Bayesian network highlights the contributing factors for efficient arsenic phytoextraction by Pteris vittata in a contaminated field.

Phytoextraction is a low-cost and eco-friendly method for removing pollutants, such as arsenic (As), from contaminated soil. One of the most studied As hyperaccumulators for soil remediation include Pteris vittata. Although phytoextraction using plant-assisted microbes has been considered a promising soil remediation method, microbial harnessing has not been achieved due to the complex and difficult to understand interactions between microbes and plants. This problem can possibly be addressed with a multi-omics approach using a Bayesian network. However, limited studies have used Bayesian networks to analyze plant-microbe interactions. Therefore, to understand this complex interaction and to facilitate efficient As phytoextraction using microbial inoculants, we conducted field cultivation experiments at two sites with different total As contents (62 and 8.9 mg/kg). Metabolome and microbiome data were obtained from rhizosphere soil samples using nuclear magnetic resonance and high-throughput sequencing, respectively, and a Bayesian network was applied to the obtained multi-omics data. In a highly As-contaminated site, inoculation with Pseudomonas sp. strain m307, which is an arsenite-oxidizing microbe having multiple copies of the arsenite oxidase gene, increased As concentration in the shoots of P. vittata to 157.5 mg/kg under this treatment; this was 1.5-fold higher than that of the other treatments. Bayesian network demonstrated that strain m307 contributed to As accumulation in P. vittata. Furthermore, the network showed that microbes belonging to the MND1 order positively contributed to As accumulation in P. vittata. Based on the ecological characteristics of MND1, it was suggested that the rhizosphere of P. vittata inoculated with strain m307 was under low-nitrogen conditions. Strain m307 may have induced low-nitrogen conditions via arsenite oxidation accompanied by nitrate reduction, potentially resulting in microbial iron reduction or the prevention of microbial iron oxidation. These conditions may have enhanced the bioavailability of arsenate, leading to increased As accumulation in P. vittata.

Temperature Dependence of Metals Accumulation and Removal Kinetics by Arabidopsis halleri ssp. gemmifera.

Cadmium (Cd), which is present in zinc (Zn) ore, is a toxic metal and causes contamination globally. Phytoremediation is a promising technology for the remediation of sites with low and moderate contamination. Temperature is an important factor in phytoremediation because it has an impact on both plant biomass and the accumulation of heavy metals. However, little is known about the influence of temperature on heavy metal accumulation by the Cd and Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera. The effect of temperature on the distribution of Cd and Zn in A. halleri ssp. gemmifera and the mechanism of metal removal from solution were investigated in this study. Our results showed that the temperature dependence of the distribution of Cd and Zn in the plant was different, which may suggest that the mechanisms of xylem loading were different between Cd and Zn. Although Cd and Zn have partially similar transport pathways, the removal kinetics based on the first-order reaction rate constant revealed that the temperature which maximized rate of absorption was different between Cd and Zn. This study suggests a potential for efficient Cd phytoextraction using A. halleri ssp gemmifera in Cd and Zn co-existing environments.

The Complete Lateral Position Method Reduced the Mortality Rate among Elderly Patients with Severe Dysphagia.

Objective This study aimed to validate the efficacy of the complete lateral position method among elderly patients with severe dysphagia. Methods We enrolled 103 patients >65 years old who were diagnosed with severe dysphagia via the fiberoptic endoscopic examination of swallowing and were treated with the complete lateral position method at Hida Municipal Hospital between February 1, 2015, and October 31, 2020. Patients treated with the complete lateral position method were included in the lateral position group, and patients treated with conventional methods were included in the control group. The mortality rates were then compared between the lateral position and control groups. Results All patients had severe dysphagia. However, the complete lateral position method significantly decreased the mortality rate in the lateral position group compared with the control group (64.7% vs. 38.8%; p<0.01). In the lateral position group, approximately 55.6% of patients who were discharged from the hospital were able to safely take food orally again in the sitting position. Furthermore, the complete lateral position method significantly shortened the fasting period and improved the prognosis in patients whose condition had progressed due to senility in the lateral position group compared with the control group (17.3 vs. 8.8 days, p<0.05; 28.4 vs. 67.5 days, p<0.05) Conclusion The complete lateral position method facilitated safe oral ingestion among elderly patients with severe dysphagia. Furthermore, safe oral ingestion decreased the mortality rate and shortened the fasting period at the end of life. The method is easy to implement and does not require the use of special devices or techniques. It can therefore be a useful approach in the care of elderly patients with severe dysphagia.

