Applying Aristotle's Doctrine of Causation to Aboriginal and Biomedical Understandings of Diabetes

Aristotle's doctrine on causationidentifies four distinct types of cause: formal, efficient,material, and final. Science is said to have differentiateditself from philosophy by concentrating solely on efficientcauses. Nonetheless, when applied to narratives of causation,Aristotle's doctrine provides a useful heuristic to explore theissues such as Aboriginal and biomedical perceptions of causalfactors for non-insulin dependent diabetes mellitus (NIDDM) onManitoulin Island, Ontario. This paper also outlines twodivergent causal stories for NIDDM and the associated moralpositions regarding the righteous pursuit of health. Biomedical narratives emphasize the role of lifestyle factors,particularly the impact of obesity, in causation. In the case ofdiabetes, the moral course of action is pursued through lifestylechoices. In contrast, Aboriginal narratives emphasize the roleof genetics in causation. These narratives describe diabetes ascollectively affecting Aboriginal people – thus identifyingAboriginal people as different. Aboriginal frameworks for healthventure beyond the efficient cause of biomedicine and thus themoral pursuit of health within this framework involves returningto an initial state of health and purity through traditionalknowledge.     

Analysis of tert-butyl hydroperoxide induced constrictions of perfused vascular beds in vitro

tert-Butyl hydroperoxide (t-BOOH), an inducer of oxidative stress in vitro, elicits constrictor responses of the isolated, rat kidney and mesenteric arteries perfused (5 ml/min) with physiological salt solutions (PSS) at 37 degrees C gassed with carbogen. We hypothesized that generation of superoxide anions (O(2)(-)) accounts for these responses. We assessed responses to t-BOOH in preparations with/without endothelium, and in the absence/presence of antioxidant compounds, catalase and tempol, scavengers of hydroxyl (OH(-)) radical and O(2)(-), respectively. t-BOOH (0.01-50 micromol) induced (expressed as % of 50 micromol KCl vasoconstriction) were abolished by endothelium denudation, perfusion with Ca(2+)-free PSS and by nifedipine, (1 nM). Infusion of t-BOOH (0.1 microM) did not significantly (P > 0.05) affect phenylepherine E(max) in the mesenteric arteries, however it reduced phenylepherine E(max) responses in the kidney from 94.9 +/- 3.9 % to 64.7 +/- 4.7 %. Nitroblue tetrazolium, as well as alpha-phenyl N-tert-butyl nitrone, at 100 microM, but not catalase (500 IU) significantly attenuated t-BOOH (10 micromol) vasoconstrictor responses. Tempol (100 microM), a membrane permeable antioxidant, also significantly reduced t-BOOH (10 micromol) responses from 17.0 +/- 1.9 % (control) to 9.6 +/- 0.5 % (+tempol) in the mesenteric arteries and from 40.4 +/- 4.2 % (control) to 20.7 +/- 1.5 % (+tempol) in the kidney. Our data suggest that t-BOOH elicits vasoconstriction via two distinct mechanisms: (i) increased influx of extracellular Ca(2+), and (ii) generation of free radicals including O(2)(-) anions.     

Cubilin, a binding partner for galectin-3 in the murine utero-placental complex

Galectin-3 is a lectin important in animal development and regulatory processes and is found selectively localized at the implantation site of the mouse embryo. To better understand the role of galectin-3 at the maternal-fetal interface, a binding partner was isolated and characterized. Homogenates of uteroplacental tissue were incubated with immobilized recombinant galectin-3, and specifically bound proteins were eluted using lactose. The principal protein, p400, had an M(r) of 400,000 in SDS-PAGE. Physical properties of p400 and amino acid sequences of seven tryptic peptides were similar to cubilin from rats, humans, and dogs, identifying p400 as the murine ortholog of cubilin. This was further supported by the tissue distribution observed only in yolk sac, kidney, and ileum with monospecific antiserum for p400. Cubilin occurred in yolk sac epithelium throughout pregnancy, but galectin-3 was there only during the last week. Unexpectedly, cubilin was found only in perforin-containing granules of uterine natural killer (uNK) cells, although galectin-3 occurred throughout the cell cytoplasm. In situ hybridization revealed cubilin mRNA in yolk sac epithelium but not uNK cells, implying that yolk sac-derived cubilin is endocytosed by uNK cells via galectin-3. This is consistent with cubilin being an endogenous partner of galectin-3 at the maternal-fetal interface and suggests an important role for cubilin in uNK cell function.     

Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury

Capillary leakage and alveolar edema are hallmarks of acute lung injury (ALI). Neutrophils and serum macromolecules enter alveoli, promoting inflammation. Vascular endothelial growth factor (VEGF) causes plasma leakage in extrapulmonary vessels. Angiopoietin (Ang)-1 and -4 stabilize vessels, attenuating capillary leakage. We hypothesized that VEGF and Ang-1 and -4 modulate vessel leakage in the lung, contributing to the pathogenesis of ALI. We examined a murine model of lipopolysaccharide (LPS)-induced ALI. C57BL/6 and 129/J mice were studied at baseline and 24, 48, and 96 h after single or multiple doses of aerosolized LPS. Both strains exhibited time- and dose-dependent increases in inflammation and a deterioration of lung mechanics. Bronchoalveolar lavage (BAL) protein levels increased significantly, suggesting capillary leakage. Increased BAL neutrophil and total protein content correlated with time-dependent increased tissue VEGF and decreased Ang-1 and -4 levels, with peak VEGF and minimum Ang-1 and -4 expression after 96 h of LPS challenge. These data suggest that changes in the balance between VEGF and Ang-1 and -4 after LPS exposure may modulate neutrophil influx, protein leakage, and alveolar flooding during early ALI.     

Effect of soil temperature and moisture on survival and infectivity of Metarhizium anisopliae to four tephritid fruit fly puparia

The infectivity of 4 isolates of Metarhizium anisopliae to puparia of Ceratitis capitata treated as late third-instar larvae in unsterilized soil was investigated in the laboratory under controlled temperature and moisture. At 20-30 degrees C, mortality in puparia was highest at water potential of -0.1 and -0.01 mega Pascal (MPa) and lowest at water potential of -0.0055 and -0.0035 MPa in all the isolates. In wetter soil however, isolates ICIPE 20 and 60 caused significantly higher mortality than ICIPE 18 and 69. The survival of conidia in drier soil (-0.1 MPa) was not adversely affected at all temperatures. However, in wet soil (-0.0035 MPa) there was drastic reduction in colony counts in ICIPE 18 and 69 at 25 and 30 degrees C but conidial density in ICIPE 20 and 60 remained at the initial level at 14 days after inoculation at all temperatures. When ICIPE 20 was evaluated against three other fruit fly species (Ceratitis cosyra, Ceratitis rosa, and Ceratitis fasciventris), significant reduction in adult emergence and higher pupal mortality occurred in C. cosyra and C. fasciventris than in C. rosa at a combination of 15 and 20 degrees C and -0.1 and -0.0035 MPa. However, at higher temperature and the same moisture level, the isolates were equally pathogenic across the 3 species. It is probable that in addition to pathogen cycling and multiplication from dead infected insects in the soil, a balance between microbial degradation and replenishment of inoculum of virulent isolates occur through fluctuations in, and intricate interactions between temperature and moisture levels. This study is indicative of the potential of using isolate ICIPE 20 for soil inoculation against pupariating third-instar larva of fruit flies, thus providing a novel alternative to chemical soil application.     

Pathogenicity of Metarhizium anisopliae (Metsch.) Sorokin and Beauveria bassiana (Balsamo) Vuillemin,to three adult fruit fly species: Ceratitis capitata (Weidemann), C. rosa var. fasciventris Karsch and C. cosyra (Walker) (Diptera :Tephritidae)

