The 1-year decline in estimated glomerular filtration rate (eGFR) after radical nephrectomy in patients with renal masses and matched living kidney donors is the same.

OBJECTIVES: To determine short-term differences in renal function evolution between patients with renal cell carcinoma (RCC) submitted to radical nephrectomy (RN) and living kidney donors matched for age and gender. To assess the role of co-morbidity as a risk factor for developing an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) . PATIENTS AND METHODS: In this retrospective study patients undergoing Radical Nefrectomy (RN) between January 2000 and February 2011 for suspicion of localised RCC were matched by age and gender to living kidney donors. Renal function was compared between the groups using the Modification in Diet and Renal Disease (MDRD) equation at 1 year after RN. Charlson co-morbidity score, incidence of hypertension, diabetes and cardiovascular disease were compared and assessed as predictors for developing an eGFR of <60 mL/min/1.73 m(2) . RESULTS: In all, 196 patients were included, 98 in each group. The mean age was respectively 60.6 (RCC group) and 59.1 years (donors). The 1-year postoperative mean eGFR (available in 89 patients with RCC and 87 donors) was similar, at a mean (sd) of 56.7 (16.4) mL/min/1.73 m(2) in patients with RCC and 56.2 (9.8) mL/min/1.73 m(2) in donors (P = 0.83). In patients with RCC the incidence and severity of co-morbidities was significantly higher. A preoperative eGFR of 60-89 mL/min/1.73 m(2) was the only independent risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) (odds ratio 4.4, confidence interval 2.1-9.5, P < 0.001, 95% confidence interval). CONCLUSIONS: In our cohorts with advanced age the 1-year follow-up eGFR was similar in both groups. Despite increased co-morbidity in the RCC group there was no increased decline in renal function. Only reduced preoperative eGFR could be identified as risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) .

Age and gender related differences in renal cell carcinoma in a European cohort.

PURPOSE: We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS: Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS: A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS: Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Visualization of lower extremity lymphedema in the same cohort using 99mTc-human serum albumin and 99mTc-phytate lymphoscintigraphy with SPECT-CT.

Lymphoscintigraphy with single-photon emission computed tomography (SPECT-CT) is useful in diagnosing lymphedema. However, there are multiple timings, techniques, and tracers utilized worldwide without any comparison. We examined and compared the image clarity with two different radiotracers, 99mTc human serum albumin (HSA) and 99mTc phytate (phytate), in the same patients. The study retrospectivity examined 46 limbs of 36 patients who underwent lymphoscintigraphy using HSA and phytate from January 2013 to September 2018. Tracer accumulation in the lymph nodes, linear pattern (LP), and dermal backflow (DBF) were qualitatively analyzed; contrast-to-noise ratios (CNR) of DBF and standardized uptake value ratio (SUVR) of LP were also quantitatively analyzed. Neither lymph node accumulation nor DBF identification showed significant difference. However, a significant difference was observed between the LP identification of the unaffected (p<0.001) and affected sides (p<0.001). On quantitative evaluation, CNR and SUVR of LP was significantly higher with HSA than with phytate (p<0.001). SUVR of LP was also significantly higher with HSA than with phytate in both unaffected (p=0.002) and affected (p=0.005) sides. Overall, images acquired with HSA were clearer than that with phytate, and the identification of LP was particularly better with HSA than with phytate. Thus, lymphoscintigraphy using HSA is preferred over phytate for both diagnosis and evaluation of disease severity and surgical site selection.

Design of microfluidic channels to prevent negative filtration in implantable hemofiltration devices.

In order to improve the quality of life of dialysis patients, our group have been developing an implantable hemofiltration device (IHFD) composed of multiple layers of dialysis membranes and microfluidic channels. To improve the hemodialysis performance of IHFD, preventing the negative filtration, which is caused by the oncotic pressure of blood, is mandatory. In this study, we fabricated IHFDs with five different microchannel designs and experimentally investigated the performance of each device in in vitro experiment. In addition, the successful IHFD was further evaluated by ex vivo experiments with a beagle dog. The experiments verified the effectiveness of the microchannel design, which will be used for the IHFD for in vivo experiments with pigs in the future.

