Hypercoagulability markers in young asymptomatic heterozygous carriers of factor V Leiden (G1691A) or prothrombin (G20210A) variant

BACKGROUND: Mutations in factor V (factor V Leiden-G1691A) and prothrombin (G20210A) genes are important risk factors for thrombophilia due to their high incidence in patients with thromboembolic events, especially among the young. However, it is not clear if levels of hypercoagulability markers are significantly altered in asymptomatic young carriers of factor V Leiden or prothrombin G20210A. METHODS: Hemostatic status of 32 asymptomatic young individuals carrying these mutations and of 18 normal control individuals was investigated through the determination of plasma thrombomodulin (TM), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and D-dimer. RESULTS: No significant differences were observed in these hemostatic markers when comparing groups of individuals carrying mutations and the control group. CONCLUSION: Analysis of these results leads to the conclusion that the presence of these mutations, in the absence of acquired risk factors, does not constantly predispose these young carriers to a state of hypercoagulability.     

Pseudo-Pelger-Huët in kidney-transplanted patients

Pelger-Hu?t anomaly is an inherited condition characterized by hyposegmentation of the neutrophil nucleus and excessive chromatin clumping. Acquired Pelger-Hu?t, also known as pseudo-Pelger-Hu?t, has been described in several clinical conditions including transplant recipients who received immunosuppressive drugs. The incidence of pseudo-Pelger-Hu?t in kidney transplant patients, characterized as neutrophil dysplasia, was observed in 9 of 170 patients (5.3%) at the S?o Francisco Hospital de Assis, Belo Horizonte, Brazil. Awareness of possible circulating neutrophil alterations in transplant patients is important for laboratory professionals who should report these findings of cell changes. It should be highlighted that the poor segmentation and the chromatin hypercondensation observed initially in pseudo-Pelger-Hu?t patients can be suggestive of early-stage neutrophils. Only a combination of laboratory and clinical data will facilitate a better understanding of this anomaly and its correct follow-up and management.     

Expanded timed up and go test with subjects with stroke: reliability and comparisons with matched healthy controls

Faria CD, Teixeira-Salmela LF, Silva EB, Nadeau S. Expanded Timed Up and Go test with subjects with stroke: reliability and comparisons with matched healthy controls.ObjectivesTo investigate the intra- and interrater reliabilities of the Expanded Timed Up and Go (ETUG) test with subjects with stroke and to compare the ETUG scores between subjects with stroke and healthy control subjects.DesignCross-sectional.SettingResearch laboratory.ParticipantsStroke participants (n=48; mean age ± SD, 59.29±15.84y) and healthy controls (n=48), matched by age, sex, and levels of physical activity.InterventionsNot applicable.Main Outcome MeasuresThe time spent to complete the ETUG in absolute (s) and ratio values regarding the percentages of the total time. Intraclass correlation coefficients (ICCs), Student t tests, and 95% confidence intervals were employed to investigate the reliability and differences between the groups (α<.05).ResultsBoth intra- and interrater reliabilities showed significant and excellent results for both groups for the absolute values (0.86≤ICC≤1.00; P<.001) and ratio values (0.55≤ICC≤0.99; P<.001). The mean time, in seconds, for all of the ETUG activities was higher for the subjects with stroke than for the control subjects (3.15≤t≤5.78; P<.001). However, when the comparisons considered the ratio values, no significant differences between the groups were found (0.45≤t≤1.15; 0.25≤P≤0.65). These results were confirmed by the 95% confidence interval.ConclusionsSubjects with stroke spent more time in all of the ETUG activities when compared with control subjects. All of the activities appeared to contribute similarly to the poorer performances observed in subjects with stroke, because the ratio values were similar between the groups. Considering the positive intra- and interrater reliability results, the ETUG could be applied to assess the functional mobility of both groups.     

