Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.     

Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

Chlorpromazine, but not chlorpromazine sulphoxide, stimulates transmitter release from motor nerve terminals

Treatment of frog neuromuscular preparations with chlorpromazine (5 mumol/l) resulted in a marked rise in miniature endplate potential (MEPP) frequency of greater than 100% within 30 min, and an increase in evoked transmitter release (quantal content 5-15) of about 35%. Treatment with chlorpromazine sulphoxide (5 microM), a derivative of chlorpromazine with a much lower affinity for calmodulin, had very little effect on either form of transmitter release. It is concluded that stimulatory effects of calmodulin-binding drugs at the nerve terminal may well be exerted through calmodulin inhibition. The stimulatory effect of chlorpromazine on MEPP frequency was markedly reduced in preparations bathed in EGTA-containing Ca2+-free saline, but the response was largely restored by raising the temperature by 3-4 degrees C. It is argued that despite this partial dependence on [Ca2+]o, stimulation of transmitter secretion by chlorpromazine is likely to be mediated by inhibition of calmodulin-activated Ca2+-ATPases, and consequent elevation of [Ca2+]i.     

The presence of 3beta-hydroxysteroid dehydrogenase in the ovarian follicles and corpora lutea of pregnant swine.

Steroid hormones play an essential role in the ovarian cyclicity control and the progress of pregnancy. One of the crucial enzymes in the steroidogenesis is 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3betaHSD). The aim of the present study was to localize both 3betaHSD mRNA and protein in the ovary of pregnant swine. The immunolocalization of 3betaHSD was performed on paraplast sections of follicles and corpora lutea obtained on various days of gestation: 10, 18, 32, 50, 71 and 90 POST COITUM (p.c.). The obtained results were compared with those concerning follicular and luteal development in the ovaries of the cycling pig. Differences in 3betaHSD distribution between the ovarian follicles of cycling and pregnant pigs were concerned mainly in the pattern of immunostaining of the theca interna cells. In the porcine ovaries obtained on various days of pregnancy, some follicles exhibited positive immunostaining in most theca interna cells, while in other follicles this enzyme was expressed only in a relatively small percentage of theca interna cells. In the corpora lutea of the estrous cycle and pregnancy changes in the pattern of immunostaining were observed. At early and mid pregnancy (up to 71 day p.c.) 3betaHSD was observed in the large luteal cells while on day 71 p.c. the enzyme was present exclusively in the small luteal cells. The expression of 3betaHSD mRNA was detected by the use of RT-PCR technique in all investigated samples isolated at different stages of pregnancy.     

Physiologic responses to heavy-resistance exercise with very short rest periods

Heavy-resistance exercise utilizing very short rest periods is commonly used by body builders to prepare for competition. The purpose of this study was to compare the acute responses of this type of heavy-resistance exercise protocol in competitive body builders (BB) and power lifters (PL). Nine male BB and eight PL were matched for age, size and experience. A ten-station heavy-resistance exercise protocol was used. Each subject performed three sets of 10 repetition maximum (RM) with 10-s rest between sets and alternated 30-s and 60-s rest periods between exercises. No differences were observed in total work between the groups, but BB used a significantly (P less than 0.05) higher percentage of their 1 RM in the bench press and leg press exercises. Heart rate, ratings of perceived exertion (RPE), and lactate levels were obtained during the exercise protocol; significant (P less than 0.05) increases were observed above rest for these variables. RPE was significantly correlated with lactate levels (r = 0.84). Plasma epinephrine, norepinephrine, dopamine, cortisol, and lactate levels significantly increased from pre- to 5 min post-exercise. Mean plasma volumes were reduced -16.6 (+/- 3.64)% and -20.6 (+/- 8.32)% following the exercise protocol for BB and PL, respectively. Significant (P less than 0.05) decreases in eosinophil counts were observed following exercise. No significant differences were observed between BB and PL for any of the physiologic responses measured. PL exhibited a higher incidence (100%) of clinical symptoms of dizziness and nausea compared to BB (11.1%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunomodulatory Effects of γ-HCH (Lindane) in Mice

Mice were fed for 24 weeks with three different subtoxic dosages of γ-HCH (0.012, 0.12 and 1.2 mg/kg) mixed in powdered feed. The immunological profile was assessed at an interval of one month during the entire exposure period. Both the cell mediated and humoral components of immunity showed a biphasic response characterized initially by stimulation followed by suppression in a dose dependent manner. However, γ-HCH did not affect the functional properties of peritoneal macrophages. Histological changes in lymphoid organs were in accordance with the biphasic immunomodulatory effects of γ -HCH.     

Tetrahymena extract protects Paramecium from oxygen-free radicals

Cells of Paramecium tetraurelia will age and die, while cells of Tetrahymena thermophilia are immortal. Both are free-living, ciliated protozoa. Whole cells and homogenates of both Paramecium and Tetrahymena were treated with iron(+2) to induce peroxidation of membrane lipids and other cellular constituents. Paramecium is far more susceptible to such peroxidative damage than Tetrahymena. Indeed, addition of Tetrahymena extract protects Paramecium from peroxidative damage. Tetrahymena’s protective molecules block the initial attack of oxygen-free radicals on Paramecium constituents. A portion of the protective molecules are high molecular weight and temperature sensitive, but others are of small size. Some of the protective molecules are tightly bound to membranes or cytoskeletal elements pelleted from Tetrahymena sonicates.