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http://hdl.handle.net/2115/20048
2024-03-29T15:38:01ZSulfotransferases (SULTs), enzymatic and genetic variation in Carnivora : Limited sulfation capacity in pinnipeds
http://hdl.handle.net/2115/91043
Title: Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora : Limited sulfation capacity in pinnipeds
Authors: Kondo, Mitsuki; Ikenaka, Yoshinori; Nakayama, Shouta M. M.; Kawai, Yusuke K.; Mizukawa, Hazuki; Mitani, Yoko; Nomyama, Kei; Tanabe, Shinsuke; Ishizuka, Mayumi
Abstract: Wild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime.2022-12-31T15:00:00ZKondo, MitsukiIkenaka, YoshinoriNakayama, Shouta M. M.Kawai, Yusuke K.Mizukawa, HazukiMitani, YokoNomyama, KeiTanabe, ShinsukeIshizuka, MayumiWild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime.Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis
http://hdl.handle.net/2115/91042
Title: Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis
Authors: Hosotani, Marina; Ichii, Osamu; Namba, Takashi; Masum, Md Abdul; Nakamura, Teppei; Hasegawa, Yasuhiro; Watanabe, Takafumi; Kon, Yasuhiro
Abstract: Homeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling-related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Fas(lpr/lpr) (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function.2022-12-28T15:00:00ZHosotani, MarinaIchii, OsamuNamba, TakashiMasum, Md AbdulNakamura, TeppeiHasegawa, YasuhiroWatanabe, TakafumiKon, YasuhiroHomeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling-related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Fas(lpr/lpr) (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function.Modified foreign body reaction to silicone imbedded in subcutaneous tissues by different mouse systemic immune conditions
http://hdl.handle.net/2115/91025
Title: Modified foreign body reaction to silicone imbedded in subcutaneous tissues by different mouse systemic immune conditions
Authors: Yamakawa, Tomohiro; Ichii, Osamu; Nakamura, Teppei; Namba, Takashi; Elewa, Yaser Hosny Ali; Masum, Md. Abdul; Otani, Yuki; Nishimura, Takanori; Kon, Yasuhiro
Abstract: Foreign body reaction (FBR) causes unexpected adverse effects due to implanted materials in humans and animals. Inflammation and subsequent fibrosis during FBR seems to be affected by recipient immunity, such as the balance of T helper (Th) response that has the potential to regulate FBR-related macrophage function. Here, the immunological effects of FBR on subcutaneously imbedded silicone tubes (ST) at 8 weeks were investigated histologically by comparing Th1-biased C57BL/6N, Th2-biased MRL/MpJ, and autoimmune disease-prone MRL/MpJ-Fas(lpr/lpr). Tissue surrounding ST (TSS) was analyzed at day (D) 7 and 14 (reaction phase) or D35 (stability phase) after surgery. In all strains, the TSS was composed of a thin layer (TL) containing fibrous tissues and loose connective tissues formed outside the TL. Few lymphocytes and mast cells, several neutrophils, and numerous macrophages infiltrated the TSS. Active vascularization was observed at D14 in all strains. For the examined indices, M1-type macrophage density in the TSS of C57BL/6N mice was significantly higher at D14 compared to other strains. No significant strain difference relating to M2-type macrophages was detected, suggesting the effects of Th1-biased immunity on FBR-related inflammation. Collagen fibers in the TSS increased in density and became stable with age in all strains. In particular, MRL/MpJ-Fas(lpr/lpr) showed progressive fibrotic features. Serum autoantibody levels in MRL/MpJ-Fas(lpr/lpr) mice were inversely correlated with M1-type macrophage density. These data from MRL/MpJ-Fas(lpr/lpr) mice suggested modifications of FBR-related inflammation and fibrosis by autoimmune abnormalities. The results provide crucial insights into the pathological modification of FBR by recipient immunity and emphasize its clinicopathological importance in humans and animals.2022-06-29T15:00:00ZYamakawa, TomohiroIchii, OsamuNakamura, TeppeiNamba, TakashiElewa, Yaser Hosny AliMasum, Md. AbdulOtani, YukiNishimura, TakanoriKon, YasuhiroForeign body reaction (FBR) causes unexpected adverse effects due to implanted materials in humans and animals. Inflammation and subsequent fibrosis during FBR seems to be affected by recipient immunity, such as the balance of T helper (Th) response that has the potential to regulate FBR-related macrophage function. Here, the immunological effects of FBR on