Analysis of cytogenetic damage induced in cultured human lymphocytes by the pyrethroid insecticides cypermethrin and fenvalerate

Two pyrethroid insecticides, cypermethrin and fenvalerate, weretested for their ability to induce chromosome structural aberrationsand sister chromatid exchanges in cultured human peripheralblood lymphocytes. Fenvalerate, but not cypermethrin, increasedthe frequencies of chromosome-type aberrations and sister chromatidexchanges. In addition, both pyrethroids affected the cell cyclecausing a decrease in the proliferative rate index at concentrations> 10 µg/ml. ¹To whom correspondence should be addressed     

Right internal thoracic artery through the transverse sinus in myocardial revascularization

Background. A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle.

Methods. Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods (“on” values) were compared with those obtained 1 week after cessation of electrical stimulus (“off” values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared.

Results. Higher ejection fractions (0.36 ± 0.07 versus 0.33 ± 0.06 at rest, 0.40 ± 0.07 versus 0.33 ± 0.07 peak exercise, and 0.37 ± 0.06 versus 0.31 ± 0.06 at recovery) and lower end-systolic volume indexes with relatively constant end-diastolic volume indexes were observed with the cardiomyostimulator on. Further, exercise response was better with the cardiomyostimulator on. Double product indirectly reflected better myocardial oxygen supply/demand ratio when on at peak exercise (17 ± 2.2 mm Hg × beats/min × 10⁻³ for on versus 19 ± 2.6 mm Hg × beats/min × 10⁻³ for off). Estimated total body oxygen consumption was improved at peak exercise when the cardiomyostimulator was functional (12 ± 2.7 mL · kg⁻¹ · min⁻¹ versus 11 ± 2.6 mL · kg⁻¹ · min⁻¹).

Conclusions. Current data suggest a true systolic assist during synchronous contractions of the latissimus dorsi muscle. It is thought, therefore, that synchronous electrical stimulation is essential for maximum benefit and all the beneficial effect of cardiomyoplasty certainly cannot be attributed to simple wrapping itself.     

Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration

Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in taupathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD.     

A novel logistic model based on clinicopathological features predicts microsatellite instability in colorectal carcinomas.

High-frequency microsatellite instability has been reported to be associated with good prognosis in colorectal adenocarcinoma. However, methods to assess microsatellite instability (MIN) are based on genetic assays and are not ideally suited to most histopathology laboratories. The aim of the present study was to develop a model for prediction of MIN status in colorectal cancer based on phenotypic characteristics. Clinicopathological features of a cohort of 204 patients with primary colon cancer were retrospectively reviewed following predetermined criteria. Genetic assessment of MIN status was performed on DNA extracted from sections of formalin-fixed, paraffin-embedded specimens by testing a panel of 11 microsatellite markers. Logistic regression analysis generated a mathematical tool capable of identifying colorectal tumors displaying MIN status with a sensitivity of 77.8% and a specificity of 96.8%. Features associated with instability included the proximal location of the lesions, occurrence of solid and/or mucinous differentiation, absence of cribriform structures, presence of peritumoral Crohn-like reaction, expansive growth pattern, high Ki67 proliferative index, and p53-negative phenotype. This approach predicts microsatellite instability in colorectal carcinoma with an overall assigned accuracy of 95.1% and a negative predictive value of 97.8%. Implementation of this tool to routine histopathological studies could improve the management of patients with colorectal cancer, especially those presenting with stage II and III of the disease. It will also assist in identifying a subset of patients likely to benefit from adjuvant chemotherapy.     

Ventromedial hypothalamus vs. lateral hypothalamic D2 satiety receptors in the body weight increase induced by systemic sulpiride

Two experiments were conducted in order to see if dopamine satiety receptors in the lateral hypothalamus or satiety mechanisms in the ventromedial hypothalamus were involved in the hyperphagia and body weight increase induced by systemic sulpiride. In the first experiment, it was shown that systemic sulpiride (20 mg/kg) does not block the anorexia caused by intraperifornical injections of amphetamine. In the second experiment, sulpiride (20 mg/kg during 18 days) did not produce an additional increase in body weight in previously VMH-lesioned female rats. This last fact cannot be explained by a ceiling effect since insulin (5 U/day during 7 days) increased body weight in the same VMH rats in which sulpiride was not effective. These results do not support the hypothesis that systemic sulpiride reaches the perifornical dopamine D2 receptors to disinhibit feeding, but suggest instead an involvement of the ventromedial hypothalamus. This last suggestion is more in agreement with the hypothesis that sulpiride alters feeding and body weight gain through the induction of a functional gonadectomy.     

Effect of ethylene on naringin, narirutin and nootkatone accumulation in grapefruit

This paper studies the effect of different concentrations of ethephon on the levels of the sesquiterpene, nootkatone, and of the flavanones, naringin and narirutin, in grapefruit fruits. The results show that nootkatone synthesis and/or accumulation was stimulated by all the concentrations of ethephon assayed, while the levels of naringin and narirutin in the rind diminished. These results open up new perspectives concerning the possible regulation of the secondary metabolism of the plants.