Supine Cycling Exercise Enhances Cerebral Oxygenation of Motor-Related Areas in Healthy Male Volunteers.

It has been reported that the cardiovascular response in the supine position is different from that in the sitting position. However, there are few reports on the effects of posture on cerebral oxygenation during exercise. Cycling exercises change oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels in motor-related areas. Therefore, this study compared O2Hb levels at motor-related areas during recumbent versus supine cycling. Eleven healthy young male performed a 30-min cycling exercise protocol at 50% of the maximal oxygen uptake (VO2 max) in the recumbent and supine positions. Near-infrared spectroscopy (NIRS) was used to measure exercise-induced O2Hb and HHb changes in the right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1). In R-PMA, L-PMA and SMA, the O2Hb obtained during supine cycling was significantly higher than that during recumbent cycling (R-PMA, 0.031 ± 0.01 vs. 0.693 ± 0.01; L-PMA, 0.027 ± 0.01 vs. 0.085 ± 0.013; SMA, 0.041 ± 0.011 vs. 0.076 ± 0.008 mM·cm, recumbent vs. supine position; p < 0.05). These results suggest that supine cycling exercise increases R-PMA, L-PMA, and SMA O2Hb levels in healthy young men.

Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis.

This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.

Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia.

This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD. INTRODUCTION: Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD. METHODS: Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 µg/kg sc daily), and TPD (40 µg/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed. RESULTS: Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism. CONCLUSIONS: BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.

Site Specificity of Changes in Cortical Oxyhaemoglobin Concentration Induced by Water Immersion.

Our previous studies have shown that water immersion (WI) changes sensorimotor processing and cortical excitability in the sensorimotor regions of the brain. The present study examined the site specificity of the brain activation during WI using functional near infrared spectroscopy (fNIRS). Cortical oxyhaemoglobin (O2Hb) levels in the anterior and posterior parts of the supplementary motor area (pre-SMA and SMA), primary motor cortex (M1), primary somatosensory cortex (S1), and posterior parietal cortex (PPC) were recorded using fNIRS (OMM-3000; Shimadzu Co.) before, during, and after WI in nine healthy participants. The cortical O2Hb levels in SMA, M1, S1, and PPC significantly increased during the WI and increased gradually along with the filling of the WI tank. These changes were not seen in the pre-SMA. The results show that WI-induced increases in cortical O2Hb levels are at least somewhat site specific: there was little brain activation in response to somatosensory input in the pre-SMA, but robust activation in other areas.

Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography.

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.

Brilliant cresyl blue staining negatively affects mitochondrial functions in porcine oocytes.

The aim of the present study was to examine the effects of brilliant cresyl blue (BCB) staining on mitochondrial functions in porcine oocytes. Cumulus-oocyte complexes (COCs) collected from slaughterhouse-derived porcine ovaries were cultured with (13 µM) or without (0 µM, control) BCB for 60 min. Mitochondrial functions in oocytes were examined immediately after staining or after in vitro maturation. The BCB-stained oocytes produced reactive oxygen species (ROS) at higher levels than control oocytes immediately after staining (2.2-fold, P < 0.001) and after maturation (1.7-fold, P < 0.001). The adenosine triphosphate (ATP) content and mitochondrial membrane potential (MMP) in oocytes were similar for the two groups immediately after staining. However, ATP and relative MMP levels were significantly (P < 0.05) lower in BCB-treated oocytes than in the control (2.18 versus 2.83 pM and 0.82 versus 1.0, respectively). There was no difference in mitochondrial DNA copy number between the two groups after maturation. The ATP content in early developmental stage embryos (3 days after parthenogenetic activation) was lower in the BCB-stained group than that in the control group but the difference was not significant. In conclusion, BCB staining of oocytes at the immature stage compromises mitochondrial functions throughout oocyte maturation, but function is restored during early embryo development.

Observation of self-binding in monolayer 3He.

We report clear experimental signatures of the theoretically unexpected gas-liquid transition in the first three monolayer systems of (3)He adsorbed on graphite. The transition is inferred from the linear density dependence of the gamma coefficient of the heat capacity measured in the degenerate region (2≤T≤80 mK) below a critical liquid density (ρ(c0)). Surprisingly, the measured ρ(c0) values (0.6-0.9 nm(-2)) are nearly the same for all these layers in spite of their quite different environments. We conclude that the ground state of (3)He in strictly two dimensions is not a dilute quantum gas but a self-bound quantum liquid with the lowest density ever found.