subcutaneously imbedded silicone tubes (ST) at 8 weeks were investigated histologically by comparing Th1-biased C57BL/6N, Th2-biased MRL/MpJ, and autoimmune disease-prone MRL/MpJ-Fas(lpr/lpr). Tissue surrounding ST (TSS) was analyzed at day (D) 7 and 14 (reaction phase) or D35 (stability phase) after surgery. In all strains, the TSS was composed of a thin layer (TL) containing fibrous tissues and loose connective tissues formed outside the TL. Few lymphocytes and mast cells, several neutrophils, and numerous macrophages infiltrated the TSS. Active vascularization was observed at D14 in all strains. For the examined indices, M1-type macrophage density in the TSS of C57BL/6N mice was significantly higher at D14 compared to other strains. No significant strain difference relating to M2-type macrophages was detected, suggesting the effects of Th1-biased immunity on FBR-related inflammation. Collagen fibers in the TSS increased in density and became stable with age in all strains. In particular, MRL/MpJ-Fas(lpr/lpr) showed progressive fibrotic features. Serum autoantibody levels in MRL/MpJ-Fas(lpr/lpr) mice were inversely correlated with M1-type macrophage density. These data from MRL/MpJ-Fas(lpr/lpr) mice suggested modifications of FBR-related inflammation and fibrosis by autoimmune abnormalities. The results provide crucial insights into the pathological modification of FBR by recipient immunity and emphasize its clinicopathological importance in humans and animals.Ureteral morphology and pathology during urolithiasis in cats
http://hdl.handle.net/2115/90938
Title: Ureteral morphology and pathology during urolithiasis in cats
Authors: Ichii, Osamu; Oyamada, Kazuhisa; Mizukawa, Hazuki; Yokoyama, Nozomu; Namba, Takashi; Otani, Yuki; Elewa, Yaser Hosny Ali; Sasaki, Noboru; Nakamura, Teppei; Kon, Yasuhiro
Abstract: Cats exhibit high susceptibility to urinary organ-related diseases. We investigated the healthy ureter morphol-ogies and compared these with ureters that were surgically resected distal to a urolithiasis obstruction in cats. Healthy ureters (total length 9.88 +/- 0.38 cm) developed adventitia composed of collagen fibers (ADCF), con-taining a longitudinal muscular layer, toward the distal segment. The healthy ureter was the smallest in the middle segment (4.71-6.90 cm from the urinary bladder) with significantly decreased luminal and submucosal areas compared to those in the proximal segment. Diseased cats exhibited a high incidence of calcium oxalate urolithiasis with renal dysfunction, regardless of age, sex, and body size. Diseased ureters showed increased perimeters, inflammation, and decreased nerves in ADCF. Collagen fibers were increased in the submucosal area, intermuscular spaces, and ADCF, particularly near the obstructed lesion. The mean resected ureter length was 5.66 +/- 0.49 cm, suggesting a high obstruction risk in the middle segment. The middle segment also increased the cross-sectional area of the ureter and ADCF, regardless of the distance from the obstructed lesion. The ureters in several cases either lacked the transitional epithelium, or exhibited transitional epithelial hyperplasia, and some of these formed the mucosal folds. In conclusion, we demonstrated the following characteristics and histo-pathological features of cat ureters: decreases in the ureter size, lumen area, and submucosa area from proximal to middle segment in healthy; ADCF changes in urolithiasis, including increased connective tissues with inflammation and decreased nerves. These data are important to understand the pathogenesis of feline ureteral obstruction.2022-12-09T15:00:00ZIchii, OsamuOyamada, KazuhisaMizukawa, HazukiYokoyama, NozomuNamba, TakashiOtani, YukiElewa, Yaser Hosny AliSasaki, NoboruNakamura, TeppeiKon, YasuhiroCats exhibit high susceptibility to urinary organ-related diseases. We investigated the healthy ureter morphol-ogies and compared these with ureters that were surgically resected distal to a urolithiasis obstruction in cats. Healthy ureters (total length 9.88 +/- 0.38 cm) developed adventitia composed of collagen fibers (ADCF), con-taining a longitudinal muscular layer, toward the distal segment. The healthy ureter was the smallest in the middle segment (4.71-6.90 cm from the urinary bladder) with significantly decreased luminal and submucosal areas compared to those in the proximal segment. Diseased cats exhibited a high incidence of calcium oxalate urolithiasis with renal dysfunction, regardless of