Chelatable zinc modulates excitability and seizure duration in the amygdala rapid kindling model

Zinc is present in high concentration in many structures of the limbic circuitry, however the role of zinc as a neuromodulator in such synapses is stilt uncertain. In this work, we verified the effects of zinc chelation in an animal model of epileptogenesis induced by amygdala rapid kindling. The basolateral. amygdala was electrically stimulated ten times per day for 2 days. A single stimulus was applied on the third day. Stimulated animals received injections of PBS or the zinc chelator diethildythiocarbamate acid (DEDTC) before each stimulus series. Animals were monitored with video-EEG and were perfused 3 h after the last stimulus for subsequent neo-Timm and Ftuoro-Jade B analysis. Zinc chelation decreased the duration of both behavioral seizures and electrical after-discharges, and also decreased the EEG spikes frequency, without changing the progression of behavioral seizure severity. These results indicate that the zinc ion may have a facilitatory role during kindling progression. (c) 2008 Elsevier B.V. All rights reserved.

Effect of+3.00 diopter and+4.00 diopter additions in multifocal intraocular lenses on defocus profiles, patient satisfaction, and contrast sensitivity

PURPOSE: To evaluate the advantages and disadvantages of the new low-addition (add) (+3.00 diopter [D]) ReSTOR multifocal IOL compared with the preceding ReSTOR model with +4.00 D add. SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Comparative case series. METHODS: Patients with a +3.00 D or +4.00 D add multifocal IOL were examined for uncorrected and distance-corrected visual acuity at distance, intermediate, and near. A defocus profile was assessed, individual reading distance and the distance for lowest intermediate visual acuity were determined. Patient satisfaction was evaluated with a standardized questionnaire. Contrast sensitivity was tested under mesopic and photopic conditions. RESULTS: Uncorrected and distance-corrected intermediate visual acuities were statistically significantly better in the +3.00 D add group (24 eyes) than in the +4.00 D add group (30 eyes); distance and near visual acuities were not different between groups. The defocus profile significantly varied between groups. The +4.00 D add group had a closer reading distance (33.0 cm) than the +3.00 D add group (43.5 cm), a closer point of lowest intermediate visual acuity (65.8 cm versus 86.9 cm) and worse lowest intermediate visual acuity (20/59 +/- 4.5 letters [SD] versus 20/48 +/- 5.5 letters). Thus, patients in the +3.00 D add group reported being more satisfied with intermediate visual acuity. The +3.00 D add group reported more glare but less halos than the +4.00 D add group; contrast sensitivity was not different. CONCLUSION: The lower addition resulted in a narrower defocus profile, a farther reading distance, and better intermediate visual acuity and thus increased patient satisfaction.

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL. (C) 2011 Elsevier Inc. All rights reserved.

Predictors of word-level literacy amongst Grade 3 children in five diverse languages

Groups of Grade 3 children were tested on measures of word-level literacy and undertook tasks that required the ability to associate sounds with letter sequences and that involved visual, auditory and phonological-processing skills. These groups came from different language backgrounds in which the language of instruction was Arabic, Chinese, English, Hungarian or Portuguese. Similar measures were used across the groups, with tests being adapted to be appropriate for the language of the children. Findings indicated that measures of decoding and phonological-processing skills were good predictors of word reading and spelling among Arabic- and English-speaking children, but were less able to predict variability in these same early literacy skills among Chinese- and Hungarian-speaking children, and were better at predicting variability in Portuguese word reading than spelling. Results were discussed with reference to the relative transparency of the script and issues of dyslexia assessment across languages. Overall, the findings argue for the need to take account of features of the orthography used to represent a language when developing assessment procedures for a particular language and that assessment of word-level literacy skills and a phonological perspective of dyslexia may not be universally applicable across all language contexts. Copyright (C) 2008 John Wiley & Sons, Ltd.