Purification and characterization of an 82-kD membrane protein as a neurite outgrowth factor binding protein: possible involvement of NOF binding protein in axonal outgrowth in developing retina.

Neurite outgrowth factor (NOF) is a glycoprotein isolated from an extract of gizzard that induces neurite outgrowth from cultured retinal or ciliary ganglionic (CG) neurons. We have reported that a glycoprotein of approximately 82 kD solubilized from gizzard muscles binds to NOF (ligand blotting) and inhibits the neurite promoting activity of NOF (inhibition assay). The 82-kD protein (NOF binding protein) was purified from gizzard muscle membranes as a doublet band on SDS-PAGE and a polyclonal antibody was raised against it. An NOF binding protein in developing retina exhibited the same physicochemical properties as that of the gizzard muscle. Quantitative decrease in NOF binding protein in embryonic retinas was observed after day 11 by the inhibition assay, ligand blotting, and immunoblotting, its decrease being parallel with reduction of NOF-induced neurite outgrowth of embryonic retinas. In an immunohistochemical study, the antibody stained only the optic fiber layers of the retinas of 8-d embryos, and this staining was no longer detectable in retinas of 18-d embryos. These results suggest that the 82-kD protein is a novel membrane protein that behaves as an NOF receptor and that the loss of neuritic response of the retinal neurons to NOF reflects a decrease in NOF receptor molecules.

SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model.

OBJECTIVE: TGF-beta plays a significant role in vascular injury-induced stenosis. This study evaluates the efficacy of a novel, small molecule inhibitor of ALK5/ALK4 kinase, in the rat carotid injury model of vascular fibrosis. METHODS AND RESULTS: The small molecule, SM16, was shown to bind with high affinity to ALK5 kinase ATP binding site using a competitive binding assay and biacore analysis. SM16 blocked TGF-beta and activin-induced Smad2/3 phosphorylation and TGF-beta-induced plasminogen activator inhibitor (PAI)-luciferase activity in cells. Good overall selectivity was demonstrated in a large panel of kinase assays, but SM16 also showed nanomolar inhibition of ALK4 and weak (micromolar) inhibition of Raf and p38. In the rat carotid injury model, SM16 dosed once daily orally at 15 or 30 mg/kg SM16 for 14 days caused significant inhibition of neointimal thickening and lumenal narrowing. SM16 also prevented induction of adventitial smooth muscle alpha-actin-positive myofibroblasts and the production of intimal collagen, but did not decrease the percentage of proliferative cells. CONCLUSIONS: These results are the first to demonstrate the efficacy of an orally active, small-molecule ALK5/ALK4 inhibitor in a vascular fibrosis model and suggest the potential therapeutic application of these inhibitors in vascular fibrosis.

Visinin: a novel calcium binding protein expressed in retinal cone cells.

Visinin is a retinal cone cell-specific protein (molecular weight 24,000, pI 5.1). To investigate its function, visinin cDNA was isolated from a chick retinal lambda gt11 cDNA library, using anti-visinin serum. The beta-galactosidase-visinin fusion protein was used for purifying epitope-selected antibody. The purified visinin antibody reacted only with a 24 kd protein in retinal cone cells. Visinin mRNA was expressed only in the retinal photoreceptor layer. The nucleotide sequence of the cDNA revealed that visinin has three E-F hand structures and is a Ca2+ binding protein. Visinin protein expressed in E. coli exhibited Ca2+ binding activity. These results suggest that visinin is a photoreceptor-specific Ca2+ binding protein and may be involved in phototransduction in the cone cells.

Molecular cloning and functional expression of gicerin, a novel cell adhesion molecule that binds to neurite outgrowth factor.

