Protective effect of ghrelin on testicular damages caused by chronic hypoxia in rats: A histopathological study.

Hypoxia can lead to changes in the blood flow, nutrition and oxygenation of male germ cells and results in fertility reduction through the increase in oxidative stress. This study aims to evaluate the effect of ghrelin on testicular damage induced by hypoxia in rats. In this experimental study, 24 male rats were randomly divided into four groups: control, hypoxia, hypoxia + ghrelin and ghrelin. Animals in the control and ghrelin groups were kept in room air with 21% oxygen. The animals in the groups of hypoxia and hypoxia + ghrelin were subjected to 11% oxygen for 14 consecutive days in the hypoxia chamber. At the end of the study, the testes were removed and histological changes, as well as the apoptotic index, were investigated. Morphometrical analysis showed that hypoxia caused a significant decrease in the seminiferous tubules diameter, the germinal epithelium thickness and main Johnson's score compared to the control group (p < .05). In addition, statistical comparisons revealed a significant increase in the apoptotic index in the hypoxia group (p < .05). Administration of ghrelin + hypoxia improved the parameters mentioned above (p < .05). The results of this study indicated that ghrelin decreases the testicular damages caused by hypoxia in the rats by antioxidative activity.

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures.

Phenotypic change of adult pancreatic islets has been implicated in the development of certain pancreatic cancers and in islet transplant failure. The aim of this study was to characterize intracellular events that mediate changes in adult islet phenotype. Using an in vitro islet-to-duct transformation model, canine islets were induced to undergo phenotypic transformation to duct-like epithelial structures through a two-stage process. Stage one was characterized by widespread islet cell apoptosis associated with the formation of cavitary spaces within the islets. During this stage, c-Jun N-terminal regulated kinase (JNK) and caspase-3 activities were elevated, while extracellular signal-regulated kinase (ERK) and Akt activities were decreased. The second stage of the process was characterized by an inversion in the balance in activity between these signal transduction pathways and by a concomitant decrease in apoptosis. The transformed islets were no longer immunoreactive for islet cell hormones, but expressed the duct epithelial cell marker CK-AE1/AE3. In contrast to islet cells, these duct epithelial cells were highly proliferative. To clarify the role of the identified changes in signal transduction events, we performed additional studies using pharmacological inhibitors of enzyme activity and demonstrated that inhibition of JNK and caspase-3 activity prevented cystic transformation. Our results indicate that the balance in signaling activity between ERK/Akt and JNK/caspase-3 appears to be an important regulator of islet cell death and differentiation.

The abnormal cytotoxicities of 2,5-diaziridinyl-1,4-benzoquinone-3-phenyl esters.

Several derivatives of 2,5-diaziridinyl-3-phenyl-1,4-benzoquinone have been synthesized and their cytotoxicities in six different human cancer cell lines (H460, H596, HT29, BE, K562 and A2780) have been determined. It was observed that certain phenol-ester derivatives were significantly more cytotoxic in all of the cell lines investigated. These esters were shown to be cleaved by esterases to form a stable meta-phenol and an unstable para-phenol. The meta-phenol was also highly cytotoxic. Several of these compounds were studied in detail using DNA cross-linking, clonogenic, apoptosis and flow cytometry assays. It is proposed that although the phenol-esters and the phenols can efficiently cross-link DNA, this mechanism alone is not sufficient to explain the toxicities of these compounds.

Fat emulsion particle-size distribution in total nutrient admixtures.

The fat particle-size distribution in and physical stability of two commercially available lipid emulsions before and after their use in total nutrient admixtures (TNAs) are reported. Four TNAs without electrolytes and four TNAs with electrolytes were prepared; each type of TNA was prepared with Liposyn II and with Intralipid. Particle size was measured in the < 1-micron range by using photon correlation spectroscopy and in the 2-60-microns range by using light blockage. Admixtures with or without electrolytes were stored for two or nine days at 4 degrees C followed by one day at 25 degrees C. For the fraction of fat particles of < 1 micron in diameter, Intralipid and Liposyn II had a mean particle size of 374 and 313 nm, respectively. The admixtures containing electrolytes showed a decrease in mean particle size of about 7%. Admixtures with Intralipid contained 2 x 10(7) particles larger than 2 microns per milliliter (1.7% of total fat), compared with 1 x 10(6) particles per milliliter (0.05-0.15% of total fat) for admixtures with Liposyn II. The addition of electrolytes increased the particle counts for Liposyn II-containing admixtures. Upon storage, Intralipid-containing admixtures with electrolytes showed an initial increase followed by a decrease in the mean diameter of particles of < 1 micron. All the admixtures were stable in terms of pH and visual appearance. Intralipid-containing admixtures with electrolytes showed a decrease in the number of particles in the 2-60-microns size range, while Liposyn II-containing admixtures with electrolytes showed an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Cleanliness assessment of supplier-cleaned stoppers.

The particulate levels found on supplier microcleaned rubber closures were compared to those of stoppers processed by a pharmaceutical manufacturer. The particle monitoring was performed using two official compendial methods: light blockage using a HIAC/ROYCO counter, and optical microscopy using a polarizing research microscope. The supplier-microcleaned stoppers were found to contain relatively few particles per stopper by both instrumental and microscopic counting. The cleaning process used by the pharmaceutical manufacturer was effective in reducing the particle load on their stoppers by factors of 2 to 20 fold as compared to the unwashed stoppers for the different size ranges measured. However, the supplier-microcleaned stoppers were found to be cleaner than those processed by the pharmaceutical manufacturer by a factor of 10 to 20 times for particle sizes greater than 10 microns using the instrumental method. Differences in the counts by microscopic and light blockage methods were attributed to the sampling and agitation procedures. Both the supplier-microcleaned and manufacturer's processed closures were found to meet the USP XXI limits for allowable particulate contamination in small volume parenterals.

Development of a diploid cell line from fetal calf lung for virus vaccine production.

Details of isolation and replication of a fetal calf diploid cell (FCDC) is given. From the karyological point of view, the fairly large number of chromosomes existing in metaphase spreads made counting rather tedious. Lack of practical classification was another problem which made reference to individual chromosomes difficult. By increasing the population doubling of this cell, a tendency of telocentric chromosomes to undergo centric fusion was observed. Susceptibility of FCDC to different viruses is described.