Effects of bisphosphonates and treadmill exercise on bone and kidney in adenine-induced chronic kidney disease rats.

INTRODUCTION: The increasing prevalence of osteoporosis and chronic kidney disease (CKD) due to the aging of society has highlighted the need for development of effective treatments for elderly patients. This study examined whether the combination of treadmill exercise therapy and alendronate (ALN) can improve bone mineral density (BMD) and bone strength without worsening renal function in adenine-induced CKD model rats. MATERIALS AND METHODS: 8-week-old male Wistar rats (n = 70) were divided into experimental groups based on the treatment protocol, i.e., non-CKD (control), vehicle only (CKD), ALN only, exercise only, and combined ALN plus exercise. A 0.75% adenine diet was used to induce CKD. Groups were killed at either 20 or 30 weeks of age. Comprehensive assessments included serum and urine biochemistry tests, renal histology, bone histomorphometry, BMD measurement, micro-computed tomography examinations, and biomechanical testing. RESULTS: Blood biochemistry tests, urine analyses and histological evaluations of the kidney demonstrated that ALN treatment did not worsen renal function or kidney fibrosis in moderate-stage CKD model rats. Both ALN and treadmill exercise significantly suppressed bone resorption (p < 0.05-p < 0.01). Moreover, ALN monotherapy and combined ALN and treadmill exercise significantly improved BMD of the lumbar spine and femur, bone microstructure, and trabecular bone strength (p < 0.05-p < 0.01). Treadmill exercise was also shown to decrease cortical porosity at the mid-diaphysis of the femur and improve kidney fibrosis. CONCLUSION: The combination of ALN and treadmill exercise is effective in improving BMD, the microstructure of trabecular and cortical bone, and bone strength, without compromising renal function in adenine-induced CKD model rats.

Effects of teriparatide and low-intensity aerobic exercise on osteopenia in type 2 diabetes mellitus rats.

INTRODUCTION: In patients with type 2 diabetes mellitus (T2DM), bone fragility increases fracture risk. Teriparatide (TPTD) improves bone strength, and exercise therapy suppresses blood glucose levels in T2DM. In this study, the combined effects of TPTD and exercise therapy on trabecular and cortical bone were examined in advanced T2DM model rats. MATERIALS AND METHODS: Thirty-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into four groups (n = 9-10 in each group at two time points): Cont group (vehicle-treated control), TPTD group (TPTD 30 µg/kg injected subcutaneously, 3 times/week), Exe group (treadmill exercise, 10 m/min, 60 min/day, 5 times/week), and Comb group (TPTD-treated and treadmill exercise combined). Five and 10 weeks after treatment, bone mineral density (BMD), bone strength, and bone micro-architecture were measured. RESULTS: TPTD and combined treatment significantly increased BMDs of the lumbar spine and femur compared to the Cont group (p < 0.05 to p < 0.01). In the three-point bending test of the femur, only combined treatment increased the maximum load at 5 weeks compared with the Cont and Exe groups (p < 0.01). In the compression test of the distal femoral metaphysis, both TPTD and combined treatment increased the trabecular bone strength compared with the Cont and Exe groups (p < 0.05 to p < 0.01). Although TPTD and combined treatment improved the micro-architecture of trabecular bone (p < 0.05 to p < 0.01), only combined treatment improved the micro-structures of cortical bone from 5 weeks of treatment (p < 0.05 to p < 0.01). CONCLUSION: The combination of TPTD and treadmill exercise increased BMD and trabecular and cortical bone strength of the femur with improved micro-architecture in T2DM model rats.

Teriparatide and exercise improve bone, skeletal muscle, and fat parameters in ovariectomized and tail-suspended rats.

