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A Carta

Publications and source records attributed to A Carta.

At least 19 recordsLinked to original sources

Chemistry, biological properties and SAR analysis of quinoxalinones.

Quinoxaline derivatives have received much attention in recent years owing to their both biological properties and pharmaceutical applications. In this review we focus the attention on quinoxalin-2(3)-ones and quinoxalin-2,3-diones. These derivatives are particularly interesting since some of them showed antimicrobial (against several bacteria, viruses, fungi, etc), or anticancer activities. Furthermore, others are reported to be potent no-NMDA glutamate receptor antagonists, endowed with anxiolytic, deconditioning, analgesic, antispastic, antiallergic, antithrombotic activities. In this article we also report SAR studies and the most important methods of synthesis of the quinoxalin-2(3)-(di)ones.

Animals↗

Feasibility of a linear scoring method of udder morphology for the selection scheme of Sardinian sheep.

Breeders are increasingly interested in improving the machine milkability of Sardinian dairy sheep by selection for udder morphology. Nine-point linear scales were developed to appraise teat placement, degree of suspension of the udder, udder depth, and degree of separation of the 2 halves. Repeatabilities within and across lactation were estimated on an experimental flock. Ewes were scored at least 3 times a year from 1999 to 2003. Within-lactation repeatabilities were greater than 0.70 for all linear traits, whereas across-lactation repeatabilities ranged from 0.59 to 0.66. The first linear combination of basic traits, obtained by principal component analysis, was highly correlated with teat placement, degree of suspension of the udder, and udder depth and showed an across-lactation repeatability of 0.76. These results indicate that an accurate evaluation of animals is possible by a single, early lifetime score. Genetic parameters of linear udder traits were estimated using a REML method applied to a sire model. Data were selected from 76,984 scores of Sardinian yearling ewes collected by 31 classifiers from 1999 to 2004. Two models were compared, one fitting the contemporary group effect as fixed and the other as random. Heritabilities of udder traits ranged from 0.19 to 0.31. The model with the random contemporary group effect produced slightly higher heritabilities and higher correlations between the sires' estimated breeding values and the daughters' average scores. As a whole, the genetic correlations between udder traits were favorable, indicating that selection for one trait will produce a positive evolution of the overall udder conformation. In particular, the degree of suspension of the udder was highly correlated with udder depth (0.82). Genetic correlations with milk yield were unfavorable but generally low, with the exception of udder depth (-0.48). Genetic trends were estimated using an animal model. Only udder depth showed a negative constant genetic trend. Overall results indicated that genetic improvement of the udder morphology of Sardinian ewes is feasible, with major emphasis on teat placement and degree of udder suspension, traits showing the highest heritabilities and low unfavorable genetic correlations with milk yield.

Animals↗

Human extraocular muscles in mitochondrial diseases: comparing chronic progressive external ophthalmoplegia with Leber's hereditary optic neuropathy.

AIMS: To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber's hereditary optic neuropathy (LHON). METHODS: Muscle samples of the medial rectus obtained from surgery in a sporadic case of CPEO associated with deleted mitochondrial DNA, and post mortem in a case of 3460/ND1 LHON were processed for electron microscopy (EM). The medial rectus from an autoptic time to fixation matched control was used to exclude postmortem artefacts. RESULTS: The CPEO specimen revealed focal areas of disruption and abnormalities of mitochondria in some muscle fibres, creating a "mosaic-like" pattern. In the LHON specimen a diffuse increase in both number and size of mitochondria (mean diameter 0.85 mum v 0.65 mum of control, p<0.0001) with swollen appearance and disorganised cristae filled all spaces of sarcoplasmic reticulum. In some areas the excessive number of mitochondria slightly distorted myofibrils. CONCLUSION: EM investigation of extraocular muscles in CPEO and LHON reveals marked differences. A "mosaic-like" pattern caused by a selective damage of muscle fibres was evident in CPEO, whereas a diffuse increase in mitochondria with preservation of myofibrils characterised the LHON case. These ultrastructural changes may relate to the different expression of the two diseases, resulting in ophthalmoplegia in CPEO and normal eye movements in LHON.

Aged↗

Quinoxaline 1,4-dioxide: a versatile scaffold endowed with manifold activities.

