The effect of a natural, standardized bilberry extract (Mirtoselect®) in dry eye: a randomized, double blinded, placebo-controlled trial.

OBJECTIVE: Dry eye, a chronic disease of lachrymal fluid and corneo-conjunctival epithelium, could significantly impact visual function, affects quality of life and work productivity. Beside several conventional treatments, nutritional supplements based on bilberry extract have been identified as effective contributors to eye health. Here, we aim at investigating the bioavailability of a standardized bilberry extract, its ability to alleviate dry eye symptoms and its antioxidant potential. MATERIALS AND METHODS: Either bilberry dried standardized extract derived from Vaccinium myrtillus L. fresh frozen fruits (Mirtoselect®) or a highly purified anthocyanin-rich extract, devoid of the non anthocyanin component and supported on maltodextrins, were each orally administrated to 5 male rats. Blood samples were collected at 5, 10, 15, 20, 30, 45, 60, 90, 120 minutes after treatment, processed and analyzed by UV spectrophotometric method. In a parallel analysis, 22 otherwise healthy subjects suffering from dry eye symptoms were enrolled randomly assigned to receive the more bioavailable bilberry extract or placebo. Ophthalmological and clinical examinations including Schirmer's test, pupil constriction, diacron-reactive oxygen metabolites (d-ROMs) test and biological antioxidant potential (BAP) test were performed at inclusion and after the 4-week study period. RESULTS: The area under the curve of plasmatic levels of anthocyanosides in rats resulted 202.34±24.23 µg·min/ml for Mirtoselect® and 130.93±4.93 µg·min/ml for the highly purified anthocyanin-rich bilberry extract, notwithstanding the fact that the highly purified anthocyanin-rich extract group received an anthocyanins dosage much higher than the Mirtoselect® group (354 mg/Kg in anthocyanosides vs. 136 mg/Kg in anthocyanosides). 21 subjects, 11 subjects in the bilberry extract (Mirtoselect®) group and 10 subjects in the placebo group completed the clinical study. Schirmer's test values indicating the volume of tear secretion were significantly improved in the bilberry extract group (p=0.019), whereas no significant changes were observed in the placebo group. A subset analysis revealed that Mirtoselect® could be more effective in subjects with higher tendency of dry eye. In terms of antioxidant potential, the bilberry extract produced significant improvement of BAP (p=0.003) and an increase of modified BAP/d-ROMs ratio, an indicator of overall balance between antioxidant potential and oxidative stress. CONCLUSIONS: Our results suggested that natural, standardized bilberry extract (Mirtoselect®) is a natural more bioavailable delivery form anthocyanins, suggesting a strong matrix effect exerted by the non-anthocyanin component. Furthermore, it can improve tear secretion and plasmatic antioxidant potential in subjects suffering from DED symptoms.

Functional morphology of the aardvark tail.

The musculoskeletal system of the aardvark (Orycteropus afer) tail was morphologically examined in two adult specimens. The tail musculature comprised three muscular groups, viz. a dorsal sacrocaudal system that consisted of the irregularly oriented Musculus sacrocaudalis dorsalis medialis and M. sacrocaudalis dorsalis lateralis, a lateral inter-vertebral connecting system, and a ventral sacrocaudal system characterized by the thick M. sacrocaudalis ventralis lateralis and M. sacrocaudalis ventralis medialis. Both the dorsal and ventral systems possessed large tendon groups that strengthened the tail structure. Computed tomography (CT) examination showed the presence of large but homogeneous cartilaginous inter-vertebral discs, whereas V-shaped bones were situated at the ventral aspect of the caudal vertebrae at the level of the inter-vertebral discs. CT visualization of the tendons and V-shaped bones in various tail positions suggested that these structures contribute to the tunnel digging action by bearing the trunk weight and lending force when the aardvark are displacing the soil by means of the forelimbs.

Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats.

