Ultrastructure of high altitude pulmonary oedema

Heath, D., Moosavi, H., and Smith, P. (1973).Thorax, 28, 694-700. Ultrastructure of high altitude pulmonary oedema. When rats are exposed for 12 hours to simulated high altitude corresponding to the summit of Mount Everest, they develop ultrastructural changes in the lungs. These consist of the formation and protrusion of multiple endothelial vesicles into the pulmonary capillaries. It seems likely that they are associated with the development of high altitude pulmonary oedema.     

Distortion Product Otoacoustic Emission (DPOAE) as an Appropriate Tool in Assessment of Otoprotective Effects of Antioxidants in Noise-Induced Hearing Loss (NIHL)

Distortion product otoacoustic emission (DPOAE) appears to be an objective sensitive test of cochlear function. The aim of this study was to investigate whether DPOAE is an appropriate tool for assessment of minute changes in cochlea due to usage of antioxidant material. 48 workers exposed to continuous noise in a textile factory were randomly assigned into three groups: (1) The Control group (n = 16) received no antioxidant drugs, (2) The N-acetyl-cysteine (NAC) group (n = 16) received oral antioxidant NAC (1200 mg/day), (3) The Ginseng group (n = 16) received oral antioxidant Ginseng (200 mg/day). All three groups had a follow-up period of 2 weeks. The cochlear changes were assessed using DPOAE test before starting the daily work shift on first and 15th day. The associations between groups and DPOAE amplitudes after 2 weeks were analyzed using linear regression analysis. Four separate models were fitted by side of ears and frequency. All models were adjusted for baseline amplitude. Reduced (better) amplitude at DPOAE test was found for NAC and Ginseng groups at high frequencies (4 and 6 kHz) in both ears after 2 weeks compared to control group. Moreover, NAC group showed better DPOAE amplitude than Ginseng group. In conclusion, DPOAE seems to be an appropriate tool in assessing minute changes in the cochlea after antioxidant drugs administration.     

Carbenoxolone induces apoptosis and inhibits survivin and survivin-ΔEx3 genes expression in human leukemia K562 cells

Background and the purpose of the study

Leukemia is a malignant disorder of the blood progenitor/stem cells which is characterized by abnormal proliferation of white blood cells. Although anti-cancer drugs induce apoptosis in cancerous cells, drug resistance is the significant problem mainly due to over-expression of inhibitors of apoptosis proteins (IAPs) such as survivin. In this content, it has been reported that an anti-inflammatory drug, Carbenoxolone (CBX), could induce apoptosis and growth inhibition in several types of cancerous cells. In the present study, effects of CBX on apoptosis and level of the expression of survivin gene and its ΔEx3 splicing variant have were evaluated in K562 cells.

Methods

K562 cells were cultured and treated with different concentrations of CBX (50-300 µM) at different time intervals (12-48 hrs). Trypan blue exclusion test was used to evaluate cell viability. Fluorescent microscopy (Acridine Orange/Ethidium Bromide double staining) and DNA fragmentation assay were used to study apoptosis. The expression level of survivin and its ΔEx3 splice variant were studied by RT-PCR.

Results and Major Conclusion

It was found that both growth inhibition and apoptosis occurred in K562 cells. In addition, down-regulation of survivin and survin-ΔEx3 were observed, after 2-4 hrs treatment with 150 µM of CBX. However, the expression level of survivin and its ΔEx3 splice variant increased in subsequent time (6-12 hrs) nearly to the level of control cells. From the results of this study, it may be concluded that CBX can be considered as a candidate for further studies in CML treatment, especially in the case of drug-resistant leukemia cells.     

Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice

In the present study, the effects of an ethanol and aqueous extract of saffron Crocus sativus and its constituents safranal and crocin on the stress‐induced reduction in food intake, weight gain and anorexic time in mice were investigated. Male albino mice (20–25 g) were irregularly exposed to a trial of electroshock stress for 7 days. Then, the anorexic time as well as the animal's food intake and weight were recorded. In addition, blood samples were obtained on days 1 and 7 for corticosterone determination. Intraperitoneal (i.p.) administration of the aqueous but not the ethanol extract (10, 50 and 100 mg/kg) significantly reduced the anorexic time. The results were similar for crocin (1, 5 and 10 mg/kg; i.p.). In addition, a reduction in weight gain was observed in the controls as well as in the groups that received alcohol extract or safranal. However, this was not observed in animals treated with aqueous extract or crocin. The plasma corticosterone level did not increase in the aqueous extract and crocin treated animals. It can be concluded that the saffron aqueous extract and its constituent crocin reduce side effects of electroshock stress in mice. Copyright © 2011 John Wiley & Sons, Ltd.     

Characterisation of 11beta-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat

Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0 x 001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease.     

Effect of chronic restraint stress on carbohydrate metabolism in rat

There is some evidence suggesting that stress may induce diabetes mellitus; the effects of restraint stress however need to be investigated. The present study investigates the role of chronic restraint stress on carbohydrate metabolism in male rats. The animals of the stressed group (n=8) were exposed to different restraint stressors (1 h twice daily) for 30 days. On days 1, 15 and 30, before stress exposure, the animals were weighed and fasting blood samples were obtained by tail snipping and subsequently oral glucose tolerance tests (OGTT) were carried out. Fasting plasma glucose levels on the 15th day and the plasma glucose concentrations, on the 15th and 30th days of the experiment at 15 and 60 min following OGTT, in the stressed group, were significantly higher as compared to the control group. In the stressed group, fasting plasma insulin levels on the 15th and 30th days of the experiment and the plasma insulin concentrations, on the 15th day at 15 and 60 min after performing OGTT, were significantly lower as compared to the control group. Fasting plasma corticosterone concentrations were significantly increased on the 15th day of the experiment in the stressed rats as compared to the control rats and to concentrations on the 1st day. The weights of the stressed rats on the 15th and 30th experimental days were significantly lower than the controls. In conclusion, chronic restraint stress for 30 days leads to low body weight gain in rats and impairs glucose metabolism perhaps by affecting corticosterone and insulin secretion and by inducing a degree of insulin resistance.