Post-Den Emergence Behavior of Polar Bears (Ursus maritimus) in Northern Alaska

We observed polar bear (Ursus maritimus) maternity den sites on Alaska’s North Slope in March 2002 and 2003 in an effort to describe bears’ post-den emergence behavior. During 40 sessions spanning 459 h, we observed 8 adults and 14 dependent cubs outside dens for 37.5 h (8.2% of total observation time). There was no significant difference between den emergence dates in 2002 (mean = 15 Mar ± 4.1 d) and 2003 (mean = 21 Mar ± 2.1 d). Following initial den breakout, polar bears remained at their den sites for 1.5 to 14 days (mean = 8.1 ± 5.1 d). The average length of stay in dens between emergent periods was significantly shorter in 2002 (1.79 h) than in 2003 (4.82 h). While outside, adult bears were inactive 49.5% of the time, whereas cubs were inactive 13.4% of the time. We found no significant relationships between den emergence activity and weather. Adult polar bears at den sites subjected to industrial activity exhibited significantly fewer bouts of vigilance than denned bears in undisturbed areas (t = -5.5164, df = 4, p = 0.00). However, the duration of vigilance behaviors at sites near industrial activity was not significantly shorter than at the other sites studied (t = -1.8902, df = 4, p = 0.07). Results for these bears were within the range of findings in other studies of denned polar bears.Nous avons observé des tanières de maternité d’ours polaires (Ursus maritimus) sur le versant nord de l’Alaska aux mois de mars 2002 et 2003 dans le but de décrire le comportement de sortie des ours après leur séjour dans la tanière. Dans le cadre de 40 séances d’observation ayant duré 459 heures, nous avons observé 8 ours adultes et 14 oursons à charge en dehors des tanières pendant 37,5 heures (soit 8,2 % de la durée d’observation totale). Il n’y avait pas de différence importante entre les dates de sortie des tanières en 2002 (moyenne = 15 mars ± 4,1 j) et 2003 (moyenne = 21 mars ± 2,1 j). Après la première sortie de la tanière, les ours polaires restaient à l’emplacement de leur tanière pendant 1,5 à 14 jours (moyenne = 8,1 ± 5.1 j). La longueur moyenne du séjour en tanière entre les périodes de sortie était beaucoup plus courte en 2002 (1,79 h) qu’en 2003 (4,82 h). Une fois sortis, les ours adultes étaient inactifs pendant 49,5 % du temps, tandis que les oursons étaient inactifs pendant 13,4 % du temps. Nous n’avons pas trouvé de lien important entre l’activité une fois sorti de la tanière et le temps qu’il faisait. Les ours polaires adultes à l’emplacement de tanières assujetties à des activités industrielles affichaient beaucoup moins de séquences de vigilance que les ours en tanière des régions tranquilles (t = -5,5164, dl = 4, p = 0,00). Cependant, la durée des comportements de vigilance aux emplacements situés près d’activités industrielles n’était pas beaucoup plus courte qu’aux autres emplacements étudiés (t = - 1,8902, dl = 4, p = 0,07). Les résultats enregistrés pour ces ours tombaient dans l’étendue des constatations découlant d’autres études d’ours polaires en tanière

The Polar Bear Management Agreement for the Southern Beaufort Sea : An Evaluation of the First Ten Years of a Unique Conservation Agreement