AIM: This study aimed to investigate the effects of vitamin C administration on skeletal muscle hypertrophy induced by mechanical overload in rats. METHODS: Male Wistar rats were randomly assigned to three groups: (i) sham-operated group (n = 8), (ii) placebo-administered group (n = 8) and (iii) vitamin C-administered group (n = 8). In the placebo-administered and vitamin C-administered groups, the gastrocnemius and soleus muscles of the right hindlimb were surgically removed to overload the plantaris muscle. Vitamin C (500 mg kg(-1)) was orally administered to the vitamin C-administered group once a day for 14 days. RESULTS: Synergist muscle ablation caused significant increases in wet weight and protein concentration of the plantaris muscle in both the placebo-administered (P < 0.01) and vitamin C-administered groups (P < 0.01) compared with the sham-operated group (SHA). However, the magnitude of plantaris muscle hypertrophy (expressed as a percentage of the contralateral plantaris muscle) was significantly smaller (P < 0.01) in the vitamin C-administered group (141%) than in the placebo-administered group (PLA) (152%). Compared with the SHA, only the PLA showed higher expressions of phosphorylated p70s6k and Erk1/2 (positive regulators of muscle protein synthesis) and a lower expression of atrogin-1 (a muscle atrophy marker). Concentrations of vitamin C and oxidative stress markers in the overloaded muscle were similar between the placebo-administered and vitamin C-administered groups. CONCLUSION: Oral vitamin C administration can attenuate overload-induced skeletal muscle hypertrophy, which may have implications for antioxidant supplementation during exercise training.

Frequent nocturnal vocalization in pure autonomic failure.

Nocturnal vocalization is frequent in Parkinson's disease patients with rapid eye movement (REM) sleep behaviour disorder (RBD). We investigated the frequency of nocturnal vocalization and other sleep problems in patients with pure autonomic failure (PAF) and compared the results with idiopathic Parkinson's disease (IPD) and dementia with Lewy bodies (DLB). We interviewed consecutive patient-caregiver pairs with PAF (n = 13), IPD (n = 200) and DLB (n = 19), and ischaemic stroke patients (controls, n = 43). Nocturnal vocalization was similarly frequent in PAF, IPD and DLB. Other dream enactments and vivid dreams also were more frequent in PAF, IPD and DLB compared with controls. Excessive night-time awakenings and daytime sleepiness were frequent in IPD but rare in PAF and controls. Clinical manifestation of sleep disturbances, at least of RBD-like symptoms including nocturnal vocalization and other dream enactments, may occur in PAF, as in IPD and DLB.

Changes in skeletal muscle size, fibre-type composition and capillary supply after chronic venous occlusion in rats.

AIM: We have previously shown that surgical occlusion of some veins from skeletal muscle results in muscle hypertrophy without mechanical overloading in the rat. The present study investigated the changes in muscle-fibre composition and capillary supply in hypertrophied muscles after venous occlusion in the rat hindlimb. METHODS: Sixteen male Wistar rats were randomly assigned into two groups: (i) sham operated (sham-operated group; n = 7); (ii) venous occluded for 2 weeks (2-week-occluded group; n = 9). At the end of the experimental period, specimens of the plantaris muscle were dissected from the hindlimbs and subjected to biochemical and histochemical analyses. RESULTS: Two weeks after the occlusion, both the wet weight of plantaris muscle relative to body weight and absolute muscle weight showed significant increases in the 2-week-occluded group ( approximately 15%) when compared with those in the sham-operated group. The concentrations of muscle glycogen and lactate were higher in the 2-week-occluded group, whereas staining intensity of muscle lipid droplets was lower in the 2-week-occluded group than those in the sham-operated group. The percentage of type I muscle fibre decreased, whereas that of type IIb fibre increased in the 2-week-occluded group when compared with the sham-operated group. Although the expression of vascular endothelial growth factor-188 mRNA increased, the number of capillaries around the muscle fibres tended to decrease (P = 0.07). CONCLUSION: Chronic venous occlusion causes skeletal muscle hypertrophy with fibre-type transition towards faster types and changes in contents of muscle metabolites.

Excitation of toroidicity-induced Alfvén eigenmodes by the electrodes inserted in a heliotron/torsatron plasma.

A novel method of exciting shear Alfvén waves using electrodes inserted in a plasma was developed for basic study of Alfvén eigenmodes in a heliotron/torsatron plasma. The electrodes can induce excitation current along the confinement field line, and generate magnetic perturbations perpendicular to the confinement field. By sweeping the frequency of the current in a cold plasma, the toroidicity-induced Alfvén eigenmode was resonantly excited at the predicted frequency and radial location. Plasma response to the applied magnetic perturbations indicates a fairly large damping rate caused by continuum damping.

Comparative molecular cytogenetic studies in the order Carnivora: mapping chromosomal rearrangements onto the phylogenetic tree.

