Meniscal cyst in the posterior intercondylar space found by magnetic resonance imaging

We report a rare case of meniscal cyst from the posterior horn of the lateral meniscus, extending in the posterior intercondylar space of the right knee of a 15-year-old boy, in whom magnetic resonance imaging was very useful for evaluation. A cyst in this location has not been reported previously. The cyst was removed surgically, while preserving the lateral meniscus. A good result was obtained, and no recurrence has been seen in 12 months. Received: 8 November 1996     

Defective function of lymphokine-activated killer cells and natural killer cells in patients with hepatocellular carcinoma

Lymphokine-activated killer activity and natural killer activity in hepatocellular carcinoma patients were assessed. Maximum lymphokine-activated killer activity was induced at 3 to 5 days of incubation, and lymphokine-activated killer activity tended to increase in a manner dose dependent of recombinant interleukin-2. However, the maximum increase of lymphokine-activated killer activity in hepatocellular carcinoma was not as high as that of normal subjects or liver cirrhosis patients. Lymphokine-activated killer activity was impaired in hepatocellular carcinoma as compared to that in normal subjects. Hepatocellular carcinoma seemed to consist of two groups: i.e. a high-lymphokine-activated killer activity group and a low-lymphokine-activated killer activity group. Reduction of natural killer activity was also observed in hepatocellular carcinoma as compared with that in normal subjects and patients with liver cirrhosis. No correlation could be demonstrated between natural killer activity and lymphokine-activated killer activity in normal subjects, liver cirrhosis patients and hepatocellular carcinoma patients. With regard to the presence of HBsAg or alpha-fetoprotein concentration in the sera, there was no significant difference in natural killer and lymphokine-activated killer activity in hepatocellular carcinoma patients. Patients with a small mass lesion showed a low lymphokine-activated killer activity, and depressed lymphokine-activated killer activity was not necessarily related to tumor size. In comparison with the high-lymphokine-activated killer group, the low-lymphokine-activated killer group showed a significant decrease in gamma-interferon production and a preserved function of indocyanine green clearance.     

Effect of therapeutic moderate hypothermia on multi-drug resistance protein 1-mediated transepithelial transport of drugs

To clarify the effect of therapeutic moderate hypothermia on drug distribution, transepithelial transport via multi-drug resistance protein 1 (MDR1) (also called P-glycoprotein or ABCB1) was evaluated at various temperatures in vitro using LLC-GA5-COL150 cells, which were established by transfecting human MDR1 complementary deoxyribonucleic acid into kidney epithelial LLC-PK(1) cells and express MDR1 on the apical membrane. MDR1 is expressed in the blood-brain barrier to limit drug distribution to the brain by exporting exogenous substances including calcium blockers and antiarrhythmic drugs. Digoxin was used as a typical substrate, as well as the non-substrate tetracycline and paracellular marker inulin. MDR1-mediated transport of digoxin decreased at lower temperatures. Transport of tetracycline also decreased at lower temperatures, probably due to changes in membrane fluidity. However, no change was found at over 32 degrees C, suggesting that passive diffusion does not change during moderate hypothermia. The distribution of MDR1 substrates should be considered during hypothermic conditions, as the clinical outcome could be affected.     

Effects of an endothelin B receptor agonist on secretory phospholipase A2-IIA-induced apoptosis in cortical neurons

Endothelin (ET), a vasoconstrictive peptide, acts as an anti-apoptotic factor, and endothelin receptor B (ETB receptor) is associated with neuronal survival in the brain. Human group IIA secretory phospholipase A2 (sPLA2-IIA) is expressed in the cerebral cortex after brain ischemia and causes neuronal cell death via apoptosis. In primary cultures of rat cortical neurons, we investigated the effects of an ETB receptor agonist, ET-3, on sPLA2-IIA-induced cell death. sPLA2-IIA caused neuronal cell death in a concentration- and time-dependent manner. ET-3 significantly prevented neurons from undergoing sPLA2-IIA-induced cell death. These agonists reversed sPLA2-IIA-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Before cell death, sPLA2-IIA potentiated the influx of Ca2+ into neurons. Blockers of the L-type voltage-dependent calcium channel (L-VSCC) not only suppressed the Ca2+ influx, but also exhibited neuroprotective effects. As well as L-VSCC blockers, ET-3 significantly prevented neurons from sPLA2-IIA-induced Ca2+ influx. An ETB receptor antagonist, BQ788, inhibited the effects of ET-3. The present cortical cultures contained few non-neuronal cells, indicating that the ETB receptor agonist affected the survival of neurons directly, but not indirectly via non-neuronal cells. In conclusion, we demonstrate that the ETB receptor agonist rescues cortical neurons from sPLA2-IIA-induced apoptosis. Furthermore, the present study suggests that the inhibition of L-VSCC contributes to the neuroprotective effects of the ETB receptor agonist.     

Omeprazole- and esomeprazole-associated hypomagnesaemia: data mining of the public version of the FDA Adverse Event Reporting System

Objective: Case reports showing that proton-pump inhibitors (PPIs), omeprazole and esomeprazole, can cause hypomagnesaemia have been accumulating since 2006. In this study, the reports submitted to the Adverse Event Reporting System (AERS) of the US Food and Drug Administration (FDA) were evaluated to assess omeprazole and esomeprazole in terms of susceptibility to hypomagnesaemia.Methods: After a revision of arbitrary drug names and the deletion of duplicated submissions, the reports involving omeprazole and esomeprazole were analyzed. Standardized official pharmacovigilance tools were used for the quantitative detection of a signal, i.e., an association between a drug and an adverse drug event, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.Results: A total of 22,017,956 co-occurrences were found in 1,644,220 reports from 2004 to 2009, where a co-occurrence was a pair of a drug and an adverse drug event. In total, 818 and 743 adverse drug events were listed as omeprazole- and esomeprazole-associated, with hypomagnesaemia ranking 85^th and 135^th, respectively. Although both PPIs were associated with hypomagnesaemia, the statistical metrics suggested that the association was more noteworthy for omeprazole.Conclusion: The data obtained in this study do not provide sufficient evidence to recommend systematic monitoring of magnesium levels in plasma, but chronic exposure to a PPI can lead to severe hypomagnesaemia.     

