The effects of ovariectomy and strech on the regulatory profile and activity of the uterus

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 μg PGF2α provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P<0.001) and the PG levels had not changed significantly, 50 μg PGF2α significantly increased cyclic IUP as compared with the day 25 value (P<0.001). At day 27, when the P levels decreased further, as little as 5 μg PGF2α provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P<0.05).Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P<0.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.     

Microbiological leaching of a chalcopyrite concentrate by Thiobacillus ferrooxidans

The microbiological leaching of a chalcopyrite concentrate has been investigated using a pure strain of Thiobacillus ferrooxidans. The optimum leaching conditions regarding pH, temperature, and pulp density were found to be 2.3, 35°C, and 22%, respectively. The energy of activation was calculated to be 16.7 kcal/mol. During these experiments the maximum rate of copper dissolution was about 215 mg/liters/hr and the final copper concentration was as high as 55 g/liter. This latter value is in the range of copper concentrations which may be used for direct electrorecovery of copper. Jarosite formation was observed during the leaching of the chalcopyrite concentrate. When the leach residue was reground to expose new substrate surface, subsequent leaching resulted in copper extractions up to about 80%. On the basis of this experimental work, a flow sheet has been proposed for commercial scale biohydrometallurgical treatment of high-grade chalcopyrite materials.     

On the reporting and review requirements of ISO 14044

The International Journal of Life Cycle Assessment -     

Loss of aPKCλ in Differentiated Neurons Disrupts the Polarity Complex but Does Not Induce Obvious Neuronal Loss or Disorientation in Mouse Brains

Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS). Recent studies have established the significance of atypical protein kinase C (aPKC) and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.     

Endovanilloid signaling in pain

Recent work has addressed the role of vanilloid receptor type 1 (VR1) in pain perception. VR1 activity is regulated both directly and indirectly by endogenous factors. For example, protein kinase C sensitizes human VR1 to mild decreases in pH, which are commonly encountered during inflammation, and renders the endocannabinoid anandamide a more potent 'endovanilloid'. Bradykinin and nerve growth factor release VR1 from the inhibitory control of phosphatidylinositol (4,5)-bisphosphate and anti-VR1 serum ameliorates thermal allodynia and hyperalgesia in diabetic mice. There is strong evidence that not only the sensitivity but also the density of expression of VR1 is enhanced during inflammatory conditions. These observations provide an empirical foundation which could explain the reduced inflammatory hyperalgesia in VR1 knockout mice, and they imply an important role for endovanilloid signaling via VR1 in the development of ongoing pain in humans that occurs in most inflammatory conditions. Conversely, downregulation of VR1 expression and/or activity is a promising therapeutic strategy for novel analgesic drugs.     

The role of heme oxygenase signaling in various disorders

Modern methods of cell and molecular biology, augmented by molecular technology, have great potential for helping to unravel the complex mechanisms of various diseases. They also have the potential to help us try to dissect the events which follow the altered physiological conditions. Thus, there is every reason to believe that some of the potential mechanisms will be translated sooner or later into the clinic. Heme oxygenase (HO)-related mechanisms play an important role in several aspects of different diseases. In the past several years, significant progress has been made in our understanding of the function and regulation of HO. The objective of this article is to review current knowledge relating to the importance of HO mechanism in various diseases including myocardial ischemia/reperfusion, hypertension, cardiomyopathy, organ transplantation, endotoxemia, lung diseases, and immunosuppression. The morbidity and mortality of these diseases remain high even with optimal medical management. Furthermore, in this review, we consider various factors influencing the HO system and finally assess current pharmacological approaches to their control.     

Functional and structural characterization of anti-β1-adrenoceptor autoantibodies of spontaneously hypertensive rats

Eighteen month old spontaneously hypertensive rats (SHR-rats) showed myocardial dysfunction and autoantibodies directed against the ₁-adrenoceptor similarly as known in human dilated cardiomyopathy or Chagas' disease. The agonist-like antibodies were able to activate the ₁-adrenoceptor mediated signal transduction cascade in cultured rat cardiomyocytes and induced a long-lasting stimulatory effect resulting in a harmful adrenergic overdrive. The antibodies recognized an epitope of the second extracellular loop of the ₁-adrenoceptor identical to that epitope identified in Chagas' disease. In conclusion, our assumption is supported that old SHR-rat are an useful animal model for investigating the role of anti-₁-adrenoceptor antibodies in the induction of human cardiomyopathy.     

Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone’s deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes.     

Co‐ordinated autophagy with resveratrol and γ‐tocotrienol confers synergetic cardioprotection

This study compared two dietary phytochemicals, grape‐derived resveratrol and palm oil‐derived γ‐tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague‐Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ‐tocotrienol + I/R, resveratrol +γ‐tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ‐tocotrienol experiments the rats were gavaged with γ‐tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ‐tocotrienol experiments, the rats were gavaged with γ‐tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ‐tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ‐toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ‐tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt‐Bcl‐2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3‐II as well as mTOR signalling, which were inhibited by either 3‐methyl adenine (3‐MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.