胎盘:遗失的神经内分泌器官

胎盘被认为是妊娠期间第1个产生功能的器官,可以反映母体健康及营养状态,通过胎盘功能的调整可优化胎儿生长.在过去20年间,Barker提出了胎儿宫内生长障碍可引起内分泌功能程序化,导致成年期冠心病、高血压和糖尿病的假说,使人们更多地去研究胎盘功能与胎儿生长的关系.研究发现母体、胎儿与胎盘及其分泌的大量活性神经激素关系密切,使胎盘成为研究胎儿环境的主要目标.     

Antioxidant idebenone-loaded nanoparticles based on chitosan and N-carboxymethylchitosan

Nanoparticles based on chitosan (Ch) and N-carboxymethylchitosan (N-CMCh) cross-linked with tripolyphosphate (TPP) were developed by co-drying with idebenone in different polymer-to-drug ratios (1.3:1 to 16:1) with 20% (wt/wt) colloidal silicon dioxide and tripolyphosphate (0.2 mg/mL). At high ratios (8:1 and 16:1) the spray-dried powder showed spherical and dense particles with a size close to 1 μm, allowing almost complete drug coating by the polymeric system and a high efficiency of drug incorporation (>90% and >80%, for Ch and N-CMCh, respectively). The nanoparticles showed a 10-fold increase of drug stability in comparison with free drug and preserved antioxidant activity in vitro. Compared with the severely irritative free form of idebenone, the nanoparticle formulation showed decreased mucous membrane irritation. These results revealed the potential of Ch and N-CMCh nanoparticles as carriers for a hydrophobic and irritative drug such as idebenone for topical or nasal use.From the Clinical EditorChitosan and N-carboxymethylchitosan nanoparticles have potential roles as carriers for hydrophobic and irritative drugs such as the antioxidant idebenone for topical or nasal use.     

Ranitidine bismuth citrate: a novel anti-ulcer agent with different physico-chemical characteristics and improved biological activity to a bismuth citrate-ranitidine admixture.

BACKGROUND: Ranitidine bismuth citrate (RBC) is a new chemical entity for the treatment of peptic ulcer disease. RESULTS: RBC is freely soluble in water (more than 600 mg/mL at pH 4.6), whereas an equimolar admixture of its component molecules, bismuth citrate and ranitidine, formed an almost totally insoluble suspension. Even at very low pH values (around 2.0), the solubility of bismuth in ranitidine bismuth citrate was at least two-fold better than in the admixture. Comparison of several physico-chemical characteristics indicated that RBC possessed significantly different melting point properties, X-ray powder diffraction patterns, infra-red spectra and 13C-NMR solid-state spectra to the admixture. Ranitidine bismuth citrate inhibited human pepsin isoenzymes 1, 2, 3 and 5 but the admixture was inactive. RBC showed approximately two-fold greater anti-Helicobacter pylori activity in vitro than the admixture (geometric mean minimum inhibitory concentrations of 12.5 and 25.7 mg/L, respectively) and was more rapidly bactericidal. In a mouse model of gastric H. pylori colonization, 200 mg/kg of bismuth, given as RBC, eradicated the organism from all mice while only 10% of infections were eradicated by equivalent levels of bismuth in admixture form. CONCLUSION: It is believed that the significantly greater solubility of RBC, especially at lower pH values, is highly relevant to its better antipepsin and anti-H. pylori action compared to the insoluble admixture of bismuth citrate and ranitidine.     

Osseous and non-osseous coalition of the middle facet of the talocalcaneal joint.

Sixteen patients (eighteen feet) who had a coalition of the middle facet of the talocalcaneal joint had operative resection of the coalition because nonoperative treatment, such as casts, failed to relieve the symptoms. The patients were symptomatic for an average of one and a half years (range, four months to two years) before they were seen by us. The average age at the time of the operation was fourteen years (range, seven to nineteen years). Three feet had resection with no material interposed, six had resection with interposition of fat, and nine had resection with interposition of half of the tendon of the flexor hallucis longus muscle. The average length of follow-up was four years (range, two to eight years). The result was excellent for eight feet, good for eight feet, and fair for one foot; for one foot, the result was poor because the coalition recurred. Three types of coalition were identified on preoperative computed-tomography scans that correlated with the operative findings. Type I was an osseous bridging of the middle facet joint (five feet). Type II (cartilaginous coalition) was marked narrowing of the middle facet joint with cortical irregularity (three feet). In Type III (fibrous coalition), there was only slight narrowing of the middle facet joint (ten feet). The type of coalition did not influence the result. Fibrous coalitions were the most difficult to detect; bone scintigraphy was used to confirm the diagnosis when other tests were equivocal. We believe that symptomatic coalition of the middle facet of the talocalcaneal joint should be treated with resection when non-operative methods fail to relieve symptoms.     

Causes of childhood deaths in Bangladesh: an update

Knowledge of the causes of child death is important for health-sector planning since they relate to available interventions. Little is known about causes of child death in Bangladesh from the conventional sources since there is no vital registration system and very few deaths are attended by a qualified physician. To determine the cause structure of child deaths, verbal autopsy interviews were conducted in the Bangladesh Demographic and Health Survey (BDHS) 1993/94 national sample. Verbal autopsy is a method of finding out the causes of death based on an interview with the next of kin or other caregivers. Between BDHS 1993/94 and BDHS 1996/97, 1-4-y-old child mortality in Bangladesh declined by about 27.0%. This impressive decline prompted a verbal autopsy study using the BDHS 1996/97 national sample to determine whether the cause structure had changed. The same verbal autopsy instrument and methods to collect the data and the same computer algorithm to assign causes of death were used in both surveys. Comparison of BDHS 1993/94 and 1996/97 cause-specific mortality rates revealed that deaths due to almost all causes had declined, although significantly so only for acute respiratory infections (ARI), persistent diarrhoea and drowning. Deaths due to neonatal tetanus, acute watery diarrhoea and undernutrition had not decreased at all. Conclusion: Despite an impressive decline in deaths due to ARI, this condition remains the most important known cause of death in Bangladeshi children. Neonatal tetanus and measles together account for about 10% of deaths in children under 5 y. Further improvements in child survival are possible by improving access to and quality of available child survival interventions.     

Investigations of the antifibrillatory activity of flunarizine and lidoflazine in isolated hearts of rabbits and guinea pigs

In Langendorff-perfused rabbit hearts, ventricular fibrillation threshold (VFT) was measured by applying rectangular impulses of 3ms duration at a frequency of 20Hz. Perfusion with 0.2 and 0.4 microM of flunarizine or 0.2 microM of lidoflazine produced a significant rise in VFT. When the hearts were perfused with higher concentrations of either drug (0.8 microM flunarizine, 0.4 and 0.8 microM lidoflazine), VFT did not continue to increase in a dose-dependent manner but rather a smaller increase in VFT than the previous dose was observed. Both drugs caused significant decrease in the spontaneous heart rate and amplitude of contraction of the isolated rabbit heart. In the Langendorff-perfused guinea pig heart, perfusion with 0.8 microM of flunarizine produced complete protection against ouabain-induced ventricular fibrillation while 7 out of 7 and 1 out of 6 hearts fibrillated in the presence of 0.2 and 0.4 microM of the drug respectively. During perfusion with 0.2, 0.4 and 0.8 microM of lidoflazine the incidence of ventricular fibrillation was 3 out of 6, and 5 out of 7 hearts respectively. These results may indicate a limited effectiveness of these 2 calcium entry blockers against ventricular fibrillation.