الفهرس 
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Abstract
Summary
The lack of sleep is a growing major health problem in modern society. This is due to work schedules as in night-shift workers and lifestyle changes that have negative effects on health. There is increasing studies to demonstrate that SD or even insufficient sleep is associated with increased risk of cardiovascular diseases, hypertension, stroke, obesity, disrupt endocrine functions and others.
Recently, in 1998 a hypothalamic neurotransmitter orexin was discovered and it is now known that orexin is involved in regulation of sleep/ wakefulness cycle and various physiological functions as food intake & hormonal regulation. Nevertheless, the role of orexin in health hazards of SD is not yet evident and the mechanisms by which orexin involved in these hazards and the protective effect of orexin receptor blockers are still debated.
In order to investigate the role of orexin in health hazards of SD, the mechanisms by which orexin involved in these hazards and the protective effect of orexin receptor blockers, a total of 72 adult male albino rats, aged 10-12 weeks and weighting 200-300 grams are arranged in four equal groups: control (G I), sleep deprived group (G II), SD-OX1R blocked group (G III) and SD-DMSO group (G IV).
The sleep deprived groups (G II, III & IV) are exposed to SD using the modified multiple platform method for 20 hours daily (from 4:00 pm to 12:00 pm of the next day) for 8 successive days. During this period, the amount of food intake, body weight, fasting levels of glucose, cortisol, insulin, total triglycerides and cholesterol were assessed daily. At the end of the experiment, intraperitoneal glucose tolerance test was done after 12 hours of fasting. The presence or absence of insulin resistence/sensitivity was assessed using HOMA-IR calculation formula.
The G II and G IV showed a DROP in body weight inspite of increased food consumption when compared with the control group. This increase in food intake was inhibited by using OX1R blocker in G III but the body weight showed a DROP by much degree than the other groups and this DROP in body weight started earlier than the other groups.
Blood cortisol level showed statistically significant higher levels in G II and G IV when compared with the G I. While G III although showed rise in blood cortisol level, it was delayed than the other groups.
A DROP in both fasting insulin level and fasting blood glucose level in both G II and G IV were noticed. In G III, no significant change in the level of insulin when compared with G I but the fasting blood glucose showed less and delayed dropping.
Assessment of insulin sensitivity showed an increase in insulin sensitivity in G II & G IV. While in G III showed also an increase in insulin sensitivity but it was delayed and less obvious.
The intraperitoneal glucose tolerance test showed an increase in blood glucose level after intraperitoneal injection of 2 gm/kg of glucose during the 1st hour in G I and then decreased toward the fasting level again during the 2nd & 3rd hours. The G II & G IV showed a rapid increase in blood glucose level after intraperitoneal glucose injection during the 1st 15 minutes reached their peaks then dropped gradually reaching their fasting values after 180 minutes. G III although showed rapid rise then rapid DROP of blood glucose level but the decline in blood glucose level was less sharp than the G II & G IV.
The cholesterol level was lower all sleep deprived groups (G II, G III & G IV). While the triglyceride level lowered in G II & G IV only. This denotes that the effect on cholesterol is orexin independent. Triglyceride levels in G III were still statistically significant higher when compared with the G II.
Conclusion and Recommendations:
Conclusion:
The current study evidenced that exposure to paradoxical SD for 8 days, could have adverse effects on the metabolic and hormonal parameters in the adult albino rats that may be a cause of metabolic disorders that affect night shift workers in the society.
The recorded embarrassment of SD on metabolic and hormonal functions may be contributed to high orexin levels during periods of SD that lead to increase in stress hormones as cortisol, increase in food intake and increase in glucose and fat utilization.
Blocking OX1Rs protects against the increase in food intake and the DROP in insulin level and partially protect against the rise in cortisol level, the DROP in blood glucose level, the increase in insulin sensitivity and the DROP in triglyceride level but not protective against the DROP in cholesterol level. It leads to more DROP in body weight.
Recommendations:
• Avoidance of SD or inverted sleep rhythm as possible.
• Night shift workers -especially the obese- are advised to take OX1R blockers to decrease some of the complications of sleep deprivation and inverted sleep rhythm.
• Night shift workers with low availability of food and decrease food intake who are liable to hypoglycemia by the increased metabolic rate with low food intake, the OX1R blocker can decrease desire for food intake and doesn’t affect their wakefulness and protect them from SD induced hypoglycemia plus help reduction of their body weight so recommended in obese persons.
• Repeating the experiment with the use of higher doses of OX1R blockers.
• Trying different OX1R blockers.
• Measuring thyroid hormone levels and TSH to test if they have a role in these changes observed in paradoxical SD.