INTRODUCTION: Although teriparatide (TPTD) and exercise may improve osteoporosis, muscle atrophy, and fat metabolism during ageing, the effects of treatment with a combination of TPTD and exercise on these factors remain unclear. Therefore, this study examined the effects of TPTD and exercise on bone, skeletal muscle, and fat in ovariectomized and tail-suspended rats. MATERIALS AND METHODS: Seven-month-old female Wistar rats were ovariectomized and subjected to tail suspension. The rats were then randomized into one of the following four groups (n = 20/group) after 4 weeks: control group, treated with TPTD vehicle and no exercise; TPTD group (30 µg/kg TPTD, 3 days/week); Exercise group (treadmill at 12 m/min, 60 min/day, 5 days/week); and Combined group treated with TPTD and treadmill exercise. After 1 and 8 weeks of treatment, bone, skeletal muscle, and fat tissue parameters were evaluated. RESULTS: TPTD improved bone mineral density (BMD), bone structure, bone strength at the femoral metaphysis, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass and the adipose volume in the bone marrow. Treadmill exercise increased BMD, bone strength of cancellous bone, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass as seen on dual-energy X-ray absorptiometry. Furthermore, combined treatment significantly affected BMD, bone structure, and bone strength of cortical bone at the femoral diaphysis. CONCLUSION: TPTD or treadmill exercise improved bone, skeletal muscle, and fat mass. Combination therapy with TPTD and exercise had synergistic effects on BMD, structure, and bone strength in ovariectomized, tail-suspended rats.

Falls from heights while clearing snow in Akita prefecture: Re-evaluation after preventive countermeasures and public service.

BACKGROUND: This study was performed to re-examine the incidence of falls from heights while clearing snow in Akita prefecture after implementation of preventive countermeasures and a public service campaign. METHODS: This was a retrospective analysis of registration data from the section regarding prevention against natural disasters in the Akita prefectural office. The study population comprised all patients who fell from heights while clearing snow and were transported to the emergency department from December 2015 to March 2018. RESULTS: In total, 168 individuals (159 male, 9 female) fell from heights while clearing snow. Their mean age was 65.7 years (range, 19-92 years). The largest proportion of falls occurred in January (54.2%; 91 patients). The most common region in which the falls occurred was the inland part of the southern district of Akita prefecture, which accounted for 73.8% of the falls (124 patients). Individuals aged ≥65 years constituted 52.9% of the patients (n = 89). The most common mechanism of injury was a fall from a rooftop, which accounted for 62.5% of the falls (105 patients), followed by a fall from a ladder (31.0%; 52 patients). The most common sites of injury were the upper and lower extremities (39.2%; 66 patients), followed by the spine (36.3%; 61 patients). Seven of the patients died. CONCLUSIONS: Compared with a previous study by Hatakeyama et al. (Falls from heights while clearing snow in Akita Prefecture. Rinsyou Seikeigeka Clin Orthop Surg 2013 Nov; 48(11): 1091-4 [in Japanese]), the total number of patients who fell from heights while clearing snow decreased by one-half. However, the number of persons aged ≥65 years increased and constituted 52.9% of the patients, reflecting the rapidly expanding older population in Akita prefecture.

Dysphagia Secondary to Myotonic Dystrophy Unveiled in a Case of Destructive Spondylitis With Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) Syndrome Presenting As Torticollis.

To report an instructive case involving destructive spondylitis and synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, presenting with torticollis and postoperative dysphagia without hoarseness, attributed to hidden myotonic dystrophy (DM). A 51-year-old male patient with a cervical deformity, who was previously managed conservatively for a metastatic tumor, underwent reconstruction surgery and subsequently experienced postoperative dysphagia. The presence of destructive spondylitis with torticollis, warranting prompt assessment to prevent paralysis, adds complexity to the delayed identification of DM. Given the rarity of DM, peculiar neurological symptoms and other systemic comorbidities did not lead to a preoperative diagnosis without prior knowledge. The patient's dysphagia induced respiratory arrest and required reintubation. Challenges in extubation and ventilator weaning arose due to hypercapnia. Superimposed COVID-19 infection elongated the duration of intubation. Extubation failed due to aspiration pneumonia and required a tracheotomy. Despite laryngeal elevation and preservation of the relaxation of the oesophageal entrance, the sensation and movement of the tracheopharynx were disturbed. The patient exhibited an oropharyngeal propulsive disorder, predominantly indicative of motor neuron disease. The patient's mother stated that his brother had been hospitalized for a long time after abdominal surgery. Finally, the patient was diagnosed with DM, which is known to cause post-anesthetic dysphagia. Recognizing the existence of severe destructive cervical spondylitis associated with SAPHO is crucial. Although DM is not very common, it is not classified as extremely rare. Therefore, surgeons should be mindful of the potential risks associated with general anesthesia in patients with DM. The complexity of preoperative conditions may hinder an accurate diagnosis. Recognizing and establishing preoperative expectations can assist surgeons in preventing complications, even if complex spinal surgery is required for patients with DM.

