Clinical estimation of vancomycin measurement method on hemodialysis patient

The fluorescence polarization immunoassay (FPIA) method is used to perform measurement of vancomycin hydrochloride (VCM) at many institutions. However, the values measured by the FPIA method are more vulnerable to overestimation than the high performance liquid chromatography (HPLC) method. In particular, it was not reported to perform exact therapeutic drug monitoring (TDM) measurement. Since overestimation is likely in patients with renal dysfunction, the HPLC method is preferable for TDM measurement. This study investigates the clinical conditions that lead to overestimation in the FPIA method, paying attention to the relation of clinical laboratory data inspection values and the existence of hemodialysis (HD). Overestimation in the evaluation of TDM using the FPIA method was clinically examined with 116 serum samples obtained from 18 cases medicated with VCM. The relevance between overestimation of patients who had not had HD performed was 72.7 +/- 61.7% (means +/- SD). In short, the overestimation was greatest in HD patients. Since overestimation did not affect the evaluation of clinical TDM, such as an effect and a side-effect, the TDM of VCM was shown to be satisfactorily evaluated by the simple FPIA method.     

Differentiation- and apoptosis-inducing activities by pentacyclic triterpenes on a mouse melanoma cell line

In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.     

Tunicamycin inhibits NMDA and AMPA receptor responses independently of N-glycosylation

In a whole-cell patch-clamp configuration, currents through N-methyl- -aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 μM), an inhibitor of protein N-glycosylation. Tunicamycin (10 μM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus.     

Luminal space enlargement by carbachol in rat parotid intralobular ducts

Carbachol (CCh) enlarges the luminal space in rat parotid intralobular ducts, but the mechanism of their enlargement remains obscure. We investigated the involvement of intracellular calcium ions in the enlargement of luminal space by monitoring the luminal space under optical sectioning in a confocal laser scanning microscope using sulforhodamine B. Carbachol increased the intracellular concentration of calcium ions ([Ca2+]i) and the inside diameter without any change in the outside diameter. Removal of extracellular calcium ions modulated CCh-induced changes in [Ca2+]i to transient, but did not markedly inhibit the CCh-induced increase in the inside diameter. Additional loading of BAPTA (1,2-bis (o-aminophenoxy-ethane-n,n,n',n'-tetraacetic acid) in the duct cells suppressed CCh-induced changes. Diphenylamine-2-carboxylate (DPC), but not cytochalasin D, calmodulin inhibitor or nitric oxide synthase inhibitor profoundly suppressed CCh-induced changes. These results suggest that CCh induces enlargement of the luminal space through the activation of DPC-sensitive channels by the release of calcium ions from the intracellular pool.     

Expression of CD44v6 in advanced gastric cancer and its relationship to hematogenous metastasis and long-term prognosis

BACKGROUND AND OBJECTIVES: Variants of CD44 have been proposed to be important in promoting tumor progression and metastasis. We attempted to determine the expression of CD44v6 product in advanced gastric cancer and to evaluate its prognostic value. METHODS: The expression of CD44v6 was analyzed immunohistochemically in advanced gastric cancers using monoclonal antibody, 44-2V. We investigated the relationship between CD44v6 expression and prognosis in 201 gastric cancer patients. RESULTS: Ninety-five (47.3%) of 201 cancer tissues expressed CD44v6. The expression of CD44v6 protein was significantly higher in differentiated, adenocarcinoma than in diffuse type carcinoma. The CD44v6-positive cancers were more frequently associated with hematogenous metastasis. There was no significant correlation between CD44v6 immunoreactivity, and prognosis among the combined cases. Among patients with differentiated adenocarcinoma, however, the prognosis was significantly poorer in patients with CD44v6-positive tumors than in those with CD44v6-negative tumors. CONCLUSIONS: CD44v6 protein may have an important role in hematogenous metastasis, and may be a biologic marker of prognostic significance in differentiated type gastric cancers.     

A case of large carcinoma of the tongue and mouth floor,in which chemotherapy using a combination of nedaplatin and 5-FU was effective

We encountered a case of extensive squamous cell carcinoma ranging from the tongue to the mouth floor, in which chemotherapy using a combination of nedaplatin and 5-FU was effective. The patient was a 46-year-old male, who noticed a small mass in the mouth floor in September 2000, and visited the department of oral and maxillofacial surgery at a hospital on October 12, 2000. A 27 x 15 mm tumor with erosion was noted on the mouth floor, which was diagnosed as squamous cell carcinoma by biopsy, and the patient was referred to our department for treatment on November 16, 2000. Intra-oral findings included a healthy-colored induration with a bulge in the area ranging from the apex of the tongue posteriorly for 30 mm, and from the right lateral edge of the tongue to the left side exceeding the median area of the tongue by approximately 7 mm. MRI detected a tumor of approximately 2 cm in diameter in the area ranging from the median area of the tongue to the right ventral side of the tongue, which protruded on the mouth floor side. Two courses of combination chemotherapy using nedaplatin and 5-FU were performed. Nedaplatin (90 mg/m2, total 143 mg) and 5-FU (700 mg/m2, total 1,113 mg) were administered in a first course during December 15-19, 2000, and in the same amounts in a second course during January 23-27, 2001. Adverse effects of gastralgia and stomatitis occurred, but they gradually disappeared with time. The tumor with erosion in the tongue and mouth floor and induration disappeared 2 weeks after administration. Tongue was recovered, so that tongue movement was almost normal. Postoperative MR showed no abnormal signals in T2-weighed images, suggesting that the tumor in the right mouth floor had almost disappeared. External irradiation (40 Gy/20 times/28 days, 2 Gy/day, opposing bilateral portal irradiation) between March 13 and April 9, 2001, and micro-selection high dose fractionated interstitial irradiation (42 Gy/7 times/6 days, 6 Gy/1 time) April 18-23, 2001 were performed as booster therapy. Outpatient observation has shown a good clinical course without recurrence.     

Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration

OBJECTIVES: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. RESULTS: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). CONCLUSIONS: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.