Since 1940s, Quinoxaline 1,4-dioxides (QdNO's) are known as potent antibacterial agents, and subtherapeutic levels have been used to promote growth and improve efficiency of feed conversion in animal feed. They have also shown a selective cytotoxicity against hypoxic cells present in solid tumours. Furthermore, recent studies have put in evidence that QdNO's are endowed with antitubercular, antiprotozoal and anticandida activities. On the other hand, several authors have reported about photoallergic and mutagenic effects of some derivatives. QdNO's may also cause the development of antibiotic-resistant bacteria and influence the horizontal transfer of virulence genes between bacteria. In this review article we report the biological properties, the mode of action and Structure Activity Relationship (SAR) studies of the QdNO derivatives. Furthermore, some cytogenetic and genotoxic effects, classical and more recent method of synthesis, the quinoxaline 1,4-dioxides, and some of their most important reactions, were also reported.

Animals↗

Determination of phenol and o-cresol by GC/MS in a fatal poisoning case.

A fatality due to the ingestion of solution containing phenol and o-cresol is described. The pathological findings were typical of acute substantial poisoning. Blood, urine and stomach content were obtained during post mortem examinations. Phenol and o-cresol were identified using GC/MS. The extractions from autopsy materials were obtained as follows: by gel permeation with cyclohexane/dichloromethane from stomach content, by solid phase extraction (SPE) from urine and by deproteinization with acetonitrile from blood. The phenol and o-cresol concentrations in the samples were found, respectively, as follows: 115.0 and 5.0 microg/g in the stomach contents, 58.3 and 1.9 microg/ml in the blood, 3.3 and 20.5 microg/ml in the urine. Distributions of phenol in fatal poisonings have been reported, but, usually, colorimetry was used as the analytical method and it cannot exclude the interference of other phenolic compounds.

Adult↗

Distribution of vascular amyloid in scrapie-affected sheep with different genotypes.

Vascular amyloidosis in the brain is a pathological feature of ovine scrapie. Its occurrence varies between sheep, but whether this variation reflects differences in the host or the infecting scrapie strain (or both) is not clear. To investigate whether amyloidosis, like vacuolation and PrPsc distribution, is associated with genotype, the brains from 131 sheep representing a range of genotypes commonly associated with scrapie were examined histologically and immunohistochemically. Vascular amyloidosis was absent in 66 sheep, 59 of which were of the ARQ/ARQ genotype and seven the ARQ/AHQ genotype. In contrast, it was found in four of 39 ARQ/VRQ sheep (10.2%) and in 10 of 26 VRQ/VRQ sheep (38.4%). The distribution of amyloid was highly variable, but the most severely affected areas were the lateral geniculate nuclei (five cases) and the ventral thalamic nuclei (four cases). No amyloidosis was found in the medulla or in the basal nuclei. From this preliminary study it was concluded that amyloidosis is relatively rare in sheep with scrapie. Moreover, its occurrence appeared to depend on the presence of at least one valine at codon 136.

Amyloid↗

[Recent findings on the genetics of gastro-intestinal nematode resistance in ruminants].

The control of helminthiases in ruminants raised in open pasture has been mainly undertaken by using prophylactic measures in the environment, but these are often inadequate due to incorrect application. With the appearance of anthelmintics, the strategy for controlling these parasitoses, passed to pharmacological treatments which became effective in reducing their impact. However, the frequent and incorrect utilisation of these molecules resulted in resistance to anthelmintics and the presence of chemical residues in animal products for human consumption. Anthelmintic resistance is widespread throughout the world, heterogeneous and probably underestimated. This has encouraged the introduction of homeopathic agents and products derived from plants whose effectiveness has not been scientifically assessed. It is well known that it is possible to detect differences in resistance to the most important parasites between breeds. In Europe, it has been reported that some ovine autochthonous breeds, Scottish Blackface and Lacaune, showed higher resistance. The implementation of breeding strategies aimed at obtaining animals with naturally low susceptibility to nematode infestations could therefore play an increasingly important role. Standard animal breeding techniques have been largely successful in improving the performance of domestic animals in the last century. Standard quantitative selection requires field data on: i) individual phenotype performance; ii) expected covariance among animals due to blood relationship between them. The whole process of predicting the breeding value of animals in order to select subsequently the genetically superior parents of the next generation is entirely based on sophisticated computations (BLUP-animal model). In sheep, the main objective is always selecting for milk yield and sometimes, in addition, milk composition. However, due to the evolution of the EU agricultural policy and consumer demand in terms of healthy and organic food, more attention is now being given to traits related to health (resistance to EST, mastitis or parasitic diseases). Some studies conducted in New Zealand and Australia showed that nematode resistance is genetically controlled with high heritabilities and quite low genetic correlations with production traits. In this sense, some studies showed that it is possible to decrease the number of parasites in the framework of a traditional breeding programme. However, in most situations, this trait is not extensively recorded due to the high cost of individual recording. Therefore, it would be useful to implement breeding strategies based on the knowledge of the genes involved in this trait expression. Traditionally, two approaches are available to locate a gene: i) genome scan; ii) candidate gene approach. The candidate gene approach attempts to link general resistance to some particular genes. To date, genetic resistance against parasites is considered to be linked with the MHC and IgE genes. Furthermore, several gene detection studies based on the genome scan approach for this trait are currently being carried out on both crossed experimental populations (fat x lean Blackface lines and Sarda x Lacaune) and pure breeds (Churra). The preliminary results seem promising as to the use of marker assisted or genotype assisted selection for this trait, which is difficult and expensive to measure on a population scale.