Gicerin is an integral membrane glycoprotein of about 82 kd that is transiently expressed in the developing CNS. Gicerin was first identified as a binding protein for neurite outgrowth factor (NOF), a member of the laminin family of extracellular matrix proteins. By isolating and sequencing a gicerin cDNA, we have found that this protein is a novel member of the immunoglobulin superfamily. The deduced protein (584 amino acids) consists of five immunoglobulin-like loop structures in an extracellular domain, a single transmembrane region, and a short cytoplasmic tail. Cells transfected stably with gicerin cDNA adhered to NOF and aggregated with each other, indicating that gicerin exhibits both heterophilic and homophilic adhesion activities.

Blood-Separating Device Without Energy Source for Implantable Medical Devices.

Coagulation of blood inside the implanted medical device is quite a critical problem to limit the lifetime. In this paper, we propose a microfluidic blood separating device using curved and branched channels. It utilizes centrifugal force on curved flow and separates blood flow into blood cell rich and blood cell poor ones at the bifurcation. Though it cannot separate the plasma from blood cells completely, the blood with small concentrations of blood cells will have low coagulatibity and extend the lifetime of the implant medical device. The device does not require any external pumps or valves, i.e., the system does not need any power sources but the blood pressure. We conducted experiments with a titanium foil which contacted to human whole blood with different hematocrit values for 7 days. The device was experimentally characterized with respect to the channel design. The former experiments suggested that lower concentration of blood cells helps avoiding blood coagulations, and the latter showed that the separation by our device is mainly affected by the flow rate and channel curvature.

A Precise Sampling Strip with Microstructures.

This paper presents a precise sampling microstructure formed as a paper strip. We have been developing dialysis system that can be implanted into a human body as an artificial kidney. For the safe use of our artificial kidney, the patients' urine needs to be constantly monitored to detect the abnormal value of ion concentration essential for human life. We are conceiving the monitoring system based on sampling by a paper strip. In this study, we fabricated the strip consisting of slanted and interlocked micropillars for the sampling, known as synthetic microfluidic paper. The paper-like substrate can be fabricated with a well-controlled geometry and subsequently enables precise sampling. Through the conducted experiments, it was shown that synthetic microfluidic paper had better mechanical properties, showed more precision in sampling than paper filter as well as corresponding liquid holding capability to the paper filter. Our proposed paper-based sampling system is expected to lead to the development of minimally invasive ion monitoring system with quantitative sampling strip.

Microbes Culture System Using Cellulose Tubes and Photocatalyst-Coated Glass Balls.

Currently, microbes are utilized in many fields, such as medicine, food and environment etc. For more application of microbes, we need a new culture system, which can culture target microbes in large quantities at low cost. Thereupon, we propose a culture system using cellulose tubes. Target microbes are encapsulated inside the cellulose tubes, where they acquire nutrients and oxygen through nano pores of the tubes and are protected from competitive microbes even in open environment. To further increase the amount of oxygen and nutritions available for the target microbes, we propose photocatalyst-coated glass balls (PCGB) to sterilize competing microbes outside the tubes. We experimentally verified the effectiveness of the proposed culture system by culturing Coryne gultamicum as the target microbes.

Enfold-type connecting system of artificial blood vessels for micro implantable dialysis device.

This paper reports the connecting mechanism for the artificial blood vessels along with the recent development of the micro implantable dialysis device. Our group has been studying the micro implantable dialysis device, which will drastically improve the quality of life of dialysis patients. We expect to replace the device every couple of years, which will involve surgery. In order to simplify the surgery to reduce the load to the patients, we develop a connector for the artificial vessels, which allows the exchange of the device by low invasive surgery. The connector needs to be designed not to induce blood coagulation. We designed a connecting mechanism that enfolds the artificial vessels to allow blood to contact only to the surface of the artificial vessels. In order to verify effectiveness of the proposed connecting mechanism, we investigated the connector surfaces with SEM after blood circulation tests. Then, we evaluated blood coagulation capacity of the connecting system as well as the set of the connecting system and the micro dialysis device with respect to the activated partial thromboplastin time (APTT). No remarkable increase of blood coagulation at the connecting point was observed after 72 hours of blood circulation tests. Short-term experiments for 120 minutes to evaluate APTT showed a small decrease of APTT, which needs to be further investigated in a longer-term experiments.