Actigraphic and parent reports of sleep patterns and sleep disorders in children with subtypes of attention-deficit hyperactivity disorder

STUDY OBJECTIVE: To describe parent-reported and actigraphically assessed sleep patterns and sleep disorders in stimulant-medication-free children with attention-deficit/hyperactivity disorder (ADHD), divided according to ADHD subtype. PARTICIPANTS: Seventy-one stimulant-medication-free children with a clinical diagnosis of ADHD (8 girls; mean 8.8 years (SD 2.6), range 3-15 years) recruited from child psychiatry clinics. MEASUREMENTS: ADHD: ADHD Rating Scale DSM IV- Home Version to subdivide children into those with predominantly attention deficit, mainly hyperactivity, and those with both aspects equally. Sleep: Parent-completed sleep diary, clinical history, and 5 nights of actigraphy. RESULTS: Parents reported a wide range of frequently occurring sleep disturbances in their children. However, the objective sleep patterns were not abnormal and did not differ between the ADHD subtypes, and objective sleep patterns did not predict ADHD severity. There was poor correspondence between parent report and actigraphy. Careful clinical consideration of each case suggested that sleep disorders may be widespread in this group of children; only 8 of the 71 children had no discernable likely sleep disorder. Symptoms of sleep-disordered breathing, sleeplessness and reports of restless legs featured prominently. CONCLUSIONS: Parents of children with ADHD may not be accurate reporters of their children's sleep pattern and/or the sleep disturbances that come to parents' attention are not best detected by actigraphy. Results highlight the prominence of parent-reported sleep disturbance in children with ADHD and the need for clinicians to routinely screen for the presence of sleep disorders and assess detailed sleep physiology where indicated.     

Clofibrate treatment up-regulates novel organic cation transporter (OCTN)-2 in tissues of pigs as a model of non-proliferating species

Recent studies have shown that treatment of rodents with agonists of peroxisome proliferator-activated receptor (PPAR)-alpha causes an up-regulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and increases carnitine concentration in the liver. This study was performed to investigate whether such effects occur also in pigs which like humans have a lower expression of PPAR alpha and are less responsive to treatment with PPAR alpha agonists than rodents. An experiment with 18 pigs was performed which were fed a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had higher relative mRNA concentrations of OCTN2 in liver (3.1-fold), skeletal muscle (1.5-fold) and epithelial cells from small intestine (1.8-fold) than control pigs (P<0.05). Pigs treated with clofibrate had also higher concentrations of free and total carnitine in the liver and a higher concentration of free carnitine in skeletal muscle than control pigs (P<0.05). Concentrations of gamma-butyrobetaine, the precursor of endogenous formation of carnitine, in liver, muscle and plasma did not differ between both groups; the activity of gamma-butyrobetaine dioxygenase, the rate limiting enzyme of carnitine synthesis, in the liver was lower in pigs treated with clofibrate than in control pigs (P<0.05). This study shows for the first time that treatment with a PPAR alpha agonist causes an up-regulation of OCTN2 in liver, muscle and enterocytes from small intestine of pigs. This in turn increases carnitine concentrations in liver and muscle probably by enhancing carnitine uptake into cells.     

Selective cytotoxicity of indomethacin and indomethacin ethyl ester-loaded nanocapsules against glioma cell lines: an in vitro study

Gliomas are the most common and devastating tumors of the central nervous system. Several studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Biodegradable nanoparticulate systems have received considerable attention as potential drug delivery vehicles. The aim of this study was to evaluate the effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules on glioma cell lines. In addition, the effect of these formulations on normal neural tissue was also evaluated. In order to investigate this, glioma cell lines (U138-MG and C6) and hippocampal organotypic cultures were used. The main finding of the present study is that indomethacin-loaded nanocapsules formulation was more potent than a solution of indomethacin in decreasing the viability and cell proliferation of glioma lines. Indomethacin and indomethacin ethyl ester associated together in the same nanocapsule formulation caused a synergic effect decreasing glioma cell proliferation. In addition, when the glioma cells were exposed to 25 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, a necrotic cell death was observed. Interestingly, 5 microM of indomethacin-loaded nanocapsules was able to cause an antiproliferative effect without promoting necrosis in glioma cells. Another important finding was that the cytotoxic effect induced by 25 microM or 50 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, in glioma cells was not observed in the organotypic cultures, indicating selective cytotoxicity of those formulations for tumoral cells. Further investigations using in vivo glioma model should be helpful to confirm the distinct effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules, in normal versus tumoral cells.