Animals↗

Visual prognosis after indirect traumatic optic neuropathy.

OBJECTIVE: To investigate a possible correlation between final visual acuity and the presence at baseline of various systemic and local (orbital/ocular) signs in patients affected by indirect traumatic optic neuropathy. METHODS: 35 cases of traumatic optic neuropathy were examined retrospectively and 13 variables were tested. Univariate analysis with "no recovery of visual acuity" as the primary outcome was performed. Relative risk (RR) and 95% confidence intervals (CI) were calculated. Fisher's exact test was used for two variables to test differences between proportions. RESULTS: Four variables showed a significantly increased risk for no recovery of visual acuity: presence of blood within the posterior ethmoidal cells (RR = 2.25, 95% CI 1.25 to 4.04); age over 40 years (RR = 1.79, 1.07 to 2.99); loss of consciousness associated with traumatic optic neuropathy (RR = 2.21, 1.17 to 4.16); and absence of recovery after 48 hours of steroid treatment (p < 0.01, Fisher's exact test). Recovery documented at the first follow up visit after treatment was significantly associated with recovery at the last follow up visit (p < 0.01, Fisher's exact test). CONCLUSIONS: These four negative prognostic signs in patients affected by traumatic optic neuropathy may be useful in predicting the visual outcome in patients developing visual loss after head trauma and in deciding on the need for surgical treatment.

Adult↗

Primary liver cancer and occupation in men: a case-control study in a high-incidence area in Northern Italy.

The objective of our study was to evaluate the association between occupation and risk of liver cancer. A hospital-based case-control study was carried out during 1997-1999 in the Province of Brescia, a highly industrialized area in Northern Italy with a high incidence of this neoplasm. The cases were 144 male patients with incident liver cancer (96% hepatocellular carcinoma). Controls were 283 male patients, matched to cases on age (+/-5 years), period and hospital of admission. Information on lifetime occupational history and alcohol consumption was obtained via interview. Specific occupational exposures to pesticides, solvents and other suspected hepatocarcinogens were evaluated. A blood sample was collected to detect hepatitis B and C infections. Odds ratios (OR) of occupational exposure and 95% confidence intervals (CI), adjusted for age, residence, education, heavy alcohol intake, hepatitis B surface antigen and hepatitis C virus antibodies positivity were computed. A statistically significant increased OR was observed for employment in repair of motor vehicles (OR 3.7; 95% CI 1.1-12.3; 9 exposed cases, 10 exposed controls). Increased ORs, although not statistically significant, were found for field-crop farm workers, food and beverage processors, blacksmiths and machine-tool operators, electrical fitters, clerical workers, manufacture of industrial machinery and personal and household services. A slightly increased OR was noted in workers exposed to toluene and xylene (OR 1.4; 95% CI 0.7-3.0, 23 cases, 36 controls); the OR was 2.8 (95% CI 1.0-7.6, 11 cases, 12 controls) for 20 or more years of exposure and 2.0 (95% CI 0.9-4.1, 21 cases, 28 controls) for 30 or more years of time since first exposure. The increase in OR seemed to be independent from that of alcohol or viral infections. Our study showed that the role of occupational exposures in liver carcinogenesis is limited. However, prolonged exposure to organic solvents such as toluene and xylene may represent a risk factor for liver cancer.

Adult↗

Peripheral oculomotor palsy affects orienting of visuospatial attention.

Patients affected by VI cranial nerve palsy were required to orient their attention in monocular vision and to detect a stimulus appearing either in attended or in unattended locations. Results showed that while during non-paretic eye vision stimulus detection in the attended location was faster than that in the unattended one, during paretic eye vision no difference in detection speed was present. However, in this latter condition, detection speed in both attended and un attended locations were as fast as that measured during non-paretic eye vision in attended location. Demonstration that peripheral oculomotor impairment influences monocular covert orienting of visuospatial attention strongly support the idea that visuospatial attention and oculomotor mechanisms share similar cortical networks.

