Application of Moment Analysis to the Sigmoid Effect Model for Drug Administered Intravenously

Pharmaceutical Research -     

Cardiopulmonary and sinoaortic baroreceptors and volume expansion in the monkey

Summary Experiments were performed to determine the effect of combined cardiopulmonary and sinoaortic baroreceptor denervation on the renal responses of the anesthetized nonhuman primate to acute intravascular volume expansion. Adult maleMacaca fascicularis monkeys underwent chronic bilateral thoracic sympathectomy (middle cervical ganglion-T₆) or sham surgery performed in two stages. After a 1–3 week recovery period, each animal was anesthetized with sodium pentobarbital and subjected to cervical vagotomy-sinoaortic denervation or further sham denervation. Estimated blood volume was then acutely expanded 20% with 6% dextran in isotonic saline. Control renal excretory function did not differ between the two groups, and both groups had similar increases in urine flow, sodium excretion, osmolar clearance, free water clearance and renal plasma flow after volume expansion. The patterns of the responses showed some group differences in that the increases in renal excretion after volume-loading had an earlier onset in the denervated animals. These results demonstrate that combined ablation of thoracic sympathetic, vagal and sinoaortic neural pathways does not compromise the ability of the nonhuman primate to increase salt and water excretion when blood volume is acutely expanded. Therefore, these neural mechanisms are not necessary for eliciting the renal responses to this hypervolemic stimulus in this species during the anesthetized state.Supported by NIH Grant No. HL31987Recipient of a Research Career Development Award (HL01383) from the National Heart, Lung and Blood Institute     

Involvement of the transforming growth factor-β system in the pathogenesis of diabetic nephropathy

The manifestation of diabetic nephropathy may be a consequence of the actions of certain cytokines and growth factors. Prominent among them is transforming growth factor-β (TGF-β), which promotes renal cell hypertrophy and stimulates extracellular matrix accumulation, the two hallmarks of diabetic renal disease. In experimental and human diabetes mellitus, several reports describe overexpression of TGF-β in the glomeruli and tubulointerstitium. In renal cell cultures, hypertrophy and matrix production are stimulated by high glucose concentrations in the culture media. High glucose, in turn, appears to act through the TGF-β system; high glucose increases TGF-β expression, and the hypertrophic and matrix stimulatory effects of high glucose are prevented by anti-TGF-β therapy. Short-term treatment with the same neutralizing monoclonal antibodies against TGF-β in type 1 diabetic mice significantly reduces kidney weight and glomerular hypertrophy and attenuates the increase in extracellular matrix mRNA. Similar treatment of type 2 diabetic mice in the long term further diminishes the renal pathology and ameliorates the functional abnormalities of diabetic nephropathy. Finally, the intrarenal TGF-β system is significantly up-regulated in human diabetes. Whereas the kidney of a nondiabetic subject extracts TGF-β1 from the circulation, the kidney of a diabetic patient elaborates TGF-β1 protein into the circulation. The data we review here strongly support the hypothesis that elevated production or activity of the TGF-β system mediates diabetic renal hypertrophy and extracellular matrix expansion. Received: June 6, 2002 / Accepted: July 12, 2002     

Free expanded scalp flap for reconstruction of the temporal hair line

A 20-year-old male who sustained a severe avulsion injury of his left scalp and face together with a cranial bone fracture on his right temple six years previously, presented with extensive alopecia over the left temporal scalp. There was also a depression in the right temple with complex scarring caused by previous operations. A simultaneous complete reconstruction of the scalp defect and the depression was obtained by expansion of the left temporoparietal scalp, followed by free-flap transfer of the expanded tissue and augmentation with a free scapular flap. The end result was very satisfactory.     

C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats.

BACKGROUND: There is accumulating evidence that C-peptide exerts beneficial renal effects in type-1 diabetes by reducing glomerular hyperfiltration, albuminuria and glomerular hypertrophy in the early stage of nephropathy. The aim of this study was to clarify further the effects of C-peptide on renal structural changes in type-1 diabetic rats. METHODS: The effects of C-peptide or placebo on glomerular volume, mesangial expansion, glomerular basement membrane thickness, albuminuria and glomerular filtration rate (GFR) were studied in three groups of rats: a non-diabetic group (N, n=9) and two groups that, during 8 weeks of diabetes, were left untreated for 4 weeks and then given a subcutaneous infusion of either placebo (D, n=11) or C-peptide (DCp, n=11) during the next 4 weeks. Furthermore, GFR was studied after 4 weeks of diabetes in an additional diabetic group (D-early, n=9) and in an age-matched non-diabetic group (N-early, n=9). RESULTS: After 4 weeks, GFR in the D-early group was 102% higher than in the N-early group. GFR after 8 weeks did not differ between the study groups. The D group presented with a 33% larger glomerular volume than the N group (P<0.001), while glomerular volume in the DCp group was similar to that in the N-group. Total mesangial and mesangial matrix fractions were increased by 46% (P<0.001) and 133% (P<0.001), respectively, in the D group. The corresponding values in the DCp group did not differ from those for the non-diabetic animals. Neither the thickness of the glomerular basement membrane nor the level of albuminuria differed significantly between the study groups. CONCLUSIONS: C-peptide administration in replacement dose to streptozotocin-diabetic rats serves to limit or prevent the glomerular hypertrophy and the mesangial matrix expansion seen in the post-hyperfiltration phase of early diabetic nephropathy.     

