Noninvasive assessment of the viscoelasticity of peripheral arteries

Currently used methods of examining the mechanical properties of blood vessel walls are either indirect or invasive, or measure vessel diameter and pressure waveforms at different sites. We developed a noninvasive technique to assess the mechanical properties and viscoelasticity of peripheral arteries. The pressure-strain elastic modulus (Ep) and the viscoelastic properties (energy dissipation ratio, EDR) of the common carotid artery (CCA), brachial artery (BA), radial artery (RA) and dorsalis pedis artery (DPA) were determined by means of palpating pressure and diameter distension waveforms extracted from high-resolution ultrasonography. The methodology was validated in vitro using an elastic tube phantom, as well as in vivo. In vivo study in 10 healthy volunteers (mean age 22 y) showed that the pressure-diameter curves were nonlinear, with an inflection at about 85–90 mmHg, and routed clockwise with slight hysteresis. The CCA (n = 5) had a mean diameter of 6.74 mm and the pulsatile diameter distension was 12.2%. The Ep calculated at the CCA was 0.44 × 10⁶ dyne/cm² with an EDR of 7.18%. The BA, RA and DPA (n = 10) had mean diameters of 3.91 mm, 2.21 mm and 2.12 mm; arterial strains of 4.60%, 4.25% and 8.91%; mean Ep of 1.39, 1.45, 0.90 × 10⁶ dyne/cm²; and mean EDRs of 6.34%, 6.15% and 5.60%, respectively. The method presented is relatively simple to implement clinically and has potential as a new diagnostic tool for detecting local vascular changes.     

Intrinsic Mode Analysis of Human Heartbeat Time Series

The human heartbeat interval is determined by complex nerve control and environmental inputs. As a result, the heartbeat interval for a human is a complex time series, as shown by previous studies. Most of the analysis algorithms proposed for characterizing the profile of heartbeat time series, such as detrended fluctuation analysis and multi-scale entropy, are based on various characteristics of dynamics. In this study, we present an empirical mode decomposition-based intrinsic mode analysis, which uses the appearance energy index (AEI) to quantify the property of long-term correlation, and structure index (SI) to characterize the internal modulation of data. This presented algorithm was used to investigate the human heartbeat time series downloaded from PhysioBank. We found the profiles of human heartbeat time series of subjects with congestive heart failure (CHF) or atrial fibrillation (AF) are significantly different from those of healthy subjects in internal modulation as shown by SI. Moreover, AEI is the critical characteristics for verifying subjects with CHF from subjects with AF in a degree of long-term correlation. Both AEI and SI contribute to presenting the characteristic profiles of a human heartbeat time series.     

A Mediated Glucose Biosensor Incorporated with Reverse Iontophoresis Function for Noninvasive Glucose Monitoring

The objective of this study was to develop a ferrocene mediated glucose biosensor for reverse iontophoresis. An amperometric ferrocene mediated glucose biosensor based on a three electrodes planar configuration was constructed using screen printing technique. Different combinations of glucose oxidase and ferrocene loading were drop coated onto the surface of the amperometric transducer. The amperometric transducer was characterized electrochemically using cyclic voltammetry and its electrochemical characteristics (ΔE _p = 70 mV, I _pa/I _pc = 0.89) were found close to an ideal amperometric transducer. The biosensor on the detection of glucose at 200 mV (vs. Ag/AgCl) showed a linear response range (0–4 mM). The response time of the biosensor was about 10 s. Finally, the biosensor was used together with reverse iontophoresis technique. By the use of an actual model for evaluation, an excellent linear relationship (r ² = 0.99) was found between the glucose concentration of the actual model and the biosensor current response. In conclusion, a ferrocene mediated glucose biosensor incorporated with reverse iontophoresis function was developed.     

Internal packing of helical membrane proteins

Helix packing is important in the folding, stability, and association of membrane proteins. Packing analysis of the helical portions of 7 integral membrane proteins and 37 soluble proteins show that the helices in membrane proteins have higher packing values (0.431) than in soluble proteins (0.405). The highest packing values in integral membrane proteins originate from small hydrophobic (G and A) and small hydroxyl-containing (S and T) amino acids, whereas in soluble proteins large hydrophobic and aromatic residues have the highest packing values. The highest packing values for membrane proteins are found in the transmembrane helix-helix interfaces. Glycine and alanine have the highest occurrence among the buried amino acids in membrane proteins, whereas leucine and alanine are the most common buried residue in soluble proteins. These observations are consistent with a shorter axial separation between helices in membrane proteins. The tight helix packing revealed in this analysis contributes to membrane protein stability and likely compensates for the lack of the hydrophobic effect as a driving force for helix-helix association in membranes.     

