12.6) million/mL (P < 0.001), but the sperm motility did not change significantly. Four (7%) of the 54 men with SO achieved paternity, with unassisted pregnancies.

CONCLUSIONS

Varicocelectomy resulted in the induction or enhancement of spermatogenesis for several men with UOA or SO; it seems to be a reasonable option in selected patients with UOA or SO.     

Regions downstream from the WW domain of dystrophin are important for binding to postsynaptic densities in the brain

In order to investigate the mechanism of dystrophin localization in the central nervous system (CNS), we generated adenovirus vectors that contained minidystrophin or truncated minidystrophin cDNA. We infected a primary neuronal culture derived from mdx mouse hippocampus with these viruses. Minidystrophin was observed along the plasma membrane as punctate dots or very short segments. In double immunofluorescence staining with anti-dystrophin and anti-postsynaptic density-95 antibodies, we observed that these proteins entirely colocalized. On the other hand, the truncated minidystrophin, which has deleted WW, cysteine-rich and C-terminal domains, was homogenously expressed in cytoplasm, neurites and axons. These findings suggest that a binding site to postsynaptic densities exists in the region extending from the WW domain to the C-terminal domain of dystrophin and that this site is necessary for binding to membrane.     

A new curved laryngoscope blade for routine and difficult tracheal intubation

We have designed a new curved laryngoscope blade based on a new concept of reversing the peardrop phenomenon to facilitate a view of the larynx sufficient for intubation in a greater variety of patients than the current Macintosh blade affords. The new design has a bifid tip and S-shaped spatula to exert more effective pressure in the vallecula area, elevate the epiglottis and change directions of the forces on the tongue to prevent posteroinferior displacement of the compressed tongue in the submandibular space during laryngoscopy. A radiograph laryngoscopy technique was used to guide the new blade curvature design and compare the performance of the new blade with the Macintosh blade in patients with or without a difficult airway. Our results confirm that the new blade provides a laryngeal view sufficient to accomplish intubation by compressing the root of the tongue in an anterocephalad direction in the submandibular space and elevating the epiglottis effectively in patients with or without unanticipated difficult airway. The new curved blade can also effectively move the U-shaped epiglottis out of the laryngeal view to facilitate intubation in pediatric patients aged 2 mo-13 yr.