Preparation-Free Measurement of Event-Related Potential in Oddball Tasks From Hairy Parts Using Candle-Like Dry Microneedle Electrodes.

This paper reports successful measurement of even-related potential (ERP) using candle-like dry microneedle electrodes, which can acquire high-quality electroencephalogram (EEG) from hairy parts without any pretreatment. In our previous work, we successfully measured spontaneous EEG activity and its application to assess the stress state of the subjects. ERPs originate from electrophysiological response to stimulus and are one of the most important indices to capture the cognitive and sensory activities. In this work, using the candle-like dry microelectrodes, we demonstrate successful measurement of ERPs elicited by oddball tasks. Two oddball tasks using pure tone stimuli and speech stimuli were assigned to the subjects, where EEG was acquired from the parietal region (Cz in international 10-20 system). Note that no pretreatment, such as removal of hairs and abrasion of the scalp, was applied. As a result, P300 and mismatch negativity (MMN) were successfully measured in the both oddball tasks from the averaged EEG after the stimuli. Based on these results and given the attractive natures of the candle-like dry microneedle electrodes; they do not need any skin treatment and conductive gels and they can measure EEG from the hairy parts, the developed electrodes will accelerate cognitive neuroscience research using ERPs.

Thyroid hormone modulation of the hypothalamic growth hormone (GH)-releasing factor-pituitary GH axis in the rat.

Both thyroid hormone and hypothalamic growth hormone (GH)-releasing factor (GRF) facilitate pituitary somatotroph function. However, the pathophysiological role of thyroid hormone in GRF secretion is less well understood. Thyrotoxicosis, induced by administration of thyroxine (T4) in rats, inhibited both pituitary GH levels and immunoreactive GRF secretion from incubated hypothalamus. At the highest dose of T4 given for 12 d, GRF secretion and pituitary GH decreased by 50 and 39%, respectively. Hypothyroidism induced by thyroidectomy (Tx) enhanced GRF secretion approximately twofold while depleting pituitary GH by greater than 99%. Both of these hypothalamic and pituitary effects were reversed by replacement of T4 but not human GH for 7 or 14 d. Human GH was as potent as T4 in restoring decreased body weight gains or serum insulin-like growth factor-1 levels in Tx rats. These results indicate that at both physiological and pathological concentrations in serum, thyroid hormone acts as an inhibitory modulator of GRF secretion, probably not involving a feedback mechanism through GH. A biphasic effect of thyroid hormone on pituitary GH levels appears to derive from the difference in primary target tissues of hyper- and hypothyroidism, the hypothalamus and the pituitary, respectively.

Development and characterization of a fully flexible stimulation system based on embedded liquid metal channels.

Neuronal stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this study is proposed a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. The use of liquid metal micro-channels encapsulated into a polymer allowed micro-stimulation pads at the tip of the channels. It presented a high degree of patternability to match different possible applications, as well as flexibility and interesting mechanic properties to make it insertable and adaptable in soft tissues. The design, fabrication process, and study of the electrical and mechanical behavior and stability of the device are discussed. Conductive U-shaped micro-channels down to a total diameter of 110 µm could be produced.

A simple method for micropatterning nanofibrous hydrogel film.

This paper propose a new fabrication process for micropatterning a nanofibrous thin film made of bacterial cellulose(BC). BC is a hydrogel produced by specific bacteria and composed of pure cellulosic nanoflbers exhibiting 3D network structure. Such nanofibrous structure is found to be appropriate for adhesion of anchorage-dependent cells. Furthermore, BC shows high biocompatibility and mechanical toughness. Thus, the microfabrication technique for BC broadens potentials for applications. In this study, we report a new method for micropatterning BC film with feature resolution comparable with photolithography technology.

