Reduced performance of male and female athletes at 580 m altitude

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.     

Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic mouse urinary tract

Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human apoB. Steady-state and pulse-chase labeling experiments demonstrated that newly synthesized human apo(a) had a prolonged residence time (approximately 60 min) in the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was inefficiently secreted by the hepatocytes and a large portion of the protein was retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex folding pathway in the ER, which included incorporation of apo(a) into high molecular weight, disulfide-linked aggregates. These folding characteristics could account for long ER residence time and inefficient secretion of apo(a). Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before appearing in the culture medium. Apo(a) could be released from the cell surface by apoB-containing lipoproteins. These studies are consistent with a model in which the efficiency of post-translational processing of apo(a) strongly influences human plasma Lp(a) levels, and suggest that cell surface assembly may be one pathway of human Lp(a) production in vivo. Transgenic mouse hepatocytes thus provide a valuable model system with which to study factors regulating human Lp(a) biogenesis.     

Modulation of cardiac sodium current by alpha1-stimulation and volatile anesthetics

BACKGROUND: Alpha1-adrenoceptor stimulation is known to produce electrophysiologic changes in cardiac tissues, which may involve modulations of the fast inward Na+ current (I(Na)). A direct prodysrhythmic alpha1-mediated interaction between catecholamines and halothane has been demonstrated, supporting the hypothesis that generation of halothane-epinephrine dysrhythmias may involve slowed conduction, leading to reentry. In this study, we examined the effects of a selective alpha1-adrenergic receptor agonist, methoxamine, on cardiac I(Na) in the absence and presence of equianesthetic concentrations of halothane and isoflurane in single ventricular myocytes from adult guinea pig hearts. METHODS: I(Na) was recorded using the standard whole-cell configuration of the patch-clamp technique. Voltage clamp protocols initiated from two different holding potentials (V(H)) were applied to examine state-dependent effects of methoxamine in the presence of anesthetics. Steady state activation and inactivation and recovery from inactivation were characterized using standard protocols. RESULTS: Methoxamine decreased I(Na) in a concentration- and voltage-dependent manner, being more potent at the depolarized V(H). Halothane and isoflurane interacted synergistically with methoxamine to suppress I(Na) near the physiologic cardiac resting potential of -80 mV. The effect of methoxamine with anesthetics appeared to be additive when using a V(H) of -110 mV, a potential where no Na+ channels are in the inactivated state. Methoxamine in the absence and presence of anesthetics significantly shifted the half maximal inactivation voltage in the hyperpolarizing direction but had no effect on steady-state activation. CONCLUSION: The present results show that methoxamine (alpha1-adrenergic stimulation) decreases cardiac Na+ current in a concentration- and voltage-dependent manner. Further, a form of synergistic interaction between methoxamine and inhalational anesthetics, halothane and isoflurane, was observed. This interaction appears to depend on the fraction of Na+ channels in the inactivated state. (Key words: Anesthetics, volatile: halothane; isoflurane; methoxamine. Patch clamp: whole-cell configuration; sodium current; ventricular guinea pig myocytes.)     

What does it take to demonstrate memory erasure? Theoretical comment on Norrholm et al. (2008).

An issue of increasing interest in Pavlovian conditioning is to identify ways to facilitate the development and persistence of extinction. Both behavioral and molecular lines of evidence demonstrate that learning during extinction can be enhanced. Similar evidence has been offered to support the idea that extinction causes the original association to be unlearned, or erased. Differentiating between extinction and erasure accounts is extremely difficult and requires many assumptions about the fundamental nature of how memory storage maps into memory expression. In this issue of Behavioral Neuroscience, Norrholm et al. (see record 2008-13280-002) describe a study of extinction with humans that has the potential to serve as a translational bridge between rodent work and clinical applications. They find less recovery of a conditioned fear response when extinction occurs 10 min compared with 72 hr after conditioning; however, the recovery of subjects' expectancies of the fearful stimulus is independent of when extinction occurred. These findings and others discussed in this article demonstrate some of the challenges in making inferences about memory erasure during extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fatty Acids Released from Milk Fat by Lipoprotein Lipase and Lipolytic Psychrotrophs

