Enhanced Effectiveness of Dimethyl-4,4‘-dimethoxy-5,6,5’,6‘-dimethylene dioxybiphenyl-2,2’-dicarboxylate in Combination with Garlic Oil against Experimental Hepatic Injury in Rats and Mice

The present study was designed to evaluate the effects of dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (PMC) in combination with garlic oil against chemical-induced hepatic injury in rats and mice. Rats insulted with carbon tetrachloride were concomitantly treated with PMC and/or garlic oil (50 and 100 mg kg^?1, respectively) for four weeks. Whereas treatment of animals with garlic oil alone was ineffective in suppressing carbon tetrachloride-induced hepatotoxicity, administration of PMC in combination with garlic oil more effectively protected the liver against the carbon tetrachloride-induced insult than PMC alone, as monitored by serum aminotransferase activity. Hepatoprotective effects of the formulation were further supported by the changes in the numbers of Kupffer cells and dead hepatocytes. Although prior treatment of rats with PMC for three days failed to protect hepatotoxicity elicited by allyl alcohol, the formulation of PMC and garlic oil was capable of blocking allyl alcohol-induced hepatotoxicity by ～ 40%. To further examine the effect of the agents on lipid metabolism in the liver, hepatic triglycerides and cholesterol contents were assessed in mice after a diet containing PMC and/or garlic oil for one week followed by a single dose of carbon tetrachloride. Garlic oil appeared to be more effective in bringing hepatic lipid levels to those of control than PMC alone. Treatment of animals with PMC in combination with garlic oil synergistically improved chemical-induced impairment of hepatic triglycerides and cholesterol. These results demonstrated that PMC in combination with garlic oil is effective in protecting (or treating) chemical-induced hepatic injury and that the formulation may be effective against chemical-induced fat-infiltration of the liver.     

Diagnosis of Atrial Fibrillation Using Electrograms from Chronic Leads: Evaluation of Computer Algorithms

This study compares the performance of three detection algorithms for the recognition of atrial fibrillation in chronic pacing leads. Multiple serial recordings were obtained of wideband and filtered electrograms from chronic atrial and ventricular leads in dogs for a period up to 55 days following implantation. Each dog was recorded in sinus rhythm and induced atrial fibrillation. Four days were chosen for processing: The day of implantation and a day in the first, second or third, and fifth weeks. Three signal processing methods were assessed for performance in detection of atrial fibrillation: software recognition of rate with automatic threshold control, amplitude distribution, and frequency spectral analysis. A software trigger for rate determination was adjusted to thresholds of 10, 20, and 30% of maximum baseline-to-peak amplitude. At 10%, a rate boundary anywhere between 420 and 560 beats per minute (bpm) perfectly separated atrial fibrillation from sinus rhythm even though atrial electrograms were contaminated with large QRS deflections and double-sensing was present. At 20% and 30%, a rate boundary around 300 bpm could be used, but sensitivity and specificity were reduced to 90%. In amplitude distribution analysis, a percent of time within a baseline window provided perfect separation of atrial fibrillation from sinus rhythm. In all cases, the signal was within this window less than 43% of the time in atrial fibrillation, and more than 43% in sinus rhythm. In spectral analysis, frequency bands were examined for power content. In the 6 to 30 Hz band atrial fibrillation contained the greater power. Choosing 58% of total power as a discriminant, sensitivity and specificity of atrial fibrillation detection were 100% and 95% respectively.     

Phase I dose-escalating study of docetaxel in combination with 5-day continuous infusion of 5-fluorouracil in patients with advanced gastric cancer

Background  

Published data suggests that docetaxel combined with 5-fluorouracil (5-FU) may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD), the recommended dose for phase II studies, and the safety of this combination.     