Abducens Nerve Diseases↗

Transcriptional up-regulation of the protooncogenes c-fos and c-jun following vitreous removal and short-term in vitro culture of bovine lenses.

Chemical (mainly oxidative) and mechanical (anterior capsule injury) stresses have been reported to up-regulate the expression of the protooncogenes c-fos and c-jun in the lens. Another potentially stressful, yet largely unexplored condition, inherent to all experiments requiring the in vitro culturing of isolated lenses, is vitreous removal. Based on the results of an extensive RNA gel blot analysis conducted on epithelial/capsule preparations isolated from calf lenses dissected and cultured under different conditions, we show, here, that lens isolation and short-term culture (1-2.5 hr, without any significant GSH depletion) result in a strong and time-dependent up-regulation of the c-jun and c-fos mRNAs. This response, which relies on transcriptional protooncogene activation and is more intense for c-fos than for c-jun, is in part prevented by the preservation of the lens-vitreous contact, but not by the culture of vitreous-stripped lenses on a vitreous bed. Supplementation of the culture medium with the antioxidant N -acetyl-cysteine slightly reduced the c-jun, but not the c-fos response. Protooncogene up-regulation thus appears to be mainly determined by the disruption of critical lens-vitreous interactions. Since this response takes place in the epithelial cells, these data also point to the existence of a communication mechanism whereby a posteriorly applied mechanical stress is transmitted to, and perceived by, the anterior lens surface.

Acetylcysteine↗

Alterations in GAD67, dynorphin and enkephalin mRNA in striatal output neurons following priming in the 6-OHDA model of Parkinson's disease.

In the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease, administration of a dopaminergic agonist sensitizes rats to a subsequent administration of dopaminergic drugs given days apart (priming). In situ hybridization was used to evaluate changes on striatal gene expression of rats primed three days previously with either L-dopa, SKF38393 or quinpirole. Double labeling was used to identify the neuronal population in which such alterations occurred. GAD67 and enkephalin mRNA were increased by the lesion whereas dynorphin mRNA was decreased as compared to the intact striatum. Priming with L-dopa and SKF38393 significantly increased GAD67 mRNA in the lesioned striatum and reversed dynorphin mRNA reduction, as compared to drug-naive rats, whereas quinpirole failed to produce any effect. Enkephalin mRNA was not affected by priming. Results suggest that 6-OHDA lesion-induced adaptive changes on striatal gene expression are modified by priming. Priming brings striatal output neurons to a higher level of activity, which may explain the sensitized behavioral response observed following a dopaminergic agonist challenge. These changes are in relation to the different types of dopamine agonists utilized and suggest that modifications in gene expression induced by priming might be predictive of the dyskinetic potential of a drug.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Novel functionalized pyrido[2,3-g]quinoxalinones as antibacterial, antifungal and anticancer agents.

A series of twelve novel pyrido[2,3-g]quinoxalinones (3-14), variously substituted at the C-3 position, was synthesized, structurally determined and submitted to a preliminary in vitro evaluation for antibacterial, anticandida and anticancer activities. Results of the antimicrobial screening showed that all compounds, with the exception of 6, 11 and 12, exhibited interesting activity against all strains tested; while compound 10 was found to have encouraging in vitro anticancer activity at a concentration of l0(-4) M.

Anti-Infective Agents↗

Prevalence of intestinal metaplasia in the distal oesophagus, oesophagogastric junction and gastric cardia in symptomatic patients in north-east Italy: a prospective, descriptive survey. The Italian Ulcer Study Group "GISU".

BACKGROUND: Incidence of adenocarcinoma of distal oesophagus and gastric cardia, probably arising from areas of intestinal metaplasia, has been increasing rapidly. AIMS: To define prevalence of intestinal metaplasia of distal oesophagus, oesophagogastric junction and gastric cardia and to evaluate potential associated factors, by means of a prospective multicentre study including University and teaching hospitals, and primary and tertiary care centres. PATIENTS: Each of 24 institutions involved in study enrolled 10 consecutive patients undergoing first-time routine endoscopy for dyspeptic symptoms. METHODS: Patients answered symptom questionnaires and underwent gastroscopy Three biopsies were taken from distal oesophagus, oesophago-gastric junction and gastric cardia, and were stained with haematoxylin and eosin. Specimens were also evaluated for Helicobacter pylori infection. RESULTS: A total of 240 patients (124 male, 116 female; median age 56 years, range 20-90) were enrolled in study. Intestinal metaplasia affected distal oesophagus in 5, oesophago-gastric junction in 19 and gastric cardia in 10 patients. Low-grade dysplasia was found at distal oesophagus and/or oesophago-gastric junction of 3/24 patients with intestinal metaplasia vs 2/216 without intestinal metaplasia (p<0.05). A significant association was found between symptoms and presence of intestinal metaplasia, regardless of location, and between Helicobacter pylori infection and intestinal metaplasia at oesophago-gastric junction. CONCLUSIONS: Intestinal metaplasia of distal oesophagus, oesophagogastric-junction and gastric cardia is found in a significant proportion of symptomatic patients undergoing gastroscopy and is associated with dysplasia in many cases. Although prevalence of dysplasia seems to decrease when specialized columnar epithelium is found in short segment, or even focally in oesophago-gastric junction, these small foci of intestinal metaplastic cells may represent source of most adenocarcinomas of cardia.

