Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

Increase of core temperature induced by corticotropin-releasing factor and urocortin: A comparative study

This study compared the ability of CRF and UCN1 to induce a thermoregulatory response when centrally injected into rats. The effects of antipyretic drugs and CRF receptor antagonists (CRF(1) and CRF(2)) on the temperature (T) changes induced by these peptides were also investigated. Rectal (rT) and tail skin (T(sk)) temperatures were measured with a thermistor probe while body (bT) temperature was measured with a battery-operated biotelemetry transmitter in male Wistar rats (200 g) every 30 min over a period of 6 h, after intracerebroventricular (i.c.v.) injection of 1 nmol of either CRF or UCN1. Rats were pre-treated with indomethacin (2 mg kg(-1), i.p.) or celecoxib (5 mg kg(-1), p.o.), dexamethasone (0.5 mg kg(-1), s.c.), astressin (a CRF(1)/CRF(2) antagonist, 7 nmol, icy.) or antalarmin (a CRF(1) antagonist, 20 mg kg 1, i.p.). The increase in body temperature induced by CRF was accompanied by a reduction in T(sk) while the response induced by UCN1 was accompanied by an elevation in T(sk). Indomethacin or celecoxib did not change the increases in rT caused by either CRF or UCN1. Although dexamethasone attenuated the increase in rectal temperature in response to CRF, dexamethasone did not modify the response induced by UCN1. Astressin blocked the UCN1-induced hyperthermia and reduced CRF-induced fever. Antalarmin did not modify the hyperthermia in response to UCN1, but reduced the fever evoked by CRF. This study demonstrated that CRF by acting on the CRF(1) receptor induces a prostaglandin-independent fever which seems to depend, at least in part, on the synthesis of other mediators while UCN1 acts on the CRF(2) receptor, promoting a hyperthermic response which seems to be independent on synthesis/release of any mediator. (C) 2010 Elsevier B.V. All rights reserved.

Elevated blood lead levels in a riverside population in the Brazilian Amazon

Lead (Pb) is recognized as one of the most toxic metals. Sources of Pb exposure have been widely documented in North America, and the removal of Pb additives from gasoline was reflected in a dramatic lowering of blood Pb concentration. In Latin America, the removal of Pb from gasoline resulted in decreased exposure, but Pb levels in many areas remain high due to occupational and environmental sources of exposure. While many of the Pb sources have been identified (mining, industries, battery recycling, lead-based paint, ceramics), new ones occasionally crop up. Here we report on blood Pb (B-Pb) levels in remote riverside communities of the Brazilian Amazon. Blood Pb (B-Pb) levels were determined in 448 persons from 12 villages of the Lower Tapajos River Basin, Par, Brazil. Socio-demographic and dietary information, as well as occupational, residential and medical history was collected using an interview-administered questionnaire. B-Pb, measured by ICP-MS, showed elevated concentrations. Mean B-Pb was 13.1 mu g/dL +/- 8.5, median B-Pb was 11.2 mu g/dL and ranged from 0.59 to 48.3 mu g/dL. Men had higher B-Pb compared to women (median: 15.3 mu g/dL vs 7.9 mu g/dL respectively). B-Pb increased with age for women, while it decreased for men. For both genders, B-Pb decreased with education. There were significant differences between villages. Exploratory analyses, using linear partition models, showed that for men B-Pb was lower among those who were involved in cattle-raising, and higher among those who hunted, farmed and fished. The distribution profile of B-Pb directed us towards artisanal transformation of manioc to flour (farinha), which requires heating in a large metal pan, with stirring primarily done by young men. In the village with the highest B-Pb, analysis of Pb concentrations (dry weight) of manioc (prior to transformation) and farinha (following transformation) from 6 houses showed a tenfold increase in Pb concentration (mean: 0.017 +/- 0.016 to 0.19 +/- 0.10 mu g/g). This was confirmed in one of these villages where we sampled manioc paste Oust before roasting) and the roasted farinha (0.05 mu g/g vs 0.20 mu g/g). While there may be other sources (ammunition, sinkers for fishing nets), the high concentrations in farinha, a dietary staple, assuredly makes an important contribution. Further action needs to reduce Pb sources in this region. (C) 2009 Elsevier Inc. All rights reserved.

