Effect of nasal continuous positive airway pressure treatment on plasma adrenomedullin levels in patients with obstructive sleep apnea syndrome: roles of nocturnal hypoxia and oxidant stress.

Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress and oxidative stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients as compared to an age and body mass index (BMI)-matched control group and an age-matched, but normal-BMI control group. We further hypothesized that nasal continuous positive airway pressure (nCPAP) treatment may decrease OSAS-induced hypoxic stress, oxidative stress and ADM levels. To examine these hypotheses, we measured circulating ADM and reactive oxygen species (ROS) from leukocytes before and after nCPAP therapy in OSAS patients. The circulating levels of ADM and amount of ROS in untreated OSAS patients were significantly greater than those in the controls. No differences in ADM levels were found between the increased-BMI controls and normal-BMI controls. We observed that nCPAP treatment decreased sleep apneas, nocturnal oxyhemoglobin desaturation, the circulating ADM, and ROS production by leukocytes in OSAS patients. The ADM levels were associated with the magnitude of oxyhemoglobin desaturation rather than the number of sleep apneas. These observations suggest that nCPAP therapy could reduce OSAS-induced nocturnal hypoxemia, generation of ROS, and ADM in patients with OSAS.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

A muscle-derived factor antagonizes the neurotoxicity of glutamate in dissociated cell cultures of chick telencephalic neurons.

Excitatory amino acids including glutamate are known to reveal considerable neurotoxicity in various nervous systems. Our previous studies revealed that the chick muscle extract contains a factor which promotes the survival of telencephalic neurons. Further investigations clearly showed that this extract contains the factor that antagonizes the neurotoxicity of glutamate in a dissociated telencephalic neuronal culture system optimized for detection of the toxicity. This factor reduced at least the toxicity mediated by non-N-methyl-D-aspartate (non-NMDA) receptor.     

Determination of the exposure concentration of propylene oxide to produce neuropathy in rats

Although propylene oxide, which is similar in chemical structure to ethylene oxide, is expected to produce neuropathy, there is no convincing evidence of the degeneration of the peripheral nervous system. To determine the exposure concentration of propylene oxide necessary to produce neuropathy in male Wistar rats, we subjected them to repeated exposures of propylene oxide at concentrations of 500, 750, 1000, 1500 and 2000 ppm. The test rats were subjected to a single 6 hour exposure of propylene oxide at a concentration of 1500 parts per million 5 times a week for 3 weeks. They developed a significant decrease in body weight, abnormal posture of the hindlegs and axonal degeneration of myelinated fibers in the peroneal and sural nerves, the nerves to the soleus muscle, and in the fasciculus gracilis of the spinal cord. Therefore, it was concluded that propylene oxide induces neuropathy in rats characterized by axonal degeneration, similar to that produced by ethylene oxide, and that the exposure to the higher concentration of propylene oxide is more necessary to produce neuropathy than in the case of ethylene oxide neuropathy in rats.     

Pseudopodia of capillary endothelium in ocular tissues

The frequencies of pseudopodia projecting from capillaries of various parts of the eye were observed in 16 human eyes with a transmission electron microscope. The pseudopodia were found mainly projecting from the choriocapillaris and rarely seen in the retina, iris or ciliary body. The frequencies of pseudopodia from the choriocapillaris were not correlated with the localization in the fundus (macular area or peripheral fundus), age, sex, time elapsed between death or enucleation and fixation. The significance of pseudopodia from the choriocapillaris is unknown. However, there is the possibility that pseudopodia are related to choroidal neovascularization or have other physiological functions.     

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.     

Effects of intrahippocampal injections of N-methyl-D-aspartate receptor antagonists and scopolamine on working and reference memory assessed in rats by a three-panel runway task.

In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type excitatory amino acid receptors in working and reference memory in rats, the effects of intrahippocampal injections of selective and competitive N-methyl-D-aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a three-panel runway task. The results were compared with the effect of the muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This also occurred after the rats were given systemic injection of these drugs at 3.2 and 10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors, whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg systemically. Working memory errors also increased significantly after intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320 ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and 3.2 micrograms/side increased significantly working memory errors, without affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Middle-ear paraganglioma masquerading as traumatic facial nerve palsy.

We report the case of a 52-year-old female with middle-ear paraganglioma masquerading as a traumatic facial palsy, and describe the diagnostic steps and surgical treatment by the tympanomastoid approach.