Differential protein kinase C ligand regulation detected in vivo by a phenotypic yeast assay

The molecular dissection of protein kinase C (PKC) action has been based in part on time-consuming functional assays such as the mouse skin model for testing the tumor promoter activity of phorbol esters and related PKC activators. To help overcome the limitations imposed by the complexity of such assays, we developed the yeast Saccharomyces cerevisiae as an alternative, rapid, and simple experimental system. This model has a specific phenotype, an increase in the cell doubling time, that is proportional to the level of enzymatic activity of expressed mammalian PKC isoforms. We used this phenotype to assay and compare the regulation of native bovine PKCα and mutants in the conserved regulatory region C1 in vivo by various activators: two diterpenes, the phorbol ester phorbol-12-myristate-13-acetate (PMA) and mezerein, and the indole alkaloid indolactam V. We found that PMA activated PKC mutants lacking either Cys-rich, zinc finger-like repeat of the conserved region C1 to comparably reduced levels, whereas indolactam V activated native PKCα but none of the mutants at normal doses. In contrast, mezerein activated native PKCα and a mutant lacking the second Cys repeat equally well but mutants lacking the first Cys repeat of C1 at a greatly reduced level. These differential rsponses were supported by the observed in vitro PKC catalytic activities. Therefore, PMA regulates PKCα activity comparably well via either Cys repeat, whereas mezerein regulation predominantly occurs via the first Cys repeat of C1. Indolactam V activation was less potent, it was greatly reduced in the absence of either Cys repeat, and displayed no preference. We introduce this phenotypic assay as a rapid and general screen for the PKC-activating or possibly inhibitory potential of drug candidates and to identify the PKC regulatory sites involved in these interactions. © 1995 Wiley-Liss Inc.     

Prospective Evaluation of Laparoscopy-assisted Colectomy versusLaparotomy with Resection for Management of Complex Polyps of theSigmoid Colon

Laparoscopy-assisted colectomy istechnically feasible, but objective evidence of its benefits remainsscarce. This study was done to evaluate the outcomes and operativestress of laparoscopy-assisted colectomy versus the traditional openmethod in the management of sigmoid complex polyps that cannot besafely or adequately removed by colonofibroscopy. Between January 1997and December 1999, a total of 42 patients were equally randomizedto the laparoscopy group and the laparotomy group by the blockedrandomization method. Three patients randomized to the laparoscopygroup did not complete the trial; therefore 18 patients treated bylaparoscopy-assisted sigmoidectomy and the other 21 treated by the openmethod were prospectively evaluated. These two groups of patients werewell matched in age, gender, symptoms, tumor location, localizationmethod, tumor size, morphology, histopathology, and the accuracy of theclinical diagnosis. Two standardized surgical strategies, thelateral-to-medial and medial-to-lateral dissection sequences, wereperformed in 14 and 4 patients of the laparoscopy group, respectively,according to whether their tumors were located above or below 20 cmabove the anal verge. After evaluating the surgical outcomes, we foundthat the laparoscopy group was significantly better than the laparotomygroup in regard to parameters that included severity of postoperativepain, wound size, postoperative complication rate, and the duration ofpostoperative ileus, hospitalization, and disability. There was nosignificant difference in the operating times for these two groups.However, the costs of the laparoscopy group were significantly higher.To evaluate the surgical stress, we measured the serum C-reactiveprotein (CRP) level, erythrocyte sedimentation rate (ESR), totallymphocyte count, and CD4+/CD8+ ratio 24 hoursbefore and after surgery. We found that the postoperative serum CRPlevel and the ESR were significantly less elevated and the totallymphocyte counts and CD4+/CD8+ ratio weresignificantly less depressed in the laparoscopy group than in thelaparotomy group. We thus concluded that laparoscopy-assistedsigmoidectomy can be safely performed with shorter convalescence andless operative stress but at a higher cost. We strongly recommended theuse of this technique in the management of sigmoid complex polyps ifthe patient's economic status permits.