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23 +/- 0.1 vs. 1.32 +/- 0.2 ms(2)) and HF (6.6 +/- 0.49 vs. 15.1 +/- 0.61 ms(2)) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3 +/- 2.7 vs. 7.4 +/- 1.01 mmHg(2)) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (- 1.83 +/- 0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23 +/- 0.06 bpm/MmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels. (c) 2008 Elsevier B.V. All rights reserved.

Hemodynamic effects of PEEP in a porcine model of HCl-induced mild acute lung injury

Positive end-expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid. Thirty-two pigs were randomly allocated into four groups (Control-PEEP, Control-SI, ALI-PEEP and ALI-SI). ALI was induced by intratracheal instillation of hydrochloric acid. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cmH(2)O in all groups. Three SIs maneuvers of 30 cmH(2)O for 20 s were applied to the assignable groups between each PEEP level. Transesophageal echocardiography (TEE), global hemodynamics, oxygenation indexes and gastric tonometry were measured 5 min after the maneuvers had been concluded and at each established value of PEEP (5, 10, 15 and 20 cmH(2)O). The cardiac index, ejection fraction and end-diastolic volume of right ventricle were significantly (P < 0.001) decreased with PEEP in both Control and ALI groups. Left ventricle echocardiography showed a significant decrease in end-diastolic volume at 20 cmH(2)O of PEEP (P < 0.001). SIs did not exert any significant hemodynamic effects either early (after 5 min) or late (after 3 h). In a mild ALI model induced by inhalation of hydrochloric acid, significant hemodynamic impairment characterized by cardiac function deterioration occurred during PEEP increment, but SI, probably due to low applied values (30 cmH(2)O), did not exert further negative hemodynamic effects. PEEP should be used cautiously in ALI caused by acid gastric content inhalation.

Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.

Surveillance of Rickettsia sp infection in capybaras (Hydrochoerus hydrochaeris) a potential model of epidemiological alert in endemic areas

Introduction. Capybaras (Hydrochoerus hydrochaeris) are considered amplifying hosts of Rickettsia sp. These rodents are usually parasitized by the tick vector, Amblyomma cajennense, the main vector of rickettsioses in humans and animals in South America. Capybaras can be used as sentinels in detection of circulation of rickettsiae. Objective. Antibodies to rickettsiae of spotted fever group were detected in capybaras in a rural area of Cordoba Province, northern Colombia. Materials and methods. Sera were analyzed from 36 capybaras in a rural area of Monteria (village of San Jeronimo) in Cordoba. For the detection of IgG antibodies, indirect immunofluorescence was performed. The antigens were derived from R. rickettsia strain Taiacu isolated in Brazil. Capybara sera were diluted 1:64 for IFA analysis. Ticks were collected from each capybara (also known as chiguiro) and identified to species. Results. The seroprevalence of spotted fever group Rickettsia was 22% (8 capybaras). Four sera had a titer of 1:64, 3 had a titer of 1:128 and one serum had a titer of 1:512. All ticks removed from the capybaras (n=933) were taxonomically identified as Amblyomma cajennense. Conclusion. Colombia has areas endemic for rickettsioses, as indicated by confirmed annual outbreaks. The current study reports the first evidence of natural rickettsial infection of the spotted fever group in capybaras from Colombia. The findings suggest that capybaras can be used as sentinels for the circulation of rickettsiae and can identify endemic areas for the transmission of rickettsial diseases.

Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma

Aims: There has been emerging interest in the prenatal determinants of respiratory disease. In utero factors have been reported to play a role in airway development, inflammation, and remodeling. Specifically, prenatal exposure to endotoxins might regulate tolerance to allergens later in life. The present study investigated whether prenatal lipopolysaccharide (LPS) administration alters subsequent offspring allergen-induced inflammatory response in adult rats. Main methods: Pregnant Wistar rats were treated with LPS (100 mu g/kg, i.p.) on gestation day 9.5 and their ovariectomized female offspring were sensitized and challenged with OVA later in adulthood. The bronchoalveolar lavage (BAL) fluid, peripheral blood, bone marrow leukocytes and passive cutaneous anaphylaxis were evaluated in these 75-day-old pups. Key findings: OVA sensitized pups of NaCl treated rats showed an increase of leucocytes in BAL after OVA challenge. This increase was attenuated, when mothers were exposed to a single LPS injection early in pregnancy. Thus, LPS prenatal treatment resulted in (1) lower increased total and differential (macrophages, neutrophils, eosinophils and lymphocytes) BAL cellularity count; (2) increased number of total, mononuclear and polymorphonuclear cells in the peripheral blood; and (3) no differences in bone marrow cellularity or passive cutaneous anaphylaxis. Significance: In conclusion, female pups treated prenatally with LPS presented an attenuated response to experimentally-induced asthma. We observed reduced immune cell migration from peripheral blood to the lungs, with no effect on the production of bone marrow cells or antibodies. It was suggested that inflammatory events such as exposure to LPS in early fetal life can attenuate allergic inflammation in the lung, which is a common symptom in asthma. (C) 2011 Elsevier Inc. All rights reserved.

Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model

To histomorphometrically investigate the repair of critical size defects (CSDs) and bone augmentation in cranial walls using block of sintered bovine-derived anorganic bone (sBDAB) graft. Forty guinea-pigs were divided into test (n=20) and CSD control (n=20) groups. In each animal, a full-thickness bone defect with 9.5 mm diameter was made in the frontal bone. The defects were filled with an sBDAB block soaked in blood in the test group and with blood clot in the CSD control group. The skulls were collected at 0 h (n=2) and 30, 90 and 180 days (n=6/group and period) postoperatively. The volume density and total volume of newly formed bone, sBDAB, blood vessels and connective tissue, vertical thickness of removed bone plug, sBDAB block and graft area were evaluated. The vertical thickness of the adapted sBDAB block was 3.8 times higher than that of the removed bone plug and did not show significant difference between periods, filling in average 29.8% of the total graft region. The sBDAB block exhibited complete osseointegration with the borders of the defect at 90 days. At 90 and 180 days, the vertical thickness of the graft was 279% in the average, and the total volume of bone augmentation was, respectively, 78.8% and 148.5% higher compared with the removed bone plug. The defects of the CDS control group showed limited osteogenesis and filling by connective tissue plus tegument. The sBDAB block can be used to promote repair of CSDs and bone augmentation in the craniomaxillofacial region, due to its good osteoconductive and slow resorptive properties. To cite this article:Cestari TM, Granjeiro JM, de Assis GF, Garlet GP, Taga R. Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model.Clin. Oral Impl. Res. 20, 2009; 340-350.doi: 10.1111/j.1600-0501.2008.01659.x.

A new integrable model of strongly correlated electrons with Hubbard-like interaction

A new completely integrable model of strongly correlated electrons is proposed which describes two competitive interactions: one is the correlated one-particle hopping, the other is the Hubbard-like interaction. The integrability follows from the fact that the Hamiltonian is derivable from a one-parameter family of commuting transfer matrices. The Bethe ansatz equations are derived by algebraic Bethe ansatz method.

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

NITRIC OXIDE SYNTHASE INHIBITION ATTENUATES L-DOPA-INDUCED DYSKINESIAS IN A RODENT MODEL OF PARKINSON`S DISEASE

Chronic L-DOPA pharmacotherapy in Parkinson`s disease is often, accompanied by the development of abnormal and excessive movements known as L-DOPA-induced dyskinesia. Rats with 6-hydroxydopamine lesion of dopaminergic neurons chronically treated with L-DOPA develop a rodent analog of this dyskinesia characterized by severe axial, limb, locomotor and orofacial abnormal involuntary movements. While the mechanisms by which these effects occur are not clear, they may involve the nitric oxide system. In the present study we investigate if nitric oxide synthase inhibitors can prevent dyskinesias induced by repeated administration Of L-DOPA in rats with unilateral 6-hydroxydopamine lesion. Chronic L-DOPA (high fixed dose, 100 mg/kg; low escalating dose, 10-30 mg/kg) treatment induced progressive dyskinesia changes. Two nitric oxide synthase inhibitors, 7-nitroindazole (1-30 mg/kg) and NG-nitro-L-arginine (50 mg/kg), given 30 min before L-DOPA, attenuate dyskinesia. 7-Nitroindazolee also improved motor performance of these animals in the rota-rod test. These results suggest the possibility that nitric oxide synthase inhibitors may be useful to treat L-DOPA.-Induced dyskinesia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