Development of a New Focal Mouse Model of Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: Developing animal models of bone metastasis in renal cell carcinoma (RCC) is challenging as immunodeficient mice are required. The aim of this study was to develop a simple immune model of RCC bone metastasis. MATERIALS AND METHODS: RENCA tumor cells were injected into the right femurs of BALB/c mice. Sixty mice were grouped into each twenty-mouse group according to the tumor cell concentration, and the presence or absence and extent of bone metastasis in the total length of the femur were compared using hematoxylin and eosin staining of the excised tissues. RESULTS: Bone metastasis was significantly higher in the high concentration group than in the other groups (p<0.05), with 10 mice developing bone metastasis at two weeks and nine mice developing bone metastasis at three weeks. The extent of bone metastasis was significantly greater in the high concentration group than in the other groups (p<0.05). Multiple logistic regression analysis was performed to examine the factors influencing bone metastasis, and only the high concentration was a significant factor (p<0.05). CONCLUSION: We developed a normal immunity mouse model of local bone metastasis from RCC. This model could prove valuable for research into the treatment of bone metastases in RCC.

Effect of Acridine Orange and Zoledronic Acid on Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC. MATERIALS AND METHODS: RENCA cells (1.0×106 cells/10 µl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively. RESULTS: The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05). CONCLUSION: AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.

Molten salt synthesis of CrMnFeNi alloy nanopowder passivated by TiO x -ZrO y shell used as a superior catalyst support in liquid-phase hydrogenation.

A molten salt method was used to prepare CrMnFeNi alloy nanopowder passivated by TiO x -ZrO y surface shell with a high specific surface area (23 m2 g-1) from the oxide precursors. Analyses by scanning electron microscopy/transmission electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy revealed the formation of an alloyed Cr-Mn-Fe-Ni-rich core surrounded by an oxide surface shell with a Ti/Zr-rich composition, confirming the formation of TiO x -ZrO y /CrMnFeNi nanopowder. It was speculated that the CrMnFeNi alloy nanoparticles were preferentially formed from the constituent metals by a faster reduction of any oxides of Cr, Mn, Fe, and Ni and a subsequent alloying with Ti and Zr could hardly occur due to the high thermodynamic stability of CrMnFeNi alloy. A Ni-loaded TiO x -ZrO y /CrMnFeNi catalyst exhibited superior catalytic performance to common Ni-loaded TiO2 and ZrO2 in the liquid-phase hydrogenation of p-nitrophenol at room temperature. The enhancement could have originated from an excellent electrical property of CrMnFeNi alloy, promoting the formation of active metallic nickel on the surface during the reaction. Leaching amounts of the constituent elements of Ti-Zr-Cr-Mn-Fe-Ni and loaded Ni was very little in the reaction solution after the reaction; the results confirmed that the prepared CrMnFeNi alloy nanopowder was very stable due to the protection of the Ti/Zr-rich oxide shell. Thus, the potential application of the alloyed powder used as catalyst support was demonstrated.

Teriparatide and etelcalcetide improve bone, fibrosis, and fat parameters in chronic kidney disease model rats.

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (N = 9-10 in each group): CKD group (vehicle administration), TPTD group (30 µg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions: With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

BACKGROUND/AIM: This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma. MATERIALS AND METHODS: CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed. RESULTS: Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS. CONCLUSION: The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

Molten Salt Synthesis of Intermetallic Compound TiNi Nanopowder Passivated by TiOx Shell Prepared from NiTiO3 for Catalytic Hydrogenation.

Titanium-nickel alloy is an attractive material due to its unique properties of shape memory effect, superior elasticity, and biocompatibility. Generally, Ti-Ni alloy powders are prepared from pure elemental powders of Ti and Ni as starting materials, but it is an energy-intensive process to obtain pure titanium. In this study, intermetallic compound TiNi powder passivated by TiOx shell was prepared by directly reducing a commercial NiTiO3 using CaH2 reducing agent in a molten LiCl at 650 °C. Analyses by X-ray diffraction, scanning electron microscopy/transmission electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy revealed that the powder had a core-shell structure, with the core of TiNi and the shell of TiOx-rich composition with scarce metallic Ni nicely catalyzing hydrogenation reactions with good recyclability and stability.

Development of New Mouse Breast Cancer Model of Local Bone Metastasis and Verification Using Bisphosphonates.