Differential expression of immunomodulatory galectin-1 in peripheral leukocytes and adult tissues and its cytosolic organization in striated muscle

Galectin-1 (Gal-1) is important in immune function and muscle regeneration, but its expression and localization in adult tissues and primary leukocytes remain unclear. To address this, we generated a specific monoclonal antibody against Gal-1, termed alpha hGal-1, and defined a sequential peptide epitope that it recognizes, which is preserved in human and porcine Gal-1, but not in murine Gal-1. Using alpha hGal-1, we found that Gal-1 is expressed in a wide range of porcine tissues, including striated muscle, liver, lung, brain, kidney, spleen, and intestine. In most types of cells, Gal-1 exhibits diffuse cytosolic expression, but in cells within the splenic red pulp, Gal-1 showed both cytosolic and nuclear localization. Gal-1 was also expressed in arterial walls and exhibited prominent cytosolic and nuclear staining in cultured human endothelial cells. However, human peripheral leukocytes and promyelocytic HL60 cells lack detectable Gal-1 and also showed very low levels of Gal-1 mRNA. In striking contrast, Gal-1 exhibited an organized cytosolic staining pattern within striated muscle tissue of cardiac and skeletal muscle and colocalized with sarcomeric actin on I bands. These results provide insights into previously defined roles for Gal-1 in inflammation, immune regulation and muscle biology.

Structural and functional properties of Bp-LAAO, a new L-amino acid oxidase isolated from Bothrops pauloensis snake venom

An L-amino acid oxidase (Bp-LAAO) from Bothrops pauloensis snake venom was highly purified using sequential chromatography steps on CM-Sepharose, Phenyl-Sepharose CL4B, Benzamidine Sepharose and C18 reverse-phase HPLC. Purified Bp-LAAO showed to be a homodimeric acidic glycoprotein with molecular weight around 65 kDa under reducing conditions in SDS-PAGE. The best substrates for Bp-LAAO were L-Met, L-Leu, L-Phe and L-Ile and the enzyme showed a strong reduction of its catalytic activity upon L-Met and L-Phe substrates at extreme temperatures. Bp-LAAO showed leishmanicidal, antitumoral and bactericidal activities dose dependently. Bp-LAAO induced platelet aggregation in platelet-rich plasma and this activity was inhibited by catalase. Bp-LAAC-cDNA of 1548 bp codified a mature protein with 516 amino acid residues corresponding to a theoretical isoelectric point and molecular weight of 6.3 and 58 kDa, respectively. Additionally, structural and phylogenetic studies identified residues under positive selection and their probable location in Elp-LAAO and other snake venom LAAOs (svLAAOs). Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents. (C) 2009 Elsevier Masson SAS. All rights reserved.

Language disorders in dementia of the Alzheimer type

The language profile of a group of 18 Alzheimer patients is documented and their performance on a standard aphasia test battery compared to a group of institutionalized, nonneurologically impaired control subjects matched for age, sex, and educational level. The Alzheimer patients scored significantly lower than the controls in the areas of verbal expression, auditory comprehension, repetition, reading, and writing. Articulation abilities were the same in each group. A language deficit was evident in all Alzheimer patients. The language disorder exhibited resembled a transcortical sensory aphasia. Syntax and phonology remained relatively intact but semantic abilities were impaired. The results support the inclusion of a language deficit as a diagnostic criterion of Alzheimer's disease.

La Pointe Saint Mathieu, Brittany, France

The "Pointe Saint Mathieu" is one of the most westerly continental landmarks of France. The promontory is located at the entrance of the "Goulet de la Rade de Brest", that is the entrance channel of the harbour of Brest in Brittany (France). It marks also the Southern end of the "Chenal du Four" that is the main navigation channel between the islands of Ouessant, Molène and Béniquet, and Brittany. The "Chenal du Four" is reputed for its dangers. The tidal range is greater than 7 m in spring tides, and the mid-tide current may exceed 5 knots. The Saint Mathieu promontory is equipped with a lighthouse and a semaphore. The former is located in the ruins of an old monastery, founded during the 6th century AD by Saint Tanguy. The present ruins are the remnants of buildings from the 11th to 15th centuries. The first lighthouse was installed in 1689, although the monks of the monastery used to maintain a signal light since the 1250s. Completed in 1835, the present "Phare de la Pointe Saint-Mathieu" is 37 m high and it reaches 58.8 m above sea level During World War 2, the Pointe Saint Mathieu was defended by a series of concrete fortifications built by the Germans. Some were based upon some earlier French bunker systems, like the coastal battery at the Rospects which included 4 main gun bunkers (4*150 mm, or 2*150 mm & 2*105 mm), an observation bunker on the Western side close to sea, and several smaller structures. There was also the large Kéringar Blockhaus system, near Lochrist, located about 1 km inland and designed for 4 guns of 280 mm. Its command bunker remains a landmark along the main road. All this area was very-heavily bombed between 1943 and 1944, and particularly during the battle of Brest in August-September 1944 ("L'Enfer de Brest").

Expertise and the perception of kinematic and situational probability information

Two experiments were conducted on the nature of expert perception in the sport of squash. In the first experiment, ten expert and fifteen novice players attempted to predict the direction and force of squash strokes from either a film display (occluded at variable time periods before and after the opposing player had struck the ball) or a matched point-light display (containing only the basic kinematic features of the opponent's movement pattern). Experts outperformed the novices under both display conditions, and the same basic time windows that characterised expert and novice pick-up of information in the film task also persisted in the point-light task. This suggests that the experts' perceptual advantage is directly related to their superior pick-up of essential kinematic information. In the second experiment, the vision of six expert and six less skilled players was occluded by remotely triggered liquid-crystal spectacles at quasi-random intervals during simulated match play. Players were required to complete their current stroke even when the display was occluded and their prediction performance was assessed with respect to whether they moved to the correct half of the court to match the direction and depth of the opponent's stroke. Consistent with experiment 1, experts were found to be superior in their advance pick-up of both directional and depth information when the display was occluded during the opponent's hitting action. However, experts also remained better than chance, and clearly superior to less skilled players, in their prediction performance under conditions where occlusion occurred before any significant pre-contact preparatory movement by the opposing player was visible. This additional source of expert superiority is attributable to their superior attunement to the information contained in the situational probabilities and sequential dependences within their opponent's pattern of play.

Random numbers from astronomical imaging

This article describes a method to turn astronomical imaging into a random number generator by using the positions of incident cosmic rays and hot pixels to generate bit streams. We subject the resultant bit streams to a battery of standard benchmark statistical tests for randomness and show that these bit streams are statistically the same as a perfect random bit stream. Strategies for improving and building upon this method are outlined.

Intuition: Myth or a Decision-making Tool?

Faced with today’s ill-structured business environment of fast-paced change and rising uncertainty, organizations have been searching for management tools that will perform satisfactorily under such ambiguous conditions. In the arena of managerial decision making, one of the approaches being assessed is the use of intuition. Based on our definition of intuition as a non-sequential information-processing mode, which comprises both cognitive and affective elements and results in direct knowing without any use of conscious reasoning, we develop a testable model of integrated analytical and intuitive decision making and propose ways to measure the use of intuition.

Special issue on advances in data mining and its applications

Data mining is the process to identify valid, implicit, previously unknown, potentially useful and understandable information from large databases. It is an important step in the process of knowledge discovery in databases, (Olaru & Wehenkel, 1999). In a data mining process, input data can be structured, seme-structured, or unstructured. Data can be in text, categorical or numerical values. One of the important characteristics of data mining is its ability to deal data with large volume, distributed, time variant, noisy, and high dimensionality. A large number of data mining algorithms have been developed for different applications. For example, association rules mining can be useful for market basket problems, clustering algorithms can be used to discover trends in unsupervised learning problems, classification algorithms can be applied in decision-making problems, and sequential and time series mining algorithms can be used in predicting events, fault detection, and other supervised learning problems (Vapnik, 1999). Classification is among the most important tasks in the data mining, particularly for data mining applications into engineering fields. Together with regression, classification is mainly for predictive modelling. So far, there have been a number of classification algorithms in practice. According to (Sebastiani, 2002), the main classification algorithms can be categorized as: decision tree and rule based approach such as C4.5 (Quinlan, 1996); probability methods such as Bayesian classifier (Lewis, 1998); on-line methods such as Winnow (Littlestone, 1988) and CVFDT (Hulten 2001), neural networks methods (Rumelhart, Hinton & Wiliams, 1986); example-based methods such as k-nearest neighbors (Duda & Hart, 1973), and SVM (Cortes & Vapnik, 1995). Other important techniques for classification tasks include Associative Classification (Liu et al, 1998) and Ensemble Classification (Tumer, 1996).

