Preparation of Fast Dissolving Films for Oral Dosage from Natural Polysaccharides

Fast-dissolving films (FDFs) were prepared from natural polysaccharides, such as pullulan, without heating, controlling the pH, or adding other materials. The release profiles of model drugs from the films were investigated. In the absence of a drug, the casting method and subsequent evaporation of the solvent resulted in the polysaccharide forming a circular film. The presence of drugs (both their type and concentration) affected film formation. The thickness of the film was controllable by adjusting the concentration of the polysaccharide, and regular unevenness was observed on the surface of 2% pullulan film. All films prepared with polysaccharides readily swelled in dissolution medium, released the incorporated compound, and subsequently disintegrated. The release of dexamethasone from the films was complete after 15 min, although this release rate was slightly slower than that of pilocarpine or lidocaine. Therefore, FDFs prepared from polysaccharides could be promising candidates as oral dosage forms containing drugs, and would be expected to show drug dissolution in the oral cavity.     

Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor ��1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation

Objective and design

To clarify the molecular mechanism of polyenylphosphatidylcholine (PPC), we examined the involvement of reactive oxygen species (ROS) and NADPH oxidase 4 (Nox4) in human hepatic stellate cells (HSCs).

Material

Using human LX-2 HSC cells, we examined the effects of PPC on expression of ??-smooth muscle actin (??-SMA) and collagen 1, generation of ROS, Nox4 expression, p38 activation and cell proliferation, induced by transforming growth factor ??1 (TGF??1).

Results

PPC suppressed ROS which are induced by TGF??1, phosphorylation of p38MAPK, and expression levels of ??-SMA and collagen 1 in a dose-dependent manner. Higher concentrations of PPC also suppressed Nox4 levels.

Conclusion

These results suggest that ROS and Nox4 induced by TGF??1 are the therapeutic targets of PPC in the suppression of human hepatic stellate cell activation.     

Prenatal exposure to bisphenol A affects adult murine neocortical structure

Prenatal exposure to low-doses of bisphenol A (BPA) has been shown to affect murine neocortical development by accelerating neuronal differentiation/migration through disrupting thyroid hormone function. We therefore studied whether prenatal exposure to low-doses of BPA affected organization of adult neocortical structures. Pregnant mice were injected with 20 microg/kg of BPA daily from embryonic day 0.5 (E0.5) and bromodeoxyuridine (BrdU) was injected at E12.5, E14.5 and at E16.5, and the fetal brains were analyzed after birth. The BrdU-positive cells labeled at E14.5 were significantly increased in the Vth and VIth cortical layers of BPA-treated mice at postnatal 3 weeks (P3W), whereas they were confined to the IVth layer of control mice, though such differences disappeared at P12W. The thalamocortical projections demonstrated by DiI-labeling were abnormal at P3W and P12W in BPA-treated mice. These results indicate that BPA might affect not only neocortical development but also thalamocortical connections.     

Low cytoplasmic pH causes fragmentation and dispersal of the Golgi apparatus in human hepatoma cells

The centrosomal localization of the Golgi apparatus in interphase cells is thought to be maintained by retrograde microtubule-based motility. It is well established that, when intracellular pH is lowered, lysosomes and endosomes, also showing pericentrosomal localization, translocate towards the plus ends of microtubules within 15 min. In this study, we found that prolonged incubation in low pH medium (pH 6.6) with 20 mM Na acetate induced the fragmentation and dispersal of the Golgi apparatus in the human hepatoma cell line PLC/PRF/5. The fraction of Golgi-dispersed cells increased in a time-dependent manner, and reached over 60% after the 16-h incubation. The cytoplasmic pH was dropped to approximately 7.10. Replacement with normal pH medium restored the structure and localization of the apparatus within 30 min. In the low pH condition, the microtubular network and endoplasmic reticulum appeared normal, and cytoplasmic dynein was still bound to the fragmented Golgi membranes. These findings suggest that low cytoplasmic pH suppresses the retrograde movement of the Golgi apparatus as well as that of lysosomes and endosomes.     

Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

Background  

Interferon-α (IFN-α) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-α receptor (IFNAR). We investigated the role of IFNAR in RCC.     

The Polycystic Ovary Syndrome Does Not Predict Further Miscarriage in Japanese Couples Experiencing Recurrent Miscarriages

Problem  It has been a matter of controversy whether the polycystic ovary syndrome (PCOS) is actually a causal factor of miscarriages because of the absence of internationally established criteria. We, therefore, in this study investigated whether PCOS and a polycystic ovary (PCO) morphology have predictive value for subsequent miscarriages using new International and Japanese criteria.
Method of study  A total of 195 patients with a history of two consecutive first trimester miscarriages and without abnormal chromosomes in either partner, antiphospholipid antibodies or uterine anomalies, were examined. The prospective pregnancy outcome was compared between patients with and without PCOS, PCO morphology, elevated luteinizing hormone (LH), hyperandrogenism and obesity.
Results  Of a total of 195 patients, 56 (28.7%) miscarried subsequently. Three (1.5%) and 12 (6.2%) were diagnosed as suffering from PCOS by Japanese and International criteria respectively. There was no relation between a diagnosis of PCOS, PCO morphology, elevated LH, free testosterone or obesity and the subsequent miscarriage rate.
Conclusion  A routine test for diagnosis of PCOS is not necessary in patients experiencing recurrent miscarriages because none of the related parameters examined in this study predicted subsequent miscarriage.     

Diagram specific to sacroiliac joint pain site indicated by one-finger test

Background  The sacroiliac joint (SIJ) can be a source of low back and lower limb pain. The SIJ pain can originate not only from the joint space but also from the ligaments supporting the joint. Its diagnosis has been difficult because the physical and radiological examinations have proved less than satisfactory. Thus, to know the specific sites of SIJ pain, if these exist, could be very useful for making the diagnosis. The purpose of the present study was to identify the main site of SIJ pain according to the patient’s pointing with one finger and to confirm the site by a pain-provocation test and periarticular lidocaine injection. Methods  Forty-six of 247 consecutive patients with low back pain at our outpatient clinic, who could indicate with one finger the main site of the pain, which presented at only one site and was reproducible, were the subjects of this study. The main site of pain was anatomically confirmed by fluoroscopy. Then, a periarticular SIJ injection was performed. The patients were blindly assessed and a diagram of the main site of the SIJ pain was made. Results  There were 19 males and 27 females and the age averaged 50 years. Eight patients showed a positive placebo response and were excluded from this study. Twenty-five of the remaining 38 patients indicated the main site of pain at the posterior-superior iliac spine (PSIS) or within 2 cm of the PSIS, and 18 of these patients showed a positive effect with periarticular SIJ block. The other 13 patients, including 2 patients with a positive response to the periarticular block, did not show the PSIS as the main site of pain. Conclusions  Our study clearly indicated that when patients point to the PSIS or within 2 cm of it as the main site of low back pain, using one finger, the SIJ should be considered as the origin of their low back pain.