BACKGROUND/AIM: Local tumor injection models require complicated procedures. The purpose was to establish a simple local bone metastasis model using normal mice, and to study the usefulness of the model with bisphosphonates (BP). MATERIALS AND METHODS: This study used a versatile C57BL/6 mouse model and E0771 cells. Tumor cells were injected into the right femur. Mice were divided into groups depending on the concentration of cells injected and the use of BP or not. The degree of bone destruction between the different conditions was compared using micro-computed tomography (µCT). RESULTS: Bone destruction was confirmed in four mice in the high-concentration group at 3 weeks, and in all other mice at 4 and 6 weeks. At 6 weeks post-injection, bone destruction was significantly suppressed in the BP group (p<0.05). CONCLUSION: We created a breast cancer mouse model of local bone metastasis. Zoledronate showed the same usefulness as in previous models. It may be an effective model for evaluating treatments for bone metastasis.

Intravascular Administration of Acridine Orange and Zoledronate in a Bone Metastasis Model of Breast Cancer.

BACKGROUND/AIM: This study evaluated the effect of haematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases. MATERIALS AND METHODS: E0771 cells (1.0×105 cells/10 µl) were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment (drugs and irradiation) and were reared and sacrificed after 6 weeks. Micro-computed tomography (µCT) was performed to calculate the destruction rate of the femur bone. We measured tumour weight and volume at sacrifice and performed terminal deoxynucleotidyl transferase dUTP Nick-End Labelling staining of tumours. RESULTS: At 4 weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At 6 weeks, the AO+ZOL group had a lower bone destruction rate than the control and radiation groups; the ZOL group had a lower rate than the radiation group. The AO and AO+ZOL groups had suppressed tumour weight and volume compared to the control and radiation groups. The number of extraosseous apoptotic cells was higher in the AO+ZOL group than in all other groups except the AO group. CONCLUSION: In a model of local bone metastasis of breast cancer, haematogenous administration of AO reduced tumour size and more so when combined with ZOL.

Pediatric spinal infection with epidural abscess: A report of two cases.

BACKGROUND: Pediatric spinal infections are rare and often accompanied by abscesses. Delayed diagnosis commonly leads to a poor neurological prognosis, emphasizing the need for early diagnosis and treatment. CASE DESCRIPTION: We report on two cases of spinal infection; one in a 5-year-old boy with a T8-11 epidural abscess and one in a 10-year-old boy with an L5-S1 epidural abscess. Both cases improved with conservative therapy. CONCLUSION: Early magnetic resonance imaging diagnosis and systemic treatment in collaboration with pediatricians are key factors in the successful management of children with spinal infections.

Analysis of bone in adenine-induced chronic kidney disease model rats.

OBJECTIVES: The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. METHODS: Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. RESULTS: In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. CONCLUSIONS: These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

Toxicological effects of chlorophenols to green algae observed at various pH and concentration of humic acid.

Humic acid (HA) is ubiquitous organic matter derived by microbial metabolisms. This polymeric substance has both hydrophilic and hydrophobic moieties, and it is known that they affect to bioavailability of environmental pollutants. Objective of this study is to investigate the toxicological effects of chlorophenols to green algae observed at various pH and concentration of HA. Toxicity was determined by algal growth inhibition rate and EC50 of green algae Chlorella vulgaris. As a result, toxicity of 2,4-dichlorophenol was mitigated with increase of the coexisting amount of HA and solution pH. In the case of coexisting 2.5 ppm HA, EC50 of 2,4-dichlorophenol was 12.2 ppm and approximately three times higher than the case of absence of HA at pH 7.5. Meanwhile, Toxicity of 2,4,6-trichlorophenol was enhanced with increase of the coexisting amount of HA. In the case of absence of HA, EC50 of 2,4,6-trichlorophenol was 13.1 ppm and approximately two times higher than the case of coexisting 2.5 ppm HA at pH 7.5. Results suggested that toxicity of chlorophenols is influenced by the electrostatic and hydrophobic interaction between HA and chlorophenols. The hypothesis of toxicity enhancement pathway was proposed in the case of equilibrium-state 2,4,6-trichlorophenol between anionic and nonionic states.

Foix-Chavany-Marie Syndrome Induced by a Unilateral Brain Abscess.

