The Effects on Skin Blood Flow of Immersing the Ischemic Legs of Patients with Peripheral Arterial Disease into Artificially Carbonated Water

It is known that carbon dioxide causes vasodilatation. Therefore, immersing the extremities into carbonated water would be expected to increase skin blood flow, given that carbon dioxide can permeate through the skin surface. We immersed the ischemic legs of patients with peripheral arterial disease (PAD) into water artificially carbonated by a new device. Sixteen Fontaine grade II PAD patients were randomly divided into two groups: eight patients whose legs were immersed into artificially carbonated water (CO₂ group), and eight patients whose legs were immersed into tap water as a control (CTL group). The water temperature was set at 35°C, and the immersion (10 min) was repeated daily for 3 weeks in both groups. During immersion, the average percent skin blood flow increase was larger in the CO₂ group than in the CTL group (426 vs. 173%, p < 0.001), and increased gradually with each immersion in the CO₂ group (272% at the first immersion, 343% after 2 weeks, and 359% after 3 weeks, p < 0.01). Leg symptoms at rest, such as a sensation of cold and/or numbness, were significantly alleviated in the CO₂ group compared to the CTL group (2.5 points, CO₂ group vs. 8.7 points, CTL group after 3-weeks based on a 10-point relative scale, p < 0.01). Immersion into artificially carbonated water appears to be a convenient treatment option for treating limb ischemia.     

Pulmonary Arterial Impedance Analysis by the Use of the Oscillated Assist Flow

Abstract: Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (>10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10–50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the he-modynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery: however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.     

The N-terminal regions of eukaryotic acidic phosphoproteins P1 and P2 are crucial for heterodimerization and assembly into the ribosomal GTPase-associated center

Acidic phosphoproteins P1 and P2 form a heterodimer and play a crucial role in assembly of the GTPase-associated center in eukaryotic ribosomes and in ribosomal interaction with translation factors. We investigated the structural elements within P1 and P2 essential for their dimerization and for ribosomal function. Truncation of the N-terminal 10 amino acids in either P1 or P2 and swapping of the N-terminal 10 amino acid sequences between these two proteins disrupted their dimerization, binding to P0 and P0 binding to rRNA. In contrast, truncation of the C-terminal halves of P1 and P2 as well as swapping of these parts between them gave no significant effects. The protein dimers containing the C-terminal truncation mutants or swapped variants were assembled with P0 onto Escherichia coli 50 S subunits deficient in the homologous protein L10 and L7/L12 and gave reduced ribosomal activity in terms of eukaryotic elongation factor dependent GTPase activity and polyphenylalanine synthesis. The results indicate that the N-terminal 10 amino acid sequences of both P1 and P2 are crucial for P1-P2 heterodimerization and for their functional assembly with P0 into the GTPase-associated center, whereas the C-terminal halves of P1 and P2 are not essential for the assembly.     

Are free radical reactions increased in the diabetic eye?

Reactive oxygen species (ROS) are thought to play a significant role in the development of diabetic retinopathy; however, no direct evidence supports ROS generation in vivo. This study used in vivo electron spin resonance (ESR) spectroscopy with a surface resonator to detect local free radical reactions. The ESR signal decay of carbamoyl-PROXYL was enhanced in the eyes of streptozotocin (STZ)-induced diabetic mice. This enhanced signal decay was suppressed by the administration of SOD or the pretreatment with aminoguanidine. We demonstrate, for the first time, specific free radical reactions in the eyes of mice with STZ-induced diabetes.     

A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells

Background Apoptosis is a crucial element in the behavior of mammalian cells in many different situations. We here report the establishment of a novel monoclonal antibody (anti-LHK mAb) that has apoptosis-inducing activity against colon cancer Colo205 cells. Methods The mechanism of anti-LHK mAb-induced cell death was assessed by microscopic morphology, Annexin V/Hoechst 33528 staining, and detection of DNA fragmentation. The molecular weight of LHK antigen was determined by Western blotting. Growth inhibition of Colo205 cells induced by anti-LHK mAb was determined by in vitro and in vivo studies. Results Anti-LHK reacted with a 70-kDa antigen and completely blocked the proliferation of Colo205 cells bearing LHK in vitro in a manner characteristic of apoptosis. Strikingly, anti-LHK mAb suppressed tumor growth in a murine peritoneal dissemination model. Conclusions LHK antigen, which is restricted to epithelial cells, may be a novel death receptor that plays a critical role in controlling the growth, invasion, and metastasis of human colon cancer cells.     

Peripheral vasodilatory dysfunction in adult patients with congenital heart disease and severely elevated pulmonary vascular resistance

Several studies have demonstrated that pulmonary vascular abnormalities precede alterations in aortic circulation downstream in animal models of heart failure. The relationship between increased pulmonary vascular resistance (PVR) and agonist-induced limb vasodilatory response remains unknown in patients with congenital cardiovascular shunt lesions (CSL). The authors hypothesized that patients with CSL and severely elevated PVR will show a defective vasomotor response in the peripheral vascular bed. To examine this hypothesis we measured forearm blood flow (FBF) responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside. The values for these FBF responses were compared with PVR in adult patients with CSL (n=20) and healthy age- and sex-matched controls (n = 15). When patients with CSL were divided into 2 subgroups by median value of PVR, in the lower PVR subgroup, acetylcholine-induced FBF changes were selectively and significantly lower than in the healthy control group (p <0.05). In the higher PVR subgroup, FBF responses to both acetylcholine and sodium nitroprusside were significantly blunted compared to healthy controls (both p < 0.01). In addition, when FBF changes above baseline for each dose of acetylcholine and sodium nitroprusside were cumulated and used as acetylcholine response and sodium nitroprusside response, the sensitivity and specificity for identifying patients with Eisenmenger's type of CSL was 100% and 80% by acetylcholine response, and 67% and 80% by sodium nitroprusside response, respectively. In conclusion, adult CSL patients with elevated PVR and severe pulmonary arterial hypertension showed generalized vasodilator dysfunction in the forearm vasculature. This result suggests that upper limb resistance vessel dysfunction may be an indicator for advanced stage of adult patients with CSL.