A patient-based model study of fixed splinting of premolars with reduced periodontal support.

The aim of this patient-based study was to assess the effect of fixed splinting of mandibular premolars having reduced alveolar support on load distribution in the periodontium. A patient's mandibular second premolar with considerably reduced alveolar bone height was restored using a metal-ceramic restoration splinted with the adjacent first premolar; an acceptable 3-year maintenance period was observed. A patient-based three-dimensional finite element model was constructed using the morphological measurements obtained from the diagnostic cast and radiographs. The model incorporated in vivo occlusal records and was used to analyze stress and strain in the periodontium for splinted and nonsplinted simulations. Modified models were also created to explore the effects of relative bone height on the stress and strain distributions. The maximum principal stress and strain on the periodontium of the second premolar were considerably higher before splinting than after splinting and were close to strain levels indicative of potential bone microdamage. In contrast, the stress and strain in the first premolar increased after splinting. The modified models showed that the increased vertical gap of alveolar height between the splinted teeth was another factor to increase the load in the first premolar. Since the prosthodontic procedure employed is not routinely used, the results cannot be generalized. However, it is suggested that fixed splinting can decrease the periodontal load on premolars with reduced periodontal support, but may increase the load on the splinted tooth.

Mucoadhesive suppositories of ramosetron hydrochloride utilizing Carbopol.

Suppositories are the preferable dosage form for patients at home or experiencing nausea. Serotonin (5-HT(3))-receptor antagonists are used to treat vomiting in intravenous or oral administration but not suppository form. Ramosetron hydrochloride (RAM) is a new 5-HT(3) antagonist which effectively inhibits vomiting, and we prepared RAM suppositories using Witepsol((R)) H-15 (H-15) containing Carbopol((R)) 934P (CP). The viscosity of suppository base and RAM release properties from suppositories were examined. Plasma RAM concentrations after administration of suppositories to rabbits were estimated and irritation of rectal tissues were observed. Antiemetic effects of suppositories were studied using ferrets. The base viscosity increased with addition of CP. Suppositories containing CP exhibited better absorption in rabbits compared to H-15 suppositories, correlated with release behavior. Suppositories containing 2% CP had 2.5 times larger AUC(0-24 h) than H-15 suppositories, and the MRT was prolonged by 5.8 h compared with i.v. administration. 10% CP suppositories administered to rabbits for 5 days did not irritate the tissues. Antiemetic studies indicated that 2% CP suppository of RAM might have the same effect as i.v. administration. These results suggest that RAM suppositories containing CP are safe and useful in once-a-day dosage form for treatment of chemotherapy-induced nausea.

Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing Carbopol and white beeswax.

In an attempt to restrict drug absorption from suppositories to only the lower rectum, mucoadhesive lidocaine (LID) suppositories were prepared using Witepsol H-15 as a base, and Carbopol 934P (CP) and white beeswax (WAX) as additives. CP has a mucoadhesive property and WAX gives the suppositories stiffness. The suppositories containing 10% CP and 20% WAX stayed in the lower recta of rats for at least 2 h. Double-phased suppositories consisting of a front layer containing 10% CP and 20% WAX and a terminal layer containing LID and various amounts of CP were prepared. In vitro release profiles of LID from double-phased suppositories were similar to conventional single-phased suppositories containing CP alone. Values of AUC(0-6 h) and MRT of LID after administration of double-phased suppositories to rabbits were larger than those for single-phased suppositories with or without CP. On the other hand, the initial plasma metabolites concentrations after administration of double-phased suppositories were significantly lower and tended to exhibit delayed T(max) compared to single-phased suppositories. These results suggest that the double-phased mucoadhesive suppositories suppress initial metabolism of LID, and may be useful for improving bioavailabilities of drugs, like LID, which accept first-pass effect considerably.

The culture fluid of Isaira japonica yasuda augments anti-sheep red blood cell antibody response in mice.

Isaria japonica YASUDA was cultured in a liquid medium, and its culture fluid (IJCE) was tested for stimulatory activity to humoral antibody production. IJCE significantly enhanced the production of anti-sheep red blood cell (SRBC) plaque forming cells (PFC) by oral ingestions at 10 and 30 mg/kg/d for 4 consecutive days, either before or after SRBC challenge. It also recovered the reduction of anti-SRBC PFC response and number of spleen cells caused by treatment with 5-fluorouracil. It is suggested that IJCE is a promising source for an immunomodulating tool or medicine.