Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice

Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression.     

Distance-dose curve for a miniature x-ray tube for stereotactic radiosurgery using an optimized aperture with a parallel-plate ionization chamber

A recently developed miniature x-ray tube operating at 40 kV has been used in a randomized trial for the treatment of small intracranial lesions. The diameter of these lesions ranges from 10 to 30 mm. A thin window parallel-plate ionization chamber was used to calibrate the output of the x-ray tube, modified by the addition of a thin platinum aperture to reduce the charge collecting area of the chamber. The effect of such an aperture on the measurement of dose versus distance from the x-ray tube in a phantom has been examined as a function of aperture diameter. Aperture diameters were varied between 0 and 5 mm and dose measurements were made for distances between the x-ray source and the front surface of the chamber of 5-30 mm in water. The ratio of doses measured with and without an aperture, when normalized to unity at a distance of 10 mm, differs significantly from unity, for distances between 7.5 and 15 mm, for aperture diameters <1.5 mm and differs from unity, but less significantly, for apertures > or =3 mm. For intermediate diameters, however, this dose dependence is minimized, indicating an aperture diameter that provides a similar distance-dose curve as the measurement taken without an aperture over this range of distances. This diameter was found to be between 2 and 2.5 mm with a dose variation of less than +/- 1%. For distances <7.5 mm, measurements made with a 1.5-mm-diam aperture agree better with those taken with a 1.7-mm-diam chamber compared with a 5.2-mm-diam chamber.     

Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice.

To clarify the role of cytokines and acinar cell apoptosis in the pathogenesis of acute pancreatitis, we investigated the expression of intrapancreatic cytokines and apoptosis-related molecules in mice after pancreatic duct ligation (PDL). From day 1 or 3 after PDL, the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor (TNF-alpha) mRNA were up-regulated in the pancreas, suggesting that these cytokines may be involved in the development of pancreatitis after PDL. Acinar cell apoptosis was observed in the pancreas at rates of 0.13 +/- 0.03, 1.32 +/- 0.38, and 0.86 +/- 0.23% on days 1, 3, and 7 after PDL, respectively. Significant increases in intrapancreatic mRNA levels of TNF-alpha, Fas ligand (FasL), and IL-1beta-converting enzyme (ICE) were observed from day 3 after PDL with the appearance of acinar cell apoptosis. The serum amylase activity peaked on day 1 after PDL and gradually decreased on days 3 and 7 after PDL. These results suggest that acinar cell apoptosis induced after PDL may modulate the progression of acute pancreatitis by reducing the release of digestive enzymes and may therefore be a host defense mechanism, and that acinar cell apoptosis after PDL may be mediated by the TNF-alpha and/or Fas/FasL and ICE system.     

Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10 mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72 h. We observed a delayed increase in pica 24-72 h after injection, compared to the 24 h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10 mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10 mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10 mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72 h post-administration of 1 and 5 mg/kg cisplatin. Administration of 5 mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72 h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.     

Impaired p53/CEP‐1 is associated with lifespan extension through an age‐related imbalance in the energy metabolism of C. elegans

In the nematode Caenorhabditis elegans, the mammalian tumor suppressor p53 ortholog CEP‐1 mediates the stress response, activates germ line apoptosis and regulates meiotic chromosome segregation. A reduction in its expression, which frequently occurs in mammalian cancer cells, extends lifespan and induces an adaptive response in C. elegans. However, these effects do not involve an increase in oxidative stress resistance. Here, we showed that intermittent exposure to hyperoxia, which induces oxidative stress resistance and lowers the production of ROS derived from mitochondrial respiration in C. elegans, slightly improved the lifespan extension of cep‐1 mutant. Interestingly, ATP levels were increased without an increase in oxygen consumption in cep‐1 mutant during aging. In the wild‐type, lactate levels and consequentially the lactate/pyruvate ratio decreased during aging in adults. Furthermore, the expression levels of mitochondrial respiration‐related sco‐1, which is a target of p53/CEP‐1, as well as those of gluconeogenesis regulation and mammalian sirtuin ortholog genes, were also increased in the aged and adaptive conditioned wild‐type animals. In contrast, the lactate/pyruvate ratio increased in cells of the cep‐1 mutant and was amplified by intermittent hyperoxia. These results suggest that impaired p53/CEP‐1 leads to an imbalance in the age‐related energy metabolic alteration between mitochondrial oxidative phosphorylation and aerobic glycolysis and plays an important role in the extension of both intact and adaptive lifespans.     

Peroxisome proliferator-activated receptor gamma co-activator 1 gene Gly482Ser polymorphism is associated with the response of low-density lipoprotein cholesterol concentrations to exercise training in elderly Japanese

Muscle peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1)α gene expression is influenced by the Gly482Ser gene polymorphism, which is a candidate genetic risk factor for diabetes mellitus and obesity. This study investigated the effects of PGC-1 gene Gly482Ser polymorphisms on alterations in glucose and lipid metabolism induced by exercise training. A 12-week intervention study was performed for 119 participants who were more than 65 years of age and completed exercise training at lactate threshold intensity. Total cholesterol and low-density lipoprotein cholesterol were significantly reduced in Gly/Gly but not in Gly/Ser and Ser/Ser participants after exercise. The Gly/Gly genotype of the PGC-1 gene Gly482Ser polymorphism influences the effects of moderate-intensity exercise training on low-density lipoprotein cholesterol and total cholesterol concentrations in older people.     

Objective quantification of trochlear dysplasia: Assessment of the difference in morphology between control and chronic patellofemoral instability patients

Background

Trochlear dysplasia is an important risk factor associated with patellofemoral instability, but it remains difficult to classify with consistency. Currently there is no objective way to quantify the dysplasia. The purpose of this study is to define and quantify objectively the trochlear morphology by volume and length via computed tomography (CT).

Effects of intragastric infusion of inosine monophosphate and <Emphasis Type="SmallCaps">l</Emphasis>-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes

In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and l-glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions.