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Nihon Naika Gakkai Zasshi 06/2011; 100(6):1582-9.
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ABSTRACT: We aimed evaluate clinical problems in the diagnosis and treatment of hospital-associated pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA-HAP) at a single institute.
Forty-two patients, diagnosed with MRSA-HAP by a primary physician, who had received antimicrobial therapy during a period of 18 consecutive months at University Hospital, Kyoto Prefectural University of Medicine, were enrolled in the study. For comparison, 36 patients in whom MRSA was recovered from the respiratory tract during the same period, but who were not treated for pneumonia, were chosen as untreated controls. A clinical pulmonary infection score (CPIS) was calculated retrospectively by a chart review. The CPIS was calculated on day 1 and day 3. In the treated group, serum concentrations of each therapeutic drug used were also evaluated.
The day-1 and day-3 CPIS showed a similar trend in the two at groups, at 2.5 +/- 1.8 and 3.9 +/-1.9, respectively, in the treated group and 2.9 +/- 1.9 and 3.8 +/- 1.6 in the control group. Only two (5%) patients in the treated group showed a CPIS of more than 6 on day 1. Only five patients (12%) in the treated group were treated with antimicrobials at appropriate target therapeutic serum concentrations. The 30-day mortality in the treated group was significantly higher than that in the control group, even when we matched the baseline morbidity of patients using the Acute Physiology and Chronic Health Evaluation II (APACHE II) score.
This study revealed the clinical problems in our setting, in that MRSA colonization in the respiratory tract was frequently treated as pneumonia, and antimicrobial dosage was frequently insufficient. Prudent differential diagnosis of and treatment for HAP due to MRSA infection should be considered.
Journal of Anesthesia 02/2008; 22(2):125-30. · 0.83 Impact Factor
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Munetaka Hirose,
Mayumi Takatori,
Yoshihiro Kuroda,
Mineo Abe,
Eri Murata,
Tetsuro Isada,
Koyo Ueda,
Kenji Shigemi,
Masayuki Shibazaki,
Fumihiro Shimizu,
Masashi Hirata,
Keita Fukazawa, Masahiro Sakaguchi,
Kyoko Kageyama,
Yoshifumi Tanaka
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ABSTRACT: As TrkA, a high-affinity receptor of nerve growth factor (NGF), is a potential target for relieving uncontrolled inflammatory pain, an effective inhibitor of TrkA has been required for pain management. To identify a specific inhibitor of TrkA activity, we designed cell-penetrating peptides combined with amino-acid sequences in the activation loop of TrkA to antagonize tyrosine kinase activity. To select a peptide inhibiting TrkA activity, we examined the effect of cell-penetrating peptides on tyrosine kinase activity of recombinant TrkA in vitro and studied their effects on NGF-stimulated neurite outgrowth and protein phosphorylation in PC12 cells. Thereafter we investigated the effect of the selected peptide on NGF-stimulated TrkA activity and the expression of transient receptor potential channel 1 in PC12 cells. The selected peptide inhibited TrkA activity, but did not inhibit tyrosine kinase activities of other receptor-type tyrosine kinases in vitro. It also suppressed NGF-stimulated responses in PC12 cells. The selected synthetic cell-penetrating peptide antagonizing TrkA function would be a candidate for inflammatory pain therapy.
Journal of Pharmacological Sciences 02/2008; 106(1):107-13. · 2.08 Impact Factor
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ABSTRACT: Local anesthetics suppress proliferation in several cancer cells. The mechanism of the suppression, however, is unknown. Our previous study shows that lidocaine, at the level of tissue concentration under topical or local administration, has a direct inhibitory effect on the activity of epidermal growth factor receptor (EGFR), which is a potential target for antiproliferation in cancer cells. Therefore, we hypothesized that lidocaine would suppress the proliferation of cancer cells through the inhibition of EGFR activity. We investigated the effects of lidocaine (40-4000 microM) on proliferation of a human tongue cancer cell line, CAL27, which has a high level of EGFR expression, and also examined the effect of lidocaine on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR in CAL27 cells. A clinical concentration of lidocaine (400 microM) suppressed both serum-induced and EGF-induced proliferation of CAL27 cells and inhibited EGF-stimulated tyrosine kinase activity of EGFR without cytotoxicity. A larger concentration of lidocaine (4000 microM) showed cytotoxicity with an antiproliferative effect. We suggest that the inhibition of EGF-stimulated EGFR activity is one of the mechanisms of the antiproliferative effect of lidocaine on CAL27 cells. Lidocaine administered topically within the oral cavity for cancer pain relief may suppress the proliferation of human tongue cancer cells.
Anesthesia and analgesia 05/2006; 102(4):1103-7. · 3.08 Impact Factor
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ABSTRACT: 1. Acetyl-KIFMK-amide (KIFMK) restores fast inactivation to mutant sodium channels having a defective inactivation gate. Its binding site with sodium channels could be considered to be the cytoplasmic linker (III-IV linker) connecting domains III and IV of the sodium channel alpha subunit. There is a close resemblance of the amino-acid sequences between the III-IV linker and the activation loop of the insulin receptor (IR). This resemblance of the amino-acid sequences suggests that KIFMK may also modulate insulin signalling. In order to test this assumption, we studied the effects of KIFMK and its related (KIYEK, KIQMK, and DIYET) and unrelated (LPFFD) peptides on tyrosine phosphorylation or dephosphorylation of IR in vitro. 2. Purified IR was phosphorylated in vitro with insulin in the presence of various synthetic peptides and lignocaine. The phosphorylation level of IR was then evaluated after SDS-PAGE separation, followed by Western blot analysis with antiphosphotyrosine antibody. 3. KIFMK and KIYEK inhibited insulin-stimulated autophosphorylation of IR. Lignocaine showed similar effects, but at a higher order of concentration. KIYEK and DIYET, but not KIFMK, dephosphorylated the phosphorylated tyrosine residues. The structurally unrelated peptide LPFFD had no effect either on phosphorylation or dephosphorylation of IR. 4. These results indicate that KIFMK, KIYEK, and lignocaine bind with the autophosphorylation sites of IR. 5. The present findings also suggest that KIFMK and lignocaine bind with the III-IV linker of sodium channel alpha subunit.
British Journal of Pharmacology 06/2004; 142(1):222-8. · 4.41 Impact Factor
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ABSTRACT: Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors' previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation.
To investigate the effect of lidocaine (4 microM-40 mM) on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs.
Lidocaine (> or =400 microM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (> or = 400 microM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR.
Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.
Anesthesiology 06/2004; 100(5):1206-10. · 5.36 Impact Factor