The pathogenicity of two isolates of Beauveria bassiana and 12 of Metarhizium anisopliae towards adult fruit flies, Ceratitis capitata and Ceratitis rosa var. fasciventris was tested in the laboratory. Fruit flies were exposed to dry conidia evenly spread on velvet material covering the inner side of a cylindrical plastic tube. All isolates tested were pathogenic to both species of fruit flies. Mortality ranged from 7 to 100% in C. capitata and from 11.4 to 100% in C. rosa var. fasciventris at 4 days post-inoculation. Six isolates, M. anisopliae ICIPE 18, 20, 32, 40, 41 and 62, were highly pathogenic to both C. capitata and C. rosa var. fasciventris. The LT90 values of the most pathogenic isolates ranged between 3-4 days in both insects. Because of the difficulties in rearing C. cosyra, only the isolates that were highly pathogenic to both C. rosa var. fasciventris and C. capitata were tested against adult C. cosyra. They caused mortality of between 72-78% at 4 days post-inoculation. The LT90 values in all the isolates did not exceed 4 days. One of the most pathogenic isolates, M. anisopliae ICIPE 20, was evaluated against C. capitata and C. rosa var. fasciventris in cage experiments using three autoinoculators (maize cob, cheesecloth and Petri dish) in an autoinoculative device consisting of plastic mineral bottle. Mortality of between 70-93% was observed in flies of both species that were captured from the cages and held under laboratory conditions. These results indicate the possibility of fruit fly suppression with entomopathogenic fungi using an autoinoculative device.     

Bombesin-like peptide and receptors in lung injury models: diverse gene expression, similar function

We previously demonstrated that bombesin-like peptide (BLP) mediates lung injury in premature infants with bronchopulmonary dysplasia (BPD). We now investigate gene expression and function of BLP (gastrin-releasing peptide, GRP) and BLP-receptors (GRP-R and BRS-3) in lung from two baboon BPD models. In the "interrupted gestation model," only GRP mRNA was up-regulated. In the "hyperoxic model," GRP-R mRNA was up-regulated. In lung explants from O2-treated animals, all BPD animals responded to 1nM bombesin, whereas non-BPD animals did not; the opposite effect was observed with a BLP blocking antibody. Cumulatively, these observations suggest that novel BLPs and/or BLP receptors are likely to be implicated in the pathogenesis of BPD.     

Ovicidal effects of entomopathogenic fungal isolates on the invasive Fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae)

Maize is a major staple food for over 300 million people in sub‐Saharan Africa. Sustainable productivity of this primary crop has been recently threatened by Fall armyworm (FAW), Spodoptera frugiperda invasion. Due to lack of environmentally safe management strategies, immediate responses by growers and governments to tackle FAW are based on rampant use of pesticides. Looking for efficient biopesticides, twenty entomopathogenic fungal isolates (14 Metarhizium anisopliae and 6 Beauveria bassiana) were screened for their efficacy against eggs and second instar larvae of FAW. A single discriminating concentration of 1 × 10⁸ conidia ml^?1 and four replicates per treatment were used in all experiments. Isolates were assessed for their ability to cause mortality of FAW second instar larvae, eggs and the neonate larvae that emerged from treated eggs. Among the isolates tested, only B. bassiana ICIPE 676 caused moderate mortality of 30% to second instar larvae. Metarhizium anisopliae ICIPE 78, ICIPE 40 and ICIPE 20 caused egg mortalities of 87.0%, 83.0% and 79.5%, respectively, and M. anisopliae ICIPE 41 and ICIPE 7 outperformed all the others by causing 96.5% and 93.7% mortality to the neonate larvae, respectively. The cumulated mortality of eggs and neonates was highest with M. anisopliae ICIPE 41 (97.5%), followed by M. anisopliae ICIPE 7, 655, 40, 20 and 78 with total mortality of 96.0%, 95.0%, 93.5%, 93.0% and 92.0%, respectively. These isolates with high cumulated mortality (≥92%), especially ICIPE 78 and 7, which are already commercialized for spider mites and ticks control respectively, would be good candidates for development as biopesticides for management of FAW in Africa if further evidence of their efficacy is obtained in the field.     

Susceptibility of Megalurothrips sjostedti developmental stages to Metarhizium anisopliae and the effects of infection on feeding, adult fecundity, egg fertility and longevity

The susceptibility of immature stages of the legume flower thrips, Megalurothrips sjostedti, to the entomopathogenic fungus Metarhizium anisopliae, was investigated under laboratory conditions. The adult stage was found to be more susceptible to infection than the larval and pupal stages. Mortality at all stages was dose-dependent, with the highest concentration of 1×10⁸ conidia ml^–1 producing the highest mortality (26, 46 and 100% for larvae, pupae and adults, respectively) at 8 days post-inoculation. At the same concentration, daily pollen consumption was significantly reduced at 2 days after treatment in infected adults but more slowly in infected larvae. Fecundity, egg fertility and longevity in adults surviving infection as larvae were significantly reduced compared to the control.