Characterization of unexpected postural changes during robot-assisted gait training in paraplegic patients.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objectives of this study were to categorize unexpected postural changes (UPCs) during gait training in paraplegic patients with wearable gait-assist robots, to reveal the incidence of the UPC and its time-dependent changes during initial gait training period and to investigate neurological level-specific differences. SETTING: This study was conducted in Fujita Health University, Aichi, Japan. METHODS: We investigated five patients (46.2±14.6 years; lesion level: T6:3, T12:2). All patients had previously achieved gait with wearable robot and walker at supervision level. The UPCs were counted for 2 years and classified according to their type. The time-course data were calculated from the incidence of UPCs for 10 days from initial gait training with the walker. The neurological level-specific differences were investigated between T6 and T12 injuries. RESULTS: Eighty-five UPCs were observed and classified into three categories: anterior breakdown, posterior breakdown (PBD) and mal-timing. The average rate over the entire period was 0.96±0.62 (incidents/h/subject). PBD, which was defined as hyperflexion of both hip joints, occurred with the highest frequency (0.64±0.64 incidents/h/subject). During initial gait training, there was a gradual decrease in the occurrence of UPC. For neurological level-specific differences, UPCs were observed more frequently in T6 injuries (1.36±0.35 incidents/h/subject) compared with T12 injuries (0.36±0.31 incidents/h/subject). CONCLUSION: PBDs might be the result of near collisions between the trunk of the user and the walker, which make it difficult for the users to move their trunk over an anterior stance limb. Training that is focused upon well-timed forward movements of the walker might be required to avoid the occurrence of this common UPC.

Effects of amlodipine and valsartan on vascular damage and ambulatory blood pressure in untreated hypertensive patients.

The present study was performed to compare the long-term effects of 24-h ambulatory blood pressure (BP) control with amlodipine versus valsartan on vascular damage in untreated hypertensive patients. Amlodipine and valsartan have benefits on cardiovascular mortality and morbidity in hypertensive patients. Although ambulatory BP is associated with severity of target-organ damage in hypertensive patients, beneficial effects of ambulatory BP control with amlodipine versus valsartan on vascular damage have not been compared. Pulse wave velocity (PWV), intima-media thickness (IMT) of the carotid arteries, urinary albumin excretion (UAE) and 24-h ambulatory BP were determined in 100 untreated hypertensive patients before and 12 months after the start of antihypertensive therapy with amlodipine or valsartan. Amlodipine and valsartan decreased ambulatory BP similarly, but the variability of 24-h and daytime ambulatory systolic BP was significantly reduced by amlodipine but not by valsartan. The reduced variability of ambulatory systolic BP caused by amlodipine significantly contributed to the improvement of PWV, although both drugs decreased PWV similarly. Carotid IMT was unaffected by treatment with either drug. Valsartan significantly decreased UAE independently of its depressor effect, but amlodipine had no effect on UAE. These results suggest that the 24-h control of ambulatory BP with amlodipine had functionally improved the stiffened arteries of hypertensive patients by the end of 12 months of treatment, in part through reducing BP variability, whereas ambulatory BP control with valsartan decreased the arterial stiffness to the same degree as amlodipine without affecting BP variability maybe through some pleiotropic effects.

Ambulatory blood pressure variability and brachial-ankle pulse wave velocity in untreated hypertensive patients.

