Melatonin reduces microvascular damage and insulin resistance in hamsters due to chronic intermittent hypoxia

Abstract: Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) associated with hypertension, insulin resistance and a systemic inflammatory response. We evaluated the effects of melatonin on vasodilation, capillary perfusion in hamster cheek pouch and insulin resistance, hypertension, and reactive oxygen species (ROS) and nitrate/nitrite levels after IH for 4 wk. Syrian hamsters were divided into four groups: control group (CON), IH group, and melatonin (10 mg/kg) intraperitoneally administered daily for 4 wk/30 min before intermittent air (MEL) or IH (IH + MEL) exposure. IH alone caused elevated blood pressure, increased hematocrit, fasting hyperglycemia, elevated ROS and nitrite/nitrate levels, and vasoconstriction and reduced microvascular perfusion. Melatonin treatment of IH‐exposed animals decreased blood pressure, blood glucose, and ROS and nitrite/nitrate levels, and increased vasodilation and capillary perfusion. An oral glucose tolerance test was performed after 4 wk of IH. During the last 30 min of the hyperinsulinemic euglycemic clamp, blood glucose, and insulin levels were identically matched between groups, but the glucose infusion rate was significantly reduced in IH (29.9 ± 1.9 mg/kg/min) versus IH + MEL group (45.4 ± 1.5 mg/kg/min, P < 0.05) demonstrating a decrease in insulin sensitivity. These results suggest that ROS and nitrite/nitrate levels play important roles in the microvascular dysfunction in IH and that this process is attenuated by melatonin. In conclusion, protection induced by melatonin against functional and metabolic impairment in IH is related to the regulation of ROS and nitrite/nitrate levels in the microcirculation. These observations may have importance to OSA pathological changes.     

Significance of a bar/bat mitzvah ceremony for parents of Jewish children with developmental disabilities

In the Jewish religion, a bar or bat mitzvah ceremony is the rite of passage from childhood towards adulthood. Twenty-one youngsters who attended two special education schools in Israel participated in group bar/bat mitzvah ceremonies. Parents were interviewed both before the learning process and after the ceremony. Findings showed that the bar/bat mitzvah experience was a positive multidimensional one. Dimensions identified were bar/bat mitzvah as a transition, a normative, and a religious experience; an event leading to a sense of connectedness; an opportunity for the enhancement of self-image; and a peak life experience.     

Ovarian tumor in a 12‐year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome

We report a 12‐year‐old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L ‐thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient. Pediatr Blood Cancer 2009;52:677–679. © 2009 Wiley‐Liss, Inc.     

Overview: what’s worked and what hasn’t as a guide towards predictive admissions tool development

Admissions committees and researchers around the globe have used diligence and imagination to develop and implement various screening measures with the ultimate goal of predicting future clinical and professional performance. What works for predicting future job performance in the human resources world and in most of the academic world may not, however, work for the highly competitive world of medical school applicants. For the job of differentiating within the highly range-restricted pool of medical school aspirants, only the most reliable assessment tools need apply. The tools that have generally shown predictive validity in future performance include academic scores like grade point average, aptitude tests like the Medical College Admissions Test, and non-cognitive testing like the multiple mini-interview. The list of assessment tools that have not robustly met that mark is longer, including personal interview, personal statement, letters of reference, personality testing, emotional intelligence and (so far) situational judgment tests. When seen purely from the standpoint of predictive validity, the trends over time towards success or failure of these measures provide insight into future tool development.     

Melatonin as a potential therapeutic agent in psychiatric illness

The aim of this review was to summarize the potential use of melatonin in the treatment of mental disorders, specifically bipolar disorders, depression, and schizophrenia. To date, melatonin has been most commonly used in psychiatry because of its hypnotic, rhythm resynchronizing, and antioxidant actions. Here, we examine other properties of the melatonin including its anti‐inflammatory, antinociceptive, anxiolytic, and drug detoxification actions as well as its protective effects against neural loss. The brain is an intricate sensory and motor organ which receives information from both the external and internal environments. It transduces information into complex chemical and electrical signals which are transmitted throughout the central nervous system (CNS) and the organism. The pathogenesis of mental disorders remains ambiguous and neuroinflammation has been proposed as a causative agent. We consider the potential contributions of melatonin as therapeutic agent in CNS and during neuroinflammation in mental disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