Micro-tube mass production device for microbial culture.

This paper describes mass production system of micro-tubes for microbial culture in an open environment. Microbes are used in many fields, such as food, medicine, environmental and energy. We proposed a microbe culture system using hydrogel micro-tubes, which can protect the target microbes inside from competitive microbes outside of the tubes while allow oxygen and nutrition to diffuse through. The hydrogel micro-tubes can be produced by a microfluidic device, which can precisely control the flow and therefore, the tube geometry. For practical applications of the micro-tube-based microbial culture, one of the biggest challenges is the scale-up of the micro-tube-based culture system, or mass production of the tubes. We developed a fluidic system that can produce multiple micro-tubes in parallel. We characterized the mass-produced micro channels and verified the effectiveness of the system.

Evaluation of biofouling for implantable micro dialysis system.

Implantable artificial kidney can drastically improve the quality of life of the renal disease patients. In previous study, our group has developed a multi-layered micro dialysis device which is composed of micro stainless steel channels and nano-porous polyethersulfone (PES) membranes. The device conducts hemofiltration without dialysis fluids, which is advantageous in miniaturization. We investigated the water-permeability of the PES membrane through in vivo experiments using rat model of renal disease for 5 hours and verified the effectiveness of the device. We investigated the permeability of PES membrane via in vitro experiments for 24 days. Biofouling on the PES membrane was found and caused deterioration of dialysis performance of the membrane. In this research, we investigated the biofouling such as thrombus, coagulation and protein adhesion on the sidewall of the micro fluidic channels. We investigated the micro fluidic channel geometry and surface condition associated with the processing methods. Conducting in vitro experiment for 7 days, biofouling was found to be mainly caused by the surface conditions. The mirror surface formed by electrolytic etching could substantially prevent biofouling.

Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial.

OBJECTIVES: To determine the immediate pain relief effect of low-level laser therapy on sports injuries in athletes and degree of pain relief by the therapy. DESIGN: Double-blind, randomized, comparative clinical study. METHODS: Participants were 32 college athletes with motion pain at a defined site. Participants were randomized into two groups in which the tested or placebo laser therapy was administered to determine pain intensity from painful action before and after laser irradiation, using the Modified Numerical Rating Scale. The post-therapeutic Modified Numerical Rating Scale score was subtracted from the pre-therapeutic Modified Numerical Rating Scale score to determine pain intensity difference, and the rate of pain intensity difference to pre-therapeutic Modified Numerical Rating Scale was calculated as pain relief rate. RESULTS: Low-level laser therapy was effective in 75% of the laser group, whereas it was not effective in the placebo group, indicating a significant difference in favor of the laser group (p<0.001). Pain relief rate was significantly higher in the laser group than in the placebo group (36.94% vs. 8.20%, respectively, p<0.001), with the difference in pain relief rate being 28.74%. CONCLUSIONS: Low-level laser therapy provided an immediate pain relief effect, reducing pain by 28.74%. It was effective for pain relief in 75% of participants.

Activation of phosphodiesterase in frog rod outer segment by an intermediate of rhodopsin photolysis I.

Guanosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.1) in frog rod outer segment prepared by a sucrose stepwise density gradient method was activated by light in the presence of GTP. Rhodopsin in rod outer segment was solubilized with sucrose laurylmonoester and then purified by concanavalin A-Sepharose column. Addition of photo-bleached preparation of the purified rhodopsin to the crude rod outer segment, which had been prepared by 43% (w/w) sucrose floatation, caused the activation of phosphodiesterase in the dark, while each component of the photo-product eluted from the column (all-trans retinal and opsin) did not. Regenerated rhodopsin prepared from 11-cis retinal and purified opsin activated phosphodiesterase when it was bleached. From these facts it is suggested that an intermediate or a process of photolysis of rhodopsin causes activation of phosphodiesterase.