An evaluation of the Keep on Talking program for maintaining communication skills into old

Communication skills change with age as a result of sensory deficits, memory loss, and increasing word finding difficulties The Keep on Talking program (L. Hickson, H. Barnett, L. Worrall, & E. Yiu, 1994) was developed to assist older people to develop their own strategies for maintaining communication skills into old age. Two hundred and fifty-two healthy older people were recruited from the community and were assessed on a battery of communication assessments on entry to the study and at 1 year after entry. The experimental group (n = 120) participated in the 5-week group Keep on Talking program run by volunteers A further 130 control subjects were assessed only. The short-term effectiveness of the program was evaluated using a short knowledge based and attitudinal questionnaire and qualitative written feedback. At the I-year follow up, subjects were also asked whether they had taken any action as a result of the project. Results concluded that there was a significant difference between the number of correct questionnaire responses on the knowledge based items and the ratings on the attitudinal items pre- and postprogram questionnaire for the experimental subjects. Qualitative written feedback was positive with many participants remarking on the amount of information that they had acquired. Forty-eight experimental and 69 control subjects (n = 117) were assessed I year later, and there was a significant difference between the groups in terms of the number of subjects who reported having taken action as a result of the program. The Keep on Talking program increased knowledge about communication, produced a positive change in attitude toward the importance of communication, and encouraged participants to take action to maintain their communication skills. Maintaining communication skills may prevent social isolation. This simple 5-hour group program has been effective in empowering participants to maintain. their communication skills as they age.

Bimanual co-ordination in Parkinson's disease

The basal ganglia may be involved in bimanual co-ordination. Parkinson's disease (which impairs basal ganglia output) is clinically reported to cause difficulties in the performance of co-ordinated bimanual movements. Nevertheless, any bimanual co-ordination difficulties may be task specific, as experimental observations are equivocal. To infer the role of the basal ganglia in co-ordinating the two arms, this study investigated the bimanual co-ordination of patients with Parkinson's disease. Sixteen Parkinson's disease patients and matched control subjects performed a bimanual cranking task, at different speeds (1 and 2 Hz) and phase relationships. All subjects performed the required bimanual in-phase movement on a pair of cranks, at fast (2 Hz) and slow (1 Hz) speeds. However the Parkinson's disease patients were unable to perform the asymmetrical anti-phase movement, in which rotation of the cranks differed by 180 degrees, at either speed; but instead reverted to the in-phase symmetrical movement. For Parkinson's disease patients, performance of the in-phase movement was more accurate and stable when an external timing cue was used; however for anti-phase movement, the external cue accentuated the tendency for patients to revert to more symmetrical, in-phase movements.

Sequence heterogeneity in Parkinsonian speech

Parkinson's disease (PD) is a neurodegenerative movement disorder primarily due to basal ganglia dysfunction. While much research has been conducted on Parkinsonian deficits in the traditional arena of musculoskeletal limb movement, research in other functional motor tasks is lacking. The present study examined articulation in PD with increasingly complex sequences of articulatory movement. Of interest was whether dysfunction would affect articulation in the same manner as in limb-movement impairment. In particular, since very Similar (homogeneous) articulatory sequences (the tongue twister effect) are more difficult for healthy individuals to achieve than dissimilar (heterogeneous) gestures, while the reverse may apply for skeletal movements in PD, we asked which factor would dominate when PD patients articulated various grades of artificial tongue twisters: the influence of disease or a possible difference between the two motor systems. Execution was especially impaired when articulation involved a sequence of motor program heterogeneous in terms of place of articulation. The results are suggestive of a hypokinesic tendency in complex sequential articulatory movement as in limb movement. It appears that PD patients do show abnormalities in articulatory movement which are similar to those of the musculoskeletal system. The present study suggests that an underlying disease effect modulates movement impairment across different functional motor systems. (C) 1998 Academic Press.