Extravascular injection of sclerotic agents does not affect vessels in the rat: experimental implications for percutaneous sclerotherapy of arteriovenous malformations.

OBJECTIVES: Sclerotherapy is useful for the treatment of arteriovenous vascular malformations. However, intravascular administration of sclerotic agents into small arteriovenous niduses is often difficult. Extravascular administration of sclerotic agents causes reduction of vascular flow on Doppler echo during clinical sclerotherapy. Therefore, we aimed to investigate whether the extravascular injection of sclerotic agents affects tiny vessels. DESIGN: Animal study. MATERIALS: The effect of extravascular injection of sclerotic agents on vessels was investigated using rat femoral and superficial inferior epigastric vessels. METHODS: After surgical exposure of vessels, absolute ethanol, 5% ethanolamine oleate and 3% polidocanol were injected into perivascular surrounding tissues, and their effect on vessels was evaluated after 14 days using histology and coloured silicone rubber injection. RESULTS: The integrity of the vascular lumen, endothelial cells and vascular patency were not affected by injection of sclerotic agents. CONCLUSIONS: Attenuation of vascular flow of an arteriovenous shunt after extravascular injection of sclerotic agents is transient and/or trivial and does not cause disruption of vessels. Therefore, sclerotic agents should be delivered to obtain sufficient destruction of arteriovenous malformation lesions and blood flow.

Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity.

Bioassay-guided fractionation of the chloroform extract of Byrsonima fagifolia leaves led to the isolation of active antitubercular compounds alkane dotriacontane (Minimal Inhibitory Concentration-MIC, 62.5 µg mL(-1)), triterpenoids as bassic acid (MIC = 2.5 µg mL(-1)), α-amyrin acetate (MIC = 62.5 µg mL(-1)), a mixture of lupeol, α- and ß-amyrin (MIC = 31.5 µg mL(-1)) and a mixture of lupeol, and acetates of α- and ß-amyrin (MIC = 31.5 µg mL(-1)). The antimycobacterial activity was determined by the Microplate Alamar Blue Assay (MABA) and the structures of promising compounds were determined by spectroscopic analysis. This investigation constitutes the first report of a chemical and antitubercular study of apolar compounds from B. fagifolia Niedenzu (IK).

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Multicentre study of nitrate reductase assay for rapid detection of rifampicin-resistant M. tuberculosis.

SETTING: Four regional laboratories belonging to the Mycobacteria Reference Laboratory of São Paulo State, Brazil. OBJECTIVE: To evaluate the nitrate reductase assay (NRA) for rifampicin (RMP) susceptibility testing of Mycobacterium tuberculosis directly from clinical sputum samples of patients with pulmonary tuberculosis (TB). DESIGN: Performance of the NRA for detection of M.tuberculosis susceptibility to RMP was evaluated with 210 clinical sputum samples received by the participating laboratories during 2005 and 2006 and compared with the results of the direct proportion method. RESULTS: Susceptibility tests performed using the NRA and the direct proportion method showed 204 susceptible isolates and six isolates resistant to RMP by both methods. NRA sensitivity and specificity for RMP was 100%. The NRA results of susceptibility tests against RMP were available in 15 days for 87% of the samples. The results showed that NRA may yield a rapid answer in determining resistance for the majority of sputum samples with smear results reported as 3+ and 2+. CONCLUSION: The results demonstrate the feasibility of NRA for screening resistant strains in sputum samples from patients with pulmonary TB. NRA represents a rapid and low-cost alternative method that might be used in microbiological laboratories where resources are scarce.

A duplicated nitrotienyl derivative with antimycobacterial activity: synthesis, X-ray crystallography, biological and mutagenic activity tests.

A duplicated nitrotienyl derivative was obtained as a by-product from the synthesis of a proposed molecular hybrid of a nitrotienyl derivative and isoniazid with an expected dual antimycobacteria mechanism. The structure was shown to be the 5,5'-dinitro-2-(2,3-diaza-4-(2'-tienyl)buta-1,3-dienyl)tiophene by X-ray crystallography. The minimal inhibitory concentration (MIC) determination of this compound proved to be promising against Mycobacterium pathogenic strains such as M. avium and M. kansasii, although it had a high level of mutagenicity, as observed in mutagenic activity tests.

