Neuroprotective effects of pramipexole against tunicamycin‐induced cell death in PC12 cells

• 1 Pramipexole (PPX), a dopamine D2 and D3 receptor agonist, exerts neuroprotective effects via both dopamine receptor‐mediated and non‐dopaminergic mechanisms. In the present study, we demonstrate that PPX reduces the toxicity of tunicamycin, a typical endoplasmic reticulum (ER) stressor, in PC12h cells, a subline of PC12 cells.
• 2 The PC12h cells were treated with 300 μmol / L PPX in the presence of 0.5 μmol / L tunicamycin for 24 h. The neuroprotective effects of PPX against tunicamycin‐induced cell death were evaluated using 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays, Hoechst 33258 staining and western blot analysis.
• 3 Tunicamycin (0.2, 0.3 and 0.5 μg / mL) dose‐dependently decreased MTT activity and increased LDH release from PC12h cells. Treatment with 300 μmol / L PPX rescued the tunicamycin‐induced decrease in cell viability.
• 4 Spiperone (10 μmol / L), a dopamine D2 and D4 receptor antagonist, had no effect on PPX neuroprotection against tunicamycin in these cells. Marker proteins of ER stress and apoptosis are known to be upregulated by tunicamycin, but we detected no significant effects of PPX on these factors.
• 5 In conclusion, we speculate that a combination of several mechanisms may be involved in PPX‐induced neuroprotection.

     

Evidence for interaction between platelet fibrinogen receptors

Previous analysis of fibrinogen binding to human aspirin-treated gel- filtered platelets yielded upwardly concave Scatchard plots. To ascertain whether this was due to the presence of independent heterogeneous receptor populations binding fibrinogen with different affinities, the dissociation of purified 125I-fibrinogen from ADP- treated gel-filtered platelets was evaluated as a function of receptor occupancy. Dissociation of bound labeled fibrinogen was measured after 50-fold dilution with buffer containing O, 0.2, 0.8, and 2.0 mg/ml unlabeled fibrinogen. Dissociation of labeled fibrinogen increased with increasing receptor occupancy and was biphasic. With buffer alone, 76.0% +/- 5.8% (SD) of labeled fibrinogen dissociated in 30 min, with an initial rate of 0.392 +/- 0.175 min-1; with 0.2 mg/ml fibrinogen, 83.7% +/- 3.9% dissociated, with an initial rate of 0.589 +/- 0.044 min- 1; with 0.8 mg/ml, 91.8% +/- 1.3% of the labeled fibrinogen dissociated, with an initial rate of 0.910 +/- 0.028 min-1; and with 2.0 mg/ml fibrinogen, 97.3% +/- 2.3% of label dissociated, with an initial rate of 1.06 +/- 0.257 min-1 (n=5). The final rates of fibrinogen dissociation were unaffected by unlabeled fibrinogen in the dilution buffer and were not statistically different from the final dissociation rate of 0.015 +/- 0.10 min-1 observed following dilution with buffer alone. These results were neither an artifact of aspirin treatment or gel filtration, as similar observations were made using non-aspirin-treated washed platelets, nor were they an artifact of the purified fibrinogen preparations, because binding studies using whole plasma as the major source of fibrinogen also yielded upwardly concave Scatchard plots. Since the data demonstrate that the initial rate and extent of fibrinogen dissociation are dependent on fibrinogen receptor occupancy, they suggest receptor interactions possibly resulting from receptor clustering or crosslinking. Because the dissociation was biphasic, the results also suggest some heterogeneity among platelet- fibrinogen interactions.     

A study of anemia in women with asymptomatic malaria parasitaemia at their first antenatal care visit at the General Hospital,Ikot Ekpene,Akwa Ibom State,Nigeria

