The synergetic improving effect of bile acids with spermine (SPM), a major polyamine, on the absorption of rebamipide, a poorly soluble and poorly absorbable drug (BCS Class IV), was evaluated in ...rats and beagle dogs. Although the absorption of rebamipide was improved by the addition of polyamines alone in normal rats, it was not improved in bile duct ligated (BDL) rats. The combinatorial use of sodium taurocholate (STC), a bile acid, with SPM improved the absorption of rebamipide even in BDL rats. In the beagle dogs, the oral administration of SPM alone did not enhance the absorption of rebamipide, but the combinatorial use of STC with SPM improved the absorption as well as in the BDL rats. These results indicate that bile acids are indispensable for the novel formulation containing SPM to improve the absorption of rebamipide after oral administration.
Bronchial asthma is a chronic inflammatory disease that has a severe impact on health worldwide.
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.
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.
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.
A 92-year-old man who had been hospitalized for dementia developed sudden-onset bilious vomiting accompanied by a fever of 40°C. Physical examination revealed an 8 cm diameter pulsatile mass in the ...upper abdomen. Computed tomography of the abdomen demonstrated a huge infrarenal saccular aneurysm with a lobulated appearance. We considered this to be a mycotic abdominal aortic aneurysm compressing the third portion of the duodenum and causing proximal duodenal dilatation and superior mesenteric artery (SMA) syndrome.
We previously reported that the fatty base suppository containing sodium laurate (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic absorption of rebamipide, a poorly ...water-soluble and poorly absorbable drug, without any serious mucosal damages in rats. In the preset study, in order to make C12-Tau suppositories available for practical use, the scaling-up studies of animal and formulation size were performed, compared with the suppositories containing sodium caprate (C10) (C10 suppository) at the same amounts as those contained in the commercial products. Twenty-mg C12 improved the dissolution of rebamipide from suppository remarkably and the addition of 30-mg Tau only slightly decreased the dissolution rate. The absorption of rebamipide from rabbit rectum was more markedly improved by suppositories containing C12 than C10 suppositories. Although Tau tended to attenuate the absorption-enhancing effect of C12, several C12-Tau suppositories kept high bioavailability values, which were much higher than control. Histopathological studies showed that Tau exerted the cytoprotective action and that C12-Tau suppositories were better than C10 suppositories in safety. Considering the balance between efficacy and safety, the suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10 suppositories as commercial products and could be promising for practical use in human.
Context: In management of community-acquired pneumonia (CAP), excellent biomarkers for inflammation would be helpful in our practice.
Objectives: Kinetics of c-reactive protein (CRP) and serum ...amyloid A (SAA) was characterized, using their biologic half-life times.
Materials and methods: Time course of CRP and SAA levels in the successfully treated 36 CAP patients were investigated and their half-life times were determined and compared.
Results & Discussions: SAA and CRP declined in an exponential mean and the biologic half-life times of SAA levels was 34.9 ± 28.7 h, significantly shorter than that of CRP, 46.4 ± 21.7 h (p = 0.0014). Conclusion: The kinetic evidence, presented as biologic half-life times of CRP and SAA, helps us make a clinical assessment of CAP patients.
Large and powerful Typhoon Hagibis (1919) made landfall on the Izu Peninsula on 12 th October 2019, and it brought widespread and record-breaking torrential rain across Japan, especially in Eastern ...Japan. Emergency warning was issued in Tokyo and 12 prefectures, and many slope failures and debris flows were caused. It marked the largest number of sediment disaster occurrences by a typhoon since 1982 that the statistics have been started to be recorded. 952 sediment disasters were caused by the typhoon (as of 24 th December 2019), and 16 people were killed and one person is missing. In Tohoku region, most disasters happened in Iwate, Miyagi, and Fukushima prefectures. From 1 : 00 am, 12 th October to 12 : 00 am, 13 th October (two days) total precipitation (observed by AMeDAS of Japan Meteorological Agency) was 594 mm in Hippo, Marumori-machi, Miyagi prefecture, and 466.5 mm in Fudai, Iwate prefecture. From the above, Japan Society of Erosion Control Engineering organized “Emergency investigation team for the sediment disasters in Tohoku region caused by Typhoon Hagibis 2019” and performed the investigation three times.
A 79-year-old man was referred to this department due to the presence of extrahepatic bile duct carcinoma with a tumor at the left chest wall. The lesion was suspected to be a metastasis of bile duct ...carcinoma to the left wall, however, computed tomography (CT) revealed no regional lymph node or liver metastases. In addition, cytological and pathological examinations did not show malignancy. At the time of admission, the white blood cell count was 21460 cells/muL (neutrophils, 18240 cells/muL) and this elevated to 106040 before death. In addition, serum granulocyte colony-stimulating factor (G-CSF) was elevated. At 28 d after admission, the patient died. An autopsy showed a poorly differentiated adenocarcinoma with sarcomatous change, which had slightly invaded into the pancreas around the bile duct, and was found in the distal bile duct with multiple metastases to the chest wall, lung, kidney, adrenal body, liver, mesentery, vertebra and mediastinal and para-aortic lymph nodes, without locoregional lymph node and liver metastasis. The cancer cells showed positive immunohistochemical staining for anti-G-CSF antibody. This is believed to be the first report of an extrahepatic bile duct carcinoma that produces G-CSF. Since G-CSF-producing carcinoma and sarcomatous change of the biliary tract leads to poor prognosis, early diagnosis and treatment are needed. When infection is ruled out, the G-CSF in serum should be examined. In addition, examinations such as bone scintigraphy and chest CT should also be considered for distant metastasis.
We study the realization of spontaneous CP violation through moduli
stabilization. In modular flavor models, the source of CP violation is the
vacuum expectation values of the complex structure ...moduli of toroidal compact
space. We demonstrate that the combined effects of Type IIB flux
compactifications with modular invariant couplings between the moduli and
matter fields can induce spontaneous CP violation without or with supersymmetry
breaking. Furthermore, some general properties of CP and modular invariant
scalar potentials are presented. It is found that certain modifications or
partial breakings of modular symmetry are useful in generating spontaneous CP
violation.
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.
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