Handedness and headache

A California handedness study involved 199 male and 74 female cluster headache sufferers as well as 477 migraineurs. Earlier reported data indicated that cluster headache patients had a left-handedness prevalence of over 15%. With the current data the prevalence in males was 11.0% and in females, 8.2%. The corresponding migraine figures were 11.8% and 8.1%. The cluster and migraine headache groups did not differ significantly from each other or from the expected 10% frequency of left-handedness in either sex.     

苦红菇化学成分的研究

从野生真菌苦红菇(Russula rosacea(Bull)Grrayem,Fr.)子实体酸性部分得到两个新的四环三萜酸化合物,经光谱(IR,¹HNMR,¹³CNMR,MS)、尤其是二维核磁共振(¹³C-¹HCOSY,COLOC,NOEDIFF)谱解析,确定其结构分别如Ⅰ和Ⅱ所示,Ⅰ命名为苦红菇酸A(rosaceaacidA),Ⅱ为苦红菇酸B(rosaceaacidB)。     

赛庚啶对大鼠心肌细胞膜[3H]-d-cis-硫氮卓酮结合部位的影响

苯并噻嗪类钙通道阻滞剂[³H]-d-cis-硫氮酮能以一种特异和可饱和的方式与离体大鼠心肌细胞膜结合,其K_D值和B_max分别为84nmol·L^-1和0.279pmol·mgprotein^-1。非标记的硫氮酮和赛庚啶均能完全抑制这种结合,其Ki值分别为102nmolL^-1和5.5umol·L^-1。上述结果证实在大鼠心肌细胞膜上也存有[³H]-硫氮酮受体,同时还提示赛马庚啶对心肌细胞膜的钙通道阻滞作用可能与作用于心肌细胞膜[³H]硫氮酮受体有关。     

重症急性胰腺炎患者早期胃内pH值变化的临床意义

目的探讨SAP患者SIRS期胃内pH值变化的临床意义及质子泵抑制剂(PPI)对其的影响。方法对2005年1月至2006年11月间,发病时间≤48h的108例SAP患者,采用试纸法检测胃液pH值变化,观测SAP患者人院时及入院后72h平均胃内pH值及pH值>4、>6的时点数变化,并与APACHEⅡ评分及上消化道出血进行比较。将入院时pH值≤4的74例患者分为PPI持续(A组)和间断(B组)静脉输注两组,观察其胃内pH值的变化及与上消化道出血的关系。结果108例患者入院时平均胃内pH值与APACHEⅡ评分呈负相关(r=-0.433,P<0.05)。pH值≤4与>4的患者分别占68.52%与31.48%.上消化道出血的患者分别有12例与1例.差异显著(x~2=3.8774,P= 0.0489)。应用PPI后0～24h,A、B组平均胃内pH值分别为5.24±0.83与4.79±0.89,24～48h时分别为6.21±1.45与5.56±1.22,差异显著(t=2.2067、2.0888,P=0.0305、0.0403),而48～72h时分别为6.42±1.18、5.98±1.05,差异无意义(t=1.6884,P=0.0957)。72h内,A、B组胃内pH值>4的时点数分别为29.22±2.38、27.97±2.92,无显著差异(t=1.9590,P=0.0540),而>6的时点数分别为25.66±4.98、20.32±3.72,差异显著(t=5.2828,P=0.0000)。两组发生上消化道出血分别为1例与11例(x~2=5.7220,P=0.0168),差异有统计学意义。结论SAP患者早期胃内pH值的高低与病情严重度及上消化道出血发生的危险性高度相关,静脉持续输注PPI能更迅速地提高胃内pH值,并能有效维持高pH值状态,减少上消化道出血的发生。     

Dopaminergic properties and experimental anti-parkinsonian effects of IPX750 in rodent models of Parkinson disease