Reaction null-space filter: extracting reactionless synergies for optimal postural balance from motion capture data.

This paper introduces the notion of a reactionless synergy: a postural variation for a specific motion pattern/strategy, whereby the movements of the segments do not alter the force/moment balance at the feet. Given an optimal initial posture in terms of stability, a reactionless synergy can ensure optimality throughout the entire movement. Reactionless synergies are derived via a dynamical model wherein the feet are regarded to be unfixed. Though in contrast with the conventional fixed-feet models, this approach has the advantage of exhibiting the reactions at the feet explicitly. The dynamical model also facilitates a joint-space decomposition scheme yielding two motion components: the reactionless synergy and an orthogonal complement responsible for the dynamical coupling between the feet and the support. Since the reactionless synergy provides the basis (a feedforward control component) for optimal balance control, it may play an important role when evaluating balance abnormalities or when assessing optimality in balance control. We show how to apply the proposed method for analysis of motion capture data obtained from three voluntary movement patterns in the sagittal plane: squat, sway, and forward bend.

Luseogliflozin, A Sodium Glucose Co-transporter 2 Inhibitor, Alleviates Hepatic Impairment in Japanese Patients with Type 2 Diabetes.

Luseogliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), was previously shown to improve the blood glucose and hemoglobin A1c (HbA1c) levels of patients with type 2 diabetes in a clinical setting. Although patients with type 2 diabetes often have hepatic impairment, few reports have been published concerning the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes accompanied by hepatic impairment. The present study was undertaken to evaluate the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes divided into 2 groups according to hepatic function parameters (a normal group and an elevated group). In this study, luseogliflozin significantly improved both HbA1c and body weight to similar extents in both the normal group and the elevated group, accompanied by marked reductions in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP) levels. These results suggested that luseogliflozin can be safely used in patients with type 2 diabetes who also exhibit hepatic impairment. The results additionally suggest the possibility that luseogliflozin might be capable of alleviating hepatic impairment in patients with type 2 diabetes.

The Beneficial Effects of the DPP-4 Inhibitor Alogliptin on Hemoglobin A1c and Serum Lipids in Japanese Patients with Type 2 Diabetes.

It has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors improve hemoglobin A1c (HbA1c) levels in diabetic patients and may also improve the serum lipids. However, few studies have examined relationship between the effects of the DPP-4 inhibitor and the pretreatment HbA1c levels in diabetic patients. Furthermore, it has been reported that prolonged treatment with DPP-4 inhibitors may make glycemic control difficult in some patients. In the present study, we investigated (1) the effect of the DPP-4 inhibitor alogliptin on HbA1c, blood glucose (BG), and serum lipid in Japanese patients with type 2 diabetes, (2) the relationship between the HbA1c levels at baseline and the effects of alogliptin, and (3) the effects of switching of the DPP-4 inhibitor to alogliptin after 12 months' administration of sitagliptin on glycemic control and serum lipids. After 6-months' treatment with alogliptin, we found reductions of HbA1c, BG, and serum total cholesterol, and LDL cholesterol levels. Pretreatment level of HbA1c was well correlated with the degree of reduction of both HbA1c and BG levels after the treatment. Also, alogliptin kept levels of HbA1c and BG reduced by sitagliptin for 12 months, and relapsing of these levels and serum lipids were not observed. This study revealed that alogliptin improved HbA1c, BG, and serum lipid profiles in type 2 diabetic patients, and the effect of alogliptin on HbA1c and BG levels was correlated with HbA1c level at pretreatment. Furthermore, long-term treatment with alogliptin did not cause relapsing of glycemic control and serum lipids.

