Cisplatin is classified as a drug with high emetic risk; thus, the use of aprepitant or fosaprepitant in addition to a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and dexamethasone is ...recommended for antiemetic therapy. Further, hydration is required to prevent renal dysfunction, and the use of magnesium has been proposed as a part of the hydration procedure. When fosaprepitant is chosen for antiemetic therapy because the patient has dysphagia, and magnesium is added to the hydration procedure, there may be an incompatibility between the two drugs that reduces the antiemetic effect. In our hospital, in a former regimen, these two drugs were administered concurrently as premedication for regimens containing cisplatin. We varied the conditions so that in a revised regimen the two drugs did not come into contact due to pharmaceutical support, and we conducted a retrospective study to determine the difference in the antiemetic effect. The observation period was 2 years (from October 2015 to September 2017) for the former regimen group (n = 89) and 2 years (from October 2017 to September 2019) for the revised regimen group (n = 177). Comparison of the former and revised regimen groups revealed sex (p = 0.012); anticancer drug dosage (p = 0.006); and variation of premedication condition (p = 0.043) as factors affected by the revised regimen. Optimization of the premedication regimen was a form of necessary pharmaceutical support to maintain the patient’s QOL.
Abstract Fosaprepitant dimeglumine relieves nausea and vomiting caused by highly emetogenic chemotherapy agents such as high-dose cisplatin. Magnesium has renoprotective effects against ...cisplatin-induced damage. Thus, both drugs are sometimes used concomitantly, but administering them together intravenously may cause occlusion of the in-line filter. We aimed to clarify the extent to which the delivery of intravenous fosaprepitant dimeglumine is reduced by magnesium sulfate. Fosaprepitant dimeglumine was combined with magnesium sulfate and then filtered. Two ratios and concentrations of magnesium sulfate were tested (1:1 and 7:3 corresponding to 1.5 mg/mL fosaprepitant dimeglumine solution to 3.85% and 0.99% magnesium sulfate solution (v/v), respectively). The concentration of fosaprepitant dimeglumine in the filtrates was measured via high-performance liquid chromatography to determine the rate of decline in fosaprepitant dimeglumine. These experiments were performed in triplicate. When the ratio of fosaprepitant dimeglumine to magnesium sulfate was 1:1, the maximum rate of decline for fosaprepitant dimeglumine was 38.67%. At a ratio of 7:3, the maximum rate of decline was 7.62%. Fosaprepitant dimeglumine likely reacted with magnesium sulfate, which might inhibit the efficacy of fosaprepitant. To prevent this, we recommend flushing the in-line filter with 50 mL of normal saline before and after the administration of fosaprepitant dimeglumine.
Pharmaceutical companies do not sell formulations for all diseases; thus, healthcare workers have to treat some diseases by concocting in-hospital preparations. An example is the high-concentration ...2% cyclosporine A (CyA) ophthalmic solution. Utilizing a filter in sterility operations is a general practice for concocting in-hospital preparations, as is the case for preparing a 2% CyA ophthalmic solution. However, whether filtering is appropriate concerning the active ingredient content and bacterial contamination according to the post-preparing quality control of a 2% CyA ophthalmic solution is yet to be verified.
We conducted particle size, preparation concentration, and bacterial contamination studies to clarify aforementioned questions. First, we measured the particle size of CyA through a laser diffraction particle size distribution. Next, we measured the concentration after preparation with or without a 0.45-µm filter operation using an electrochemiluminescence immunoassay. Finally, bacterial contamination tests were conducted using an automated blood culture system to prepare a 2% CyA ophthalmic solution without a 0.45 μm filtering. Regarding the pore size of the filter in this study, it was set to 0.45 μm with reference to the book (the 6th edition) with recipes for the preparation of in-hospital preparations edited by the Japanese Society of Hospital Pharmacists.