With a view toward improving the neural bioavailability of administered dopaminergic compounds, including dopamine, synthetic efforts have been directed toward enhancing the brain bioavailability of these compounds by accessing cellular sugar transport systems with stereoselective dopaminergic drugs. While synthesis and chemistry of the resultant class of compounds has recently been described in US Patent No. 6,548,484, the associated biologic properties have not previously been reported. One member of this new class, IPX-750, is a pro-drug dopamine-gluconamine designed to retain stereospecificity of binding at: glucose transporters (GLUT 1/GLUT 3 and intestinal Na/glucose co-transporters SGLT1), dopamine transporter (DAT); and, dopaminergic receptors of the D1/D2 families. Designed to be cleavable by tissue amidases, results reported here show that intact IPX-750 pro-drug retains dopaminergic agonist binding and biologic activities both in vitro and in vivo. IPX-750, like dopamine, exhibited predominant D5/D1 binding specificity with lower binding activity at D2. As expected, binding was highly stereo-specific, ie, IPX-760, a benzamide differing in just a hydrogen atom and keto oxygen from IPX-750, bound with 6-fold lower activity at D5. In cell culture, activation resulted from binding of IPX-750 at D1 or D5 in transfected cells was measured by increased intracellular cAMP. Interestingly, considering prior reported in vitro toxicity of dopamine oxidized and metabolic product dopamine, no evidence of in vitro toxicity was observed at up to 72 hrs in cell cultures at the EC50 of IPX-750 for increasing intracellular cAMP. IPX-750 was evaluated in the Parkinson's disease animal models, including MPTP mouse model, the 6-hydroxydopamine (6-OHDA) rat model and the Nurr1(+/-) knockout mouse model. In MPTP-lesioned and Nurr1+/- knockout mice, IPX-750 significantly increased Rota-rod time. In 6-OHDA-lesioned rats, IPX-750 significantly decreased apomorphine (APO)-induced rotation. Worthy of note, after cessation of IPX-750 treatments the anti-parkinsonian activity in MPTP-lesioned and Nurr1+/- mice required about 2 weeks to washout, suggesting a possible biologic reservoir of drug. In addition, after eight weeks of twice daily administration of 20 mg/kg IPX-750, mice did not show statistical difference in the total number of TH-positive neurons in substantia nigra (SN). These combined results suggest (i) that stereo-specific glycoconjugation may be an effective method to improve penetrability of drugs through the blood brain barrier; (ii) treatment with bioavailable IPX-750 in vitro did not show evidence for neurotoxicity; and, (iii) IPX-750 possesses dopaminergic properties and exerts anti-parkinsonian effects in three different PD rodent models, suggesting therapeutic potential for this new class of drugs in treating dopamine deficiency diseases.     

Mutations in the lipid-binding domain of alpha-synuclein confer overlapping, yet distinct, functional properties in the regulation of dopamine transporter activity

Alpha-synuclein and its missense mutants (A30P, A53T) have been linked to the genesis of idiopathic and rare familial forms of Parkinson's disease, respectively. Here we show that, similar to the wild-type alpha-synuclein, the A30P mutant forms a strong complex with the human dopamine transporter (hDAT), through direct protein:protein interactions between the nonamyloid beta component (NAC) domain of the A30P mutant and the last 22 aminoacyl residues of the carboxy-terminal tail of hDAT. The A30P mutant negatively modulates hDAT functional activity and to a greater extent than wild-type alpha-synuclein, with reduced uptake of extracellular dopamine and dopamine-mediated, hDAT-dependent cytotoxicity. By contrast, the A53T mutant neither forms a strong protein:protein complex with hDAT nor modulates dopamine uptake by hDAT, and dopamine-mediated, hDAT-dependent cytotoxicity is higher than with either wild-type or the A30P variant of alpha-synuclein, but not significantly different from that of cells expressing hDAT alone. Confocal microscopy shows substantial overlap in colocalization of all three alpha-synuclein variants with hDAT, with only minor differences. Although the complex formation with hDAT occurs through the NAC domain of the alpha-synuclein variants, it is the familial Parkinson's disease-linked missense mutations present in the amino-terminal lipid binding domain of the alpha-synuclein variants that dictate the extent of the regulation of hDAT function. These studies highlight previously unknown properties of the A30P and the A53T mutants of alpha-synuclein with respect to the modulation of hDAT activity and/or regulation, and its subsequent functional outcome, which are uniquely distinct.     

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.     

Acute spinal cord injury: MR imaging at 1.5 T

Thirty-seven magnetic resonance (MR) imaging studies were performed with a 1.5-T magnet and surface coils in 27 patients with suspected spinal cord injuries. Imaging was performed 1 day to 6 weeks after injury. Cord abnormalities were seen with MR in 19 patients, while skeletal and/or ligamentous injuries were seen in 21 (78%). Three types of MR signal patterns were seen in association with cord injuries. Acute intraspinal hemorrhage was seen in five patients with cord injuries and demonstrated decreased signal intensity on T2-weighted images obtained within 24 hours of injury. Cord edema and contusion had high signal intensity on T2-weighted images and were observed in 12 cases with cord injury. Neurologic recovery, determined in 16 patients, was insignificant in patients with intraspinal hemorrhage; however, patients with cord edema or contusion recovered significant neurologic function. MR at 1.5 T is extremely useful in the diagnosis of acute cord injury and also demonstrates potential in predicting neurologic recovery.