Experimental study of non-alcoholic fatty liver disease (NAFLD) on a model of starving chickens: is generalization of steatosis accompanied by fibrosis of the liver tissue?

The objective of this work was to study the mechanism of liver parenchyma development under the influence of restriction of diet. Useful information is presented about the pathologic features associated with diet restriction in a chicken animal model of NAFLD. There were 96 chickens of two genotypes, Ross 308 and Cobb 500, in the experiment. The control group was fed a standard mixture ad libitum (ADL). The first experimental group, under restriction from the age of 2 weeks, was fed 80% ADL. The second experimental group was fed 65% ADL from the age of 2 weeks. There were 16 animals in each group. The experiment lasted 5 weeks. Liver parenchyma samples were obtained at the age of 35 days by the necropsy method and then processed by standard histologic methods. The slices were stained by standard staining: hematoxylin-eosin and by Sirius red kit for collagen type I and reticulin visualization. Hepatocyte diameter and the proportion of interstitial tissue to the parenchyma of the liver were measured objectively. Microvesicular liver steatosis was observed after 35 days of restriction. Hepatocyte diameter was significantly influenced by sex, genotype, and the experimental group. The proportion of interstitial tissue to the liver parenchyma was highly influenced by genotype and group, but there were no interactions. An increase in the steatosis histologic grade is associated with inflammatory changes, with decrease of hepatocyte diameter and with a decreasing proportion of interstitial tissue to the liver parenchyma. The results show that early restriction is not associated with the development of fibrosis of the liver tissue.     

Could statins exert a protective effect on epistaxis of systemic origin?

Epistaxis, that is a relatively frequent occurrence of hemorrhage from the nose, is reported in up to 60% of the population with peak incidences in subjects under the age of ten ("essential" epistaxis, usually linked to an altered vasomotor regulation) and, with even greater entity, over the age of 60. The cause of nosebleeds can generally be divided into two categories, local and systemic factors, although it should be remembered that a significant number of nosebleeds occur with no obvious cause. Actually, according to the common observation the epistaxis prone subject is an elderly with hypertension associated to some degree of vascular alteration. The statins essentially exert a competitive inhibition of 3-hydroxy-3 methyl glutaryl coenzyme A (HMG-CoA) reductase that results in cholesterol synthesis inhibition. In the last years, however, there has been a growing evidence that these drugs exert a number of vascular actions that are independent of lipid lowering and result in a vasoprotective effect. Due to their favourable influence on the vascular wall, and the consequent possible modulatory effect on blood pressure, a possible utility of statins in preventing many cases of nosebleed is hypothesized, to our knowledge for the first time.     

Niacin for treatment of nonalcoholic fatty liver disease (NAFLD): novel use for an old drug?

Niacin has been widely used clinically for over half a century for dyslipidemia. Recent new evidence indicates that niacin may be useful in the treatment of nonalcoholic fatty liver disease (NAFLD) and its sequential complications including nonalcoholic steatohepatitis and fibrosis. There is an urgent unmet need for a cost-effective solution for this public health problem affecting nearly one in three adults. Niacin inhibits and reverses hepatic steatosis and inflammation in animals and liver cell cultures. It prevents liver fibrosis in animals and decreases collagen in cultured human stellate cells. Its mechanism of action is by oxidative stress reduction and inhibition of diacylglycerol acyltransferase 2 and other possible targets. An uncontrolled clinical trial in 39 hypertriglyceridemic patients with steatosis showed reduction of liver fat by 47% and reductions in liver enzymes and C-reactive protein from the baseline when treated with niacin extended-release for 6 months These hypothesis-generating data indicate a novel repurposed use of niacin for NAFLD. Niacin beneficially affects NAFLD at 3 major stages directly and, by affecting steatosis, it indirectly decreases the cascade effect on inflammation and fibrosis. It offers the advantage potentially of combination with other drugs in development for evolving synergistically more intense and broader efficacy. In select patients, it may benefit frequently associated atherogenic dyslipidemia. A randomized placebo-controlled double-blind parallel trial (with niacin alone or in combination with another drug in development) to assess the safety and efficacy of niacin on steatosis, inflammation, and fibrosis in patients with nonalcoholic steatohepatitis/NAFLD is warranted.     

High-dose vitamin C: Does it exacerbate the effect of psychosocial stress on liver? Biochemical and histological study

AimChronic stress has been implicated as a contributing factor in liver injury. However, other factors that can contribute to the severity of stress effect in liver injury have not been well characterized. In this study, the combined effect of chronic psychosocial stress and variable dosing levels of vitamin C on liver injury, have been studied.MethodsStress was chronically induced using intruder method. Vitamin C was administered by oral gavage. Both biochemical and histopathological measures were undertaken.ResultsThe results showed that low (50 mg/kg/day) and moderate (150 mg/kg/day) doses of vitamin C alone or in combination with chronic stress had no effect on liver. However, combination of high dose of vitamin C (500 mg/kg/day) and chronic stress induced various histopathological liver lesions in most of animals in the group that was stressed and supplemented with high dose vitamin C.ConclusionResults of this study show a dose-dependent effect for vitamin C in exacerbating stress contribution to liver injury.     

