Arterial And Venous Impacts Of Transdermally Administered Vasodilators On The Local Microvasculature

Microcirculatory function is an important component of cardiovascular pharmacology as related to cardiovascular dysfunction. We used photoplethysmography (PPG) to compare the microcirculatory effects of transdermal patches of rivastigmine (Exelon, Novartis), nicotine, nitroglycerin (NTG) and topically applied EMLA (eutectic mixture of lidocaine/prilocaine). We anticipate that this initial pilot comparison of single doses of each medication will catalyze future multi-dose comparisons of the various vasodilatory features of these and other drugs. Methods: With IRB approval, 10 healthy volunteers were monitored with PPG at the time each transdermal patch was applied and every 8 minutes afterwards for a total of 40 minutes. 1x1 cm portions of patches of rivastigmine, nicotine, and NTG were placed and monitored on different sites of the forehead. Another site was isolated and pretreated 6 hours earlier with EMLA, since this drug requires many hours to induce vasodilation.1 All voltage changes were changed to ACmults, i.e., in multiples of the change in voltage associated with delivery of the stroke volume to the given site under resting conditions2. A linear mixed model was used to compare patch effects on maximum change in AC, DC, and ΔAC/ΔDC. This model accounts for the variance that can be attributed to an individual’s multiple measurements within an unstructured covariance matrix. A p-value \u3c0.05 was given to be statistically significant. Data were expressed as mean within a 95% confidence interval. Results: The max ∆AC change for each drug were significantly different from that of its control while only the max ∆DC of NTG was significantly greater than that of its control. Changes in the ΔAC/ΔDC ratio were found to be inconsistent. Rivastigmine and control had significantly lower ΔAC/ΔDC values at 8 minutes compared to that of EMLA; the differences were not significant at following time points. Discussion: These results may provide some insight into the cardiovascular effects of the study agents used. NTG, a direct NO donor, caused significant increases in AC (arteriolar) and DC (venous) values. Acting at the pre/post ganglionic junction of local parasympathetic pathways to the region of the precapillary sphincter, nicotine caused a significant increase in AC, whereas the change in DC was not found to be significant. Rivastigmine, which inhibits the metabolic degradation of acetylcholine, caused a selective increase in AC. The local anesthetic (EMLA) caused a significant increase in AC. Rivastigmine caused significantly lower ΔAC/ΔDC ratio at 8 minutes when compared to EMLA (which had been on for 6 hours previously). At \u3e16 minutes, the ΔAC/ΔDC values of rivastigmine and EMLA did not differ significantly, findings that may reflect the time needed for acetylcholine to to increase over time via the inhibition of its breakdown as opposed to an immediate introduction of additional agonist via the nicotine or NTG patch. Future studies using different and/or additional drug combinations may help give further insight into the convoluted physiology of the microvasculature

Contemporary Chinese Historical TV Drama as a Cultural Genre:Production, Consumption and the State Power

In the mid-1990s a wave of dramatic serials featuring the legendary figures of China’s bygone dynasties began to dominate dramatic programming on Chinese prime time television. The trend reached its height in the late 1990s and the early 2000s with saturatio

Efficient multistep methods for tempered fractional calculus: Algorithms and Simulations

In this work, we extend the fractional linear multistep methods in [C. Lubich, SIAM J. Math. Anal., 17 (1986), pp.704--719] to the tempered fractional integral and derivative operators in the sense that the tempered fractional derivative operator is interpreted in terms of the Hadamard finite-part integral. We develop two fast methods, Fast Method I and Fast Method II, with linear complexity to calculate the discrete convolution for the approximation of the (tempered) fractional operator. Fast Method I is based on a local approximation for the contour integral that represents the convolution weight. Fast Method II is based on a globally uniform approximation of the trapezoidal rule for the integral on the real line. Both methods are efficient, but numerical experimentation reveals that Fast Method II outperforms Fast Method I in terms of accuracy, efficiency, and coding simplicity. The memory requirement and computational cost of Fast Method II are $O(Q)$ and $O(Qn_T)$, respectively, where $n_T$ is the number of the final time steps and $Q$ is the number of quadrature points used in the trapezoidal rule. The effectiveness of the fast methods is verified through a series of numerical examples for long-time integration, including a numerical study of a fractional reaction-diffusion model

The Sorting Index and Permutation Codes

In the combinatorial study of the coefficients of a bivariate polynomial that generalizes both the length and the reflection length generating functions for finite Coxeter groups, Petersen introduced a new Mahonian statistic $sor$, called the sorting index. Petersen proved that the pairs of statistics $(sor,cyc)$ and $(inv,rl\textrm{-}min)$ have the same joint distribution over the symmetric group, and asked for a combinatorial proof of this fact. In answer to the question of Petersen, we observe a connection between the sorting index and the B-code of a permutation defined by Foata and Han, and we show that the bijection of Foata and Han serves the purpose of mapping $(inv,rl\textrm{-}min)$ to $(sor,cyc)$. We also give a type $B$ analogue of the Foata-Han bijection, and we derive the quidistribution of $(inv_B,{\rm Lmap_B},{\rm Rmil_B})$ and $(sor_B,{\rm Lmap_B},{\rm Cyc_B})$ over signed permutations. So we get a combinatorial interpretation of Petersen's equidistribution of $(inv_B,nmin_B)$ and $(sor_B,l_B')$. Moreover, we show that the six pairs of set-valued statistics $\rm (Cyc_B,Rmil_B)$, $\rm(Cyc_B,Lmap_B)$, $\rm(Rmil_B,Lmap_B)$, $\rm(Lmap_B,Rmil_B)$, $\rm(Lmap_B,Cyc_B)$ and $\rm(Rmil_B,Cyc_B)$ are equidistributed over signed permutations. For Coxeter groups of type $D$, Petersen showed that the two statistics $inv_D$ and $sor_D$ are equidistributed. We introduce two statistics $nmin_D$ and $\tilde{l}_D'$ for elements of $D_n$ and we prove that the two pairs of statistics $(inv_D,nmin_D)$ and $(sor_D,\tilde{l}_D')$ are equidistributed.Comment: 25 page