新螯合剂对铍中毒的解毒和促排效果

本文报道了新蟹合剂8102,S186对铍中毒动物的解毒和促排作用,并与811,DTPA 进行比较,大、小鼠BeSO_4中毒后,给予不同剂量的螯合剂解毒,结果表明,8102,S186对铍中毒动物的解毒效果均优于后两种,对大鼠的解毒作用8102优于S186,但S186对小鼠的解毒作用优于8102。螫合剂对大鼠BeSO_4染毒的排铍效果实验结果证明:各螫合剂的排铍效果强弱:8102>S186>811>DTPA。8102和S186对大鼠急性铍中毒有明显的排铍效果,若染毒前1h 或延迟4h 给药,仍有显著的排铍作用,但低于即刻用药组的效果。8102对亚急性染毒带铍状态亦有较高促排铍的作用。     

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 μM PAN-811 (an optimal neuroprotective concentration) for 1 h, 4 h, or 24 h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.     

Effect of Huanshuai Recipe Oral Liquid (缓衰口服液) on Renal Dysfunction Progression in Patients with Atherosclerotic Renal Artery Stenosis

Objective:To investigate the effect of Huanshuai Recipe Oral Liquid(缓衰口服液,HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis(ARAS).Methods:A total of 52 ARAS patients with the Chinese medicine(CM) syndrome of qi deficiency and blood stasis,phlegm and dampness retention were recruited and randomly assigned into the treatment group(36 cases) and the control group(16 cases).Both groups received a basic treatment(high-quality low-protein diet,blood pressure control,lipid-lowering,correcting the acidosis,etc.).In addition,the treatment group received 20 mL HSR and the control group received placebo,3 times a day for 6 months.Renal function(serum creatinine,blood urea nitrogen and uric acid) and blood lipids(cholesterol,triglycerides and low density lipoprotein) were examined monthly.The estimated glomerular filtration rate(eGFR) and CM syndrome score were compared between groups.Results:After treatment,compared with the control group,the serum creatinine level,uric acid level and CM syndrome score of the treatment group were significantly decreased(P0.05 or P0.01),and the eGFR in the treatment group were significantly increased(P0.05).Conclusion:HSR can effectively improve the renal function and clinical symptoms of ARAS patients.     

Spectrophotometric analysis of crown discoloration induced by MTA- and ZnOE-based sealers

Crown discoloration can be induced by root canal sealer remnants following root canal treatment.

Objective:

The aim of this study was to evaluate chromatic alterations in human tooth crowns induced by a Mineral Trioxide Aggregate-based sealer (MTA Fillapex^® and a commonly used ZnOE-based sealer (Roth-811). The tested null hypothesis was that the application of the materials did not induce clinically perceptible crown discoloration (Ho: CIE color difference ΔE<3.7).

Material and Methods:

Forty five fully developed, intact, mandibular third molars were sectioned 1 mm below the cemento-enamel junction. The pulp chambers were chemomechanically debrided via the cervical access. The specimens were randomly assigned into three groups Group 1: MTA Fillapex, Group 2: Roth 811, Group 3: Negative control (unfilled) and immersed in individually marked vials containing distilled water up to the cervix (37±1º C). The spectral reflectance lines were recorded by utilizing a UV-VIS spectrophotometer equipped with integration sphere in the visual spectrum at baseline, 1 week, 1 and 3 months after material placement. Data were transformed into values of the CIE L*a*b* color system and the corresponding ΔE values were calculated. Statistical analysis was performed using two-way mixed ANOVA models, at p=0.05 level of significance.

Results:

A statistically significant increase in a* and b* chromatic parameters of the MTA Fillapex Group was measured. However, ΔE values did not exceed the human eye perceptibility threshold (set at ΔE<3.7) during the experimental period (ΔEt3=2.88). In Roth-811 Group, a statistically significant decrease in L* and a statistically significant increase in a* and b* chromatic parameters was measured, during all observation periods. Resultant ΔE values exceeded the human eye perceptibility threshold after 1 week (ΔEt1=5.65).

Conclusions:

Application of MTA Fillapex in tooth crowns resulted in minimal color alterations, while Roth 811 induced severe discoloration, in vitro. It could be suggested that, in terms of aesthetics, the use of MTA Fillapex appears to be favorable.     

Extrapolation: Experience gained from original biologics

Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of ‘extrapolation’, that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars.     

