BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

A alpha-glycerophosphate dehydrogenase is present in Trypanosoma cruzi glycosomes

alpha-glycerophosphate dehydrogenase (alpha-GPDH-EC.1.1.1.8) has been considered absent in Trypanosoma cruzi in contradiction with all other studied trypanosomatids. After observing that the sole malate dehydrogenase can not maintain the intraglycosomal redox balance, GPDH activity was looked for and found, although in very variable levels, in epimastigotes extracts. GPDH was shown to be exclusively located in the glycosome of T. cruzi by digitonin treatment and isopycnic centrifugation. Antibody against T. brucei GPDH showed that this enzyme seemed to be present in an essentially inactive form at the beginning of the epimastigotes growth. GPDH is apparently linked to a salicylhydroxmic-sensitive glycerophosphate reoxidizing system and plays an essential role in the glycosome redox balance

Alpha-glycerophosphate dehydrogenase activity in flight muscles of triatomine bugs Panstrongylus megistus and Triatoma sordida

The alpha-glycerophosphate dehydrogenase (alpha-GPDH) activity in flight muscles of Panstrongylus megistus and Triatoma sordida, vectors of Chagas disease in Brazil, was studied. Both species showed higher enzymatic activities in fliers than in non-fliers insects. T. sordida exhibited a higher proportion of flier insects than P. megistus. A possible role of alpha-GPDH on triatomines flight is discussed.

Ontogenetic patterns and genetic variations in Anopheles (Anopheles) intermedius Chagas, 1908 and Anopheles (Anopheles) mattogrossensis Lutz & Neiva, 1911 (Diptera: Culicidae) in the Brazilian amazon

Changes in the expression of genes were observed during development in populations of Anopheles (Anopheles) intermedius and Anopheles (Anopheles) mattogrossensis. Esterase showed seven zones of activity: EST1 was present in all developmental stages of both species; EST2 was observed only in larvae of A. intermedius and larvae and pupae of A. mattogrossensis, with greater activity in pupae; EST3 and EST5 were present in all development stages, with greater intensity in larvae; EST4 and EST6 showed weak activity in larvae of A. mattogrossensis and was not found in A. intermedius. Leucine aminopeptidase showed four zones of activity, of which LAP1 and LAP2 were found in all stages of A. intermedius, with highest activity in larvae, and in only of A. mattogrossensis. LAP3 was detected in all stages of A. mattogrossensis and in larvae only of A. intermedius. LAP4 was detected only in larvae and pupae of A. mattogrossensis, with greater intensity in pupae. Alpha-Glycerophosphate dehydrogenase showed a single zone of activity, detected in older fourth-instar larvae and becoming more intense from the pupal stage onwards.

Effect of FSH and insulin on lipogenesis in cultures of Sertoli cells from immature rats

Follicle-stimulating hormone (FSH) and insulin regulate glycide metabolism in Sertoli cells, thus stimulating lactate production. These stimulatory effects of FSH and insulin do not require protein synthesis, suggesting a modulation of enzyme activity and/or regulation of glucose transport. The present investigation was performed to characterize the hormonal control of lipid metabolism in Sertoli cells. The data indicate that FSH and insulin have a regulatory effect on lipid metabolism in Sertoli cells. After 8 h of preincubation with insulin (5 mug/ml), the activity of the enzyme ATP-citrate lyase in sultured Sertoli cells was increased from 0.19 to 0.34 nmol NAD+ formed mug protein(-1) min(-1). FSH (100 ng/ml) had no effect on this enzyme. Glycerol phosphate dehydrogenase activity was not affected by any of the hormones tested. When Sertoli cells from 19-day old rats were incubated with [1,2-14C] acetate for 90 or 360 min, the [14C] label was present predominantly in triglyceride and phospholipid fractions with minor amounts in other lipids. In Sertoli cells pretreated for 16 h with insulin and FSH, an increase in acetate incorporation into lipids was observed. Most of the label was in esterified lipids and this percentage increased with the time of treatment; this increase was remarkable in triglycerides of control cells (18.8 percent to 30.6 percent). Since Sertoli cell triglycerides participate in the control of spermatogenesis, the present data suggest that the hormonal control of lipid metabolism in Sertoli cells is important not only for maintaining the energy of the cell itself, but also for the control of the spermatogenesis process.

Biology of amazonian anopheline: XX. Ontogeny of esterases, leucine aminopeptidase and alpha-glycerophosphate dehydrogenase in Anopheles (Nyssorhynchus) darlingi Root, 1926 (Diptera, Culicidae)

The esterases, leucine aminopeptidase and alpha-glycerophosphate dehydrogenase revealed modifications in gene expressions during the development of Anopheles darlingi. The esterases showed five activity bands, 1 and 2 being more deeply stained during the larval stages than in pupae or adults, esterases 3 and 4 more deeply stained in pupae and adults whereas esterase 5 was present throughout development. Leucine aminopeptidase showed five activity bands: LAP2 and LAP5 were characteristic of larvae, LAP3 was specific for pupae and adults, LAP4 was detected only in pupae, and LAP1 and LAP6 were detected in all stages. Alpha-Glycerophosphate dehydrogenase presented one activity band on starch gel whose intensity increased with development. Two activity bands were detected on polyacrylamide gel (alpha-GPDH1 and alpha-GPDH2) in 4th-instar larvae (old pigmented larvae) and this activity increased with development.

