Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network.

Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.

Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic response and acute vascular rejection in cardiac xenografts.

BACKGROUND: Xenografts ultimately fail as a result of acute vascular rejection (AVR), a process characterized by intravascular thrombosis, fibrin deposition, and endothelial cell activation. METHODS AND RESULTS: We studied whether targeted deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2-/-) in the donor prevents AVR in a mouse-to-rat cardiac xenotransplantation model. By 3 days after transplant, Fgl-2+/+ grafts developed typical features of AVR associated with increased levels of donor Fgl-2 mRNA. Grafts from Fgl-2-/- mice had reduced fibrin deposition but developed cellular rejection. Treatment with a short course of cobra venom factor and maintenance cyclosporine resulted in long-term acceptance of both Fgl-2+/+ and Fgl-2-/- grafts. On withdrawal of cyclosporine, Fgl-2+/+ grafts developed features of AVR; in contrast, Fgl-2-/- grafts again developed acute cellular rejection. Rejecting Fgl-2+/+ hearts stained positively for IgG, IgM, C3, and C5b-9, whereas rejecting Fgl-2-/- hearts had minimal Ig and complement deposition despite xenoantibodies in the serum. Furthermore, serum containing xenoantibodies failed to stain Fgl-2-/- long-term treated hearts but did stain wild-type heart tissues. Treatment of Fgl-2-/- xenografts with mycophenolate mofetil and tacrolimus, a clinically relevant immune suppression protocol, led to long-term graft acceptance. CONCLUSIONS: Deletion of Fgl-2 ameliorates AVR by downregulation of xenoantigens and may facilitate successful clinical heart xenotransplantation.

Tratamento da forma mucosa de Leishmaniose sem resposta a glucantime, com anfotericina B liposomal / Treatment of mucosal leishmaniasis unresponsive to glucantime, with liposomal amphotericin B

Tratamos com ambisome (2 a 5g totais de dose) seis pacientes com leishmaniose mucosa sem resposta a tratametno com glucantime (20mg sbv/kg/dia). A dose diária usada foi 2 a 3mg/kg/dia, aplicada por um mínimo de 20 dias. Após 26 a 38 meses de acompanhamento, cinco pacientes estäo clinicamente curados. Um recidivou aos 6 meses. Näo foram observados efeitos colaterais além de cefaléia, após a injeçäo. O ambisome constitue uma opçäo terapêutica para os pacientes com leishmaniose mucosa sem resposta aos antimoniais.

Hookworm infection and intestinal absorption amongst Africans in Uganda

Intestinal parasitic infections may impair electrolyte transport and protein absorption from the intestinal lumen in animals and man; and recently hookworm infection has been found to cause stearrhoea and malabsorption in Puerto Rico and North India. However; in a study of hookworm anemia in Nigeria; West Africa Gilles; Watson Williams; and Ball found evidence of mild steatorrhoea in only one of 11 patients; and no evidence of malabsorption was detected in studies performed in Egypt; Venezuela; and Costa Rica. The present investigation was carried out where hookworm anemia was both the second most common cause of admission to the medical wards of the hospital and a serious cause of mortality and morbidity in the community. The purpose of this study was to investigate whether hookworm infection caused malabsorption of chronic pancreatic disease; which is now the most common cause of steatorrhea in Uganda