Effect of Methamidophos on cerebellar neuronal cells.

Methamidophos is a toxic organophosphorus compound that inhibits acetlycholinesterase activity, and induces neurotoxicity. It is a synthetic chemical commonly used as pesticides to limit pest damages to cultivated plants. Currently, there is serious public health concern over its safety and use due to its global nature, persistence and bioaccumulations. We have previously reported that methamidophos suppressed thyroid hormone receptor (TR)-mediated transcription, but did not dissociate the interaction between TR and its response element (thyroid hormone response element; TRE), neither did it interact with nuclear cofactors. In the present study, we investigated the effects of methamidophos on cerebellar neuronal cells. Using primary cerebellar culture from new born rats, We observed that Purkinje cell dendrite arborization were greatly impaired in the absence of thyroid hormone (TH), However, low dose methamidophos 10-6 M did not significantly impair dendrite arborization of cerebellar Purkinje cells in the presence of thyroid hormone (TH). However, using granule cell reaggregate culture, we observed that low dose methamidophos 10-6 M remarkably suppressed granule cell neurite extension in the presence of TH. Taken together, our study shows that low dose methamidophos may negatively impact TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal events.

Temporal effects of thyroid hormone (TH) and decabrominated diphenyl ether (BDE209) on Purkinje cell dendrite arborization.

Thyroid hormones (TH) 3,3',4-tri-iodothyronine (T3) and 3,3',4,4'-tetra-iodothyronine (T4) plays crucial role in cerebellar development. Deficiency of TH consistently results in aberrant growth and development of the cerebellum including reduced growth and branching of the Purkinje cells. In rodents, the critical period of thyroid hormone action on cerebellum development is within the first two to three weeks, after which thyroid hormone replacement cannot fully reverse abnormal cerebellar development induced by thyroid hormone insult. Decabrominated diphenyl ether (BDE209) is an industrial reagent used as an additive flame retardant to reduce flammability of various commercial and household produce. BDE209 has bio-accumulative potential and is neurotoxic. Previously, we have shown that T4 (10-8 M) induced extensive dendrite arborization of Purkinje cells and low dose BDE209 (10-10 M) remarkably suppressed TH-induced Purkinje cell dendrite arborization. In the present study, we show that the critical period for TH-induced Purkinje cell growth and dendrite arborization in culture is much earlier than reported in animal models. Also, we show for the first time that low dose BDE209 suppressed TH-induced dendrite arborization in a time-dependent manner. Taken together, our study indicates that hypothyroidism and exposure to BDE209 during critical stage of cerebellar development can lead to impaired Purkinje cell growth and dendrite arborization and may consequently disrupt normal cerebellar functions.

Thyroid hormone receptor-mediated transcription is suppressed by low dose phthalate.

SUMMARY: Phthalates are synthetic chemicals used mainly as solvents, additives and plasticizers in polyvinylchloride (PVC) products to increase their flexibility. Phthalate plasticizers are not chemically bound to PVC, so they easily leach into the environment. There is currently heightened concern about potential health risk, especially endocrine disrupting effects associated with the use of these chemicals. We therefore investigated the effects of phthalate on thyroid hormone receptor (TR)-mediated transcription using transient transfection studies and found that low dose phthalate (10-7) M suppressed thyroid hormone (TH)-induced TR-mediated transcription by 30%. We further examined the effect of phthalate on TR-thyroid hormone response element (TRE) binding, and found no dissociation of TR from TRE. Phthalate did not also dissociate coactivator (steroid receptor coactivator-1) from TR neither did it recruit corepressor (nuclear corepressor; NCoR) to TR in the presence of TH. Our results indicate that low phthalate can disrupt TR-mediated gene expression and interfere with TH balance in TH-sensitive organs including the developing brain.

Assessment of the influence of age on the rate of heart rate decline after maximal exercise in non-athletic adult males.

This study investigated the influence of age on heart rate (HR) decline after exercise in non-athletic adult males. One hundred and fourteen adult males (66 young, 25 +/- 6.26 years; 48 old, 53 +/- 8.54 years) participated in the study. Subjects performed maximum-effort ergometer exercise in incremental stages. HR was measured at rest and continuously monitored during and after exercise. Maximum oxygen uptake (VO(2max)) was measured during the exercise using respiratory gas analyser. Body mass index (BMI) was computed from weight and height measurements, while rating of perceived exertion (RPE) was obtained immediately after the exercise. Results indicated age differences in the rate of HR decline with the young presenting significantly higher %HR decline (P<0.001) than old adults at both levels of recovery. When linearly correlated with age, the rate of HR decline in 1 and 3 min indicated variances of (52%,56%) in young adults, and (54%,49%) in the old adults. After controlling for VO(2max), resting HR, BMI and RPE, the influence of age on rate of HR decline in the two phases of recovery disappeared in young. In the older adult group, it reduced greatly in the 1-min recovery (r(2) = 25%; P = 0.001) and disappeared in the 3-min recovery. Pattern of HR recovery did not differ between the two age groups while age threshold was observed in HR recovery in 1 min. In summary, the influence that age appeared to have on the rate of HR decline could not hold when factors affecting HR recovery were taken into account.

Hypertension, and blood pressure response to graded exercise in young obese and non-athletic Nigerian university students.

Hypertension, and the effect of graded exercise on blood pressure (BP), in 60 obese non-athletic young medical students (40 females and 20 males) with body mass index (BMI) greater than 30 were studied. The subjects were in the age range of 18-22 years with mean age of 20.30 +/-1.32 years. Twenty percent of the males and 7 percent of the females were found to be hypertensives [P < 0.05] and the severity of the hypertension significantly [P < 0.05] increased linearly with increase in BMI (r =0.6). Our study reveals a positive direct correlation between obesity and socioeconomic status and BP. Marked increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), time of return (RT) were observed in the obese individuals compared to control at all levels of graded exercise with the highest rises seen during severe exercise. Among the obese subjects, the increases in BP were more in the males than females, but time of return was higher in females than males. This study further confirms that obese young individuals are prone to early onset of hypertension and thus other cardiovascular diseases and less tolerant to physical exercises. Our results add to the evidence that hypertension is common among obese young adults.