Effect of serum triglyceride concentration on the fluctuation of whole blood concentration of cyclosporin A in patients.

The methodology to distinguish the patients showing considerable fluctuation of the whole blood concentration of cyclosporin A (CYA) was investigated from a viewpoint of laboratory test values. First, we retrospectively examined the CYA trough blood concentrations monitored continuously. The patients were classified into three groups by the fluctuation of CYA trough blood concentrations during the examination period (Cmax/Cmin): Group 1 (Cmax/Cmin=100-200%; n=21), Group 2 (Cmax/Cmin=200-300%; n=25), and Group 3 (Cmax/Cmin=more than 300%; n=32). In the laboratory tests examined, the serum triglyceride concentrations were considerably different among the groups, and it was the highest in Group 3. Next, to elucidate the effect of serum triglyceride concentration on the CYA blood concentration, in vivo pharmacokinetic studies after single intravenous or repetitive oral administration of CYA were conducted in the model rats with pseudo-hypertriglyceridemia, hypocythemia, and acute renal failure. Only in pseudo-hypertriglyceridemia rats, the CYA blood concentration after a single intravenous injection was significantly higher than that in normal rats because of the restriction of CYA distribution to the extravascular tissues. On the other hand, the increase in the serum triglyceride concentration did not affect the fluctuation of CYA trough blood concentration after repetitive oral administration. Taken together, the fluctuation of CYA trough blood concentrations observed in the clinical situation could be due to the fluctuation of serum triglyceride concentration, and the patients with such fluctuation of serum triglyceride concentrations might also be distinguishable by the higher concentration of serum triglyceride in laboratory tests.     

Experimental polymicrobial osteomyelitis produced by both aerobic and anaerobic opportunistic pathogens

Experimental models of polymicrobial osteomyelitis were prepared using clinical isolates of Staphylococcus epidermidis and Enterococcus faecalis as aerobes and Bacteroides fragilis and Bacteroides bivius as anaerobes. These pathogens were used because of their opportunistic properties. Two 8 mm long silk threads with the microorganism were inserted into the bone marrow of a rat. The microorganism inoculated was about 10(5) c.f.u. for aerobes and 10(6) c.f.u. for anaerobes. Infected parts observed in the roentgenograms, histopathological changes, and bacterial counts all showed the evolution of osteomyelitis. It was found that our models caused osteomyelitis both when each of S. epidermidis, E. faecalis, B. fragilis, and B. bivius was implanted individually and in their combinations. The patterns of the radiological and the histological observations were almost similar in all cases examined, but their characteristics differed depending on the kinds and combinations of the pathogens.     

Dissolving microneedles for enhanced local delivery of capsaicin to rat skin tissue

Capsaicin-loaded dissolving microneedles (DMNs) were prepared to investigate the analgesic effect of capsaicin on the skin. The dimensions of each microneedle (MN) were as follows: diameter of the basement, 17?mm; length, 500?μm; and width, 300?μm. The average capsaicin content in the DMNs loaded with a low and high dose of capsaicin was 8.8?±?0.5?mg and 12.5?±?0.4?mg. Almost all the capsaicin, 99.3?±?4.1% and 99.7?±?2.2% for low-dose and high-dose DMNs were released within 20?min. High amounts of capsaicin were recovered with 102.8?±?0.1% of capsaicin after storage at 23?°C for 90 days. The pharmacological activity of capsaicin DMNs was compared to that of capsaicin cream as a positive control, by measuring the idiospasm of depilated rat skin. The time required to achieve 50% idiospasm suppression was 26.3?±?1.9?min and 53.0?±?2.3?min for low-dose and high-dose DMNs. A pharmacokinetic study showed high tissue capsaicin levels of 660.2?±?120.6 and 1805.3?±?218.1?μg/g wet weight for low-dose and high-dose DMNs at 5?min after administration. The results suggest that DMNs could exert a rapid local analgesic action on the skin.     

IL-1beta genotype-related effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells under acute inflammation

Glucocorticoids such as prednisolone are used for their anti-inflammatory properties. But there is evidence to suggest that under certain conditions, glucocorticoids have pro-inflammatory effects, for example, enhancement of IL-1beta production. To date, it has been reported that IL-1beta production intensity was associated with single nucleotide polymorphisms at positions -1470, -511, and -31 in the promoter region and at position 3954 in exon 5 of the IL-1beta gene. In the present study, it was examined whether these IL-1beta genotypes were associated with the suppressive effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). A midrange concentration (10(-6) M) of prednisolone suppressed the LPS-induced increase in IL-1beta mRNA expression and protein release, while higher concentrations (10(-5) M, 10(-4) M) exhibited less suppression or had a synergistic stimulative effect on IL-1beta production in certain subjects. Under treatment with 10(-4) M prednisolone, the levels of IL-1beta protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1beta TT(-31), TC(-31), and CC(-31) genotypes were suppressed to 6.0+/-3.4%, 31.4+/-57.0%, and 87.7+/-84.8%, respectively, of the level in prednisolone-untreated control cells (TT(-31) vs. CC(-31), p<0.05). Glucocorticoid-based anti-inflammatory therapy might be less effective in patients with the IL-1beta TC(-31) and CC(-31) genotypes than those with the TT(-31) genotype.