Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat

To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n?=?10), 2 [triple partial portal vein ligation (TPVL); n?=?9], 3 (TAA; n?=?11), and 4 (TPVL plus TAA; n?=?9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL?+?TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations.     

The decrease in serum IL-18 levels after bariatric surgery in morbidly obese women is a time-dependent event

Background We have evaluated the impact of the reproductive status of morbidly obese women, and of the time elapsed since surgery, on the response of the proinflammatory serum cardiovascular risk marker interleukin-18 (IL-18) to the sustained and marked weight loss achieved after bariatric surgery. Methods Serum IL-18 levels were measured in 33 morbidly obese women before bariatric surgery and after losing at least 15% of the initial weight, irrespective of the time needed to achieve this goal (5 to 33 months). Results Patients lost 30.7 ± 7.8% of the initial weight, with a concomitant reduction of serum IL-18 concentrations (P < 0.001). A stepwise multiple regression analysis showed that the percentual decrease in serum IL-18 levels was determined by the interaction between the time elapsed since surgery and the percentual reduction of waist circumference (R² = 0.333, F = 15.500, β = 0.577, P < 0.001), but not by the individual effects of the time elapsed since surgery, percentual body weight loss, percentual reduction of waist circumference, menopausal status or type of surgical procedure, or by the interaction between the time elapsed since surgery with the percentual body weight loss or with menopausal status. Conclusion Serum IL-18 levels decrease after bariatric surgery in a time-dependent manner, in relation to the reduction in waist circumference. The fact that the amelioration of the obesity-associated inflammatory process requires time and not only weight loss, might contribute to explain early non-surgical cardiovascular complications of bariatric surgery.     

Comparison and validation of scoring systems in a cohort of patients treated for perforated peptic ulcer

Background and aims The aim of this study is to evaluate the predictive accuracy of different scoring systems on surgery for perforated peptic ulcer referred to an academic department of general surgery in a tertiary reference center. Patients and methods Seventy-five consecutive patients (Male/female ratio = 64:11; mean age, 44 years; range, 16–85) with perforated peptic ulcer disease were investigated. Disease severity scores and mortality predictions were calculated using the collected data during admission. Discrimination and calibration characteristics of each system, namely, the acute physiology and chronic health evaluation II and III, the simplified acute physiology score II, and the mortality probability models (MPM) II, were determined by using the area under receiver operating characteristics curve and the Hosmer–Lemeshow goodness-of-fit test, respectively. Results Among the 75 patients included, there were eight (10.6%) mortalities. All systems had a reliable power of discrimination and calibration. Among the systems tested, MPM II was the best performing as far as discrimination and calibration characteristics were considered. The parameters of MPM II system that were related to systemic perfusion of the patient were significantly positive in patients who died compared to those who survived. Conclusions MPM II that predicted mortality at admission is better than the other systems in predicting mortality. Results also indicate the importance of maintenance of systemic perfusion of the patient at the early phases of peptic ulcer perforation.     

Basal forebrain cholinergic system of the anuran amphibian Rana perezi: evidence for a shared organization pattern with amniotes

The organization of the basal forebrain cholinergic system (BFCS) in the frog was studied by means of choline acetyltransferase (ChAT) immunohistochemistry. The BFCS was observed as a conspicuous cholinergic cell population extending through the diagonal band, medial septal nucleus, bed nucleus of the stria terminalis, and pallidal regions. Abundant fiber labeling was also found around the labeled cell bodies. The combination of retrograde tract tracing with dextran amines and ChAT immunohistochemistry revealed intraseptal and intra-BFCS cholinergic connections. In addition, an extratelencephalic cholinergic input from the laterodorsal tegemental nucleus was demonstrated. The possible influence of monoaminergic inputs on the BFCS neurons was examined by means of tyrosine hydroxylase and serotonin immunohistochemistry combined with ChAT immunolabeling. Our results showed that catecholaminergic fibers overlapped the BFCS, with the exception of the medial septal nucleus. Serotoninergic innervation was widespread, but less abundant in the caudal extent of the BFCS. Taken together, our results on the localization of the cholinergic neurons in the basal forebrain and their relationship with cholinergic, catecholaminergic, and serotoninergic afferents have shown numerous common features with amniotes. In particular, anurans and mammals (for which most data is available) share a strikingly comparable organization pattern of the BFCS.     

High prevalence of self-reported depressive mood during the winter season among Swedish senior high school students

OBJECTIVE: There are few studies regarding the prevalence of seasonal variation in mood among children and adolescents. The main objective of this study was to estimate the prevalence of self-reported depressive mood during the winter season among Swedish adolescents and to investigate gender differences. Another aim was to analyze the factor structure and internal consistency of the Kiddie SPAQ (K-SPAQ), a pediatric version of the Seasonal Pattern Questionnaire (SPAQ). METHOD: All students 17 to 18 years old, registered in the second year of senior high school in Falun, a district in central Sweden, were screened with the K-SPAQ in January 2003 (response rate 87.3%, n = 756). RESULTS: The prevalence of self-reported depressive mood during the winter season was estimated at 20.1% (n = 151/751) and was higher among girls (25.5%) than boys (13.8%). Approximately 8% reported more severe depressive symptoms. Depressive mood during the summer was rare (0.1%, n = 1/751). Factor analysis of the General Seasonal Score items in the K-SPAQ revealed a two-factor structure. A Cronbach's alpha of 0.87 demonstrated a good internal consistency. CONCLUSIONS: Depressive symptoms during autumn and winter were common among Swedish senior high school students, especially among girls. This is probably an underdiagnosed condition among adolescents that ought to receive more attention from the health and school authorities.     

