Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-β, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-β.Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120–127; http://dx.doi.org/10.1289/ehp.1408094     

Clinical significance of intrahepatic biliary stricture in efficacy of hepatic resection for intrahepatic stones

In the Far East, hepatic resection is the definitive treatment for complicated intrahepatic stones (IHS). However, many investigators have reported that the associated intrahepatic biliary stricture is the main cause of treatment failure. A retrospective comparative study was undertaken to clarify the long-term efficacy of hepatic resection for treatment of IHS and to investigate the clinical significance of intrahepatic biliary stricture in treatment failure after hepatic resection performed in 44 patients with symptomatic IHS. The patients were divided into two study groups: group A, with intrahepatic biliary stricture (n = 28) and group B, without stricture (n = 16). Residual or recurrent stones, recurrence of intrahepatic biliary stricture, late cholangitis, and final outcomes were analyzed and compared statistically between the two groups. The patients were followed up for a median duration of 65 months after hepatectomy. The overall incidence of residual or recurrent stones was 36% and 11%, respectively, in groups A and B. The initial treatment failure rate was 50% in group A and 31% in group B. Intrahepatic biliary stricture recurred in 46% of patients in group A, while none of the group B patients had biliary stricture recurrence (P = 0.001). More than two-thirds of the restrictures in group A were identified at the primary site. The incidence of late cholangitis was higher in group A (54%) than in group B (6%) (P = 0.002). Three-quarters of the patients with cholangitis in group A had severe cholangitis, that was recurrent, and related to stones and strictures (n = 11). They and 2 asymptomatic patients in group B required secondary procedures done at a median of 12 months after hepatectomy. Final outcomes after hepatectomy with or without secondary management were good in 80%, fair in 16%, and poor in 4% of our 44 patients. Most recurrent cholangitis after hepatectomy in patients with IHS was related to recurrent intrahepatic ductal strictures. Therefore, to be effective, hepatic resection should include the strictured duct. However, with hepatectomy alone it is difficult to clear the IHS or relieve the ductal strictures completely, particularly in patients with bilateral IHS, so perioperative team approaches that include both radiologic and cholangioscopic interventions should be combined for the effective management of IHS.     

Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: results from the Hanyang lupus cohort in Seoul, Korea

The rates of mortality and cancer have not been compared between Korean systemic lupus erythematosus (SLE) patients and the general population. The objective of this study was to compare the observed mortality and cancer incidence rates of SLE patients with the expected age-, sex- and calendar-matched incidence rates of a comparable general control population. This study included 466 SLE patients who were in the Hanyang Lupus Cohort, Seoul and we excluded the males from the analyses because the number of males was too small to expect any incidence of cancer or death. We used the national female mortality rates from 1992 to 2001 as recorded by the Korean National Statistical Office as the standard mortality rates, and the Seoul Cancer Registry data as the standard cancer incidence rate. Ten of the females in our study died, giving a crude mortality rate of 596.0/100 000 person-years (PY) and a standardized mortality ratio (SMR) of 3.02. The crude cancer incidence was 179.3/100 000 PYand the standard incidence ratio was 1.04. These results demonstrate that the SMR is significantly higher in SLE patients than in the general population, whereas the incidence of cancer is the same in these two groups.     

Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase

Aging is characterized by progressive loss of cognitive and memory functions as well as decrease in physical activities. In the present study, a human neural stem cell line (F3 NSC) over-expressing choline acetyltransferase (F3.ChAT), an enzyme responsible for acetylcholine synthesis, was generated and transplanted in the brain of 18-month-old male ICR mice. Four weeks post-transplantation, neurobehavioral functions, expression of ChAT enzyme, production of acetylcholine and neurotrophic factors, and expression of cholinergic nervous system markers in transplanted animals were investigated. F3.ChAT NSCs markedly improved both the cognitive function and physical activity of aging animals, in parallel with the elevation of brain acetylcholine level. Transplanted F3 and F3.ChAT cells were found to differentiate into neurons and astrocytes, and to produce ChAT proteins. Transplantation of the stem cells increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhanced expression of Trk B, and restored host microtubule-associated protein 2 and cholinergic nervous system. The results demonstrate that human NSCs over-expressing ChAT improve cognitive function and physical activity of aging mice, not only by producing ACh directly but also by restoring cholinergic neuronal integrity, which might be mediated by neurotrophins BDNF and NGF.     

Change in Electromyographic Activity of Wrist Extensor by Cylindrical Brace

Purpose

To verify the effect of a newly-developed cylindrical type forearm brace, which was designed to give focal counterforce perpendicularly on the muscle belly of the wrist extensor.

Materials and Methods

The dominant hands of 24 (12 males, 12 females) healthy subjects were tested. Two types of forearm braces (focal cylindrical type and broad pneumatic type) were examined. The braces were applied at the extensor carpi radialis brevis, 5 to 7 cm distal to the lateral epicondyle. Two surface electrodes were attached to the proximal and distal parts of the brace. By quantitative electromyography, the mean amplitudes of voluntary extensor carpi radialis brevis contraction before and after applying each brace were recorded and analyzed.

Results

The mean amplitudes of the focal cylindrical brace and broad pneumatic brace were reduced significantly compared to no brace (p<0.05), with a larger reduction for the cylindrical brace than the pneumatic brace (p<0.05). There was no significant difference between the proximal and distal mean amplitudes with each brace.

Conclusion

A cylindrical type brace decreased electromyographic activity in the wrist extensor more effectively than did the pneumatic type brace.     

Pulmonary Tuberculosis and Lung Cancer Risk in Current Smokers: The Seoul Male Cancer Cohort Study

Authors evaluated pulmonary tuberculosis (PTB) history as a risk factor for lung cancer in current male smokers in a prospective, population-based cohort study. The subjects were the 7,009 males among the participants in the Seoul Male Cancer Cohort Study for whom there was full information on PTB history and smoking habits. With a 16-yr follow-up, 93 cases of lung cancer occurred over the 99,965 person-years of the study. The estimated relative risk (RR) of PTB history of current smokers in lung cancer after adjusting for three confounders - intake of coffee and tomatoes, and age at entry - was 1.85 (95% CI: 1.08-3.19). The observed joint RRs and attributable risks (ARs) across strata of three confounders were greater than the expected, indicating a positive interaction. Thus a history of PTB in current smokers may be another risk factor for lung cancer. Based on a synergic interaction, a heavy male smoker with a PTB history would be expected to belong to the group at high risk of lung cancer.     

Studies on interstitial carbon doping from a Ti precursor in a hierarchical TiO2 nanostructured photoanode by a single step hydrothermal route

Carbon doping from a Ti precursor in TiO₂ synthesized by a hydrothermal method was studied. The structural, optical and morphological study of the deposited material was carried out using X-ray diffraction, UV-vis spectroscopy and scanning electron microscopy characterization techniques. The elemental composition of the TiO₂ deposited with different precursor concentrations was studied using X-ray photoelectron spectroscopy and electron dispersive X-ray spectroscopy. The amount of elemental carbon in the TiO₂ matrix is found to be increased as the Ti precursor concentration is increased, which strengthens the proposed idea of carbon doping via a Ti precursor.

Interstitial carbon doping is possible directly from a Ti precursor (titanium(iv) isopropoxide) without using any other carbon source.