A class of potent antimalarials and their specific accumulation in infected erythrocytes

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.     

Transnationalism through the life course: Hong Kong immigrants in Canada

Abstract: Transnationalism needs to be understood as a set of practices fashioned through the life course as well as in relation to contextual factors that include state policy and experiences of discrimination that affect entry to the labour force. The paradox of transnationalism is that families make strategic decisions to separate in order to maintain family unity and to advance the welfare of children. Emigrants from Hong Kong to Canada in the latter decades of the twentieth century were motivated by concern for family welfare and the quality of education in Canada. Yet economic livelihood prospects remained greater in Hong Kong than in Canada, prompting many families to become transnational ‘astronaut’ families with one or more members working in Hong Kong. Migration decisions tend to occur around key points of life‐course transition involving entry to and graduation from education, and entry to and exit from the labour force. Transnational practices are complex and multigenerational, involving different patterns for young adults, those in their middle years and the elderly.     

Pituitary-adrenal function in dogs with acute critical illness

OBJECTIVE: To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV). DESIGN: Cohort study. ANIMALS: 31 ill dogs admitted to an intensive care unit (ICU) at Washington State University or the University of Pennsylvania; all dogs had acute critical illness for < 48 hours prior to admission. PROCEDURES: Baseline and ACTH-stimulated serum cortisol concentrations and baseline plasma ACTH concentrations were assayed for each dog within 24 hours after admission to the ICU. The change in cortisol concentrations (Delta-cortisol) was calculated for each dog. Morbidity and mortality data were recorded for each patient. RESULTS: Overall, 17 of 31 (55%) acutely critically ill dogs had at least 1 biochemical abnormality suggestive of adrenal gland or pituitary gland insufficiency. Only 1 (3%) dog had an exaggerated response to ACTH stimulation. Dogs with Delta-cortisol < or = 83 nmol/L were 5.7 times as likely to be receiving vasopressors as were dogs with Delta-cortisol > 83 nmol/L. No differences were detected among dogs with sepsis, severe trauma, or GDV with respect to mean baseline and ACTH-stimulated serum cortisol concentrations, Delta-cortisol, and baseline plasma ACTH concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Biochemical abnormalities of the hypothalamic-pituitary-adrenal axis indicative of adrenal gland or pituitary gland insufficiency were common in critically ill dogs, whereas exaggerated responses to ACTH administration were uncommon. Acutely ill dogs with Delta-cortisol < or = 83 nmol/L may be more likely to require vasopressors as part of the treatment plan.     

Suspected panosteitis in a camel

CASE DESCRIPTION: A 6-month-old male Bactrian camel was examined because of a 3-week history of lameness of the left hind limb. CLINICAL FINDINGS: Lameness was initially detected in the left hind limb but resolved and was detected in the right hind limb during treatment. Lameness increased during periods of rapid growth. Radiography revealed multiple small opacities of the medullary cavity of several long bones throughout treatment. Core bone biopsies of lesions in the tibiae revealed lamellar bone with areas of loose connective tissue, osteoblasts in the medullary cavity, and periosteal new bone formation, all which were consistent with panosteitis. TREATMENT AND OUTCOME: Palliative treatment was attempted with epidural and transdermal administration of analgesics. Flunixin meglumine was administered PO, which coincided with an abrupt increase in serum creatinine concentration. Performance of multiple diagnostic bone biopsies led to remission of clinical signs of pain. CLINICAL RELEVANCE: Panosteitis should be a differential diagnosis for shifting limb lameness in young camels. Bone biopsies can be useful for diagnosis of panosteitis and possible relief of pain associated with the disease. Bactrian camels may be susceptible to the renal toxicity of flunixin meglumine, especially when dehydrated.     

Location and the Innovation Performance of Commercial GIS Companies

This paper looks at the role of firm size, location, and in‐house research and development (R&D) in the innovation performance of U.S. firms in the commercial geographic information systems (GIS) industry. Data from a survey of 300 GIS firms are presented. The results suggest that innovation‐intensity varies directly with in‐house R&D spending (scaled as a proportion of company sales), but inversely with company size (total employment). Significant regional variations in the innovation performance of GIS firms are identified. It is argued that the geography of innovation is influenced by the spatial distribution of young and/or small firms, in that R&D‐productivity is found to vary inversely with company size. An important finding is that creative inputs to support innovation are almost evenly divided between internal and external sources. A surprising result is that the academic community is not viewed as a particularly important source of new ideas for innovative firms. The paper concludes with a discussion of the implications of the survey data for future empirical work on the GIS sector.     

Band gap fluorescence from individual single-walled carbon nanotubes

Fluorescence has been observed directly across the band gap of semiconducting carbon nanotubes. We obtained individual nanotubes, each encased in a cylindrical micelle, by ultrasonically agitating an aqueous dispersion of raw single-walled carbon nanotubes in sodium dodecyl sulfate and then centrifuging to remove tube bundles, ropes, and residual catalyst. Aggregation of nanotubes into bundles otherwise quenches the fluorescence through interactions with metallic tubes and substantially broadens the absorption spectra. At pH less than 5, the absorption and emission spectra of individual nanotubes show evidence of band gap-selective protonation of the side walls of the tube. This protonation is readily reversed by treatment with base or ultraviolet light.     

The fate of dinobuton and dinoseb on growing apples

After topical application of dinobuton or dinoseb to apple fruits approximately 75% and 72% respectively of the applied material was lost after 28 days. From apples treated with dinobuton the unchanged compound was the major component present up until 8 days but at later times the amounts of polar transformation products and water-soluble compounds predominated. Only small amounts of dinoseb were found at all times. A similar pattern of results was obtained from apples treated with dinoseb. The maximum amounts of material absorbed through the fruit skin were 3% from dinobuton-treated apples and 7% from dinoseb-treated applies.     

Does l‐Asparaginase Influence Efficacy or Toxicity When Added to a Standard CHOP Protocol for Dogs with Lymphoma?

The purpose of this study was to evaluate response rates, 1st remission duration (FRD), and toxicity in dogs with previously untreated lymphoma receiving an identical CHOP-based combination chemotherapy protocol with or without L-asparaginase (LASP). One hundred fifteen dogs with lymphoma were scheduled to receive an identical CHOP-based chemotherapy protocol that included L-ASP. However, because of manufacturer-imposed random rationing, 31 dogs did not receive L-ASP as scheduled. The 2 treatment groups were statistically similar with respect to signalment and presence of historical negative prognostic factors. No difference was observed in the median FRD whether dogs did or did not receive L-ASP (206 versus 217 days, respectively; P = .67). No difference was observed in the median overall survival times between dogs receiving or not receiving L-ASP (310 versus 308 days, respectively; P = .84). No statistical difference was observed with respect to overall response rate between dogs that did or did not receive L-ASP (89.3% versus 87.1%, respectively; P = .75). Complete response rates between the groups also were no different (83.3% and 77.4% for L-ASP and non-L-ASP groups, respectively; P = .59). Prevalence of toxicity (neutropenia, diarrhea, or vomiting) and treatment delays (P = .80) also were similar between groups. The results of this study suggest that exclusion of L-ASP in this multidrug protocol does not significantly impact outcome. Therefore, it may be more appropriate to reserve the use of L-ASP for treating relapse in dogs with lymphoma that have failed induction therapy.