Enzymatic changes in lung tissue of asbestotic guinea pigs.

The changes in the activities of some mitochondrial and soluble enzymes in the lungs of guinea pig, caused by three varieties of asbestos dust 120 days after intratracheal injection, were studied. Marked increase was observed in mitochondrial cytochrome oxidase, diaphorase and malic dehydrogenase. Among the soluble enzymes, lactic dehydrogenase showed the maximum variation.     

A study of the age factor in experimental silicosis in rats.

In order to study the progress of pulmonary silicosis in rats of different ages, intratracheal injections of (50 mg/150 g body weight) quartz dust of particle size less than 5 mu were given as a single dose and studies were made over a period of 180 days. The pulmonary macrophage reaction and phagocytosis in the younger age group of rats was different from that in the older animals at 30 days postinoculation. The formation of silicotic nodules was delayed in the younger animals. They consisted of thick reticulin fibers and some collagen fibers; in the older group of rats large silicotic nodules with dense collagination developed towards the termination of the experiment (180 days). The present results indicate a possible direct relationship between age and the development of experimental pulmonary silicosis in rats.     

The nature of the carbohydrate binding module determines the catalytic efficiency of xylanase Z of Clostridium thermocellum

Xylanase Z of Clostridium thermocellum exists as a complex in the cellulosome with N-terminus feruloyl esterase, a carbohydrate binding module (CBM6) and a dockerin domain. To study the role of the binding modules on the activity of XynZ, different variants with the CBM6 attached to the catalytic domain at its C-terminal (XynZ-CB) and N-terminal (XynZ-BC), and the CBM22 attached at N-terminus (XynZ-B′C) were expressed in Escherichia coli at levels around 30% of the total cell proteins. The activities of XynZ-BC, XynZ-CB and XynZ-B′C were 4200, 4180 and 20,700 U μM⁻¹ against birchwood xylan, respectively. Substrate binding studies showed that in case of XynZ-BC and XynZ-CB the substrate birchwood xylan remaining unbound were 51 and 52%, respectively, whereas in the case of XynZ-B′C the substrate remaining unbound was 39% under the assay conditions used. The molecular docking studies showed that the binding site of CBM22 in XynZ-B′C is more exposed and thus available for substrate binding as compared to the tunnel shape binding pocket produced in XynZ-BC and thus hindering the substrate binding. The substrate binding data for the two constructs are in agreement with this explanation.     

Seminal parameters in rhesus monkeys under physiological conditions and in studies for male fertility control using FSH antibodies or LH-RH-agonists

To characterize the male rhesus monkey as a nonhuman primate model for human testicular functions, parameters of exocrine and endocrine testicular function were monitored in 16 adult male-rhesus monkeys for 1 and 5 years respectively. Testicular volumes in-season (October–January) were twice as great as in out-of-season animals (March–June). Ejaculations, both spontaneous and electrostimulated, ceased out-of-season. In 37 ejaculates obtained by electrostimulation in-season, sperm counts ranged from 110–1,100 million/ejaculate, 65% of sperm were motile and 60% were normally formed. Testicular histology showed regression of spermatogenesis out-of-season, with the diameter of the tubules being only one third of that in-season. Circannual changes in exocrine testicular function were accompanied by parallel fluctuations in pituitary and endocrine testicular functions, as evidenced by basal hormone levels and the production rate of testosterone, as well as the response to LH-RH throughout the year. As FSH is required for spermatogenesis in rhesus monkeys, we initiated a study on the long-term effects of active immunization against FSH as a possible means of fertility control. After the first 2 years of observation we can conclude that the production of specific antibodies to FSH results in suppression of spermatogenesis (oligospermia and occasional azoospermia) without affecting endocrine function. The lack of adverse side effects may encourage further investigations on this approach to fertility control. LH-RH-agonists exert degenerative effects on testicular function in rats via a down regulation of the pituitary and testis. A 12 week treatment of four adult monkeys in-season with Hoe 766 (Hoechst; 4μg/day for eight weeks, 20μg/day for 4 weeks sc) did not reveal any change in sperm counts or motility, although some pituitary desensitization was evident. It remains to be investigated whether even higher doses may result in a suppression of spermatogenesis.     

Human MC4R variants affect endocytosis,trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation

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A hypothesis for the local control of osteoclast function by Ca2+, nitric oxide and free radicals

Several important conclusions have recently emerged fromin vitro studies on the resorptive cell of bone, the osteoclast. First, it has been established that osteoclast function is modulated locally, by changes in the local concentration of Ca²⁺ caused by hydroxyapatite dissolution. It is thought that activation by Ca²⁺ of a surface membrane Ca²⁺ receptor mediates these effects, hence providing a feedback control. Second, a number of molecules produced locally by the endothelial cell, with which the osteoclast is in intimate contact, have been found to affect bone resorption profoundly. For instance, the autocoid nitric oxide strongly inhibits bone resorption. Finally, reactive oxygen species have been found to aid bone resorption and enhance osteoclastic activity directly. Here, we will attempt to integrate these control mechanisms into a unified hypothesis for the local control of bone resorption.