ObjectiveTo assess the prevalence of anemia and asymptomatia malaria parasitemia and the effect of prior antimalarials therapy on the parasite density in pregnant women at their first antenatal visit at the secondary level health care facility in Nigeria.MethodsThis cross sectional observational study was carried out in the antenatal clinic of General Hospital, Ikot Ekpene, Akwa Ibom State, Nigeria for 3 months period (1^st June to 31^st August, 2009). Five hundred and fourteen women attending their first antenatal registration visits in the hospital were recruited in the study. Socio-demographic information was obtained using pre-tested questionnaires. The malaria parasite was obtained by examining thick and thin blood films prepared on 2 glass slides while the hematocrit was obtained through 2 capillary tubes read by a Hawksleys microhematocrit reader.ResultsA total of 514 pregnant women participated in the study with a mean maternal age of 21.4 years and a mean gestational age at booking of 18.3 weeks. The primigravid women booked at significantly lower gestational age than multigravidae (16.2 weeks vs 21.6 weeks). Most of the women (59.3%) were anemic, out of which 60.4% were primigravida. More than half of the women had moderate to high parasite density and only 6.8% had no malaria parasitemia. All patients with severe anemia were parasitemic. Out of the 479 (93.2%) women with parasitemia, a third had taken antimalarial drugs. A majority (60.3%) of those without prior antimalarial drugs had moderate to high density parasitemia.ConclusionsThis study shows high prevalence of anemia in women with asymptomatic malarial parasitemia, particularly the primigravida. The severity of anemia is directly related to the density of malaria parasitemia. Those with effective antimalarial therapy appear to have low density parasitemia and therefore mild anemia. Routine screening for anemia and malaria parasites at booking, prompt parasite clearance and correction of anemia would reduce the associated maternal and perinatal complications.     

Quantitative assessment of the contribution of sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) to the hepatic uptake of rosuvastatin,pitavastatin and fluvastatin

Hepatic uptake transport is often the rate‐determining step in the systemic clearance of drugs. The ability to predict uptake clearance and to determine the contribution of individual transporters to overall hepatic uptake is therefore critical in assessing the potential pharmacokinetic and pharmacodynamic variability associated with drug–drug interactions and pharmacogenetics. The present study revisited the interaction of statin drugs, including pitavastatin, fluvastatin and rosuvastatin, with the sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) using gene transfected cell models. In addition, the uptake clearance and the contribution of NTCP to the overall hepatic uptake were assessed using in vitro hepatocyte models. Then NTCP protein expression was measured by a targeted proteomics transporter quantification method to confirm the presence and stability of NTCP expression in suspended and cultured hepatocyte models. It was concluded that NTCP‐mediated uptake contributed significantly to active hepatic uptake in hepatocyte models for all three statins. However, the contribution of NTCP‐mediated uptake to the overall active hepatic uptake was compound‐dependent and varied from about 24% to 45%. Understanding the contribution of individual transporter proteins to the overall hepatic uptake and its functional variability when other active hepatic uptake pathways are interrupted could improve the current prediction practice used to assess the pharmacokinetic variability due to drug–drug interactions, pharmacogenetics and physiopathological conditions in humans. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of Cardiomyoplasty on Cardiac Growth in Rats

A bstract Background and aim of the study : Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. Methods : Six-week-old rats (body weight 203.8 ± 5.4 g, mean ± SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. Results : Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 ± 21.5 g and group II, 617.3 ± 20.3 g), but were significantly less than those of control animals (727.6 ± 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 ± 0.06 g; group III 1.45 ± 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 ± 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 ± 0.07 mL; group II, 0.66 ± 0.07 mL; and group III, 0.69 ± 0.10 mL; p = ns). Conclusions : A major surgical procedure impairs growth in juvenile rats. No evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.     

改良尺骨鹰嘴截骨治疗肱骨髁间骨折

目的:探讨改良尺骨鹰嘴截骨治疗肱骨髁间骨折的手术方法和疗效。方法:2007年5月至2012年12月采取改良尺骨鹰嘴截骨入路治疗肱骨髁间骨折32例,男21例,女11例;年龄18~65岁,平均46.3岁;右侧19例,左侧13例。AO分型,C1型7例,C2型11例,C3型14例;开放性骨折5例(GustiloⅠ型3例,GustiloⅡ型2例)。6例合并其他处骨折,4例合并尺神经损伤,2例合并桡神经损伤。术后定期复查及X线检查,按Cassebaum评分系统评定肘关节功能。结果:32例均获随访,时间9个月~5年,平均1.9年;截骨块愈合时间6~10周,平均7.4周。未发生尺骨鹰嘴关节内骨折,无截骨块不愈合。2例肘后内固定隆起处屈肘轻度疼痛不适,1例骨折块松动,2例出现异位骨化。肘关节功能评定:优19例,良8例,可4例,差1例。结论:改良尺骨鹰嘴截骨治疗肱骨髁间骨折具有不侵袭关节、术中截骨简便、固定简单、截骨块力学稳定性好、截骨并发症发生率低等优点。