We have made a set of chromosome-specific painting probes for the American mink by degenerate oligonucleotide primed-PCR (DOP-PCR) amplification of flow-sorted chromosomes. The painting probes were used to delimit homologous chromosomal segments among human, red fox, dog, cat and eight species of the family Mustelidae, including the European mink, steppe and forest polecats, least weasel, mountain weasel, Japanese sable, striped polecat, and badger. Based on the results of chromosome painting and G-banding, comparative maps between these species have been established. The integrated map demonstrates a high level of karyotype conservation among mustelid species. Comparative analysis of the conserved chromosomal segments among mustelids and outgroup species revealed 18 putative ancestral autosomal segments that probably represent the ancestral chromosomes, or chromosome arms, in the karyotype of the most recent ancestor of the family Mustelidae. The proposed 2n = 38 ancestral Mustelidae karyotype appears to have been retained in some modern mustelids, e.g., Martes, Lutra, Ictonyx, and Vormela. The derivation of the mustelid karyotypes from the putative ancestral state resulted from centric fusions, fissions, the addition of heterochromatic arms, and occasional pericentric inversions. Our results confirm many of the evolutionary conclusions suggested by other data and strengthen the topology of the carnivore phylogenetic tree through the inclusion of genome-wide chromosome rearrangements.

Complex structure of B-chromosomes in two mammalian species: Apodemus peninsulae (Rodentia) and Nyctereutes procyonoides (Carnivora).

B-chromosomes (Bs) of two mammalian species, raccoon dog (Nyctereutesprocyonoides, Carnivora) and Asian wood mouse (Apodemus peninsulae, Rodentia) were investigated using chromosome segment microdissection and double-colour FISH. In the raccoon dog, all B-chromosomes showed homology with each other but not with the A-chromosomes. Two segment-specific probes (from proximal and distal parts of B) have been localized in corresponding chromosome parts, with significant variation in their sizes. In Asian wood mice, two types of B-specific chromatin were revealed--B1 and B2. Most Bs were either B1 or B2 specific; furthermore, some Bs were found to be composed of both types of chromatin. B-chromosome-specific libraries of A. peninsulae contain sequences homologous to the heterochromatic regions of sex and some A-chromosomes and dispersed repeated sequences. B1-specific probes gave signals on sex chromosomes of Apodemus speciosus and Apodemus agrarius. The origin and evolution of B-chromosomes in mammals are discussed.

Efficiency of an air filter at the drainage site in a closed circuit with a centrifugal blood pump: an in vitro study.

In a closed circuit with a centrifugal blood pump, one of the serious obstacles to clinical application is sucking of air bubbles into the drainage circuit. The goal of this study was to investigate the efficiency of an air filter at the drainage site. We used whole bovine blood and the experimental circuit consisted of a drainage circuit, two air filters, a centrifugal blood pump, a membrane oxygenator, a return circuit, and a reservoir. Air was injected into the drainage circuit with a roller pump, and the number and size of air bubbles were measured. The air filter at the drainage site could remove the air bubbles (>40 microm) by itself, but adding a vacuum removed more bubbles (>40 microm) than without vacuum. Our results suggest that an air filter at the drainage site could effectively remove air bubbles, and that adding the filter in a closed circuit with a centrifugal blood pump would be safer.

Intraoperative assessment of coronary artery bypass graft: transit-time flowmetry versus angiography.

BACKGROUND: Transit-time flowmetry has been used to assess graft status intraoperatively. This study examines the validity of this method by comparing its results with the findings of simultaneously performed graft angiography. METHODS: The left internal thoracic artery (LITA) anastomosed to the left anterior descending artery (LAD) was assessed intraoperatively with both transit-time flowmetry and graft angiography in 30 patients. The patients were stratified into two groups based on intraoperative angiographic findings. In 18 patients (group A), the LITA and the LAD were well filled with contrast medium and the anastomosis was widely patent. In the other 12 patients (group B), spastic LITA or LAD was observed. Postoperative angiography was also performed before discharge from the hospital. RESULTS: The mean graft flow was 44.0 +/- 25.4 mL/min in group A and 23.4 +/- 10.0 mL/min in group B (p = 0.0129). Diastolic-dominant flow pattern was observed in both groups, and the ratio of peak diastolic flow to peak systolic flow and the percent diastolic time-flow integral were not statistically different between the groups. The pulsatility index was almost the same between the two groups and was acceptable in both. Postoperative angiography revealed that all grafts were patent without spasm or anastomotic stenosis. CONCLUSIONS: LITA graft status is satisfactory when high graft flow with diastolic dominance is obtained. When there is vasospasm but no anastomotic problems, decreased graft flow with an acceptable pulsatility index and diastolic augmentation is observed.

A durable, non power consumptive, simple seal for rotary blood pumps.