Determination of hydrogen concentration in solids by transmission ERDA under nuclear-elastically enhanced recoiling of H by 8 and 9 MeV He.

Hydrogen concentrations in thin self-supporting samples of polyphenylene sulfide (PPS) and muscovite have been determined by nuclear-elastic recoil detection analysis (ERDA) of transmission layout. The analysis procedure is based only on the database of stopping power and recoil cross section for material analysis, without using any reference sample of known H content. For the PPS sample, the determined value of(2.87±0.26)×1022H cm-3is in good agreement with the calculated value of3.01×1022H cm-3. For the muscovite sample, the H concentration originating each from bound water and absorbed water is uniform over the entire thickness of the sample. The determined concentration(9.43±0.75)×1021H cm-3of the muscovite agrees excellently with the value of9.36×1021H cm-3obtained from other quantitative analyses typically applied for minerals. The present results demonstrate the capability of accurate determination of H contents in materials and minerals by transmission ERDA.

Increased medial laxity of the elbow in preadolescent baseball players with or without medial elbow apophysitis.

BACKGROUND: Medial elbow apophysitis is a traction apophysitis observed in the medial epicondyle of the elbow in preadolescent baseball players. The purpose of this study was to determine the relationship between medial elbow apophysitis and elbow valgus instability in preadolescent baseball players. METHODS: The participants were classified into a control group and an injury group; the injury group included participants diagnosed with a medial elbow injury (inclusion criteria were only symptoms of the elbow joint or positive findings on physical examinations, or both). Elbow valgus instability was assessed by measuring the differences in ulnohumeral joint gapping width, with and without gravity stress induced by weight loading of the forearm using ultrasonography. RESULTS: The control and injury groups consisted of 81 and 23 preadolescent baseball players, respectively. In the throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (1.07 vs. 0.57 mm, P = .001). In the non-throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (0.57 vs. 0.37 mm, P = .011). The area under the curve for valgus instability of the throwing elbow was 0.89 mm (95% confidence interval, 0.64-0.77), and the cut-off value for elbow pain appearance was 0.80 mm. CONCLUSION: The increased elbow valgus instability in the injury group was associated with a medial elbow injury. For the elbow valgus instability of the non-throwing side in the injury group, we considered that players with medial elbow apophysitis inherently have elbow laxity.

Depth resolution of transmission ERDA for H in Al under nuclear-elastically enhanced recoiling of H by 8 MeV He.

Using stacked samples of Al foil and H-containing resin film, we have carried out elastic recoil detection analysis with transmission layout (T-ERDA) to investigate the depth resolution in the measurements of H distribution in Al. For narrow and wide acceptance conditions of the detector, the depth resolutions of 1.5-4.9µm at several depths in Al of 50 and 80µm thicknesses have been determined for incidence of 8 MeV4He. While the main factor to degrade the depth resolution is the energy straggling of recoil H for narrow acceptance conditions, it is the extended low-energy side of the H spectrum for wide acceptance conditions. The knowledge obtained in this work is useful for analysis of 3D images of H distribution measured by T-ERDA, for example, future analysis of minerals or natural glass samples to determine abundances and distributions of water or OH in the samples.

Effects of Growth Stage and Cd Chemical Form on Cd and Zn Accumulation in Arabidopsis halleri ssp. gemmifera.