Clonidine Inhibits Postprandial Response of Antral Myoelectrical Activity

Clonidine, an 811w501457q2073/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenergic agonist, is known to inhibit gastric motility and delay gastric emptying in both humans and animals, but its effect on gastric myoelectric activity is unclear. The aim of this study was to investigate the effect of clonidine on postprandial gastric myoelectric activity. The experiment was performed in eight hound dogs (14.5–22.6 kg) implanted with three pairs of bipolar serosal electrodes with an interval of 4 cm and the most distal pair 2 cm above the pylorus. Each dog was studied twice on two separate days after a complete recovery from surgery. Gastric myoelectrical activity was recorded for 30 min in the fasting state and 90 min after a solid test meal of 838 kcal. Two tablets of clonidine (0.4 mg) were given with the meal in one of the sessions. The dominant frequency and power of the slow waves from the most distal pair were calculated by computerized spectral analysis. All data were expressed as mean ± se. A significant postprandial increase in the dominant power of the slow wave and an increase in the percentages of gastric slow waves with spike bursts were observed in the control session, whereas the dominant frequency of gastric slow waves showed a significant postprandial decrease after the meal. The dominant power increased 8.24 ± 0.5, 8.6 ± 0.2, and 7.5 ± 0.3 dB, respectively, in the first, and second, and third 30-min period after the meal (all P < 0.01 vs baseline). Clonidine completely abolished the postprandial increase in the dominant power of the gastric slow wave and significantly inhibited spike bursts. The dominant power only increased 2.4 ± 1.1 dB (P > 0.05 vs baseline; P < 0.01 vs the first postprandial period in the control session), 0.6 ± 1.5 dB (P > 0.05 vs baseline; P < 0.05 vs the second postprandial period in the control session) and –1.5 ± 2.2 dB (P > 0.05 vs baseline; P < 0.05 vs the third postprandial period in the control session) respectively during the first, second, and third periods after the meal and clonidine. However, it did not affect the postprandial change of the dominant frequency of gastric slow waves. No significant changes in percentage of regular slow waves were noted with the meal or with clonidine (P > 0.05). In conclusion, the postprandial response of gastric myoelectrical activity in dogs to a solid meal is featured with an increase in amplitude and spike bursts, which is inhibited by clonidine.     

AP-811, a novel ANP-C receptor selective agonist

AP-811 is a derivative of the Phe8-Ile15 region of atrial natriuretic peptide (ANP) and is one of the smallest linear ligands for ANP receptors. The binding and agonist activities of AP-811 have been compared with those of other ANP analogs for the ANP-A and ANP-C receptors. AP–811 binds with a high binding affinity to and is a strong agonist for the ANP-C receptor, indicating that the binding and agonist sites for this receptor are the same or near each other in the ANP sequence. In contrast, AP-811 showed no agonistic effect for the ANP-A receptor, although it could bind to this receptor. Comparing the biological activities of AP-811 with those of other ANP analogs, we propose that the binding and agonist sites for the ANP-A receptor may consist of separate regions of ANP. In conclusion, AP-811 is the smallest C-receptor-selective agonist.     

Complex coronary angioplasty: Multiple coronary dilatations

Selected patients underwent PTCA of multiple stenoses in different vessels or in the same vessel. Three hundred nine patients underwent 685 PTCA procedures in various combinations of arterial and vein graft stenoses. A multiple dilatation procedure was defined as successful when all lesions attempted were successfully dilated, or when the considered-critical-stenosis was successfully dilated and this resulted in a patient clinical improvement. Angiographic success was achieved in 599 of 685 lesions attempted (87.4%) and in 285 of 309 patients (92.2%). Complications included a mortality rate of 1.0%, an MI rate of 4.2% per patient and 1.9% per lesion attempted, and a 3.6% incidence of emergency CABG. Follow-up data show that 58 patients (20.4%) had clinical evidence of a lesion recurrence, and that 92.5% (37 of 40 patients) who underwent repeat angioplasty had a successful procedure. A sustained clinical improvement was obtained in 264 of 309 patients (85.4%). The data indicate that multiple dilatations are feasible with good success rates and acceptable complication rates. Further evaluation of this extended application of PTCA is needed to clearly establish its role in the therapy of CAD.     

Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats

Previous studies have shown that diabetes mellitus leads in rats to a 45% decrease in cardiac Ca++ activated myosin ATPase, a change in myosin isoenzyme distribution and a lowering of plasma T4 and T3 levels. Hypothyroidism causes similar changes in myosin ATPase and myosin isoenzyme distribution. We determined if thyroid hormone administration in physiological replacement dose (0.3 microgram T3/100 g BW) or pharmacological doses (3 micrograms T3/100 g BW and 10 micrograms T4/100 g BW) can normalize myosin ATPase and isoenzyme distribution in diabetic rats. Control animals have a Ca++ myosin ATPase activity of 1.23 +/- 0.14 mumol Pi/mg protein/min and myosin V1 represented 70% and myosin V3 15% of total myosin. Four weeks after streptozotocin administration myosin ATPase was 0.61 +/- 0.14, and myosin V3 represented 67% of total myosin. Administration of 0.3 microgram T3/100 g BW/day for four weeks to diabetic animals resulted in no significant increase in myosin ATPase (0.69 +/- 0.07 mumol Pi/mg protein/min) or in myosin isoenzyme distribution. In contrast, administration of 3 micrograms T3/100 g BW/day or 10 micrograms T4/100 g BW/day for 4 wk led to a normalization of myosin ATPase activity (for T3 1.03 +/- 0.18, for T4 1.06 +/- 0.15). In addition the myosin isoenzyme distribution pattern normalized. These findings may point to a diminished thyroid hormone responsiveness in diabetic rats or could result from diabetes related disturbances of cellular metabolism, which are normalized by pharmacologic doses of thyroid hormone.