One of the key technologic requirements for rotary blood pumps is the sealing of the motor shaft. A mechanical seal, a journal bearing, magnetic coupling, and magnetic suspension have been developed, but they have drawbacks such as wear, thrombus formation, and power consumption. A magnetic fluid seal was developed for an axial flow pump. A magnetic fluid seal is durable, simple, and non power consumptive. Long-term experiments and finite element modeling (FEM) analyses confirmed these advantages. The seal body was composed of a Ned-Fe magnet and two pole pieces; the seal was formed by injecting ferrofluid into the gap (50 microm) between the pole pieces and the motor shaft. To contain the ferrofluid in the seal and to minimize the possibility of ferrofluid making contact with blood, a shield with a small cavity was attached to the pole piece. While submerged in blood, the sealing pressure of the seal was measured and found to be 188 mm Hg with ferrofluid LS-40 (saturated magnetization, 24.3 kA/m) at a motor speed of 10,000 rpm and 225 mm Hg under static conditions. The magnetic fluid seals performed perfectly at a pressure of 100 mm Hg for 594 + days in a static condition, and 51, 39+, and 34+ days at a motor speed of 8,000 rpm. FEM analyses indicated a theoretical sealing pressure of 260 mm Hg. The state of the magnetic fluid in the seal in water was observed with a microscope. Neither splashing of magnetic fluid nor mixing of the magnetic fluid and water was observed. The specially designed magnetic fluid seal for keeping liquids out is useful for axial flow blood pumps. The magnetic fluid seal was incorporated into an intracardiac axial flow pump.

Free right internal thoracic artery as a second arterial conduit: modification of proximal anastomosis for improvement of graft patency.

The applicability of the right internal thoracic artery (RITA) for coronary artery bypass grafting is higher when used as a free graft than as a pedicled graft. However, the technical difficulty of directly connecting the proximal end of the free RITA to the much larger aorta leads to poor patency. To overcome this technical limitation, we have used a modification that places the proximal end of this artery onto the hood of an accompanying vein graft at the aortic anastomosis instead of directly onto the aorta. We performed isolated coronary artery bypass grafting on 43 patients using the free RITA as a second arterial graft following pedicled left internal thoracic artery grafting. The mean patient age was 60 years and 38 patients were male. There was no mortality and no incidence of morbidity related to free RITA use. Postoperative coronary angiography performed in all patients revealed that all proximal anastomoses were widely patent, making the patency rate of the free RITA 100%. With these encouraging results, the free RITA graft with the described modification is thought to be a more promising second arterial graft with greater versatility than the pedicled graft. The long-term evaluation of a large patient population will determine the significance of this modification.

Port-access cardiac surgery. Experience with 34 cases at Keio University Hospital.

OBJECTIVES: We reviewed our experience with port-access cardiac surgery and evaluated the medical effects and benefits of this technique in view of postoperative quality of life and medical expenses incurred during hospitalization. METHODS: From June 1998 to August 2000, port-access cardiac surgery was conducted on 34 patients--22 with atrial septal defect, 6 with mitral regurgitation, 2 with coronary artery disease, 2 with partial endocardial cushion defect, 1 with ventricular septal defect, and 1 with atrial and ventricular septal defects. Two types of endoaortic-balloon catheters were used to execute aortic cross-clamping. Skin incisions were 5 cm long. RESULTS: No hospital or late deaths were observed. Patients with atrial septal defect were discharged on postoperative day 3.7, patients of mitral regurgitation on postoperative day 4.2, and patient of ventricular septal defect on postoperative day 4.0 on the average. None were readmitted. Patients appeared undisturbed by early discharge and were able to resume physical work on day 22 on the average after discharge. CONCLUSION: Patients undergoing port-access cardiac surgery recovered quickly from surgery and resumed work quickly. This technique thus proved satisfactory both physically and mentally to patients and improved their quality of life. Medically and economically this technique proved extremely beneficial. We confirmed it to constitute a viable approach and option for cardiac surgery in selected patients.

Detection and management of concomitant coronary artery disease in patients undergoing thoracic aortic surgery.

OBJECTIVES: No method has been established to detect and manage coronary artery disease in patients undergoing thoracic aortic surgery. METHODS: Subjects were 192 patients scheduled for elective thoracic aortic surgery. Selection criteria for coronary angiography included a history of coronary artery disease or a positive dipyridamole myocardial perfusion imaging test. RESULTS: Four patients were inoperable due to complications associated with coronary angiography or aneurysm rupture following coronary revascularization. A total of 55 patients with coronary angiography (group A) underwent 57 thoracic aortic operations and 133 patients without coronary angiography (group B) underwent 143 similar operations. Of 13 group A patients with significant coronary stenosis, 9 underwent either preoperative percutaneous transluminal coronary angioplasty (n = 3) or concomitant coronary artery bypass (n = 6). Perioperative myocardial infarction occurred in 3 group A patients (5%) and in 4 group B patients (1%, ns). The incidence of cardiac events--perioperative myocardial infarction or cardiac death--in group A (11%, 6/57) was higher than that in group B (3%, 4/143; p < 0.05). Multivariate analysis demonstrated incomplete revascularization of major coronary arteries with significant stenosis as a risk factor for cardiac events (p = 0.0106). CONCLUSIONS: Although dipyridamole myocardial perfusion imaging was useful, additional selection criteria for coronary angiography is needed. Complete revascularization of major coronary arteries with significant stenosis is essential to reduce postoperative cardiac events.

