An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Abnormal movements in Rett syndrome are present before the regression period: a case study.

The suspicion of a diagnosis of Rett syndrome (RTT) is based on clinical criteria that are often not present in the first two stages of the disease, as many of its symptoms will appear at a later age. This sometimes postpones the genetic diagnosis and an early clinical intervention. We present the case of 19-months-old girl who came to the consultation because of an arrest of psychomotor development noticed 5 months earlier without change in sleep pattern, behavior, or social communication. In the observation of 1 hour videotape, she presented subtle stereotypic movements of the face and hands as well as repetitive dystonic posturing of her limbs. A genetic test confirmed the diagnosis of RTT, showing a truncating mutation in the MECP2 gene (R270X). This case confirms that stereotypic movement anomalies, albeit infrequent and subtle, are already present before the regression stage and while maintaining prehension and that, in addition, repetitive dystonic postures may occur. Recognition of these early movement disorders will improve clinicians' ability to perform an earlier diagnosis of RTT.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

Clinical performance of non-contact tonometry by Reichert AT550® in glaucomatous patients

Measuring intraocular pressure (IOP) by non-contact tonometry (NCT) has been demonstrated to be a valid and reliable technique to be used in primary eye care; it is easier to use, it does not transmit infectious diseases, and it is not necessary to use anaesthetic or staining eye drops. Recently, a new NCT device has showed an excellent level of agreement with Goldmann tonometry, but there are no records of its performance in glaucomatous eyes. To rectify this, IOP was measured in twenty-two patients (44 eyes) receiving medical treatment to control elevated IOP, with AT550 and Goldmann tonometry. Mean values of IOP were 18.98 +/- 2.77 and 19.08 +/- 3.02 mmHg using Goldmann and AT550, respectively. Plots of differences against means displayed good agreement (mean difference +/- limits of agreement, -0.09 +/- 3.30); this value was not significantly different from zero (t-test for dependent samples, p = 0.709). In conclusion, IOP values as measured with the AT550 NCT are clinically comparable with those obtained with Goldmann tonometry in glaucomatous patients. This validates this NCT not only for screening of IOP but to follow-up glaucomatous patients with a rapid, non-invasive method.     

Copper,Zinc and Lead Enrichments in Sediments from Guacanayabo Gulf,Cuba, and Its Bioaccumulation in Oysters,Crassostrea rhizophorae

Levels of iron, copper, zinc and lead were determined in sediments and soft tissue of the oyster Crassostrea rhizophorae collected from Guacanayabo Gulf, Cuba. Metal-to-Iron ratio in sediments shows an average enrichment for Cu (5,1), Pb (11,7) and Zn (1,3) in the last 20 years. Metal concentrations found in soft tissue of C. rhizophorae are site dependent. The average biota-sediment accumulation factors (BSAFs) obtained for Fe, Cu and Pb are less than unity in all cases, indicating that only a little fraction of Cu and Pb in the sediments is bioavailable, independently of their enrichments. Zinc has an average BSAF value of 2.4 and may represent a serious impact in the area. The concentrations of zinc and copper in some of the oysters are above typical public health recommended limits.     

Lack of developmental toxicity of D-003: a mixture of long-chain fatty acids in rats.

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax, the major component of which is 1-octacosanoic acid and which possesses effective antiplatelet, antithrombotic and cholesterol-lowering effects. D-003 was suspended in 1% acacia gum solution, and given daily by gavage to rats at dose levels of 5, 100 and 1000 mg/kg/day on days 6 through 15 of gestation. Cyclophosphamide, serving as a positive control, was given at the dose of 50 mg/kg/day on day 15 of gestation. Evidence of maternal or developmental toxicity was not observed in the groups treated with D-003. Maternal clinical signs of toxicity were not observed and the analysis of initial body weight and the body weight gain during the treatment period was comparable among the groups treated with D-003 and control. As expected, cyclophosphamide caused both embryotoxic and teratogenic effects in rats. Meanwhile, no adverse effects on reproductive performance, or on embryonic or fetal development, including visceral and skeletal examination, were seen in any of the groups administered D-003. It is concluded that D-003 administered up to 1000 mg/kg/day did not induce any evidence of developmental toxicity.