CyA had various particle sizes; approximately 30% of the total particles exceeded 0.45 μm. The mean ± standard deviation of filtered and non-filtered CyA concentrations in ophthalmic solutions were 346.51 ± 170.76 and 499.74 ± 76.95ng/mL, respectively (p = 0.011). Regarding bacterial contamination tests, aerobes and anaerobes microorganisms were not detected in 14 days of culture.
Due to the results of this study, the concentration of CyA may be reduced by using a 0.45-µm filter during the preparation of CyA ophthalmic solutions, and furthermore that the use of a 0.45-µm filter may not contribute to sterility when preparing CyA ophthalmic solutions.
Feline gastrointestinal eosinophilic sclerosing fibroplasia was diagnosed in an 8-month-old Scottish fold that had a primary gastrointestinal mass involving the stomach, duodenum and mesenteric lymph ...nodes. Histopathologically, the most characteristic feature of this mass was granulation tissue with eosinophil infiltration and hyperplasia of sclerosing collagen fiber. Immunohistochemically, large spindle-shaped cells were positive for smooth muscle actin and vimentin. This case emphasizes the importance of feline gastrointestinal eosinophilic sclerosing fibroplasia as a differential diagnosis of gastrointestinal neoplastic lesions such as osteosarcoma and mast cell tumor in cats.
We have established rat models of pancreatic ductal adenocarcinoma (PDAC) in which expression of a human H-ras(G12V) or K-ras(G12V) oncogene regulated by the Cre/lox system drives pancreatic ...carcinogenesis. Pancreatic ductal adenocarcinoma which develops in H-ras(G12V) and K-ras(G12V) transgenic rats is cytogenetically and histopathologically similar to human PDAC. The present study was designed to determine the feasibility of using the commercially available H-ras(G12V) transgenic rat to find diagnostic protein biomarkers for human pancreatic cancer.
For an animal model to be useful for searching for protein biomarkers for a disease, it is essential that proteins that are up-regulated in the model are also up-regulated in humans. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare H-ras(G12V) transgenic rat PDAC with surrounding normal pancreas tissue.
We identified 30 up-regulated proteins in the H-ras(G12V) transgenic rat PDAC lesions; importantly, 21 human homologs of these 30 rat proteins are up-regulated in human pancreatic cancer patients.
These results indicate that numerous proteins that are up-regulated in H-ras(G12V) transgenic rat PDAC are also up-regulated in human pancreatic cancer; therefore, this rat model can be used to search for diagnostic biomarkers for this disease.
Hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) is a novel agent for the treatment of renal anemia. HIF-PHI increases endogenous erythropoietin production by inhibiting the ...degradation of an erythropoietin transcription factor. Although beneficial effects are expected from HIF-PHI, its novel mechanism raises concerns regarding the risk of potential adverse events. The cases of hypothyroidism, which had not been reported in clinical trials, were reported after the administration of roxadustat in a real-world setting. However, the effects of HIF-PHIs on thyroid function have not yet been fully evaluated. This study aimed to assess the clinical impact of HIF-PHIs on thyroid function using the Japanese Adverse Drug Event Report database, a spontaneous reporting system in Japan, because HIF-PHIs were made available in Japan before they were available in other countries. Although a disproportionality signal for hypothyroidism was detected with roxadustat (reporting odds ratio ROR:22.1, 95% confidence interval CI:18.3-26.7, no signals were detected with another HIF-PHI, daprodustat (ROR:1.3, 95%CI:0.3-5.4), and epoetin beta pegol (ROR:1.2, 95%CI:0.5-2.7). Signals of hypothyroidism due to roxadustat were also detected regardless of age or sex. Approximately 50% of hypothyroidism cases were reported within 50 days of starting roxadustat use. These results indicate that roxadustat use may be related to the development of hypothyroidism. The need for monitoring of thyroid function should be alerted during roxadustat administration regardless of age or sex.
Nitric oxide (NO)-induced nitrative stress of nucleic acids, as evidenced by guanine nitration, appears to be involved in inflammation-induced carcinogenesis. A high incidence of lung cancer in ...idiopathic pulmonary fibrosis (IPF) is the major reason for poor prognosis in patients with IPF.