Optimal positioning of temporary epicardial atrial pacing leads after cardiac surgery.

OBJECTIVES: Atrial pacing plays an important role in preventing low output syndrome and arrhythmia after cardiac surgery. We studied the optimal positioning for temporary epicardiac atrial pacing. METHODS: The performance of temporary epicardiac atrial pacing leads was examined after 13 cases of elective coronary artery bypass grafting between October 1999 and January 2000. Two bipolar electrode leads were used--1 on the cephalic atrial wall between the left and right atrial appendages, where the Bachmann bundle indwells (site A), and the other on the interatrial groove (site B). To assess pacing performance on postoperative days 1, 2, and 7, we measured 3 pacing patterns--bipolar use of sites A and B leads, and combined use of the 2 with the site A lead acting as the negative electrode and the site B lead as the ground. The pacing threshold was measured at a 0.5 ms pulse width, using the P wave amplitude and slew rate as indicators of sensing performance. RESULTS: Bipolar pacing both at sites A and A-B was superior to that at site B in pacing threshold and sensing parameters. CONCLUSIONS: The negative electrode at site A is mandatory for high atrial pacing and sensing performance.

Phylogenetic implications of the 38 putative ancestral chromosome segments for four canid species.

Chromosome homologies between the Japanese raccoon dog (Nectereutes procyonoides viverrinus, 2n = 39 + 2-4 B chromosomes) and domestic dog (Canis familiaris, 2n = 78) have been established by hybridizing a complete set of canine paint probes onto high-resolution G-banded chromosomes of the raccoon dog. Dog chromosomes 1, 13, and 19 each correspond to two raccoon dog chromosome segments, while the remaining 35 dog autosomes each correspond to a single segment. In total, 38 dog autosome paints revealed 41 conserved segments in the raccoon dog. The use of dog painting probes has enabled integration of the raccoon dog chromosomes into the previously established comparative map for the domestic dog, Arctic fox (Alopex lagopus), and red fox (Vulpes vulpes). Extensive chromosome arm homologies were found among chromosomes of the red fox, Arctic fox, and raccoon dog. Contradicting previous findings, our results show that the raccoon dog does not share a single biarmed autosome in common with the Arctic fox, red fox, or domestic cat. Comparative analysis of the distribution patterns of conserved chromosome segments revealed by dog paints in the genomes of the canids, cats, and human reveals 38 ancestral autosome segments. These segments could represent the ancestral chromosome arms in the karyotype of the most recent ancestor of the Canidae family, which we suggest could have had a low diploid number, based on comparisons with outgroup species.

Optimal position of atrial epicardial leads for temporary pacing in infants after cardiac surgery.

BACKGROUND: The atrial epicardial wall of pediatric patients was topographically assessed to identify the optimal position for temporary atrial pacing. METHODS: Unipolar electrodes were fixed at the cephalic wall between the right and left atrial appendages, the interatrial groove, and the right atrial appendage of fifteen pediatric patients who underwent definitive surgical repair. The performance of the three electrodes in terms of pacing patterns and six combinations of bipolar pacing were evaluated in terms of the pacing threshold, P-wave amplitude, slew rate, and lead impedance. RESULTS: Unipolar pacing of the right atrial appendage showed a significantly higher threshold than the other groups. A bipolar configuration of the cephalic atrial wall and interatrial groove had a significantly higher P-wave amplitude than groups without the electrode at the cephalic atrial wall, and a significantly higher slew rate than a unipolar configuration of the atrial appendage. CONCLUSIONS: Bipolar pacing with the negative electrode at the cephalic atrial wall and the indifferent electrode at the interatrial groove is the most efficient method for pediatric patients.

Endoluminal stent-grafting for thoracoabdominal aortic aneurysm in Takayasu's disease.

We report a case with occlusion of multiple branches of the aorta and a pseudoaneurysm due to rupture of a severely calcified non-aneurysmal thoracoabdominal aorta in a patient with Takayasu's disease. The patient was successfully treated by endoluminal stent-grafting without mesenteric ischemia.