Cadmium is a hazardous heavy metal and causes contamination globally. Phytoremediation can potentially become a low-cost and eco-friendly technique for mitigating Cd contamination. Arabidopsis halleri ssp. gemmifera hyper-accumulates Cd and Zn, and may be used to remediate Cd-contaminated sites. However, few studies have focused on Cd accumulation by A. halleri ssp. gemmifera. Herein, we demonstrate the accumulation of Cd by A. halleri ssp. gemmifera. The biomass, Cd, and Zn concentration of the plant increased in the 103 days of experimentation. Cd concentration of soil significantly decreased compared to its initial concentration (≈10%). The material balance of Cd uptake by plant and Cd decrement from soil ranged from 63.3% to 83.7% in each growth stage. Analysis indicated that the water-eluted and exchangeable forms of Cd were stable during the experiment. However, Cd concentration extracted with 0.1 M HCl decreased (25% of initial), and this fraction was not bioavailable. The study exhibits the mass balance of Cd between plant uptake and decrement from the soil and the changes in the chemical form of Cd during stages of A. halleri ssp. gemmifera cultivation.

[The effectiveness of the complete lateral position method in elderly patients with severe dysphagia].

AIM: This study aimed to clarify the effectiveness of using the complete lateral position method to treat elderly patients with severe dysphagia. METHODS: We enrolled 47 patients >65 years of age who had been diagnosed with severe dysphagia using a video endoscopic examination of swallowing at Hida City Hospital between February 1, 2015, and October 31, 2017. We collected and analyzed data pertaining to patient characteristics, the onset of aspiration pneumonia, and treatment outcomes. RESULTS: Although all patients had severe dysphagia, adopting the complete lateral position method enabled 25 patients (53.2%) to safely perform oral ingestion and be discharged home or to a nursing home. Thirteen (52.0%) of the patients who were discharged were able to safely receive oral intake in the sitting position again. In addition, the serum albumin level and Barthel index were significantly improved. In the patients whose condition worsened due to senility, the fasting period in the complete lateral potion group was significantly shorter than in the control group (7.3 days vs. 17.3 days). CONCLUSIONS: The present study showed that the complete lateral position method enabled safe oral ingestion in elderly patients with severe dysphagia. Safe oral ingestion contributed to improved nutrition and rehabilitation. The complete lateral position method is easy to assume and does not require the use of special appliances or techniques. We believe that the complete lateral position method will prove to be a breakthrough approach in the care of elderly patients with severe dysphagia.

Connexin 43 expression in satellite glial cells contributes to ectopic tooth-pulp pain.

Pulpitis often causes referred pain in opposing teeth. However, the precise mechanism underlying ectopic pain associated with tooth-pulp inflammation remains unclear. We performed the present study to test the hypothesis that functional interactions between satellite glial cells (SGCs) and trigeminal ganglion (TG) neurons are involved in ectopic orofacial pain associated with tooth-pulp inflammation. Digastric muscle electromyograph (D-EMG) activity elicited by administration of capsaicin into the upper second molar pulp (U2) was analyzed to evaluate noxious reflex responses. D-EMG activity was significantly increased in rats with lower first molar (L1) inflammation relative to saline-treated rats. Significantly increased expression of glial fibrillary acid protein (GFAP), a marker of activated glial cells, and connexin 43 (Cx43), a gap-junction protein, was observed in activated SGCs surrounding U2-innervating TG-neurons after L1-pulp inflammation. Daily administration of Gap26, a Cx43-inhibiting mimetic peptide, into the TG significantly suppressed capsaicin-induced D-EMG activity enhancement and reduced the percentage of fluorogold-labeled (U2-innervated) cells that were surrounded by GFAP-immunoreactive (IR) and Cx43-IR cells after L1-pulp inflammation. These findings indicate that tooth-pulp inflammation induces SGC activation and subsequent spread of SGC activation in the TG via Cx43-containing gap junctions. Thus, remote neuron excitability becomes enhanced in the TG following tooth-pulp inflammation, resulting in ectopic tooth-pulp pain in the contralateral tooth.

Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical granulomas.