扩张法全耳廓Ⅰ期再造术的临床研究

目的：探讨耳廓I期再造的临床效果及操作要点。方法：采用软组织扩张术获得耳区薄而面积较大的无毛发皮肤，用自体肋软骨雕刻成形，I期完成耳廓再造。结果：本组治疗21例，19例效果良好，1例扩张期血肿取出扩张器终止手术，1例再造耳廓部分坏死，经修复后效果满意。结论：扩张法耳再造利用耳区皮肤，经扩张使无发区皮肤表面积增加，皮肤变薄，为再造耳提供了薄而无毛发的皮肤，又由于此法在扩张后一次成形耳廓，在软骨的雕刻上提供了耳立体成形的条件，增加了耳廓立体逼真的效果。     

皮肤软组织扩张术对创伤致畸病人病理心理影响的调查研究

目的 研究使用皮肤软组织扩张器病人在扩张过程中的躯体症状及心理特征。方法 用自编调表的形式，对曾在我院行扩张术治疗的57例创伤致畸病人，分别在扩张器置入前、扩张过程中及扩张皮瓣转移后3个时期问卷调查。结果 扩张过程中，胀、痛、痒的发生率分别为52.63%,47.37%及42.11%。其中胀感最具特征性。病变的痛、痒等症状在扩张器置入前及扩张皮瓣移转后也有较高的发生率。在扩张过程中，多数病人呈明显的紧张和焦虑，对手术效果有很高的期望值（84.21%）。病人对自我情感和健康的评价在整个治疗过程中呈现出两个明显的过程。结论 扩张过程中，胀感是最典型的局部症状，紧张、焦虎是常见的心理状态，病人对皮肤软组织扩张术有很高的期望值，治疗过程中呈现先喜后忧的心理变化过程。     

镍钛记忆合金牵张犬腭骨-上颌骨缝超微结构的研究

目的 利用透射电镜观察不同时间段犬腭骨-上颌骨缝内细胞超微结构的变化,以探索颅面部骨缝组织在张力作用下的变化.方法 制作镍钛形状记忆合金(NiTi-SMA)扩张器,并用口腔矫形测力器测定其最大力值为3.5 N.选择8周龄杂种犬45只,随机分为空白对照组、实验对照组、实验组.实验对照组和实验组在全麻下,去除硬腭中部后部骨质,缝合口腔和鼻腔侧黏膜,形成宽约8 mm的腭裂模型.实验组将NiTi-SMA安置在硬腭上,分别于牵张后3、7、14、28、56 d处死动物,并制作电镜标本.透射电镜下观察腭骨-上颌骨缝内细胞的变化过程.结果 电镜下腭骨-上颌骨缝牵张,首先表现为组织断裂,渗出,细胞死亡,随后是骨和纤维生成细胞群增殖活跃,成骨细胞和成纤维细胞功能增强,最终恢复正常缝组织结构.结论 电镜下可以区分缝细胞的类型和功能状态,提示缝牵张是组织修复与再生并存的过程,张力引发细胞反应特别是成骨反应是导致骨缝增宽的主要因素.     

联合应用前方牵引与快速扩弓对恒牙早期安氏Ⅲ类错的矫治效果及稳定性研究

目的　研究联合应用上颌前方牵引与快速扩弓对恒牙早期Ⅲ类骨性错牙合的矫治效果及稳定性。方法　恒牙早期安氏Ⅲ类患者 1 2例 ,应用联合法解除反牙合后 ,应用方丝弓矫治技术 ,对 1 2例患者矫治前、联合牵引及扩弓治疗 ,矫治病例完成后及保持结束 1年后的头颅侧位片进行分析。选择错牙合类型、年龄、性别等与之相匹配的恒牙早期反牙合患者 ,采用方丝弓矫治器治疗做对照。结果　恒牙早期患者 ,前方牵引加快速扩弓治疗 ,上颌A点前移不明显 ,下颌少量后退 ,覆盖改变骨性变化较少 ,牙性变化占比例较大 ,保持期结束后 ,覆盖分别减少了 1 1mm和 1 5mm。实验组疗程平均缩短 3 6个月。结论　恒牙早期前方牵引与快速扩弓联合应用 ,矫形作用不明显 ,但可缩短治疗时间     

造血生长因子对脐血单个核细胞的体外增殖效应

目的 :探讨不同造血生长因子组合对人脐血造血细胞的体外增殖效应 .方法 :采用免疫荧光染色和祖细胞集落测定 ,观察人脐血单个核细胞 (MNC)经多种造血生长因子的不同组合作用 2wk后其有核细胞、CD34+ 细胞和祖细胞数量的变化 ,并用脾结节形成实验和骨髓祖细胞培养等观察其在小鼠体内的短期造血能力 .结果 :脐血MNC分别与A(SCF /IL 3/IL 6 /G CSF/GM CSF) ,B(SCF/IL 3/IL 6 /FL/EPO) ,C(SCF/IL 3/IL 6 /EPO ) ,3种造血生长因子组合悬浮培养 2wk ,有核细胞、CD34+ 细胞和祖细胞数量增加 .有核细胞总数在B组因子作用下增加最显著 [(2 6± 5 )倍 ],而CD34+ 细胞数量在A组因子作用下增加最明显 [(8± 2 )倍 ].3种因子组合对不同种类祖细胞的增殖效应不同 ,其中A组因子主要刺激早期混合系祖细胞CFU Mix扩增 [(11± 2 )倍 ],B组因子主要刺激粒单系祖细胞CFU GM扩增 [(2 2± 3)倍 ],C组因子主要刺激早期红系祖细胞BFU E扩增 [(13± 4 )倍 ].此外 ,给受照小鼠输注A组因子作用后的人脐血细胞 ,13d在小鼠脾脏形成脾结节 (CFU S) ,30d从小鼠骨髓检出造血祖细胞(CFU GM和CFU E) ,造血细胞数量与从输注新鲜脐血细胞的小鼠体内检出的结果无显著性差异 (P >0 .0 5 ) .结论 :造血细胞生长因子对人脐血单个核细胞具有体外