Polar bears (Ursus maritimus) of the southern Beaufort Sea population, distributed from approximately Icy Cape, west of Point Barrow, Alaska, to Pearce Point, east of Paulatuk in Canada, are harvested by hunters from both countries. In Canada, quotas to control polar bear hunting have been in place, with periodic modifications, since 1968. In Alaska, passage of the United Sates Marine Mammal Protection Act (MMPA) of 1972 banned polar bear hunting unless done by Alaska Natives for subsistence hunt, leaving open the potential for an overharvest with no possible legal management response until the population was declared depleted. Recognizing that as a threat to the conservation of the shared polar bear population, the Inuvialuit Game Council from Canada and the North Slope Borough from Alaska negotiated and signed a user-to-user agreement, the Polar Bear Management Agreement for the Southern Beaufort Sea, in 1988. We reviewed the functioning of the agreement through its first 10 years and concluded that, overall, it has been successful because both the total harvest and the proportion of females in the harvest have been contained within sustainable limits. However, harvest monitoring needs to be improved in Alaska, and awareness of the need to prevent overharvest of females needs to be increased in both countries. This agreement is a useful model for other user-to-user conservation agreements.Les ours polaires (Ursus maritimus) constituant la population de la mer de Beaufort méridionale sont répartis d'environ Icy Cape, à l'ouest de Point Barrow (Alaska), à Pearce Point, à l'est de Paulatuk (Canada). Ils sont prélevés par des chasseurs des deux pays. Au Canada, les quotas visant le contrôle de la chasse à l'ours polaire sont en vigueur - avec des modifications périodiques - depuis 1968. En Alaska, l'adoption en 1972 de la loi américaine (MMPA) visant la protection des mammifères marins a interdit la chasse à l'ours polaire sauf la chasse de subsistance pratiquée par les Autochtones alaskiens. La MMPA n'a toutefois placé aucune restriction sur le nombre ou la composition de la chasse de subsistance, laissant la porte ouverte à une éventuelle surexploitation sans possibilité d'une réaction de gestion sur le plan légal jusqu'à ce que la population soit déclarée décimée. Reconnaissant en cela une menace à la conservation de la population commune d'ours polaires, le Conseil canadien de gestion du gibier et le North Slope Borough de l'Alaska ont négocié et signé en 1988 une entente entre usagers, le Polar Bear Management Agreement pour la mer de Beaufort méridionale. On a examiné le fonctionnement de l'entente durant sa première décennie pour conclure que, dans l'ensemble, elle a porté fruit car le total des prises et la proportion de femelles prélevées ont été maintenus dans des limites viables. Il faut toutefois améliorer le contrôle du prélèvement en Alaska et accroître dans les deux pays la sensibilisation à la nécessité de prévenir une surexploitation des femelles. Cette entente constitue un modèle pour d'autres accords entre usagers en matière de conservation

Apoptosis in Normal Rectal Mucosa, Baseline Adenoma Characteristics, and Risk of Future Adenomas

Low apoptosis in the normal rectal mucosa has been associated with colorectal adenomas in cross-sectional studies. It is unknown whether apoptosis can predict the occurrence of new adenomas. We evaluated whether apoptosis at baseline colonoscopy, as well as patient and adenoma characteristics, could predict future occurrence of adenomas. Study subjects were participants in the Diet and Health Study III, a cross-sectional study of adenoma risk factors between August 1998 and March 2000. At baseline, subjects underwent colonoscopy and provided normal rectal mucosal biopsies to evaluate apoptosis as well as information about diet and lifestyle. The present study includes 257 subjects who returned for follow-up colonoscopy between 2000 and 2005. Apoptosis, number of adenomas, size, and atypia at baseline colonoscopy were evaluated as predictors of new adenomas. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). At baseline, low apoptosis was significantly associated with increased risk of adenomas (P = 0.0001). Compared with those in the lowest tertile, subjects with high apoptosis were less likely to have an adenoma at follow-up (crude OR, 0.25; 95% CI, 0.09–0.65; adjusted OR, 0.29; 95% CI, 0.08–1.06). Having three or more adenomas at baseline was associated with increased risk of new adenomas (crude OR, 2.46; 95% CI, 1.14–5.31; adjusted OR, 3.74; 95% CI, 1.01–13.83). This study suggests that lower apoptosis is associated with increased risk of future adenoma development. If confirmed in larger studies, apoptosis could potentially be used to identify patients at highest risk for developing new adenomas

Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas

AbstractBackground & Aims: Observational studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal neoplasia. The mechanism of this effect could be via modification of apoptotic activity in colonic mucosa. We examined grossly normal rectal mucosa in patients with adenomas and adenoma-free controls to assess the associations between NSAID use, adenomatous polyps, and apoptosis. Methods: Study participants were drawn from consecutive patients who underwent colonoscopy between August, 1998, and February, 2000. Biopsy specimens were taken from normal-appearing rectal mucosa 10 cm from the anal verge. Apoptosis was scored from coded, H&E-stained sections using morphologic methods. Proliferation was scored using whole crypt mitotic counts. Univariate and multivariate regression analyses were conducted to estimate crude and adjusted odds ratios (ORs). Results: There were 226 patients with adenomas and 493 adenoma-free controls. After adjusting for sex, age, race, and body mass index (BMI), individuals in the highest tertile of regular NSAID use were substantially less likely to have adenomas (OR 0.4; 95% CI: 0.2–0.7) compared with occasional or nonusers. Similarly, compared with the lowest tertile, persons in the highest tertile of rectal mucosal apoptotic activity were much less likely to have adenomas (OR 0.12; 95% CI: 0.07–0.20). NSAID use and apoptotic activity were not correlated (r = 0.10). Mucosal proliferation was not related to adenomas or NSAID use. Conclusions: Our observations suggest that NSAID use and higher levels of mucosal apoptosis are independently associated with a lower prevalence of adenomas. The study shows a strong field effect for apoptosis.GASTROENTEROLOGY 2002;123:1770-177