Silent information regulator 2 homolog 1 (SIRT1) inhibits oxidative injury and has anti-inflammatory effects. SIRT1 may be involved in healing of periapical periodontitis; however, SIRT1 expression in periapical periodontitis lesions has not been investigated. This study evaluated SIRT1 expression and a marker of oxidative stress-8-hydroxy-2'-deoxyguanosine (8-OHdG)-in periapical granulomas. First, we used real-time polymerase chain reaction to determine whether U-937 monocytes express SIRT1. U-937 cells treated with the SIRT1 activator resveratrol exhibited the highest SIRT1 mRNA level after 6-h incubation. By contrast, treating cells with the SIRT1 inhibitor sirtinol returned SIRT1 expression level to that of the control. In addition, immunocytochemical analysis using cytospin specimens showed that U-937 cells co-expressed SIRT1 and Ki-67. Dual-color immunofluorescence imaging showed that round cells in periapical granulomas co-expressed SIRT1 and 8-OHdG; however, neither was expressed in healthy gingival tissues. The number of 8-OHdG-expressing cells was significantly greater than the number of SIRT1-expressing cells. Our findings suggest that macrophages express SIRT1 and that wound healing in periapical granulomas is enhanced by a SIRT1-mediated reduction in the level of oxidative stress.

A PRELIMINARY STUDY OF INCREASING SELF-EFFICACY IN JUNIOR HIGH SCHOOL STUDENTS: INDUCED SUCCESS AND A VICARIOUS EXPERIENCE.

Bandura's self-efficacy source hypothesis was examined by testing whether success and a vicarious experience of success would enhance self-efficacy among 159 7th graders (81 boys, 78 girls). Unknown to themselves or their classmates, 20 students (Success condition) were presented with easier anagram tasks, allowing them to outperform their 60 classmates (Control condition). The Success and Control students had been paired with classmates (Cheerers; Vicarious condition) who were to cheer on their partners during the task. The participants rated their self-efficacy for the anagram task before and after the performance. The results showed that successful performance significantly promoted the self-efficacy of Success students. However, the cheerers of Success students did not have increased self-efficacy through the vicarious success experience.

Molecular mechanism of aggravation of hypertensive organ damages by short-term blood pressure variability.

There is increasing evidence that not only the elevation of systolic and diastolic blood pressure (BP) but also the increase in BP variability (or fluctuation) are associated with hypertensive organ damages and the morbidity and mortality of cerebrovascular and cardiovascular events. However, the molecular mechanism whereby the increase in BP variability aggravates hypertensive organ damages remains unknown. Thus, we created a rat chronic model of a combination of hypertension and large BP variability by performing bilateral sino-aortic denervation in spontaneously hypertensive rat. A series of our studies using this model revealed that large BP variability induces chronic myocardial inflammation by activating local angiotensin II and mineralocorticoid receptor systems and thereby aggravates cardiac hypertrophy and myocardial fibrosis, leading to systolic dysfunction, in hypertensive hearts. In addition, large BP variability induces the aggravation of arteriolosclerotic changes and ischemic cortical fibrosis in hypertensive kidney via local angiotensin II system.

Large blood pressure variability aggravates arteriolosclerosis and cortical sclerotic changes in the kidney in hypertensive rats.

BACKGROUND: It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV. METHODS AND RESULTS: Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV. CONCLUSIONS: Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.

Blood pressure variability activates cardiac mineralocorticoid receptor and induces cardiac remodeling in hypertensive rats.