Interleukin 2 leads to dose-dependent expression of the alpha chain of the IL-2 receptor on CD25-negative T lymphocytes in the absence of exogenous antigenic stimulation

Expression of the alpha chain of the interleukin 2 receptor on T lymphocytes is restricted, increasing in the setting of activation, particularly after antigenic stimulation via the TCR. The effects of IL-2 in vitro on the expression of CD25 and proliferation as well as the cytokine induction in CD25-depleted T cells were studied. CD25-depleted and PBMC of healthy donors were cultured for 7 days with 0, 10, or 100 IU/ml of IL-2. Phenotypic analysis and measurement of cytokines in the culture supernatants were performed. IL-2 led to a dose-dependent induction of the IL-2R alpha chain on both CD4 and CD8 T lymphocytes. In the CD25-depleted cultures, IL-2 treatment (100 IU/ml) increased the percentage of CD4 T cells expressing CD25 by 30.6% (P = 0.05) and of CD8 T cells by 48.2% (P = 0.01) on day 7 compared to no treatment. In the PBMC cultures the increase on day 7 was 36.4% for CD4 (P = 0.01) and 50.8% (P = 0.025) for CD8 T lymphocytes. The patterns of cytokine induction in the CD25-depleted and control cultures were similar with increases of IFN-gamma, GM-CSF, IL-16, TNF alpha, and soluble IL-2 receptor in the IL-2-containing cultures. CFSE experiments demonstrated the proliferative capacity of both CD25-positive and -negative T cells. Interleukin 2 alone can lead to a dose-dependent induction of the alpha chain of its receptor on resting CD4 and CD8 T lymphocytes. IL-2 as a sole stimulant is also associated with generation of a cytokine milieu that includes IFN-gamma, GM-CSF, IL-16, and TNF alpha.     

Suppression of postganglionic sympathetic discharges by pentobarbital in endotoxic cats

Pentobarbital (7–9 mg/kg) profoundly suppressed the sympathetic postganglionic cardiac and splenic discharges in endotoxic cats under chloralose anesthesia. Concurrently, the pre-existent tachycardia was replaced by bradycardia, and the blood pressure fell further. The findings are interpreted to imply a pentobarbital-induced syrnpatolysis.     

BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro

Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity.     

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) in the duodenum: the first visceral case

An ulcerated tumour was removed by a Whipple's operation from the descending part of the duodenum of a 38-year-old male. The tumour cells were mainly spindle-shaped, arranged in nests and had very prominent nucleoli. A few cells contained melanin and melanosomes. Immunoreactivity for S-100 protein and focally for HMB-45 was observed. These features are diagnostic for clear cell sarcoma of tendons and aponeuroses. Because no other primary tumour could be found and the search for similar cases from the literature was unsuccessful, we believe that this tumour is the first reported clear cell sarcoma in a visceral location.     

EMG-activity and muscular performance of lower leg during stretch-shortening cycle after cooling

To test the effect of cooling on EMG-activity of muscles working as an agonist and antagonist in the lower leg, 12 men dressed in shorts and jogging shoes performed a drop-jump exercise after 60 min exposures to 27 °C and 10 °C. Cooling decreased mean skin temperature 5.6±0.4 °C (mean±SD, P<0.001), whereas rectal temperature was unaffected. The muscle temperature measured from m. gastrocnemius medialis decreased 4.1±0.3 °C (P<0.01) at the depth of 30 mm below skin surface. To find the optimal stretching velocity for potentiation of elastic energy, the drop-jump exercise was performed from six different bench heights (10, 20, 30, 40, 50 and 60 cm). The optimal velocity was not altered on account of cooling. In cooled subjects during the stretch phase of the drop jumps the EMG-activity of m. triceps surae complex (agonist) increased (P<0.05–0.001) while the activity of m. tibialis anterior (antagonist) remained unchanged. After cooling during the shortening phase of the jumps the EMG-activity of m. triceps surae complex decreased (P<0.05–0.001), whereas the activity of m. tibialis anterior increased (P<0.05–0.001). In addition, after cooling the peak EMG-activity appeared on the average 28 ms earlier, which shifted the peak activity from the shortening phase (at 27 °C) to the stretch phase (at 10 °C). Cooling increased the mean duration of stretch and shortening phases by 28±3 ms (P<0.001) and 23±2 ms (P<0.001), respectively. The average force production during the shortening phase was 26% less (P<0.05) after cooling, which resulted in a decreased rise of body centre of gravity (P<0.05–0.01). It is concluded that during a stretch-shortening cycle cooling alters the EMG-activity of agonist and antagonist muscles on a contradictory manner and results in an earlier peak EMG-activity. Therefore, alterations in motor unit recruitment could be responsible for the prolonged muscle contraction and decreased force production on account of cooling.