111 research outputs found
Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni
Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics
Can forest management based on natural disturbances maintain ecological resilience?
Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance
Metastability Driven by Soft Quantum Fluctuation Modes
The semiclassical Euclidean path integral method is applied to compute the
low temperature quantum decay rate for a particle placed in the metastable
minimum of a cubic potential in a {\it finite} time theory. The classical path,
which makes a saddle for the action, is derived in terms of Jacobian elliptic
functions whose periodicity establishes the one-to-one correspondence between
energy of the classical motion and temperature (inverse imaginary time) of the
system. The quantum fluctuation contribution has been computed through the
theory of the functional determinants for periodic boundary conditions. The
decay rate shows a peculiar temperature dependence mainly due to the softening
of the low lying quantum fluctuation eigenvalues. The latter are determined by
solving the Lam\`{e} equation which governs the fluctuation spectrum around the
time dependent classical bounce.Comment: Journal of Low Temperature Physics (2008) Publisher: Springer
Netherland
Influência de fatores ambientais na distribuição de famílias de insetos aquáticos em rios no sul do Brasil
Perspectives on the Role of Radiotherapy in Organ-Confined and Locally Advanced Prostate Cancer
Erratum: NOE data demonstrating a compact unfolded state for an SH3 domain under non-denaturing conditions (Journal of Molecular Biology (1999))
10.1016/S0022-2836(03)00400-5Journal of Molecular Biology3291185-187JMOB
Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer
PubMedID: 20924975Soy isoflavones sensitize prostate cancer cells to radiation therapy by inhibiting cell survival pathways activated by radiation. At the same time, soy isoflavones have significant antioxidant and anti-inflammatory activity, which may help prevent the side effects of radiation. Therefore, we hypothesized that soy isoflavones could be useful when given in conjunction with curative radiation therapy in patients with localized prostate cancer. In addition to enhancing the efficacy of radiation therapy, soy isoflavones could prevent the adverse effects of radiation. We conducted a pilot study to investigate the effects of soy isoflavone supplementation on acute and subacute toxicity (6 mo) of external beam radiation therapy in patients with localized prostate cancer. Forty-two patients with prostate cancer were randomly assigned to receive 200 mg soy isoflavone (Group 1) or placebo (Group 2) daily for 6 mo beginning with the first day of radiation therapy, which was administered in 1.8 to 2.5 Gy fractions for a total of 73.8 to 77.5 Gy. Adverse effects of radiation therapy on bladder, bowel, and sexual function were assessed by a self-administered quality of life questionnaire at 3 and 6 mo. Only 26 and 27 patients returned completed questionnaires at 3 and 6 mo, respectively. At each time point, urinary, bowel, and sexual adverse symptoms induced by radiation therapy were decreased in the soy isoflavone group compared to placebo group. At 3 mo, soy-treated patients had less urinary incontinence, less urgency, and better erectile function as compared to the placebo group. At 6 mo, the symptoms in soy-treated patients were further improved as compared to the placebo group. These patients had less dripping/leakage of urine (7.7% in Group 1 vs. 28.4% in Group 2), less rectal cramping/diarrhea (7.7% vs. 21.4%), and less pain with bowel movements (0% vs. 14.8%) than placebo-treated patients. There was also a higher overall ability to have erections (77% vs. 57.1%). The results suggest that soy isoflavones taken in conjunction with radiation therapy could reduce the urinary, intestinal, and sexual adverse effects in patients with prostate cancer. Copyright © 2010, Taylor & Francis Group, LLC
Prognostic value of cardiopulmonary exercise testing in heart failure with reduced, midrange, and preserved ejection fraction
sem informaçãoThis study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ej611sem informaçãosem informaçãosem informaçã
Inhibiting Escherichia coli cytochrome c nitrite reductase: voltammetry reveals an enzyme equipped for action despite the chemical challenges it may face in vivo.
Method for preparing large specimens obtained by disarticulation or amputation for histological examination.
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