To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and ...poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or
l-glutamine (
l-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and
l-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much. Rectal absorption of rebamipide examined in rats was remarkably improved by FB suppository containing C12 or both C12 and Tau, while the enhancing effect of C12 was relatively small in the case of WB suppositories. Biochemical and histopathological studies have confirmed that FB suppository containing both C12 and Tau or
l-Gln did not cause any serious local damage, while FB suppository containing C12 only caused the erosion and shrinkage for a lot of rectal epithelial cells. In conclusion, FB suppository employing the combinatorial use of C12 with Tau could be a promising formulation that is effective and safe enough for poorly absorbable drugs to be practically administered.
We study slow-roll inflation model controlled by the modular flavor symmetry. In the model, the modulus field plays a role of inflaton and the introduction of the stabilizer field coupled to a ...modular form in the superpotential produces the inflaton potential. In order to generate the flat direction for the slow-roll inflation, we consider the K\"{a}hler potential corrected by the modular form. It is noted that the modulus field perpendicular to the inflaton direction is stabilized during the inflation. The model turns out to be consistent with the current observations and behaves similarly to the \(\alpha\)-attractor models in some parameter spaces. The inflaton rolls down to the CP-symmetric vacuum at the end of inflation.
BACKGROUND
It has been reported that the c‐erbB‐2 protooncogene is frequently amplified and overexpressed in many types of cancers, except sarcomas and hematological malignancies.
METHODS
Expression ...of ErbB‐2 in the tumors of 26 patients with conventional osteosarcoma was evaluated by immunoblotting. DNA from osteosarcoma tissues that expressed ErbB‐2 were analyzed by Southern blot hybridization to examine gross rearrangement of the gene. The DNA was also surveyed for the presence of genetic mutation in the transmembrane domain of ErbB‐2 by polymerase chain reaction–single‐stranded DNA conformation polymorphism analysis. In addition, possible correlation of ErbB‐2 expression with gender, age, histopathologic subtype, and response to chemotherapy was analyzed. Survival analysis was performed by the Kaplan‐Meier test using the approximate chi‐square statistic for the log‐rank test.
RESULTS
The ErbB‐2 protein was detected in 11 of 26 osteosarcoma tissues (42%) by immunoblot analysis. Expression of ErbB‐2 was confirmed by immunohistochemical studies using specific anti‐ErbB‐2 monoclonal antibody. However, neither amplification of the c‐erbB‐2 gene nor evidence of significant genetic mutation was found in these osteosarcomas. Expression of ErbB‐2 examined by immunoblotting was most strongly correlated with early pulmonary metastases (P < 0.05). Among the entire group of 26 patients in this study, Kaplan‐Meier life table survival of the patients with apparent ErbB‐2 expression was significantly worse than that of the patients with little ErbB‐2 expression (P < 0.01).
CONCLUSIONS
In 42% of the osteosarcomas, the tumor cells expressed ErbB‐2. Expression of ErbB‐2 was strongly correlated with early pulmonary metastasis and poor survival rate for the patient. These data suggest that ErbB‐2 plays a significant role in aggressive tumor growth and in the promotion of metastatic potential in osteosarcomas. ErbB‐2 in the osteosarcoma tissues would be a useful prognostic marker for patients. Cancer 1996;77:71‐8.
Abstract
Recently, combination treatment with a macrolide and a steroid for Mycoplasma pneumoniae (Mp) pneumonia has been reported to be effective. Thus, the effect of this combination on a mouse ...model of lung inflammation associated with Mp extract (the LIMEX mouse) was studied. Interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were induced in Mp extract-treated RAW264.7 cells, and this induction was inhibited by dexamethasone, parthenolide, SB203580 or LY294002. This suggested that Mp extract activates nuclear factor κB-, p38- and PI-3K-linked pro-inflammatory signals. The LIMEX mice were then either treated with or without clarithromycin and/or dexamethasone. Clarithromycin administration enhanced the production of IL-6, TNF-α, macrophage inflammatory protein-1α, monocyte chemotactic protein-1 and RANTES, while their production was perfectly suppressed by the combination of clarithromycin and dexamethasone. IL-17, IL-23, keratinocyte-derived chemokine (KC) and interferon-γ levels were not affected by clarithromycin treatment, but they were significantly suppressed by the combination of dexamethasone and clarithromycin. Collectively, some components of Mp extract provoked an inflammatory reaction in the RAW 264.7 cell line and LIMEX mice. Whereas the lung reaction in LIMEX mice was further exacerbated by clarithromycin treatment, it was resolved by the combinational treatment with clarithromycin and dexamethasone.
