Growth, abnormalities, and mortality of tadpoles of American toad exposed to combinations of malathion and nitrate

American toad tadpoles (Bufo americanus) were exposed to malathion and nitrate in a fully factorial experiment that crossed four concentrations of malathion ranging between 0 and 1,000 μg malathion/L, and five concentrations of nitrate ranging from 0 to 16 mg NO(3) -N/L to identify single and interactive effects. In this 21-d experiment, we recorded tadpole length, mass, survivorship, and frequencies of diamond-shaped and stiff-tail abnormalities. Malathion increased frequency of diamond-shaped and stiff-tail abnormalities, and negatively affected survivorship, but did not affect tadpole size. Nitrate did not affect survivorship but did have sublethal effects, including effects on tadpole length and the frequency of both abnormalities. The interaction of malathion and nitrate has no effect on survivorship or tadpole size but did affect the frequency of abnormalities, with nitrate reducing malathion's effect. Results of the present study suggest that at the environmentally realistic concentrations used in our experiment, malathion has both lethal and sublethal effects, but nitrate had only sublethal effects on American toad tadpoles. The combination of malathion and nitrate had limited effects at the tested concentrations under laboratory conditions. However, the effect of the combined treatments on the frequency of tadpole developmental abnormalities suggests that such interactions may play a role under field conditions, in which pesticide and nitrate fertilizers are typically applied simultaneously.     

Moment based regression algorithms for drift and volatility estimation in continuous‐time Markov switching models

Summary We consider a continuous time Markov switching model (MSM) which is widely used in mathematical finance. The aim is to estimate the parameters given observations in discrete time. Since there is no finite dimensional filter for estimating the underlying state of the MSM, it is not possible to compute numerically the maximum likelihood parameter estimate via the well known expectation maximization (EM) algorithm. Therefore in this paper, we propose a method of moments based parameter estimator. The moments of the observed process are computed explicitly as a function of the time discretization interval of the discrete time observation process. We then propose two algorithms for parameter estimation of the MSM. The first algorithm is based on a least‐squares fit to the exact moments over different time lags, while the second algorithm is based on estimating the coefficients of the expansion (with respect to time) of the moments. Extensive numerical results comparing the algorithm with the EM algorithm for the discretized model are presented.     

Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis

Purpose

Constitutive activation of the Wnt signaling pathway and its downstream effectors plays a key role in neoplastic transformation. The objective of this study was to investigate the effect of ellagic acid, a plant-derived polyphenol on Wnt/β-catenin signaling and its downstream circuits- NF-κB and mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.

Methods

Hamsters were divided into six groups. The right buccal pouches of animals in groups 1–4 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 2–4 received in addition basal diet containing ellagic acid at a concentration of 0.1, 0.2, and 0.4% in the diet. Group 5 animals were given 0.4% ellagic acid alone. Group 6 animals served as control. The expression of the members of Wnt and NF-κB signaling and intrinsic apoptosis was evaluated by western blot analysis.

Results

Dietary supplementation of 0.4% ellagic acid suppressed the development of HBP carcinomas by preventing the constitutive activation of Wnt pathway through the downregulation of Fz, Dvl-2, GSK-3β and nuclear translocation of β-catenin. Abrogation of Wnt signaling by ellagic acid was also associated with inactivation of NF-κB and modulation of key components of the mitochondrial apoptotic network.

Conclusions

Our findings suggest a functional crosstalk between Wnt and NF-κB signaling pathways in HBP carcinomas that is blocked by ellagic acid supplementation. Dietary ellagic acid that targets the Wnt/β-catenin pathway as well as its downstream signaling mediators is a unique candidate for cancer chemoprevention.     

Non-Hodgkin's lymphoma of prostate: a rare site of primary extranodal presentation (a report of two cases)

We report two cases of primary extranodal lymphoma of the prostate, an unusual site for extranodal presentation. The clinical presentation and treatment is discussed.     

Comparison of fatty meal and intravenous cholecystokinin infusion for gallbladder ejection fraction.

Gallbladder ejection fraction (GBEF) measured with a fatty meal (half-and-half milk) was compared with that measured with 2 equal sequential intravenous infusions of cholecystokinin (CCK-8) in a paired study of healthy subjects. METHODS: GBEF was measured by (99m)Tc-hepatic iminodiacetic acid cholescintigraphy in 13 healthy subjects. Each subject received 2 sequential doses of CCK-8 (3 ng/kg/min for 10 min) on day 1, followed by, on day 2, a 240-mL (8 oz) fatty meal (half-and-half milk) per 70 kg of body weight. RESULTS: The mean +/- SD GBEF of 53.6% +/- 20.2% with fatty meal was significantly lower than the mean of 75.8% +/- 16.3% (P < 0.01) with the first dose of CCK-8 and 71.3% +/- 17.4% (P < 0.05) with the second dose. Fatty meal GBEF varied widely, from 23.5% to 91.8%. Percentile rankings of the fatty meal GBEF were determined as the preferred methodology for reporting results. Latent and ejection periods were significantly longer with fatty meal than with either dose of CCK-8. CONCLUSION: GBEF measured with fatty meal can serve as an alternative method to intravenous injection of CCK-8 when the hormone is no longer available for clinical use. The measurement of GBEF with fatty meal requires careful attention to the details of the meal and the measurement time sequence.     

Neuroleptic malignant syndrome.

Five patients with neuroleptic malignant syndrome (NMS) are described. The syndrome developed earlier and took longer to resolve in patients with schizophrenic disorders. Deterioration in the level of consciousness presented earlier than rigidity and fever in all five patients and was thus considered a major criterion. A significant proportion of the patients showed abnormalities of gaze. In four of the five patients spontaneous recovery occurred without the need for specific drugs.     

Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases.

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.     

Treatment satisfaction, functional status, and health-related quality of life of migraine patients treated with almotriptan or sumatriptan

BACKGROUND: Patient-reported outcomes, such as treatment satisfaction, functional status, and health-related quality of life (HRQOL) are essential components of migraine research. Almotriptan is a new selective serotonin 1B/1D agonist triptan migraine treatment. OBJECTIVE: The purpose of this double-blind, multicenter, randomized, parallel-group study was to compare treatment satisfaction, functional status, and HRQOL of patients treated with oral almotriptan versus sumatriptan, the leading triptan on the market. METHODS: Migraine patients, aged 18 to 71 years, took equivalent oral doses of 12.5 mg almotriptan or 50 mg sumatriptan for the abortive treatment of a migraine headache. Treatment satisfaction differences between study groups were assessed using a 6-item measure to determine patients' satisfaction with pain relief and satisfaction with side effects 48 hours after drug administration. Functional status was assessed by analyzing the change in patients' ability to perform normal activities during the course of the migraine. HRQOL was compared between treatment groups at 24 hours using the Migraine Quality of Life Questionnaire. End points were assessed using entries from patients' 48-hour diaries. RESULTS: A total of 1173 patients were treated with almotriptan or sumatriptan. There were no significant differences between the 2 treatment groups in terms of satisfaction with pain relief; however, patients in the almotriptan group were significantly more satisfied (less bothered) with side effects than those receiving sumatriptan (P = 0.016). Functional status and HRQOL outcomes were not significantly different between groups. CONCLUSIONS: In this study, migraine patients treated with almotriptan were significantly more satisfied with the side-effect profile of the drug than patients treated with sumatriptan. The results of this study may help inform practicing physicians and neurologists about the potential treatment satisfaction advantages of almotriptan.