Enteral Absorption of Insulin in Rats from Mucoadhesive Chitosan-Coated Liposomes

Purpose. The mucoadhesiveness of polymer-coated liposomes was evaluated to develop a novel drug carrier system for oral administration of poorly absorbed drugs such as peptide drugs. Methods. Multilamellar liposomes consisting of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) (DPPC:DCP = 8:2 in molar ratio) were coated with chitosan (CS), polyvinyl alcohol having a long alkyl chain (PVA-R) and poly (acrylic acid) bearing a cholesteryl group. The adhesiveness of the resultant polymer-coated liposomes to the rat intestine was measured in vitro by a particle counting method with a Coulter counter. The CS-coated liposomes containing insulin were administered to normal rats and the blood glucose level was monitored. Results. The existence of polymer layers on the surface of liposomes was confirmed by measuring the zeta potential of liposomes. The CS-coated liposomes showed the highest mucoadhesiveness and the degree of adhesion was dependent on the amount of CS on the surface of the liposomes. The blood glucose level of rats was found to be significantly decreased after administration of the CS-coated liposomes containing insulin. The lowered glucose level was maintained for more than 12h after administration of the liposomal insulin, which suggested mucoadhesion of the CS-coated liposomes in the intestinal tract of the rats.     

Open reduction and varus-detorsion osteotomy with femoral shortening in treatment of congenital dislocation of the hip

In this study, we clinically and radiographically evaluated open reduction with shortening of the femur in children more than 1 year old with refractory congenital dislocation of the hip. In 19 children (aged 1–4 years), 22 joints were operated on. The patients were followed-up for an average of 8.7 years (range, 2–13 years). Functional results were satisfactory in all joints, and differences in limb length were not significant. Radiographically, good results (grades I and II) were obtained in 16 of the 22 joints, according to Severin's criteria. This surgical procedure may be indispensable for treating refractory congenital dislocation of the hip in children over 1 year old. Received for publication on May 2, 1997; accepted June 3, 1998     

Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Dynamic graciloplasty for urinary incontinence: the potential for sequential closed-loop stimulation

Muscle tissue transplantation applied to regain or dynamically assist contractile functions is known as 'dynamic myoplasty'. Success rates of clinical applications are unpredictable, because of lack of endurance, ischemic lesions, abundant scar formation and inadequate performance of tasks due to lack of refined control. Electrical stimulation is used to control dynamic myoplasties and should be improved to reduce some of these drawbacks. Sequential segmental neuromuscular stimulation improves the endurance and closed-loop control offers refinement in rate of contraction of the muscle, while function-controlling stimulator algorithms present the possibility of performing more complex tasks. An acute feasibility study was performed in anaesthetised dogs combining these techniques. Electrically stimulated gracilis-based neo-sphincters were compared to native sphincters with regard to their ability to maintain continence. Measurements were made during fast bladder pressure changes, static high bladder pressure and slow filling of the bladder, mimicking among others posture changes, lifting heavy objects and diuresis. In general, neo-sphincter and native sphincter performance showed no significant difference during these measurements. However, during high bladder pressures reaching 40 cm H(2)O the neo-sphincters maintained positive pressure gradients, whereas most native sphincters relaxed. During slow filling of the bladder the neo-sphincters maintained a controlled positive pressure gradient for a prolonged time without any form of training. Furthermore, the accuracy of these maintained pressure gradients proved to be within the limits set up by the native sphincters. Refinements using more complicated self-learning function-controlling algorithms proved to be effective also and are briefly discussed. In conclusion, a combination of sequential stimulation, closed-loop control and function-controlling algorithms proved feasible in this dynamic graciloplasty-model. Neo-sphincters were created, which would probably provide an acceptable performance, when the stimulation system could be implanted and further tested. Sizing this technique down to implantable proportions seems to be justified and will enable exploration of the possible benefits.     

PATHOLOGICAL STUDY ON AMYLOIDOSIS —RELATIONSHIP OF AMYLOID DEPOSITS IN THE AORTA TO AGING—

Senile aortic amyloidosis in 224 autopsy cases over 40 years was investigated comparing cardiac and pancreatic amyloidosis in them. A total of 176 cases of aortic amyloidosis was found for an average incidence of 79%. Under the 5th decade the incidence was 51% and it rose sharply with age and reached 95% in over the 8th decade. The incidence of cardiac amyloidosis also increased with age, but it was always higher in the aorta. Aortic and cardiac amyloid were both positive in the DMAB method for tryptophan. The major part exposed to amyloidosis in the aorta was the media. The medial amyloid consisted of numerous minute deposits and had no relation to atherosclerosis. Some comments about the pathogenesis of senile amyloidosis were also mentioned.     

Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel

Addition of various heparinoids to the lactose-introduced, water-soluble chitosan (CH-LA) aqueous solution produces an injectable chitosan/heparinoid hydrogel. In the present work, we examined the capability of the chitosan/non-anticoagulant heparin (periodate-oxidized (IO(4)-) heparin) hydrogel to immobilize fibroblast growth factor (FGF)-2, as well as the controlled release of FGF-2 molecules from the hydrogel in vitro and in vivo. The hydrogel was biodegraded in about 20 days after subcutaneous injection into the back of a mouse. When the FGF-2-incorporated hydrogel was subcutaneously injected into the back of both mice and rats, a significant neovascularization and fibrous tissue formation were induced near the injected site. These results indicate that the controlled release of biologically active FGF-2 molecules is caused by biodegradation of the hydrogel, and that subsequent induction of the vascularization occurs.     

Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.     

Gaps and fragmentation of the superficial cortex in the abdominal and pelvic lymph nodes of elderly Japanese

Gaps and fragmentation of the superficial lymph node cortex are considered to provide intranodal shunt flow between the afferent and efferent vessels. Using serial sections of 205 nodes obtained from 27 donated cadavers more than 70 years of age, we examined the histological architecture of the abdominal and pelvic nodes in elderly Japanese. Secondary follicles were rare in the specimens. Cortex gaps were, to a greater or lesser degree, found in all nodes. We classified these nodes into three types according to how often the gap occurred. Type 1 nodes, with a relatively complete shield for the afferent lymph, were most frequently found in gastric nodes, whereas type 3 nodes, with numerous gaps, were often observed in the colic, para-aortic and pelvic nodes. The type 3 nodes showed a specific architecture characterized by a fragmented superficial cortex, three-dimensionally assembled cords and a common sinus between them. Primary follicles were located in the assembled cord structures as well as at the superficial cortex. Irrespective of the type, B and T lymphocyte areas were intermingled in the cortex-like areas. The present results reveal region-specific histological heterogeneity in aged human visceral nodes. Due to increased surface areas, the type 3 architecture seemed to accelerate systemic immunity rather than act as a local barrier in the para-aortic and pelvic nodes, which are located centrally along the lymphatic drainage routes. However, thick trabeculae often seemed to develop in the type 3 sinus to decrease nodal function with aging.