DPP-4 Inhibitor Teneligliptin Improves Insulin Resistance and Serum Lipid Profile in Japanese Patients with Type 2 Diabetes.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to improve the glycemic control and blood hemoglobin A1c (HbA1c) concentrations. However, there are few reports as yet suggesting that DPP-4 inhibitors may also improve insulin resistance and the serum lipid profile in the clinical setting. This study was aimed at investigating the effect of 14-week treatment with teneligliptin (20 mg/day) on the homeostasis model assessment ratio (HOMA-R), an indicator of insulin resistance, and serum lipid profile in 9 patients with type 2 diabetes. The treatment produced a significant decrease of the blood glucose and HbA1c concentration (blood glucose: p=0.008; HbA1c: p=0.038), and also improved HOMA-R (p=0.039). Furthermore, the patients showed elevation of the serum HDL-cholesterol level (p=0.032), and a tendency towards reduction of the serum triglyceride level. The results indicate that teneligliptin acts not only to improve the blood glucose control, but also to improve the insulin resistance and serum lipid profile in Japanese type 2 diabetes patients.

Correlation of minimum coronary lumen diameter with left ventricular functional impairment induced by atrial pacing.

To understand whether quantitative measurement of minimal coronary luminal diameter is a better method than percent diameter narrowing for assessing the functional impairment of myocardial contractility produced by coronary artery stenoses, measurements were made from 37 stenotic segments in 27 patients with coronary artery disease and from corresponding segments in 10 subjects without coronary artery narrowing. An assessment of the reliability of the 2 types of measurements was made by correlating them with the physiologic parameters of both segmental wall motion and global ejection fraction response induced by atrial pacing. Digitally acquired coronary angiograms were used to facilitate quantitative analysis. Measurements by edge detection and videodensitometry correlated closely (r = 0.94). Percent diameter narrowing correlated moderately with the change in ejection fraction (r = -0.41) or with the change in segmental wall motion (r = -0.44). The measurement of minimal lumen diameter correlated with the change in global ejection fraction (r = 0.61) and did so even better with the change in segmental wall motion (r = 0.78, p less than 0.05). A minimal lumen diameter of less than or equal to 1.5 mm identified patients likely to have a functional impairment during atrial pacing as assessed by either global ejection fraction or segmental wall motion defects. We conclude that minimal coronary luminal diameter provides a better method than percent diameter narrowing calculations to measure the anatomic severity of coronary artery narrowing.

Videodensitometric determination of minimum coronary artery luminal diameter before and after angioplasty.

Quantitative measurements of coronary stenoses were made from digital coronary angiograms in 19 patients before and after percutaneous transluminal coronary angioplasty (PTCA). Two methods of measurement were compared. Mean stenosis before PTCA was 67 +/- 10% by the edge detection method and 67 +/- 12% by videodensitometry (difference not significant). After PTCA, the mean stenosis was 32 +/- 14% by edge detection and 30 +/- 13% by videodensitometry (difference not significant). In addition, a new method was developed to rapidly calculate the absolute minimum luminal area and diameter by videodensitometry. The minimum luminal diameter before PTCA was 1.0 +/- 0.5 mm and after PTCA increased to 2.4 +/- 0.5 mm (p less than 0.001). The validity of the videodensitometric method was analyzed in a series of Lucite phantom studies, which suggested that when there is an irregular angiographic appearance, the densitometric method may be more accurate than standard edge detection methods. Digital acquisition of coronary angiograms provides a means for rapid application of quantitative analysis during coronary interventional procedures.

Solitary beta-blocker therapy for idiopathic life-threatening ventricular tachyarrhythmias.

To determine the clinical characteristics of patients with life-threatening ventricular tachyarrhythmias with no identifiable heart disease, we analyzed six patients who presented with either cardiac arrest or syncope associated with documented ventricular tachycardia or fibrillation. Electrocardiographic and echocardiographic examination and cardiac catheterization results were normal in all patients. Electrocardiographic monitoring revealed ventricular tachycardia in all patients. Exercise testing did not provoke sustained ventricular tachycardia in any patient. Programmed extrastimulation did not induce ventricular tachycardia in any patient. Isoproterenol infusion facilitated provocation of sustained ventricular tachycardia in only one patient. All six patients were treated with solitary beta-blocker therapy. Following treatment, there was a significant reduction in the incidence of ventricular tachycardia, couplets and total ventricular ectopic beats. During a follow-up period ranging from 16 to 36 (mean 22) months, all patients remain alive without clinically significant recurrence. Therefore, patients with life-threatening ventricular tachyarrhythmias without identifiable heart disease may respond to solitary beta-blocker therapy.