Efectos del frío sobre la respiración mitocondrial del miocardio de ratas hipotiroideas tratadas con triiodotironina / Effects of cold on myocardial mitochondria respiration of rats with hypothyroidism treated with triiodothyronine

El presente trabajo estudió el efecto del frío sobre el consumo del oxígeno (CO) y la actividad *-glicerofosfato deshidrogenasa (*-GPD) en mitocondria cardíaca de ratas hipotiroideas (hipo) tratadas con T3, T4 o T4 más Acido lopanoico (IOP). Se usaron ratas Wistar macho de 200g de peso hechas hipotiroideas con la administración de I. Los animales fueron inyectadoss s.c., en dosis divididas, por 10 días, con una de las siguientes sustancias: T3, 300 ng/100g peso/día; T4, 2 *g/100g peso/día o T4 más IOP, 5 mg/100g peso/día, por 72 hs. previas al experimento. Una mitad de cada grupo fue mantenida a 4§C y el resto a 22§C, por 24 hs., y logo decapitados. Se aislaron las mitocondrias de corazón por métodos de rutina. El CO se midió polarográficamente usando L-malato, L-glutamato y malonato como sustratos. La actividad mitocondrial *-GPD se medió por un método microcolorimétrico. Los resultados correspondientes a 16 o 20 ratas/grupo (4 o 5 "pooles" de 4 corazones cada uno) fueron los isguientes: En las ratas mantenidas a 22§C el CO (en ng at. de oxíg./min/mg prot.; Estado 3) de las Hipo+T4 fue de 69 ñ 10; en el grupo tratado con T4+IOP fue de 75 ñ 11 y ...

Sex-related differences in the activity of liver mitochondrial alfa-glycerophosphate dehydrogenase in the rat

Alfa-glicerofosfato deshidrogenasa mitocondrial del hígado de rata es una enzima que responde marcadamente a la administración de la hormona tiroidea. Su actividad es considerada como buen índice del estado tiroideo en tejidos periféricos. En este estudio, la actividad de alfa-GPD y las características de unión del receptor nuclear de T3 (capacidad máxima de unión, MBC y constante de afinidad, Ka) fueron comparadas en ratas machos y hembras. La actividad basal de alfa-GPD en hembras adultas fue significativamente más alta que en machos de la misma edad. La misma diferencia se observó en animales inmaduros. Las variaciones fisiológicas cíclicas en las hormonas esteroideas ováricas durante el ciclo estrual no afectó significativamente la actividad de alfa-GPD, MBC y Ka. La orquiectomía o la administración de testosterona a ratas orquiectomizadas no tuvo efecto sobre la actividad de alfa-GPD cuando se compararon con machos normales con cirugía simulada. En hembras, ni la ovariectomía ni la administración de testosterona a animales ovariectomizados indujeron cambios en al actividad de la enzima. El contenido de T3 en núcleos hepáticos, la MBC y Ka fueron similares en ambos sexos. La actividad de alfa-GPD inducida por una dosis única de T3, suficientemente para mantener totalmente ocupados los receptores nucleares de T3 por un período de 24 h, fue significativamente más alta en las hembras que en los machos. Los estudios de la cinética de alfa-GPD mostraron una Km idéntica en ambos sexos, en tan

Will latent iron deficiency affect the mitochondrial iron-containing enzymes?

Since information pertinent to the effect of prelatent or latent iron deficiency on tissue iron is scare, the present study was aimed at producing this stage of iron deficiency in rats by phlebotomy and to determine whether the mitochondrial iron-containing enzymes, succinate dehydrogenase (SDH) and glycerophosphate dehydrogenase (GPDH) were affected. These phlebotomized rats showed a subclinical aneamic picture in the blood together with reduced plasma iron and storage iron in the spleen and liver, but an elevated plasma total iron-binding capacity (TIBC). Under this latent iron deficient state, the SHD in the heart and the skeletal muscle with mixed-fibre types (gastrocnemius and plantaris) but not the red (soleus) and white fibres (vastus lateralis) showed reduced activities. No significant changes in GPDH activities were found in these organs. This finding is consistent with our early report (Quisumbing et al., 1985) that even in mild iron deficiency, some loss of mitochondrial functions could have occurred and this could affect the muscular endurance. SDH was more affected by latent iron deficiency than GPDH.