The kinematics of eating with a spoon: bringing the food to the mouth, or the mouth to the food?

In traditional reach-to-point and reach-to-grasp studies an increase in accuracy demands typically results in a lengthening of the deceleration phase of the reach and a freezing of the more distal joints. The purpose of the present experiment was to examine whether similar changes in the reach kinematics could be observed during a tool-using skill, as would be predicted from an effector independence perspective. Five subjects were required to eat two substances (i.e. a solid and a liquid one) that imposed different requirements on the accuracy of the movement. The subjects transported the substances from the plate into the mouth. A prolonged movement duration was found for the liquid as compared to the solid substance. However, rather than being exclusively due to a lengthening of deceleration phase, the larger movement duration resulted from a slowing down of the whole movement. Therefore, the skewed velocity profiles found in the traditional reach-to-grasp studies may well be the result of the accuracy demands only impinging on the final part of the movement trajectory, rather than being a consequence of central, effector-independent, organising principles. In addition, under increased accuracy demands subjects were shown to redistribute their movement in a proximodistal direction. Movements of the distal components were reduced to a minimum and the involvement of trunk and head movement increased. Received: 18 May 1998 / Accepted: 13 May 1999     

An update on bronchopulmonary dysplasia: is there a relationship to the development of childhood asthma?

There appears to be some interesting commonalities between asthma and BPD. The prevalence of both conditions is on the rise, both conditions tend to cluster in families, and they share wheezing phenotypes, i.e., mild-moderate reversible airway obstruction and a similar degree of response to pharmacological provocation. Furthermore, significant overlap exists with regard to the presence of elevated concentrations of airway inflammatory mediators concurrent with reduced levels of anti-inflammatory activity, in serum and BAL fluid, as well as histological evidence for airway 'remodelling'. Both BPD and asthma are characterized by increased smooth muscle contraction, and in asthma, the smooth muscle may be involved in the primary development of the asthmatic phenotype. Since wheezing is a common finding among children with BPD, an interesting question is whether BPD is a phenotypic variant of asthma?     

Has the Picture Archiving and Communication System (PACS) Become a Commodity?

The Picture Archiving and Communication System (PACS) market has been transformed by disruptive innovations from the information technology industry. The cost of storage alone has dropped by a factor of 100 within the past 10 years. Improvements in display, processing, and networking have likewise enabled PACS to be a capable replacement for film. The maturity of PACS has permeated the US healthcare industry from large academic hospitals to small outpatient imaging centers. Can PACS continue to be a platform for innovation or has it become a commodity?Key words: PACS, cost analysis, computer hardware     

Facial hemangioma and malformation of the cortical development: a broadening of the PHACE spectrum or a new entity?

Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.     

The effect of social roles on mental health: a matter of quantity or quality?

The effect of social roles (partner, parent, worker) on mental health may depend on the total number or the quality of the individual occupied social roles. With longitudinal data from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), the effect of the number and quality of occupied social roles on mental health over three years was examined among 2471 men and women aged 25-55 years without mental disorders at baseline. Mental health was assessed using 3-year change in the SF-36 mental health scale as well as using the 3-year incidence of anxiety and depressive disorders defined by DSM-III criteria. The quality of social roles was assessed by the GQSB (Groningen Questionnaire Social Behavior). The number of social roles had no significant effect on the risk of developing depressive and anxiety disorders, but particularly the partner-role had a significant positive effect on mental health (beta of mental health=1.19, p=0.01; HR of incident disorders=0.75, 95% CI:0.51-1.00, p=0.05). A good quality of each of the three social roles was associated with higher levels of mental health and lower risks of incident disorders over 3 years. More than the number of social roles, knowledge about social role quality might provide opportunities for prevention of depressive and anxiety disorders.     

Early development of a somatosensory fovea: a head start in the cortical space race?

Star-nosed moles have 11 mechanosensory appendages surrounding each nostril, and primary afferents from a single appendage-the tactile fovea-are greatly over-represented in somatosensory cortex. It was found that the foveal appendage led development in the periphery, had the greatest innervated surface area in embryos, and developed mature nerve terminals and epidermal sensory organs first; also, in developing cortex, markers for metabolic activity (cytochrome oxidase) appeared first in the fovea representation. This developmental sequence may provide the fovea with an advantage in a competition for cortical space, and account for the much larger areas of cortex devoted to foveal afferents.     

Novel vaccines protecting against the development of allergic disorders: a double-edged sword?

The severity and incidence of allergic disorders is steadily increasing despite the widespread use of steroids and other drugs. Recent results obtained in animals suggest that it may be possible to develop novel anti-allergy vaccines for human use, thereby stopping this alarming worldwide increase in allergic diseases. The most promising approaches are the induction of allergen-specific T helper 1 or allergen-specific T regulatory responses. However, both approaches potentially harbour negative side effects that need to be ruled out before vaccinating young children -- the best candidates for the primary prevention of allergic disorders.     

