Use of ultrathin shell microcapsules of hepatocytes in bioartificial liver-assist device

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-microm microcapsules, using an electrostatic droplet generator. The microencapsulated hepatocytes exhibited good in vitro urea synthesis activity in plasma from rats with fulminant hepatic failure (FHF). The ex vivo hemoperfusion was conducted in FHF rats by perfusing plasma at a rate of 1-2 mL/min through 1.5-2 x 10(8) encapsulated hepatocytes packed into a packed-bed bioreactor. Hemoperfusion with the bioreactor was initiated 5 h after operative induction of liver failure and continued for 7 h. The BLAD-treated rats showed improvements over the control groups in survival time and metabolic indicators, including ammonia and total bilirubin levels. Furthermore, expanded bed adsorption (EBA) detoxification technology using Streamline-SP resin was explored to complement the bioreactor with microencapsulated hepatocytes. In vitro experiments indicated that serum ammonia could be specifically removed in dose-dependent manner, whereas the total serum proteins were unaffected by the resin. In ex vivo experiments, hemoperfusion with the resin was initiated 3 h after operative induction of liver failure and continued for 7 h. The resin-treated rats showed obvious serum ammonia removal with no observable total blood protein and blood cell adsorption. Therefore, Streamline-SP resin can potentially be integrated into a BLAD for improved efficacy.     

Collagen-based fibrous scaffold for spatial organization of encapsulated and seeded human mesenchymal stem cells

Living tissues consist of groups of cells organized in a controlled manner to perform a specific function. Spatial distribution of cells within a three-dimensional matrix is critical for the success of any tissue-engineering construct. Fibers endowed with cell-encapsulation capability would facilitate the achievement of this objective. Here we report the synthesis of a cell-encapsulated fibrous scaffold by interfacial polyelectrolyte complexation (IPC) of methylated collagen and a synthetic terpolymer. The collagen component was well distributed in the fiber, which had a mean ultimate tensile strength of 244.6 ± 43.0 MPa. Cultured in proliferating medium, human mesenchymal stem cells (hMSCs) encapsulated in the fibers showed higher proliferation rate than those seeded on the scaffold. Gene expression analysis revealed the maintenance of multipotency for both encapsulated and seeded samples up to 7 days as evidenced by Sox 9, CBFA-1, AFP, PPARγ2, nestin, GFAP, collagen I, osteopontin and osteonectin genes. Beyond that, seeded hMSCs started to express neuronal-specific genes such as aggrecan and MAP2. The study demonstrates the appeal of IPC for scaffold design in general and the promise of collagen-based hybrid fibers for tissue engineering in particular. It lays the foundation for building fibrous scaffold that permits 3D spatial cellular organization and multi-cellular tissue development.     

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka: a case series

The sting of Giant Asian honeybee (Apis dorsata) or Bambara in Sinhala and Karunge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions, which could be fatal in sensitized individuals. We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients' skin.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

The quality of life outcome following treatment for lower urinary tract symptoms

This study aims to assess the impact of medical and surgical treatment on treating lower urinary tract symptoms (LUTS) on pain, prostatic symptoms, disease-specific quality of life and health-related quality of life. Patients scheduled for medical (alpha-blockers) and surgical treatment (transurethral resection of the prostate, TURP) were recruited in the study. The patients were assessed using the Visual Analogue Scale (VAS), Present Pain Intensity (PPI), International Prostate Symptom Score (I-PSS) and Health-Related Quality of Life (HRQOL) at 3-month, 6-month and 12-month (baseline). Before treatment, most of the patients with LUTS had severe pain, LUTS and deterioration of health-related quality of life. Following treatment, both medical and surgical treatment improved their pain, LUTS and health-related quality of life. Both treatments are effective in relieving the symptoms of pain, LUTS and health-related quality of life.     

Long term endocrine complications of acute leukemia therapy--a case report.

We report a patient with acute lymphoblastic leukemia who underwent treatment comprising chemotherapy, radiotherapy (cranial and testicular) and then a bone marrow transplant from an identical twin. He was cured of his leukemia and has been disease-free for nine years. With long term survival, there were problems, notably those of growth and endocrine insufficiency, which needed special considerations in management.     

Reliability and validity of the Malay version of the International Index of Erectile Function (IIEF-15) in the Malaysian population

The objective of this study was to validate the Malay version of the International Index of Erectile Function (IIEF-15) in patients with lower urinary tract symptoms. Reliability and validity was assessed by using the test-retest while Cronbach's alpha was used to assess internal consistency. Effect size 5was evaluated to assess the sensitivity to change in the pre-transurethral resection of the prostate (TURP) vs post-TURP. Internal consistency was excellent. A high degree of internal consistency was observed for each of the 15 items and five domains (Cronbach's alpha value=0.56 and higher and 0.74 and higher, respectively). Test-retest correlation coefficient for the 15 items and domains scores showed no significant changes. Intraclass correlation coefficient for 15 items and domains were high (ICC=0.59 and above). It can be concluded that the Mal-IIEF-15 is suitable, reliable, valid and sensitive to clinical change in the Malaysian population.