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The metabolic syndrome is defined by the concurrent presence of at least three metabolic disorders that are associated with an increased risk of cardiovascular disease and diabetes. Results from prospective and cross-sectional studies also point to an association between the metabolic syndrome and chronic kidney disease. Visceral obesity and insulin resistance are two important features of the metabolic syndrome that might explain renal injury. We reviewed the literature to examine whether treatment of the metabolic syndrome can favorably influence renal outcomes. Weight loss, regular exercise, and a low-calorie, low-fat diet are first-line treatments of the metabolic syndrome, yet few data are available to indicate that such lifestyle interventions can prevent or reverse renal damage. Similarly, results from few studies show little or no beneficial effect of blood pressure control, use of statins, fibrates, thiazolidinediones or metformin on renal parameters in patients with metabolic syndrome. The reasons for the lack of trials in this research field are also discussed. This Review identifies the need to improve understanding of the role of metabolic syndrome in chronic kidney disease, define consistent criteria for metabolic syndrome and perform clinical trials that analyze renal outcomes as primary end points.

There is significant variability in the serum concentrations of tacrolimus attained early post-transplant due to drug interactions and genomic variation. We evaluated whether tacrolimus concentrations early post-transplant correlate with incidence of acute graft-versus-host disease in 120 consecutive patients allografted with a uniform reduced-intensity conditioning regimen. All patients received standard prophylaxis with oral tacrolimus and intravenous methotrexate. The primary variable of interest was mean weekly tacrolimus concentrations in the initial 4 weeks post-transplant. In multivariate analysis, week 1 tacrolimus concentration was an independent predictor of acute grade 2 – 4 graft-versus-host disease (HR, .90; 95% CI, .84 to .97; P < .01). This association was driven by a lower risk of acute grade 2 – 4 graft-versus-host disease in patients with week 1 tacrolimus concentrations >12 ng/mL (HR .47; 95% CI, .25 – .88; P = .02). Week 1 tacrolimus concentrations were not associated with chronic graft-versus-host disease, relapse, or overall survival. Lower tacrolimus concentrations at weeks 2, 3, and 4 were not associated with a higher incidence of graft-versus-host disease. In summary, we found that higher tacrolimus concentrations during the first week after allografting with a reduced-intensity conditioning regimen were associated with significantly reduced risk of acute grade 2 – 4 graft-versus-host disease without increasing risk of relapse.

Comparative pharmacokinetics of i.v. and oral ciprofloxacin was studied in 24 healthy male subjects given 400 mg i.v. tds or 750 mg po bd in a randomized, double-blind, placebo controlled, crossover fashion with at least a 10 day washout period. Blood and urine samples were obtained following the first (single dose) and last (steady state) dose in each treatment period. After single dosing and under steady state conditions, the calculated 24 h area under the serum concentration versus time curve, (AUC0-24) after 400 mg i.v. tds (AUC0-8 x 3) was equivalent to the AUC0-24 after 750 mg po bd (AUC0-12 x 2). Peak serum concentrations produced by the i.v. regimen were very similar to those observed after the 750 mg oral dose. The extent of accumulation was similar following either dosing regimen and was approximately 35%. Overall, the incidence of adverse effects (none of which was serious) was higher with the i.v. regimen than with the oral regimen, mainly due to injection site reaction, which was the most commonly reported adverse event.

Al wire bonding, also called ultrasonic wedge-wedge bonding, is a microwelding process used extensively in the microelectronics industry for interconnections to integrated circuits. The bonding wire used is a 25 mu m diameter AlSi1 wire. A friction power model is used to derive the ultrasonic friction power during Al wire bonding. Auxiliary measurements include the current delivered to the ultrasonic transducer, the vibration amplitude of the bonding tool tip in free air, and the ultrasonic force acting on the bonding pad during the bond process. The ultrasonic force measurement is like a signature of the bond as it allows for a detailed insight into mechanisms during various phases of the process. It is measured using piezoresistive force microsensors integrated close to the Al bonding pad (Al-Al process) on a custom made test chip. A clear break-off in the force signal is observed, which is followed by a relatively constant force for a short duration. A large second harmonic content is observed, describing a nonsymmetric deviation of the signal wave form from the sinusoidal shape. This deviation might be due to the reduced geometrical symmetry of the wedge tool. For bonds made with typical process parameters, several characteristic values used in the friction power model are determined. The ultrasonic compliance of the bonding system is 2.66 mu m/N. A typical maximum value of the relative interfacial amplitude of ultrasonic friction is at least 222 nm. The maximum interfacial friction power is at least 11.5 mW, which is only about 4.8% of the total electrical power delivered to the ultrasonic generator

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Perifosine given according to a loading and maintenance schedule can safely sustain concentrations of drug, approaching concentrations achieved in preclinical models with evidence of anti-tumor effect.