We immunohistochemically analyzed the formation and localization of 8-nitroguanine in lung tissues from control subjects, patients with IPF, and patients with lung cancer.
Immunohistochemical analysis of control smoker and nonsmoker lungs showed weak immunoreactivity for 8-nitroguanine, mainly in cytoplasm of bronchial epithelial cells. In addition to the bronchial epithelial cells, metaplastic regenerated epithelial cells overlying dense fibrotic lesions in IPF showed strong 8-nitroguanine staining in the cytoplasm. The staining in these metaplastic cells colocalized with staining of inducible and endothelial NO synthases and 8-oxodeoxyguanosine, as evidenced by double-immunostaining analysis. Confocal and immunoelectron microscopy revealed localization of 8-nitroguanine in metaplastic epithelial cytoplasm, mostly in mitochondria. Appreciable 8-nitroguanine immunostaining was also observed in both nuclei and cytoplasm of malignant epithelial cells in squamous cell carcinoma. No significant difference was found in the epithelial 8-nitroguanine formation between control smokers and nonsmokers, but much higher guanine nitration was observed in patients with IPF than in control subjects and patients with lung cancer, via a quantitative immunofluorescence image analysis.
The present study indicates that not only oxidative stress but also nitrative stress induced by NO may participate in the pathogenesis of epithelial cell damage and aberrant regeneration occurring in IPF. Thus, guanine nitration may be a major risk factor for lung cancer development in IPF.
In Japan, China, and Singapore, several studies have reported increased incidences of peripheral venous catheter-related bloodstream infection by
during the summer. Therefore, we hypothesized that ...bed bathing with a
-contaminated "clean" towels increases
contact with the catheter and increases the odds of contaminating the peripheral parenteral nutrition (PPN). We found that 1) professionally laundered "clean" towels used in hospitals have
(3.3×10
colony forming units (CFUs) / 25cm
), 2)
is transferable onto the forearms of volunteers by wiping with the towels (n=9), and 3)
remain detectable (80∼660 CFUs /50cm
) on the forearms of volunteers even with subsequent efforts of disinfection using alcohol wipes. We further confirmed that
grow robustly (10
CFUs /mL to more than 10
CFUs /mL) within 24hours at 30°C in PPN. Altogether we find that bed bathing with a towel contaminated with
leads to spore attachments to the skin, and that
can proliferate at an accelerated rate at 30°C compared to 20°C in PPN. We therefore highly recommend ensuring the use of sterile bed bath towels prior to PPN administration with catheter in patients requiring bed bathing.
Interactions of multiple genes and associated factors are involved in the differentiation and de-differentiation of embryonic stem (ES) cells. Quantitative analysis of these genes and factors is ...essential for the elucidation of their mechanism. To meet this requirement, we have investigated various experimental conditions for high performance microinjection into mouse ES cells. A speedy and rhythmic operation was found to be important and was accomplished robotically by using a single-cell manipulation technique and XY-address registrable culture dishes. Among many experimental parameters, the tip size of an injection capillary, the pressure condition, and the DNA concentration in the injection capillary were of critical significance. Their optimum values were 0.5-0.8 μm, 0.7 kgf/cm² for 30 ms, and 1-100 ng/μl, respectively. Under these conditions, semi-quantitative control of the EGFP gene expression in mouse ES cells and its knockdown was successfully demonstrated.
Spontaneous iron accumulation in hepatocytes was observed in a 7-week-old female Han Wistar GALAS rat. Very fine yellowish brown pigments, which showed a positive reaction with Berlin Blue stain, ...were apparent in the cytoplasm close to the bile canaliculi, with a diminishing periportal-to-centrilobular gradient. There were also differences in distribution between and within lobes. Transmission electron microscopy revealed cytosolic ferritin and pericanalicular siderosomes in hepatocytes. No degeneration or necrotic changes were observed, and non-hepatocyte cells did not demonstrate any obvious accumulation of iron. There were no abnormalities in the animal other than this finding in the liver.
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