Bile formation and biliary lipid composition under the influence of clofibrate and phenobarbital pretreatment in the rat

Summary The effect of the two enzyme inducing agents, clofibrate and phenobarbital, on bile formation and biliary lipid composition was compared in male rats. Clofibrate (100 mg per kg body weight per day for 14 days) and phenobarbital (at first 60 mg per kg body weight per day for 3 days, then 100 mg per kg body weight per day for 11 days) increase the spontanous bile flow, the ¹⁴C-erythritol clearance but do not alter the bile salt excretion, indicating a stimulation of the bile acid independent fraction of bile. The bile of rats pretreated with clofibrate contains less cholesterol than the bile of saline treated control animals, whereas the concentrations of bile acids, phospholipids and cholesterol are reduced in the bile of the rats of the phenobarbital group. Both drugs diminish the cholesterol saturation of bile. If the biliary bile acid concentration and excretion are augmented by an infusion of sodium taurocholate (1000 nmol per min per 100 g body weight), the biliary concentration of cholesterol remains unchanged in the clofibrate group but increases in the phenobarbital group as compared with the saline control animals. The biliary phospholipid concentration is enhanced after clofibrate as well as after phenobarbital pretreatment. These studies indicate that the biliary excretion of cholesterol and phospholipids is at least to some extent regulated by the bile acid excretion. The importance of the synthesis of cholesterol and phospholipids for their biliary excretion, however, seems to be limited: a reduced cholesterol synthesis by clofibrate results in a reduced biliary cholesterol elimination. By contrast, an increased synthesis of cholesterol by phenobarbital and of the phospholipids by both drugs, however, may enlarge the intrahepatic lipid pools and may place more lipids available for biliary secretion.     

BCR-ABL-negative chronic myeloid leukemia

Constitutive activation of protein tyrosine kinases plays a central role in the pathogenesis of myeloproliferative disorders, including BCR-ABL-negative chronic myeloid leukemia. Current research is focused on elucidating the full spectrum of causative mutations in this rare, heterogeneous disease. Activated tyrosine kinases are excellent targets for signal transduction therapy, and an accurate diagnosis including morphology, karyotyping, and molecular genetics will become increasingly important to direct individualized treatment. In addition, new molecular findings need to be incorporated into disease classification systems.     

Survey of german clinical prescribing philosophies for hyperopia.

PURPOSE: We surveyed a group of German ophthalmologists to evaluate their prescribing philosophies for hyperopic refractive error in symptom-free children and to compare them with the two groups of U.S. pediatric ophthalmologists and U.S. pediatric optometrists as surveyed by Lyons et al. METHODS: Practitioners were selected from a list of ophthalmologists on the Internet. They were either in general practice in three cities in northern Bavaria or affiliated with large ophthalmology teaching hospitals in Wuerzburg and Erlangen. The survey questions of Lyons et al. were translated into German and mailed to 103 ophthalmologists. The data received from the German ophthalmologists were compared with those of the U.S. optometrists and ophthalmologists. RESULTS: A total of 45 surveys (44%) were returned to us and analyzed. In cases of asymptomatic bilateral hyperopia, German ophthalmologists did not prescribe significantly differently from U.S. optometrists at all patient age groups (p > or = 0.05), but they did differ significantly from U.S. ophthalmologists (p < 0.001). Prescribing fractional amounts of hyperopia or astigmatism was not a popular rule of thumb among the German ophthalmologists, and there was no statistical difference between the German and U.S. practitioners. German ophthalmologists would prescribe for anisometropia for all patient age groups in the same way as both U.S. optometrists and U.S. ophthalmologists. CONCLUSION: The prescribing philosophies of German ophthalmologists for pediatric patients did not differ from those of U.S. ophthalmologists and U.S. optometrists when prescribing for anisometropia; they did differ from those of U.S. ophthalmologists but not of those of the U.S. optometrists when prescribing for asymptomatic bilateral hyperopia.