ABSTRACT: The ability of 13 different strains of psychrotrophs to release free fatty acids in milk was evaluated by using GC analysis. The 13 strains could be categorized into 3 groups: Group 1 consisted of bacteria that grew well and released large quantities of free fatty acids, group 2 consisted of bacteria that grew well but released low amounts of free fatty acids, and group 3 consisted of bacteria that did not grow well nor released large quantities of fatty acids. In group 1, 3 strains were determined to be highly lipolytic, releasing short‐chain fatty acids in amounts greater than reported threshold values. Group 3 consisted of 2 strains, which did not grow well in heat‐treated milk, and the subsequent release of free fatty acids was minor during the 10‐d monitoring time. The other 8 strains tested showed no specific pattern of fatty acid release and quantities of short‐chain fatty acids were not large, despite the ability to grow to high numbers in the treated milk. This work indicates that the lipolytic activity of psychrotrophs common in raw milk is specific to the species and a general prediction of free fatty acid release may not be possible.     

Exposure to environmental and mainstream tobacco smoke and risk of spontaneous abortion

The present nationwide, multicenter clinical study was carried out in 26 departments of surgery to define the incidence and attendant mortality of intestinal infarction following abdominal aortic surgery, and to identify patients at risk of it. The data consist of 1752 patients who underwent abdominal aortic reconstruction during 1991-1993 as recorded in the Finnish national vascular registry (FINNVASC). Among the 1752 operations, 27 patients treated at 14 different hospitals had intestinal ischemia, and the complete patient records of all 27 cases were reanalyzed. The incidence of bowel infarction was 1.2%. Among patients operated on for a ruptured aneurysm it was 3.1%, whereas 1.0% of patients with nonruptured aneurysm and 0.6% of those operated on for aortoiliac occlusive disease developed intestinal infarction. In 14 patients (67%) the lesion affected the left colon. The overall 30-day mortality rate was 13% but reached 67% among those with intestinal infarction. We conclude that acute intestinal ischemia with bowel infarction is an infrequent but serious complication of abdominal aortic surgery. It is mainly related to surgery due to aneurysmal disease, and patients with occlusive aortoiliac disease present ischemic complications in the intestines less often. Hypotensive patients being treated for ruptured aneurysm are at greatest risk of intestinal ischemia.     

Microencapsulation of α-Amylase by Carrying Out Complex Coacervation and Drying in a Single Step Using a Novel Three-Fluid Nozzle Spray Drying

The aim of this research was to develop an enzyme encapsulation process in which both the complex coacervation and drying processes are combined into a single step. For this purpose, we used a novel three-fluid nozzle at the atomization step of spray drying. α-Amylase as a model enzyme was encapsulated by coacervation in calcium (Ca) alginate and Ca-alginate + chitosan shell matrices and the powder was obtained in a single step through spray drying. The single-step process was compared to carrying out the complex coacervation and drying processes in two steps using freeze drying, in which α-amylase was encapsulated by carrying out the complexation process in the above-mentioned shell matrices using the same three-fluid atomizer and collecting the coacervates, which were subsequently freeze dried. The results showed that the microcapsules obtained from the single-step encapsulation process (three-fluid nozzle spray drying) had smaller particle sizes, were less porous, and provided better enzyme stability compared to the microcapsules obtained by carrying out the complexation and drying in two steps and the single-step process was faster. It was observed that the egg-box structure was formed in both types of powder particles; however, the complexation with chitosan partially disrupted the formation of this structure. The three-fluid nozzle–based spray drying is a promising technology in which both the complex coacervation and drying processes can be carried out in a single step.     

Calculating the Risk of Batch Failure in the Manufacture of Drug Products

A statistical tool has been developed to estimate the risk of batch failure in commercial production from the results of the development scale-up campaigns. This tool serves to indicate the robustness of the manufacturing procedure and its ability to meet the specifications set. Other uses include assistance in the resetting of specifications in the light of actual scale-up batch manufacturing experience and assessing the impact of changes in specifications proposed by the registration authorities. A template is given that simplifies the calculations required.