Background: Bronchial asthma is a chronic inflammatory disease that has a severe impact on health worldwide. Methods: A survey of 10,771 patients with bronchial asthma in the Tama region, Tokyo was ...conducted for 5 years to examine treatment and quality of life (QOL). Subjects were patients aged ≧ 16 years and their physicians who replied to a questionnaire sent in November from 2002 to 2006. Symptoms of bronchial asthma, visits to an emergency room, use of drugs, and severity of asthma were investigated. Results: Asthmatic symptoms improved over the 5 years, with a reduction in the number of emergency room visits. Since inhaled corticosteroids (ICS) were used by > 80% of patients in 2002, we suspected that increased use of concomitant leukotriene receptor antagonists (LTRA) and long-acting β2 agonists (LABA) might have contributed to these findings. The effects of these drugs were compared between ICS + LTRA (n = 45) and ICS + LABA (n = 54) groups of patients. There was no significant difference in the ICS dose between these groups. In the ICS + LABA group, 18.5% and 22.2% of patients visited an emergency room before and after initiation of combination therapy, respectively, with no statistically significant difference. In contrast, the rate of emergency room visits in the ICS + LTRA group decreased from 24.4% to 6.6% after addition of LTRA. Conclusions: These results suggest that the frequency of visits to an emergency room was decreased by complementing the anti-inflammatory effect of ICS with further treatment of inflammation, particularly with LTRA.
We investigated the effects of high-density lipoprotein (HDL) on the intracellular pH (pH
i), and on the proliferation of human vascular endothelial cells (HUVEC), as well as on their production of ...prostacyclin (PGI
2). The pH
i was slightly acidified when extracellular Ca
2+ was chelated with EGTA. Pretreatment of HUVEC with amiloride, the Na
+/H
+ exchange inhibitor, caused the pH
i to become strongly acidic. The addition of HDL produced a biphasic shift in pH
i, with a brief initial acidification followed by a rapid alkaline shift. The initial decrease in pH
i was abolished in the cells pretreated with EGTA, and subsequent alkalinization was inhibited. The alkalinization of pH
i disappeared in the cells pretreated with amiloride. These results suggest that pH
i depends mainly on Na
+/H
+ exchange and partially on the extracellular Ca
2+ of the HUVEC either in the resting unstimulated state or during HDL stimulation. In contrast, the addition of LDL produced an acidification of pH
i, which was increased by LDL in the Ca
2+-free condition. In the cells pretreated with amiloride, pH
i was not further acidified by LDL. As a result, HDL promoted the proliferation of cells, an action that was inhibited by pretreatment with EGTA. However LDL inhibited cell proliferation, an action unaffected by EGTA pretreatment. The addition of HDL also enhanced the generation of prostacyclin in endothelial cells, the enhancement of PGI
2 generation resulted from an increase in the release of Ca
2+ from storage sites, due not only to an increased production of inositol 1,4,5-trisphosphate (IP
3), but also to the alkalinization of pH
i. These effects may be involved in the mechanism of HDL's anti-atherosclerotic action.
A 70-year-old man with diabetes mellitus seen for fever, right chest pain, and right-lung field consolidation on chest X-ray was found in thoracoabdominal computed tomography (CT) to have ...variable-sized nodules in both lung fields and multiple low-density hepatic areas. On physical examination, his pulse was 145 beats per minute and blood pressure 92/68mmHg, indicating a preshock state. Laboratory tests showed elevated WBC of 15,200/μL, serum-C-reactive protein (CRP) of 34.4mg/dL, and a decreased platelet count of 16,000/μL. Suspecting liver abscesses complicated by aseptic pulmonary embolism, we immediately conducted percutaneous transhepatic abscess drainage (PTAD). Liver abscess blood culture and drainage fluidgrew the Klebsiella pneumoniae hypermucoviscosity phenotype, carrying the rmpA gene. Although the man had been in critical condition on admission, broad-spectrum antibiotics and PTAD treatment improved his clinical condition to where he could be discharged without problem.
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