Pronounced individual variation in the response to the stimulatory action of exercise on immature hippocampal neurons

In the adult hippocampus, neurogenesis is influenced both by external stimuli, such as physical exercise, and by intrinsic conditions like age and disease. However, the way in which many of these external and internal cues interact in this process remains poorly understood. We have used a new, more precise, stereological cell counting method that involves confocal microscopy to analyze the effects of exercise on adult neurogenesis in the mouse. We found that treadmill exercise increases the number of differentiating neurons (doublecortin/calretinin cells) in the granule cell layer of the mouse hippocampus in a manner that is directly related to the size of the mature granule cell population. More immature neurons were found after exercise in animals that had a larger dentate gyrus (DG), while no changes were observed in those with a smaller DG. This differential response to physical exercise suggests that the pre-existing neuronal population regulates the neurogenic response in the DG to external stimuli. These data raise the possibility of anticipating an individuals' response to therapeutic interventions (like exercise) aimed at augmenting dentate neurogenesis and alleviating or preventing cognitive decline.     

The generalized quadratic knapsack problem. A neuronal network approach.

The solution of an optimization problem through the continuous Hopfield network (CHN) is based on some energy or Lyapunov function, which decreases as the system evolves until a local minimum value is attained. A new energy function is proposed in this paper so that any 0-1 linear constrains programming with quadratic objective function can be solved. This problem, denoted as the generalized quadratic knapsack problem (GQKP), includes as particular cases well-known problems such as the traveling salesman problem (TSP) and the quadratic assignment problem (QAP). This new energy function generalizes those proposed by other authors. Through this energy function, any GQKP can be solved with an appropriate parameter setting procedure, which is detailed in this paper. As a particular case, and in order to test this generalized energy function, some computational experiments solving the traveling salesman problem are also included.     

Localization of metabotropic GABA receptor subunits GABAB1 and GABAB2 relative to synaptic sites in the rat developing cerebellum

The highest densities of the two metabotropic GABA subunits, GABAB1 and GABAB2, have been reported as occurring around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. In order to determine how this distribution is achieved during development, we investigated the expression pattern and the cellular and subcellular localization of the GABAB1 and GABAB2 subunits in the rat cerebellum during postnatal development. At the light microscopic level, immunoreactivity for the GABAB1 and GABAB2 subunits was very prominent in the developing molecular layer, especially in Purkinje cells. Using double immunofluorescence, we demonstrated that GABAB1 was transiently expressed in glial cells. At the electron microscopic level, immunoreactivity for GABAB receptors was always detected both pre- and postsynaptically. Presynaptically, GABAB1 and GABAB2 were localized in the extrasynaptic membrane of parallel fibres at all ages, and only rarely in GABAergic axons. Postsynaptically, GABAB receptors were localized to the extrasynaptic and perisynaptic plasma membrane of Purkinje cell dendrites and spines throughout development. Quantitative analysis and three-dimensional reconstructions further revealed a progressive developmental movement of the GABAB1 subunit on the surface of Purkinje cells from dendritic shafts to its final destination, the dendritic spines. Together, these results indicate that GABAB receptors undergo dynamic regulation during cerebellar development in association with the establishment and maturation of glutamatergic synapses to Purkinje cells.     

Relationship between the perifornical hypothalamic area and oral pontine reticular nucleus in the rat. Possible implication of the hypocretinergic projection in the control of rapid eye movement sleep

The perifornical (PeF) area in the posterior lateral hypothalamus has been implicated in several physiological functions including the regulation of sleep–wakefulness. Some PeF neurons, which contain hypocretin, have been suggested to play an important role in sleep–wake regulation. The aim of the present study was to examine the effect of the PeF area and hypocretin on the electrophysiological activity of neurons of the oral pontine reticular nucleus (PnO), which is an important structure in the generation and maintenance of rapid eye movement sleep. PnO neurons were recorded in urethane-anesthetized rats. Extracellular recordings were performed by means of tungsten microelectrodes or barrel micropipettes. Electrical stimulation of the ipsilateral PeF area elicited orthodromic responses in both type I (49%) and type II (58%) electrophysiologically characterized PnO neurons, with a mean latency of 13.0 ± 2 and 8.3 ± 5 ms, respectively. In six cases, antidromic spikes were evoked in type I PnO neurons with a mean latency of 3.2 ± 0.4 ms, indicating the existence of PnO neurons that projected to the PeF area. Anatomical studies showed retrogradely labeled neurons in the PeF area from the PnO. Some of these neurons projecting to the PnO contained hypocretin (17.8%). Iontophoretic application of hypocretin-1 through a barrel micropipette in the PnO induced an inhibition, which was blocked by a previous iontophoretic application of bicuculline, indicating that the inhibitory action of hypocretin-1 may be due to activation of GABA_A receptors. These data suggest that the PeF area may control the generation of rapid eye movement sleep through a hypocretinergic projection by inhibiting the activity of PnO neurons.