Comparing bacterial genomes through conservation profiles

We constructed two-dimensional representations of profiles of gene conservation across different genomes using the genome of Escherichia coli as a model. These profiles permit both the visualization at the genome level of different traits in the organism studied and, at the same time, reveal features related to the genomes analyzed (such as defective genomes or genomes that lack a particular system). Conserved genes are not uniformly distributed along the E. coli genome but tend to cluster together. The study of gene distribution patterns across genomes is important for the understanding of how sets of genes seem to be dependent on each other, probably having some functional link. This provides additional evidence that can be used for the elucidation of the function of unannotated genes. Clustering these patterns produces families of genes which can be arranged in a hierarchy of closeness. In this way, functions can be defined at different levels of generality depending on the level of the hierarchy that is studied. The combined study of conservation and phenotypic traits opens up the possibility of defining phenotype/genotype associations, and ultimately inferring the gene or genes responsible for a particular trait.     

Effects of estrogen deficiency and low bone mineral density on healthy knee cartilage in rabbits

The purpose of this study was to compare the effects of estrogen deficiency and bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy (OVX) was performed in 13 rabbits, 6 of which also received systemic glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as controls. Bone mineral density (BMD) was measured by dual X‐ray absorptiometry in lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks after OVX. After sacrifice, the knees were dissected, macroscopy was assessed, and histological cartilage abnormalities were evaluated according to the Mankin score. Correlations of Mankin with BMD at different regions were also performed. When compared to baseline, differences in BMD were only found in spine and knee of the animals receiving glucocorticoids. All the animals subjected to OVX had a significantly higher Mankin score than controls. Mankin was upper in OVX animals receiving glucocorticoids, but differences were not significant. The Mankin score was inversely related with BMD in lumbar spine (r = ?0.67; p < 0.01). Although low bone mineral density contributes to the minor osteoarthritic alterations observed in our model, estrogen deficiency itself seems to act directly to induce the main pathogenic effects in healthy cartilage of the rabbit. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:812–818, 2010     

On the track of the white tiger: Pigmentation could be linked to prion diseases, and location explains why

Certain rodent pigmentation mutants spontaneously develop brain spongiform changes. It is hypothesized that animals, and possibly humans, characterized by certain pigmentation gene variants could be more susceptible to prion diseases, which are characterized by this type of neuropathology. This hypothesis could be explained by the common location of the prion protein and several important pigmentation genes in the same chromosome. This common location can promote the joint transfer of both pigmentary and prion protein genes to the progeny. Pigmentation genes could also play a role in regulating protein folding and aggregation. Understanding the relationship between pigmentation genes and prion genes could lead to identify pigmentation variants at higher risk of prion diseases and understand the etiopathogenesis of these still invariably lethal disorders.     

Mycoviruses are common among different species of endophytic fungi of grasses

A survey of mycoviruses was made in a collection of 103 isolates belonging to 53 different species of endophytic fungi of grasses. Double-stranded RNA (dsRNA) elements were detected in isolates of 12 of the species analyzed. The banding characteristics and sizes of some of the dsRNA elements suggest that they might belong to previously described mycovirus families. The observed incidence (22.6%) indicates that the presence of mycoviruses could be common among species of this group of ubiquitous fungi.     

Risk factors associated with renal lithiasis during uricosuric treatment of hyperuricemia in patients with Gout

Objective

To find factors associated with the development of renal colic during uricosuric therapy.

Methods

We performed a prospective cohort followup study of patients with gout and no previous history of kidney stones who had been treated with uricosurics. Clearance of creatinine and urate, 24‐hour urinary uric acid (UA), undissociated urinary UA concentration, 24‐hour undissociated urinary UA, and pH and urine sediment were obtained. Cox proportional hazards regression analysis was used to identify variables associated with renal colic as the outcome. The rate of renal colic was compared with that of control patients receiving allopurinol who had no previous history of renal stones.

Results

We analyzed a 784 patient‐year exposure from 216 patients: 206 with renal underexcretion of UA and 10 with normal excretion. There were 21 clinical events. Two variables showed increased risk hazard for developing lithiasis: clearance of UA at baseline and undissociated urinary UA concentration during followup. When only patients with underexcretion of UA were included in the analysis, undissociated urinary UA during followup remained the only statistically significant variable. Patients who showed an undissociated UA concentration <20 mg/dl did not show an increase in the rate of lithiasis or events compared with patients receiving allopurinol.

Conclusion

Clearance of UA at baseline may be useful for selecting patients suitable for uricosuric treatment. The estimation of the concentration of undissociated urinary UA is useful for evaluating the risk of lithiasis during followup.     

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.     

NCX-701 (nitroparacetamol) is an effective antinociceptive agent in rat withdrawal reflexes and wind-up

1. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic drugs although they also induce unwanted side effects due to the inhibition of the physiological effects regulated by prostaglandins. This has led to the search for new compounds with fewer side effects, such as the nitro-NSAIDs (NO-NSAIDs). Paracetamol is an analgesic drug devoid of some of the side effect of the NSAIDs but without anti-inflammatory activity. NCX-701 is a nitric oxide releasing version of paracetamol with anti-inflammatory and analgesic properties. 2. We have tested, in the single motor unit technique, the antinociceptive actions of intravenous cumulative doses of NCX-701 vs paracetamol, studying their antinociceptive effects in responses to noxious mechanical and electrical stimulation (wind-up). 3. Paracetamol did not induce any significant effect at the doses tested (maximum of 480 micromol kg(-1), 72.5 mg kg(-1)). NCX-701 however was very effective in reducing responses to noxious mechanical stimulation (32+/-10% of control response) and wind-up (ED(50) of 147+/-1 micromol kg(-1), 41.5+/-0.3 mg kg(-1)). The inhibition was not reversed by 1 mg kg(-1) of the opioid antagonist naloxone. In control experiments performed with either the vehicle or the NO donor NOC-18, no significant changes were observed in the nociceptive responses studied. 4. We conclude that NCX-701 is a very effective non-opioid antinociceptive agent in normal animals and its action is located mainly at central areas. The antinociceptive effect was not due solely to the release of NO.     

Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception

The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with alpha-chloralose. The effective dose 50 (ED(50)) observed with fentanyl was 22.4 +/- 1.5 microg kg(-1) and full recovery was apparent 20 min later. The administration of a total dose of 40 microg kg(-1) of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED(50) for fentanyl was 5 fold lower than before: 3.8 +/- 1.1 microg kg(-1) and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 microg kg(-1)) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action.     

Susac syndrome as a cause of sensorineural hearing loss

Susac's syndrome is an extremely rare clinical manifestation characterized by the triad of fluctuating sensorineural hearing loss, sudden visual loss and encephalopathy. Probably underdiagnosed, it affects young women who start the clinical history with headache, visual and hearing disturbances, with neurological findings in MRI. With unknown aetiology, pathogenesis is based on arteriolar microinfarcts in retina, cochlea, and grey and white matter in the brain. Treatment is, as stated in the bibliography and our experience, intravenous high doses of steroids followed by oral steroids together with hyperbaric oxygen to minimize ischaemic lesions. Aspirin associate to nimodipine has been useful to date in the treatment of our patient. We present a case and review the existing literature.