Foix-Chavany-Marie syndrome (FCMS) is a rare cortical type of pseudobulbar palsy characterized by the loss of voluntary control of the facial, pharyngeal, lingual, and masticatory muscles with preserved reflexive and autonomic functions. FCMS is generally associated with cerebrovascular diseases affecting the bilateral opercular regions. We herein report the clinical features of an 84-year-old right-handed Japanese man with FCMS due to a unilateral brain abscess. The patient's symptoms were resolved after treating the brain abscess. The present clinical results suggest that a unilateral brain abscess in the temporal operculum with a persistent old lesion in the contralateral insular cortex can induce FCMS.

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients.

PURPOSE: To evaluate the efficacy and safety of nab paclitaxel (nab-P) plus gemcitabine (GEM) in elderly patients ≥ 75 years old with unresectable pancreatic cancer (PC) compared with younger patients. METHODS: The data of 27 unresectable PC patients treated with nab-P plus GEM as first-line chemotherapy were retrospectively analyzed. The patients were divided into two groups according to their age at inclusion: an elderly group (9 patients ≥ 75 years old) and a younger group (18 patients <75 years old). We compared the disease control rate, median overall survival (OS), and adverse events (AEs) between the two groups. Predictive factors for the OS were also evaluated. RESULTS: The clinical characteristics of patients of the two groups were not significantly different except for the age. The respective values for the disease control rate (66.7% vs. 77.8%, P = 0.542) and median OS (277 days vs. 312 days, P = 0.722) were also not significantly different between the elderly and younger group, although the relative dose intensity of GEM/nab-P in the elderly group (56.6%/53.1%) was significantly lower than that in the younger group (67.3%/63.1%) (P = 0.016/0.04). The absence of biliary drainage and CEA ≥ 6.5 were found to be poor prognostic factors in a multivariate analysis. The most common grade ≥ 3 AE was neutropenia (44% in both groups). No significant differences in the frequency of all AEs were observed between the two groups. CONCLUSIONS: Nab-P plus GEM appears effective and well-tolerated for elderly patients ≥ 75 years old with unresectable PC.

Effect of dissolved organic matter source on phytotoxicity to Lemna aequinoctialis.

The effect of dissolved organic matter (DOM) on metal toxicity to aquatic organisms has been reported. Biotic ligand model (BLM) can account for this factor to predict metal toxicity. However, few attempts have been made to assess the effect of the DOM on metal phytotoxicity to duckweeds. The objectives of this study were to examine the effect of DOM on copper toxicity to the duckweed Lemna aequinoctialis, and to determine if DOM concentration alone, regardless of DOM source, is an acceptable input parameter for the BLM for copper. Nine different DOM isolates from nine different sites in Japan were used in this study. A significant difference was observed between the lowest and the highest copper binding capacity. Phytotoxicity for copper decreased with increasing DOM concentration. These observations support use of the copper biotic ligand model (BLM) with AFA% (active fulvic acid percent) as a regulatory tool to predict copper phytotoxicity on duckweeds.

The influences of method of calcium correction and the timing of blood collection on application of the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Japan.

We investigated the treatment of renal osteodystrophy (ROD) in Japan and problems concerning the K/DOQI Guidelines. The subjects were 3698 hemodialysis patients (2328 males and 1370 females) with a mean age of 61.4 years. On average, they had been on hemodialysis for 8.34 years. The serum phosphorus level was <3.5 mg/dL in 5% of the subjects, 3.5-5.5 mg/dL in 49%, 5.6-7.0 mg/dL in 33%, and >7.0 mg/dL in 13%. The serum calcium level was <8.4 mg/dL in 16% of the subjects, 8.4-9.5 mg/dL in 47%, 9.5-10.2 mg/dL in 22%, and >10.2 mg/dL in 15%. The intact PTH level was <150 pg/mL in 57%, 150-300 pg/mL in 27%, and >300 pg/mL in 16% of the patients. The first problem is that correcting Ca is not always performed in clinical fields. The uncorrected calcium level was 9.14+/-0.92 mg/dL, while the corrected calcium level [Ca = Ca + 0.8 x (4-Alb)] was 9.26+/-0.93 mg/dL (P < 0.05). The second problem is that the timing of blood collection is not described in the K/DOQI Guidelines. Subjects with a serum phosphorus level >7.0 mg/dL at 3 days after the previous dialysis were selected for assessment. In these patients, the midweek serum phosphorus level (7.13+/-0.15 mg/dL) at was significantly lower than that (8.11+/-0.15 mg/dL) at the beginning of the next week (P < 0.001). These results suggest that it is necessary to specify the timing of measurement and the method of Ca correction when guidelines for management of ROD are established in the future.