NSAID对胰腺癌中COX-2的表达及其生长活力的影响

目的 :检测胰腺癌中COX 2表达 ,探讨COX 2抑制剂非甾体类消炎药 (NSAID)的抑癌机制。方法 :胰腺癌组织和细胞株中的COX 2检测分别采用免疫组化和细胞免疫化学分析 ,并使用MTT法及流式细胞仪检测细胞株生长活力和凋亡。结果 :胰腺癌组织中COX 2的表达增强 ,阳性率 73.3% (P <0 .0 5 )。SW 1 990和Capan 2细胞株均有COX 2表达 ,前者高表达 ,后者低表达。两种NSAID(NS398及ASA)均可抑制两种细胞株的生长 ,诱导细胞凋亡率显著升高 ,并与细胞株COX 2表达强度有关 ;对SW 1 990细胞株的作用强于Capan 2 ,NS398的抑制作用又强于ASA。结论 :COX 2在胰腺癌组织和细胞株中表达增强 ,NSAID抗胰腺癌机制可能是通过抑制COX 2活性 ,诱导胰腺癌细胞凋亡     

Anti-glomerular basement membrane disease and dual positivity for antineutrophil cytoplasmic antibody in a patient with membranous nephropathy

We present the case of a 50-year-old man who underwent kidney biopsy for nephrotic syndrome. In addition to a membranous pattern, anti-glomerular basement membrane (anti-GBM) staining was noted before manifestations of anti-GBM disease. Hematuria and renal failure ensued 2 weeks later. In addition, he had simultaneous circulating levels of anti-GBM antibody and both perinuclear (P-) and cytoplasmic (C-) antineutrophil cytoplasmic antibody (ANCA).     

A rehabilitation tool for functional balance using altered gravity and virtual reality

Background  

There is a need for effective and early functional rehabilitation of patients with gait and balance problems including those with spinal cord injury, neurological diseases and recovering from hip fractures, a common consequence of falls especially in the elderly population. Gait training in these patients using partial body weight support (BWS) on a treadmill, a technique that involves unloading the subject through a harness, improves walking better than training with full weight bearing. One problem with this technique not commonly acknowledged is that the harness provides external support that essentially eliminates associated postural adjustments (APAs) required for independent gait. We have developed a device to address this issue and conducted a training study for proof of concept of efficacy.     

The global burden of congenital heart disease

Abstract

Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. In a country with a fertility rate of about eight per woman, the population has to support four times as many children with CHD as in a country with a fertility rate of two. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity. Countries with high fertility rates have more children with congenital heart disease per wage earner. Improving local health services and controlling infectious diseases (diarrhoeal illness, rheumatic fever, measles, rotoviral infection) are important but are mere ‘band-aids’ compared to improving education, empowering women and reducing birth rates.     

Glucose metabolic phenotype of pancreatic cancer

AIM: To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma(PDAC) reflecting tumour-related metabolic enzyme expression.METHODS: A systematic review of the literature was performed using Ovid SP and Pub Med databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation(MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.     

URINARY BILE ACID CONJUGATES IN EXTRAHEPATIC BILIARY ATRESIA

The urinary excretion of bile acid conjugates was studied after the administration of 24-¹⁴C-labelled chenodeoxycholic acid and cholic acid and their corresponding glycine conjugates labelled with glycine-l-¹⁴T in 5 infants with extrahepatic biliary atresia. Chenodeoxycholic acid-24-¹⁴C and chenodeoxycholyl[l-¹⁴C]glycine were mainly excreted in the form of labelled metabolites with the TLC behaviour of monosulphates of tauro- and glycochenodeoxycholate and glycochenodeoxycholate, respectively. Most of the cholic acid-24-¹⁴C and the cholyl[l-¹⁴C]glycine were found to be excreted in the form of glycocholate. All labelled bile acids were excreted in conjugated form.     

AIDS-RELATED BEHAVIOUR IN ADOLESCENTS: INTERVENTION PROGRAMME WITH INTERNATIONAL APPLICATION

SUMMARY Adolescents and young adults comprise one of the fastest-growing categories of AIDS cases. The results of an opinion survey taken of 3242 adolescents raise serious doubts about the prevalent view that high-risk behaviour is attributable to insufficient information and education on AIDS: female adolescents are found to be at risk despite having the proper knowledge. Five chief factors affected the knowledge and behaviour of adolescents: age, gender, origin, family profession, and parental education. Each of the subpopulations (females, younger adolescents, children in rural areas) has its own characteristics and needs. We describe a permanent and long-term intervention programme, which might be applied in any country.     

Extracellular matrix components in Kimmelstiel Wilson nodules

Summary: The distribution of collagen types I, III, IV, V, VI, fibronectin laminin, tenascin, heparan sulfate proteoglycan and chondroitin sulphate proteoglycan was examined by light microscopy immunocytochemistry (ICC) in paraffin-embedded renal biopsies with nodular diabetic glomeruloscierosis. Immunoglobulin A, G and M, complement (C3c and C1q), fibrinogen and k and γ light chain deposition was also sought by ICC in the same tissue.
Kimmelstiel Wilson (KW) nodules were graded as either evolving (>3 nuclei present +/ - fibrillary appearance) or as late stage (amorphous and acellular). the extracellular matrix (ECM) components present in the evolving KW nodules were the same as those present in normal mesangial matrix but with an increased density. Late stage nodules displayed negative binding for all antibodies in their core with accentuated expression of the normal mesangial matrix components together with complement and 1gM at their periphery. Occasionally, when ruptures in Bowman's capsule (BC) were detected and adhesions between the capsule and the nodular tuft occurred, the interstitial collagens I and III were detected within laminations of Bowman's capsule, in Bowman's space, at adhesion sites and within some nodules.
The results suggest nodular lesions are initially formed by aggregation and/or increase in the normal components of mesangial matrix. the normal mesangial matrix constituent proteins are subsequently relocated to the periphery by amorphous material in which these ECM components are not detected. When BC is disrupted, interstitial collagens I and III may appear in Bowman's space and within nodules.     

The Mitochondrial Genome And Human Mitochondrial Diseases

To date, more than 100 point mutations and several hundreds of structural rearrangements of mitochondrial DNA (mtDNA) are known too be connected with characteristic neuromuscular and other mitochondrial syndromes varying from those causing death at the neonatal stage to diseases with late ages of onset. The immediate cause of mitochondrial disorders is a defective oxidative phosphorylation. Wide phenotypic variation and the heteroplasmy phenomenon, which some authors include in mutation load, are characteristic of human mitochondrial diseases. As the numbers of cases identified and pedigrees described increase, data on the genotype-phenotype interaction and the structure and frequency of pathogenic and conditionally pathogenic mtDNA mutations in human populations are rapidly accumulated. The data on the genetics and epidemiology of mitochondrial diseases are not only important for differential diagnosis and genetic counseling. Since both neutral and mildly pathogenic mutations of mtDNA are progressively accumulated in maternal phyletic lines, molecular analysis of these mutations permits not only reconstruction of the genealogical tree of modern humans, but also estimation of the role that these mutations play in natural selection.     

Effect of saturable binding on the pharmacokinetics of drugs: a simulation

The time-courses of both total and unbound drug concentrations with time were simulated under conditions of saturable binding to either plasma proteins or tissues, or both, following a single intravenous dose. The curves were either linear, convex, or concave, depending upon the extent of distribution and the intrinsic ability of an eliminating organ to remove drug from the body. Saturable binding should therefore be considered whenever data showing nonlinear semilogarithmic decline are to be interpreted.