Investigator-Initiated IBD Trials in the United States: Facts, Obstacles, and Answers

Investigator initiated randomized clinical trials (IITs) are the backbone of academic clinical research. IITs complement the large clinical studies sponsored by industry and address questions, which are usually not the main focus of a commercially directed research but have the purpose to confirm, improve or refute clinically important questions with regard to diagnostic and therapeutic approaches in patient care. The aim of this review is to illustrate the necessary steps to start and complete an IIT in the field of inflammatory bowel diseases (IBD) in the US. The initial milestones for an investigator include structuring a protocol, planning and building of the trial infrastructure, accurately estimating the costs of the trial and gauging the time span for recruitment. Once the trial has begun it is important to keep patient recruitment on target, monitor of the data quality, and document treatment emergent adverse events. This article provides a framework for the different phases of an IIT and outlines potential hurdles, which could hinder a successful execution

Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743

Apoptosis in Normal Rectal Mucosa, Baseline Adenoma Characteristics, and Risk of Future Adenomas

Low apoptosis in the normal rectal mucosa has been associated with colorectal adenomas in cross-sectional studies. It is unknown whether apoptosis can predict the occurrence of new adenomas. We evaluated whether apoptosis at baseline colonoscopy, as well as patient and adenoma characteristics, could predict future occurrence of adenomas. Study subjects were participants in the Diet and Health Study III, a cross-sectional study of adenoma risk factors between August 1998 and March 2000. At baseline, subjects underwent colonoscopy and provided normal rectal mucosal biopsies to evaluate apoptosis as well as information about diet and lifestyle. The present study includes 257 subjects who returned for follow-up colonoscopy between 2000 and 2005. Apoptosis, number of adenomas, size, and atypia at baseline colonoscopy were evaluated as predictors of new adenomas. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). At baseline, low apoptosis was significantly associated with increased risk of adenomas (P = 0.0001). Compared with those in the lowest tertile, subjects with high apoptosis were less likely to have an adenoma at follow-up (crude OR, 0.25; 95% CI, 0.09–0.65; adjusted OR, 0.29; 95% CI, 0.08–1.06). Having three or more adenomas at baseline was associated with increased risk of new adenomas (crude OR, 2.46; 95% CI, 1.14–5.31; adjusted OR, 3.74; 95% CI, 1.01–13.83). This study suggests that lower apoptosis is associated with increased risk of future adenoma development. If confirmed in larger studies, apoptosis could potentially be used to identify patients at highest risk for developing new adenomas

Inflammatory cytokines increase extracellular procathepsin D in permanent and primary endothelial cell cultures

The protease cathepsin D (Cath D) and its proteolytically inactive proform, procathepsin D (ProCath D), turned out to be multifunctional within and outside the cell. Elevated levels of ProCath D occur in malignant tumors and in organs under chronic inflammation. One important source for this increase of ProCath D might be endothelial cells. Here we examined the expression of Cath D in the human endothelial cell line EA.hy 926 and in primary endothelial cells isolated from human umbilical cord veins (HUVEC). After serum-free incubation with or without human interferon-γ (hIFN-γ) and/or human tumor necrosis factor-α (hTNF-α) immature and mature Cath D forms were examined in cell extracts and in cell-conditioned medium concentrates by Western blotting. Lysates of EA.hy 926 cells as well as of HUVEC contained active Cath D as two-chain form, but only negligible amounts of ProCath D and Cath D intermediates. Yet both endothelial cell cultures accumulated ProCath D in their conditioned media in the absence of any stimulus. The treatment with hIFN-γ and/or hTNF-α had little effect on intracellular levels of Cath D, whereas the cytokine stimulation increased the extracellular presence of ProCath D in both endothelial cell cultures. The extracellular increase of ProCath D was not related to induction of apoptosis, as validated by cleaved caspase-3 in cell lysates. Acidification of cytokine-treated media converted ProCath D into Cath D, which was associated with cathepsin-like activity using a fluorogenic substrate-linked assay. We conclude, in vitro, endothelial cells are a cytokine-dependent source for extracellular ProCath D.Sabine Erdmann, Albert Ricken, Katja Hummitzsch, Claudia Merkwitz, Nicole Schliebe, Frank Gaunitz, Rainer Strotmann and Katharina Spanel-Borowsk