Barrett Esophagus↗

Phylogenetic analyses of Klebsiella species delineate Klebsiella and Raoultella gen. nov., with description of Raoultella ornithinolytica comb. nov., Raoultella terrigena comb. nov. and Raoultella planticola comb. nov.

The phylogenetic relationships of the type strains of 9 Klebsiella species and 20 species from 11 genera of the family Enterobacteriaceae were investigated by performing a comparative analysis of the sequences of the 16S rRNA and rpoB genes. The sequence data were phylogenetically analysed by the neighbourjoining and parsimony methods. The phylogenetic inference of the sequence comparison confirmed that the genus Klebsiella is heterogeneous and composed of species which form three clusters that also included members of other genera, including Enterobacter aerogenes, Erwinia clusters I and II and Tatumella. Cluster I contained the type strains of Klebsiella pneumoniae subsp. pneumoniae, Klebsiella pneumoniae subsp. rhinoscleromatis and Klebsiella pneumoniae subsp. ozaenae. Cluster II contained Klebsiella ornithinolytica, Klebsiella planticola, Klebsiella trevisanii and Klebsiella terrigena, organisms characterized by growth at 10 degrees C and utilization of L-sorbose as carbon source. Cluster III contained Klebsiella oxytoca. The data from the sequence analyses along with previously reported biochemical and DNA-DNA hybridization data support the division of the genus Klebsiella into two genera and one genogroup. The name Raoultella is proposed as a genus name for species of cluster II and emended definitions of Klebsiella species are proposed.

DNA, Bacterial↗

A 1-year controlled trial of acetyl-l-carnitine in early-onset AD.

OBJECTIVE: To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients. METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders-Alzheimer's Disease and Related Disorders Association criteria and had a Mini-Mental State Examination (MMSE) score between 12 and 26. They were treated with ALCAR (1 g tid) or placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Secondary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activities of Daily Living Scale (ADL), and a Clinician-Based Impression of Change (CIBIC). RESULTS: Two-hundred twenty-nine patients were enrolled and randomized to drug treatment, with 117 taking placebo and 112 taking ALCAR. There were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis. In the completer sample only, there was less deterioration in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm. CONCLUSION: Overall, in a prospectively performed study in young-onset AD patients, ALCAR failed to slow decline. Less decline was seen on the MMSE in the completer sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity.

Acetylcarnitine↗

Ultrastructural analysis of extraocular muscle in chronic progressive external ophthalmoplegia.

Extraocular muscles are primarily involved in many mitochondrial diseases, but no reports exist regarding the morphological appearance of the muscles in cases of long-standing ocular myopathies. For this reason, muscle samples obtained from surgery in a sporadic case of chronic progressive external ophthalmoplegia (CPEO) were used for ultrastructural investigation and molecular analysis of mitochondrial DNA. Genetic testing revealed a heteroplasmic macrodeletion of about 5.0 kilobases in length, localized between the 9570- and 14619-base pair regions. Electron microscopy revealed focal areas of both disruption and abnormality of mitochondria in only some of the muscle fibers, producing "selective vacuolization." This ultrastructural pattern was highly selective and limited to some extraocular muscle fibers, sparing all the others. The "selective damage" observed in this case of CPEO resembles that case occurring in another mitochondrial disease, Leber hereditary optic neuropathy, where damage occurs only in the papillomacular bundle of the retina, sparing peripheral axons. It is possible that some anatomical and physiological factors play a leading role in both Leber hereditary optic neuropathy and ocular myopathies. The ultrastructural aspect herein observed needs to be further investigated to better understand whether a particular muscle fiber type is the target of mitochondrial impairment in CPEO.

Base Sequence↗