Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells

Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation. These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.     

Atherogenic effect of oxidized products of cholesterol

Cholesterol under certain in vitro and possibly in vivo conditions may be oxidized to oxysterols, which are suspected of being initiators of atherosclerotic plaques. Oxysterols inhibit HMG-CoA reductase activity resulting in a decreased cholesterol concentration in the cell membrane, which leads to endothelial membrane injury and probable premature cell death. Exogenous oxidation of cholesterol in human tissues under certain unusual conditions is highly probable. Dietary oxysterols are absorbed in the gastrointestinal tract and are selectively transported by the athrogenic lipoproteins LDL and VLDL. The oxysterols cholestanetriol and 25-OH cholesterol have been shown to be atherogenic. Oxysterols are commonly found in dried egg products, powdered milk, cheeses and in a variety of high temperature dried animal products.     

Quantitative evaluation of diabetic gastrointestinal paresis by measuring transit time of the stomach and the digestive canal

Our subjects comprised eighty six diabetes mellitus (DM) patients without severe complication. To evaluate gastrointestinal motility quantitatively, we measured gastric emptying time by acetaminophen (APAP) method using serum APAP value and oro-cecal transit time (OCTT) by lactulose hydrogen breath test in the subjects and normal controls (NC). Comparing DM patients and NC, mean APAP value was lower and mean OCTT was prolonged in the former. Analysing DM patients' background, patients with peripheral neuropathy had prolonged OCTT than patients without neuropathy did. Comparing patients with higher HbA1c levels and patients with normal HbA1c levels, mean APAP value, which was closer to normal levels, was higher in the former. Analysing symptoms, some of them were apparently related to abnormal gastrointestinal motility. From these results, it was concluded that measuring both gastric emptying and OCTT was a useful method to evaluate slight abnormal motility in DM patients.     

Requirements for high-frequency LD FM response in an optical CPFSKheterodyne delay demodulation system

The required high-frequency laser diode (LD) FM responses for a continuous phase frequency shift keying (CPFSK) heterodyne delay modulation system were investigated. The degradations due to insufficient high-frequency FM response are evaluated, considering the FSK waveform distortion, which gives undesired phase error at the demodulation circuit. From the phase error, bit error rate (BER) degradation is calculated. The calculated results indicate that the delay-time adjustment for the demodulation circuit is effective in minimizing the power penalty. The theoretical evaluation, including the demodulation circuit optimization, explains the experimental results fairly well. Using the same evaluation procedure, required high-frequency LD FM responses are derived. The results, together with the required low-frequency FM responses, give guidelines for transmitter LD selection for coherent CPFSK systems     

Identification and field evaluation ofAnomala octiescostata (Coleoptera: Scarabaeidae) sex pheromone

Using GC-EAD, the sex pheromone of the scarab beetleAnomala octiescostata was identified to be a 8:2 binary mixture of (R,Z)-5-(–)-(oct-1-enyl)oxacyclopentan-2-one and (R,Z)-5-(–)-(dec-1-enyl)oxacyclopentan-2-one. These semiochemicals have been also reported as sex pheromone constituents of otherAnomala species, either geographically or seasonally isolated fromA. octiescostata. Synthetic sex pheromone was highly attractive in the field; 0.1 mg captured significantly more males than two virgin females. Buried traps were significantly more attractive than those positioned at 30, 90, and 150 cm above the ground. In a dose-response test (0.1–100 mg), no saturation due to overdose of pheromone was observed, but in most cases, two dosages differing by 10-fold were not significantly different. Response of males to traps baited with different ratios of the two components was tested in two experiments with randomized blocks and Latin-square designs. Deviation from the natural ratio (8:2) of sex pheromone did not significantly diminish the response of males. Peak flight activity of beetle was recorded at 9:00–10:00 AM JST on sunny days in the end of April 1993.Presented in part at the 10th Annual ISCE Meeting, July 31–August 4, 1993, Clearwater Beach, Florida.     

Transformation of Lower Alkanes into Aromatic Hydrocarbons over ZSM-5 Zeolites

Much attention has been paid to the transformation of lower alkanes such as propane and butanes into aromatic hydrocarbons from both industrial and academic points of view. The aromatic hydrocarbons can be utilized as a booster for high octane number gasoline and are fundamental raw chemicals in petroleum chemistry. The activation of lower alkanes is an intriguing subject. In early work, Csicsery [1-5] described dehydrocyclodimerization of lower alkanes over bifunctional catalysts such as platinum on alumina and Cr₂O₃ on alumina.     

Threshold-voltage balance for minimum supply operation [LV CMOS chips]

The difference between the threshold voltages V/sub t/ of pMOS and nMOS transistors is a critical issue in the low-voltage operation of CMOS circuits. The pMOS/nMOS V/sub t/ balancing profit is analyzed in terms of subthreshold leakage current and the performance of CMOS LSIs and the minimum supply voltage of logic circuits. Matching the pMOS/nMOS V/sub t/ improves LSI performance and reduces the lowest supply voltage by 0.15 V. We propose a new concept of body bias management that uses forward biasing, fluctuation compensating, and V/sub t/ matching technologies to resolve the issue.