Release phenomena of insulin from an implantable device composed of a polyion complex of chitosan and sodium hyaluronate

An implant controlled-release system for protein drug delivery based on a polyion complex device composed of chitosan (CS) and sodium hyaluronate (HA) was investigated. The conditions which generated the greatest amount of the polyion solid complex were studied to ascertain the formation of polyion complex between CS and HA. The greatest amount of the polyion complex was formed at the weight ratio of 3 to 7 (CS:HA) at pH 3.5. Furthermore, the CS–HA pellets were prepared and then drug release from CS–HA pellets was evaluated using insulin as a model drug. The results demonstrated that the insulin release from CS–HA pellets was markedly influenced by both the change in the polymer mixing ratio and the total pellet weight, whereas the compression pressure did not affect the release significantly. An artificial neural network (ANN) and biharmonic spline interpolation (HSI) were employed to predict the actual relation between causal factors and the release rate constant of insulin. Although both the ANN and HSI successfully represented a non-linear relationship between the formulation factors and the release rate constant, HSI methodology gave a better estimation than that of the ANN.     

Mitral valve repair for mitral insufficiency due to infective endocarditis in a patient with idiopathic thrombocytopenic purpura.

A 63-year-old woman with an 18-year history of idiopathic thrombocytopenic purpura (ITP) was admitted with a persistent fever of unknown cause. Blood culture was positive for alpha-Streptococcus and echocardiography revealed severe mitral regurgitation and vegetation on the mitral valve. After antimicrobial therapy for six weeks, she underwent mitral valve repair using a Cosgrove ring. The platelet count increased and remained stable by perioperative treatment with intravenous high-dose gamma-globulin and platelet transfusion without steroids therapy or splenectomy. The hospital course was uneventful. Perioperative high-dose gamma-globulin therapy and platelet transfusion for the cardiac operation were useful to increase and maintain the platelet count for an ITP patient complicated with infective endocarditis.     

Erk pathways negatively regulate matrix mineralization

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.     

The use of a biventricular assist device for postcardiotomy profound biventricular failure

A 58-year-old woman who could not be weaned from cardiopulmonary bypass was treated with a biventricular assist device (BVAD) using a centrifugal pump for the left side and a pneumatic pulsatile pump for the right side. At the initiation of the BVAD support, predominant right ventricular failure was recognized and therefore weaning was begun from the left side. The left ventricular assist device was discontinued after 87 h and the patient was finally weaned from the right ventricular assist device after 205 h. Despite the complete recovery of cardiac function, the patient developed renal failure followed by an intractable infection and died of multiple organ failure on the 59th postoperative day (POD).     

Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection

Background

Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer.

Methods

A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer.

Results

Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different.

Conclusions

LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.     

Definite familial multiple system atrophy with unknown genetics

Multiple system atrophy (MSA) is an oligodendrogliopathy of presumably sporadic origin, characterized by prominent α‐synuclein inclusions with neuronal multisystem degeneration, although a few Mendelian pedigrees have been reported. Here we report two familial cases of MSA of unknown genetic background. One patient was diagnosed as a possible MSA‐C (cerebellar dysfuntion) case, and the other as clinically possible MSA‐P (parkinsonism), which turned out to be definite MSA, based on a detailed autopsy. The neuropathology showed extensive deposition of α‐synuclein in the glia as well as in the neurons located in the cerebral cortices and hippocampal systems, although neither multiplication of the SNCA gene or mutations in COQ2 gene were identified in the family concerned.     

Optimization of the Manufacturing Process for Oral Formulations Using Multivariate Statistical Methods

Multivariate statistical analysis has and will continue to play an important role in the development of pharmaceutical products. Although many examples have been reported, few have applied multivariate statistical analysis to the overall manufacturing process. In this study, the model drug core tablets were manufactured under different conditions, and the challenge to understand the cause-and-effect relationship between process parameters and response variables was addressed by applying three different multivariate statistical methods. It was confirmed that conventional multivariate statistical methods were able to extract the process parameters (granulation time, drying temperature, blending time, and compression force) that affected both the average and the variance of the response variables (hardness, content uniformity, and dissolution) with a science-based rationale. In order to overcome the multiobjective optimization problem among the response variables, an advanced multivariate statistical method was also applied. It was confirmed that the mathematical models of response variables were determined with sufficiently high accuracy and the optimal levels of both process parameters and response variables were determined with high reliability, which provided a more profound understanding of the process. These methods enable us to develop pharmaceutical products more efficiently and accurately.