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.     

Reduced influence of the ipsilateral ear on spatial tuning of auditory neurons in the albino superior colliculus: a knock-on effect of anomalies of the acoustic chiasm?

Auditory brainstem abnormalities affecting decussation patterns and nuclei involved in the acoustic chiasm exist in a variety of albino mammals, suggesting that binaural processes underlying spatial hearing may be disrupted in these mutants. To evaluate this we have compared the contribution of the two ears in albino and normally pigmented guinea pigs to the spatial tuning of auditory neurons in the deep layers of the superior colliculus (SC). Broadband noise stimuli at threshold and at suprathreshold intensities were presented from different azimuthal loudspeaker locations under free-field anechoic conditions, and auditory receptive fields were plotted before, during and after occluding the ipsilateral ear. We show that the deep layers of the albino SC contain a map of contralateral auditory azimuth along its anteroposterior axis, which is aligned with the visual map in the superficial layers above, just as in normal animals. We also show that threshold spatial responses are elicited only via the contralateral ear and at similar stimulus intensities (mean~30 dB SPL) in the two pigmentation phenotypes. The mechanisms that maintain spatial tuning at sound intensities of 10–40 dB above threshold, however, differ markedly in these animals. Plugging the ipsilateral ear in normal guinea pigs caused significant expansions of their auditory receptive fields and loss of directional tuning, but in the albinos occlusion had little effect on these spatial properties. The results suggest that while spatial selectivity for relatively loud sounds among SC neurons is normally maintained via the binaural combination of contralateral excitatory drive and ipsilateral inhibition, it is achieved in albinos almost exclusively by monaural input from the contralateral ear. This finding is consistent with an excessive contralateral ear dominance of higher levels of the albino auditory system caused by anomalies of their acoustic chiasm, analogous to the monocular dominance of the visual system that results from excessive axon crossing at the optic chiasm in these animals.     

The Genetic Basis of Emotional Behavior: Has the Time Come for a Drosophila Model?

Abstract: The aim of this review was to summarize the studies potentially relevant to whether Drosophila can be used as a genetically tractable model to study the genetic and molecular basis of emotional behavior. Can these studies contribute to a better understanding of neural substrates of abnormal emotional states and specific neuropsychiatric illnesses, such as depression and anxiety?     

The effects of inverting prisms on the horizontal–vertical illusion: a systematic effect of downward gaze

The purpose of this work is to compare the relative contributions from the extraocular and sensory systems on the magnitude of the horizontal–vertical illusion (HVI). The visual HVI refers to the general tendency to overestimate vertical extensions of small-scale lines on a picture plane relative to the horizontal by 4–16% depending on the method of measurement. The HVI line stimuli consisted of luminous vertical and horizontal lines forming “L-profiles” located in the frontoparallel plane at a 45 cm viewing distance, collinearly with a binocular gaze. The home position of gaze was aligned to the center of the screen with the ear–eye angle concordant with the environmental horizontal. Illusion strength was quantified when subjects fixated the HVI line stimuli in four quadrants of the visual field. The HVI was also viewed through prism lenses that inverted the retinal images by 180°, thereby dissociating the sensory “up-down” direction from the oculomotor up-down frame of reference. The results revealed a systematically lower magnitude of the HVI in the bottom visual field regardless of whether subjects fixated the HVI with the distorting prisms or without. Taken together, these results suggest that the HVI is sensitive to small-angle gaze shifts. In agreement with several recent findings, these results are interpreted as implying that the brain imposes an enhanced analytic structure on the ascending sensory information during downward gaze. Hans O. Richter and Jaanus Raudsepp contributed equally to this work.     

Impaired function of dendritic cells translocating the liver sinusoids: A veto effect contributing to intrahepatic tolerance?

Due to its unique architecture and conditions of blood flow, the liver is acknowledged as an immunologically unusual organ associated with primary activation of naïve T cells and the induction of tolerance. Several mechanisms have been proposed to be involved in this process. Most suggest that naïve T cells activated in situ in the hepatic sinusoids are deleted or silenced following activation by liver cells acting as antigen presenting cells. Hepatocytes, liver sinusoidal endothelial cells and bone marrow‐derived cells (including Kupffer cells and DC) have been shown to support primary activation in situ and play some role in tolerance induction. Although most liver DC have been described to be immature and located in sites inaccessible to naïve T cells, some blood‐borne DC have been shown to translocate via the sinusoids where naïve T cells recirculate. Thus, the presence of mature DC with potential immunogenicity in the sinusoids might give contradictory signals to the naïve T cells activated within this organ. In this issue of the European Journal of Immunology, liver sinusoidal endothelial cells are shown to impair the DC ability to induce the proliferation of naïve T cells in vitro via an unknown mechanism. Although these findings need to be confirmed in a physiological setting, regulation of the function of DC translocating the sinusoids might represent a new mechanism contributing to T cell tolerance in the liver. See accompanying article: http://dx.doi.org/10.1002/eji.200738060