The expression of plasminogen activator system in a rat model of periodontal wound healing

Background: The plasminogen activator system has been proposed to play a role in proteolytic degradation of extracellular matrices in tissue remodeling, including wound healing. The aim of this study was to elucidate the presence of components of the plasminogen activator system during different stages of periodontal wound healing. Methods: Periodontal wounds were created around the molars of adult rats and healing was followed for 28 days. Immunohistochemical analyses of the healing tissues and an analysis of the periodontal wound healing fluid by ELISA were carried out for the detection of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and 2 plasminogen activator inhibitors (PAI-1 and PAI-2). Results: During the early stages (days 1 to 3) of periodontal wound healing, PAI-1 and PAI-2 were found to be closely associated with the deposition of a fibrin clot in the gingival sulcus. These components were strongly associated with the infiltrating inflammatory cells around the fibrin clot. During days 3 to 7, u-PA, PAI-1, and PAI-2 were associated with cells (particularly monocytes/macrophages, fibroblasts, and endothelial cells) in the newly formed granulation tissue. During days 7 to 14, a new attachment apparatus was formed during which PAI-1, PAI-2, and u-PA were localized in both periodontal ligament fibroblasts (PDL) and epithelial cells at sites where these cells were attaching to the root surface. In the periodontal wound healing fluid, the concentration for t-PA increased and peaked during the first week. PAI-2 had a similar expression to t-PA, but at a lower level over the entire wound-healing period. Conclusions: These findings indicate that the plasminogen activator system is involved in the entire process of periodontal wound healing, in particular with the formation of fibrin matrix on the root surface and its replacement by granulation tissue, as well as the subsequent formation of the attachment of soft tissue to the root surface during the later stages of wound repair.

Structural effects of lipophilic methotrexate conjugates on model phospholipid biomembranes

Lipophilic conjugates of the antitumor drug methotrexate (MTX) with lipoamino acids (LAAs) have been previously described as a tool to enhance MTX passive entrance into cells, overcoming a form of transport resistance which makes tumour cells insensitive to the antimetabolite. A knowledge of the mechanisms of interaction of such lipophilic derivatives with cell membranes could be useful for planning further lipophilic MTX derivatives with an optimal antitumour activity. To this aim, a calorimetric study was undertaken using a biomembrane model made from synthetic 1,2-dipalmitoyl-glycero-3-phosphocholine (DPPC) multilamellar liposomes. The effects of MTX and conjugates on the phase transition of liposomes were investigated using differential scanning calorimetry. The interaction of pure MTX with the liposomes was limited to the outer part of the phospholipid bilayers, due to the polar nature of the drug. Conversely, its lipophilic conjugates showed a hydrophobic kind of interaction, perturbing the packing order of DPPC bilayers. In particular, a reduction of the enthalpy of transition from the gel to the liquid crystal phase of DPPC membranes was observed. Such an effect was related to the structure and mole fraction of the conjugates in the liposomes. The antitumour activity of MTX conjugates was evaluated against cultures of a CCRF-CEM human leukemic T-cell line and a related MTX resistant sub-line. The in vitro cell growth inhibitory activity was higher for bis(tetradecyl) conjugates than for both the other shorter- and longer-chain derivatives. The biological effectiveness of the various MTX derivatives correlated very well with the thermotropic effects observed on the phase transition of DPPC biomembranes. (C), 2001 Elsevier Science B.V All rights reserved.