BACKGROUND: Hypertensive patients with large blood pressure variability (BPV) have aggravated target organ damage. Because the aldosterone/mineralocorticoid receptor (MR) system is a possible mechanism of hypertensive organ damage, we investigated in spontaneously hypertensive rats (SHRs) whether a specific MR blocker, eplerenone, would prevent BPV-induced aggravation of hypertensive cardiac remodeling. METHODS AND RESULTS: A rat model of a combination of hypertension and large BPV was created by performing bilateral sinoaortic denervation (SAD) in SHRs. SAD increased BPV without changing mean BP. SAD induced perivascular macrophage infiltration and aggravated myocardial fibrosis and cardiac hypertrophy, resulting in LV systolic dysfunction. Immunohistostaining revealed SAD-induced translocation of MRs into the nuclei (ie, MR activation) of the intramyocardial arterial medial cells and cardiac myocytes. SAD increased phosphorylation of p21-activated kinase1 (PAK1), a regulator of MR nuclear translocation. Chronic administration of a subdepressor dose of eplerenone prevented MR translocation, macrophage infiltration, myocardial fibrosis, cardiac hypertrophy, and LV dysfunction, while not affecting BPV. Circulating levels of aldosterone and cortisol were not changed by SAD. CONCLUSIONS: Eplerenone inhibited the aggravation of cardiac inflammation and hypertensive cardiac remodeling, and thereby prevented progression of LV dysfunction in SHRs with large BPV. This suggests that the PAK1-MR pathway plays a role in cardiac inflammation and remodeling induced by large BPV superimposed on hypertension, independent of circulating aldosterone.

Matrix metalloproteinase-9 contributes to the mobilization of bone marrow cells in the injured liver.

Effective mobilization of hematopoietic stem cells (HSCs) in injured organs has not been established. Matrix metalloproteinase-9 (MMP-9) is known to release HSCs from bone marrow (BM) into the peripheral blood, but its role in the recruitment of HSCs to injured organs is unclear. In this study we tried to clarify the role of the host MMP-9 in trafficking of HSCs toward the injured liver, especially the relation of MMP-9 with the chemokine receptor 4 (CXCR4)-chemokine ligand 12 (CXCL12) axis, and to examine whether MMP-9 deficiency affects BM cell trafficking to the injured liver in mice. In vitro, we investigated the effect of MMP-9 on migration activity and CXCR4 expression on lineage-negative (Lin(-)) BM cells. In vivo, we induced acute and chronic liver injury in MMP-9 knockout (KO) and control mice by inoculation of carbon tetrachloride, followed by transplantation of Lin(-) BM cells obtained from enhanced green fluorescent protein (EGFP)-transgenic mice, and counted the BM cells mobilized in the injured liver. In a migration assay, active MMP-9, but not proMMP-9, increased the number of migrated Lin(-) BM cells, which was inhibited by tissue inhibitor of metalloproteinase-1 or a MMP inhibitor. This chemoattractant function by MMP-9 was synergistic when cotreated with CXCL12. CXCR4 expression on Lin(-) BM cells was dose- and time-dependently increased by active MMP-9. At the same time, treatment with MMP-9 enhanced CXCL12 expression, and CXCL12 reciprocally increased MMP-9 expression in BM cells. In in vivo studies, many EGFP(+) cells were seen in control recipient mice. In contrast, few EGFP(+) cells were observed in MMP-9 KO mice. BM cells tended to differentiate into desmin(+) cells. In conclusion, MMP-9 contributes to the mobilization of BM cells in the injured liver by upregulating the expression of CXCR4 on Lin(-) BM cells and attracting BM cells along its gradient of CXCL12. Therefore, host MMP-9 plays an important role in BM cell migration in the injured liver.

Morbidity of stereotactic biopsy for intracranial lesions.

The safety of stereotactic biopsy (STB) was studied in this article. CT-guided STB (Brown-Roberts-Wells; BRW) was performed 58 times for 56 patients (male: 29, female: 27) at Hyogo Cancer Center between 1988 and 2007. The age distribution ranged from 15 to 83 (mean: 55) years old. Histological diagnoses were established for 58 samples, with 35 cases of glioma, eight of metastatic brain tumor, nine of malignant lymphoma and leukemia, two of germ cell tumor, two of abscess, one necrosis, and one case with normal tissue. There were 3 cases (5.2%) in which an intratumoral hemorrhage with neurological deficits was occurred. They were needed surgically removal and those histological pathology revealed glioma. Concerning location of biopsy, STB for basal ganglia (putamen or globus pallidus) and thalamus were caused complication of the intratumoral hematoma after biopsy. The review of the 575 cases indicates that glioma was the relative risk factor for morbidity associated with CT-guided STB (odds ratio 5.36). The overall morbidity rate was 6.4% (37/575). We considered that tumors of the basal ganglia (putamen or globus pallidus), thalamus and glioma were risk factors of morbidity for CT-guided STB.