Blood pressure (BP) variability is estimated as the standard deviation of 24-h ambulatory BP. The present study was performed to determine the effect of the mean 24-h ambulatory BP values and standard deviations on arterial wall stiffness assessed by brachial-ankle pulse wave velocity (baPWV). Brachial-ankle pulse wave velocity, carotid intima-media thickness (IMT), urinary albumin excretion (UAE) and 24-h ambulatory BP were measured before the start of antihypertensive therapy in 203 newly diagnosed hypertensive patients (53.3+/-0.7 years old; clinic systolic/diastolic BP: 154+/-1/98+/-1 mm Hg), and univariate and multivariate regression analyses of these clinical and biological parameters were performed. Univariate regression analyses revealed a significant association between mean baPWV values and the standard deviations of ambulatory systolic/diastolic BP. Mean ambulatory systolic/diastolic BP values were also associated with UAE, and the standard deviations of ambulatory systolic BP were associated with maximum carotid IMT. Quintile analyses showed that patients with a mean 24-h ambulatory mean BP value and standard deviation below 110 and 20 mm Hg, respectively, had the lowest baPWV. Moreover, the multivariate regression analyses confirmed a significant correlation between baPWV and the standard deviation of 24-h ambulatory systolic BP. In conclusion, untreated hypertensive patients with a higher 24-h ambulatory systolic BP variability had stiffer arterial walls. Ambulatory systolic BP variability may be involved in stiffening of the arteries of hypertensive patients.

Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats.

Increased macula densa cyclooxygenase-2 (COX-2) is observed in diabetic rats and may contribute to hyperfiltration states. However, the signals mediating increased COX-2 expression in diabetic rats remain undetermined. We recently found that non-proteolytic activation of prorenin by site-specific binding proteins, such as prorenin receptor, plays a pivotal role in the development of diabetic nephropathy. The present study was designed to determine the contribution of prorenin receptor to renal cortical COX-2 expression. The COX-2 mRNA and protein levels of six 4-week-old male wild-type rats and six human prorenin receptor gene-transgenic (hProRenRcTg) rats were measured by real-time polymerase chain reaction methods, Western blotting, and immunohistochemistry, and compared. There were no differences between the two groups in arterial pressure measured by telemetry, urinary sodium excretion, or renal levels of rat prorenin receptor mRNA. The renal cortical COX-2 mRNA levels of the hProRenRcTg rats were significantly higher than those of the wild-type rats, and the renal cortical COX-2 protein levels were also higher in hProRenRcTg rats than in the wild-type rats. Immunohistochemical analysis revealed that COX-2 immunostaining was predominantly present in the macula densa cells, and significantly more COX-2-positive cells were present in the hProRenRcTg rats than in the wild-type rats. In addition, COX-2 inhibition with NS398 significantly decreased renal cortical blood flow in the hProRenRcTg rats but not in the wild-type rats. These results strongly suggest that human prorenin receptor directly or indirectly contributes to the regulation of renal cortical COX-2 expression.

Characterization of the binding of factor Xa to fibrinogen/fibrin derivatives and localization of the factor Xa binding site on fibrinogen.

The binding of human factor Xa to fibrinogen and its derivatives was characterized. Factor Xa bound to immobilized fibrin with a concentration at half-maximal binding (C50) of 100 nM. The 4-carboxyglutamic acid (Gla) domain of factor Xa is important in factor Xa binding to fibrin monomer, based on the following observations; the binding requires Ca2+; Gla-domain-lacking factor Xa could not bind to fibrin; factor Xa binding was significantly reduced by prior treatment of factor Xa with factor IX/factor-X-binding protein from the venom of Trimeresurus flavoviridis which specifically binds to the Gla domain of human factors IX and X. Factor Xa also bound to fibrinogen, fibrinogen degradation products (FDP)-D and FDP-E, with a similar affinity (C50 = 75-131 nM). In a solution-phase equilibrated binding assay, approximately 0.76 mol factor Xa bound to 1 mol fibrinogen with a dissociation constant of 180 nM. The binding of 125I-labeled factor Xa to the fibrin monomer was inhibited markedly by unlabeled factor Xa, but only slightly by thrombin, suggesting that the binding site of factor Xa on fibrin monomer differs from that of thrombin. We localized the binding site of factor Xa on fibrinogen: factor Xa bound strongly to the A alpha chain, but weakly to the B beta and gamma chains of fibrinogen. The A alpha chain was then digested with lysyl endopeptidase and separated by reverse-phase HPLC. Among resulting peptides, factor Xa bound specifically to a peptide corresponding to residues Asp82-Lys123 of the A alpha chain. This factor-Xa-binding site is located in the boundary between the central E domain and the terminal D domain of fibrinogen and is apparently distinct from the reported thrombin-binding site.