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women.

Diastolic dysfunction is more prevalent in individuals with hypertension, particularly postmenopausal women; however, the pathogenesis of diastolic dysfunction remains unknown. Pressure overload activates cardiac inflammation, which induces myocardial fibrosis and diastolic dysfunction in rats with a suprarenal aortic constriction (AC). Therefore, we examined the effects of bilateral ovariectomy (OVX) on left ventricle (LV) remodeling, diastolic dysfunction and cardiac inflammation in hypertensive female rats. Rats were randomized to OVX+AC, OVX and AC groups as well as a Control group receiving sham operations for both the procedures. Rats underwent OVX at 6 weeks and AC at 10 weeks (Day 0). At Day 28, OVX did not appear to affect arterial pressure, cardiac hypertrophy or LV fractional shortening in AC rats. However, OVX increased myocardial fibrosis, elevated LV end-diastolic pressure and reduced the transmitral Doppler spectra early to late filling velocity ratio in AC rats. AC-induced transient myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration, both of which peaked at Day 3 and were augmented and prolonged by OVX. At Day 28, dihydroethidium staining revealed superoxide generation in the intramyocardial arterioles in the OVX+AC group but not in the AC group. NOX1, a functional subunit of nicotinamide adenine dinucleotide phosphate oxidase, was upregulated only in the OVX+AC group at Day 28. Chronic 17ß-estradiol replacement prevented the increases in macrophage infiltration, NOX1 upregulation, myocardial fibrosis and diastolic dysfunction in OVX+AC rats. In conclusion, we suggest that estrogen deficiency augments cardiac inflammation and oxidative stress and thereby aggravates myocardial fibrosis and diastolic dysfunction in hypertensive female rats. The findings provide insight into the mechanism underlying diastolic dysfunction in hypertensive postmenopausal women.

Simvastatin prevents large blood pressure variability induced aggravation of cardiac hypertrophy in hypertensive rats by inhibiting RhoA/Ras-ERK pathways.

Pronounced variability in blood pressure (BP) is an aggravating factor of hypertensive end-organ damage. However, its pathogenesis remains unknown. Statins have various protective effects on the cardiovascular system. Thus, we determined whether simvastatin would attenuate the aggravation of hypertensive cardiac remodeling in a rat model of hypertension with large BP variability, and also investigated the signaling mechanism involved in its effect. A model of hypertension with large BP variability was created by performing bilateral sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). A SAD or sham operation was performed in 12-week-old rats. Thereafter, simvastatin (0.2 mgkg(-1) per day) or vehicle was intraperitoneally administered every day. After 6 weeks , telemetric recordings revealed that SAD enhanced BP variability without changing the mean BP. SAD increased myocyte hypertrophy, myocardial fibrosis and macrophage infiltration associated with the upregulation of brain natriuretic peptide (BNP), type I procollagen, transforming growth factor (TGF)-ß and monocyte chemoattractant protein (MCP)-1, and activation of RhoA, Ras and ERK1/2. Simvastatin did not change the mean BP or BP variability in SAD-operated SHRs. In SAD-operated SHRs, simvastatin attenuated myocyte hypertrophy and BNP expression, as well as RhoA, Ras and ERK1/2 activities. In contrast, simvastatin did not change myocardial fibrosis, macrophage infiltration, or the expression of procollagen and TGF-ß or MCP-1 in SAD-operated SHRs. Simvastatin did not affect serum lipid levels. In conclusion, simvastatin attenuated the large BP variability-induced aggravation of cardiac hypertrophy, but not myocardial fibrosis, in SHRs. The activation of RhoA/Ras-ERK pathways may contribute to the aggravation of cardiac hypertrophy by a combination of hypertension and large BP variability.

Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil.

We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B virus infection. The patient had generalized bone pain, with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10 mg/d. It was also found that ADV affected the metabolism of tacrolimus, a calcineurin-inhibitor, and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels, which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.