age, sex, and body size. Diseased ureters showed increased perimeters, inflammation, and decreased nerves in ADCF. Collagen fibers were increased in the submucosal area, intermuscular spaces, and ADCF, particularly near the obstructed lesion. The mean resected ureter length was 5.66 +/- 0.49 cm, suggesting a high obstruction risk in the middle segment. The middle segment also increased the cross-sectional area of the ureter and ADCF, regardless of the distance from the obstructed lesion. The ureters in several cases either lacked the transitional epithelium, or exhibited transitional epithelial hyperplasia, and some of these formed the mucosal folds. In conclusion, we demonstrated the following characteristics and histo-pathological features of cat ureters: decreases in the ureter size, lumen area, and submucosa area from proximal to middle segment in healthy; ADCF changes in urolithiasis, including increased connective tissues with inflammation and decreased nerves. These data are important to understand the pathogenesis of feline ureteral obstruction.Necroptosis of neuronal cells is related to the neuropathology of tick-borne encephalitis
http://hdl.handle.net/2115/90730
Title: Necroptosis of neuronal cells is related to the neuropathology of tick-borne encephalitis
Authors: Tsujino, Dai; Yoshii, Kentaro; Kajiyama, Misa; Takahashi, Yuji; Maekawa, Naoya; Kariwa, Hiroaki; Kobayashi, Shintaro
Abstract: Tick-borne encephalitis virus (TBEV) is a zoonotic virus that causes tick-borne encephalitis (TBE) in humans. Infections of Sapporo-17-Io1 (Sapporo) and Oshima 5-10 (Oshima) TBEV strains showed different pathogenic effects in mice. However, the differences between the two strains are unknown. In this study, we examined neuronal degeneration and death, and activation of glial cells in mice inoculated with each strain to investigate the pathogenesis of TBE. Viral growth was similar between Sapporo and Oshima, but neuronal degeneration and death, and activation of glial cells, was more prominent with Oshima. In human neuroblastoma cells, apoptosis and pyroptosis were not observed after TBEV infection. However, the expression of the necroptosis marker, mixed lineage kinase domain-like (MLKL) protein, was upregulated by TBEV infection, and this upregulation was more pronounced in Oshima than Sapporo infections. As necroptosis is a pro-inflammatory type of cell death, differences in necroptosis induction might be involved in the differences in neuropathogenicity of TBE.2022-10-31T15:00:00ZTsujino, DaiYoshii, KentaroKajiyama, MisaTakahashi, YujiMaekawa, NaoyaKariwa, HiroakiKobayashi, ShintaroTick-borne encephalitis virus (TBEV) is a zoonotic virus that causes tick-borne encephalitis (TBE) in humans. Infections of Sapporo-17-Io1 (Sapporo) and Oshima 5-10 (Oshima) TBEV strains showed different pathogenic effects in mice. However, the differences between the two strains are unknown. In this study, we examined neuronal degeneration and death, and activation of glial cells in mice inoculated with each strain to investigate the pathogenesis of TBE. Viral growth was similar between Sapporo and Oshima, but neuronal degeneration and death, and activation of glial cells, was more prominent with Oshima. In human neuroblastoma cells, apoptosis and pyroptosis were not observed after TBEV infection. However, the expression of the necroptosis marker, mixed lineage kinase domain-like (MLKL) protein, was upregulated by TBEV infection, and this upregulation was more pronounced in Oshima than Sapporo infections. As necroptosis is a pro-inflammatory type of cell death, differences in necroptosis induction might be involved in the differences in neuropathogenicity of TBE.Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice
http://hdl.handle.net/2115/90626
Title: Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice
Authors: Masugi, Misato; Ichii, Osamu; Otani, Yuki; Namba, Takashi; Kon, Yasuhiro
Abstract: Regeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Fas(lpr/lpr) and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1(+) neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3(+) T cells was remarkably higher in MRL/MpJ-Fas(lpr/lpr) than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220(+) B cells. The numbers of IBA1(+) macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7(+) satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Fas(lpr/lpr).2023-09-25T15:00:00ZMasugi, MisatoIchii, OsamuOtani, YukiNamba, TakashiKon, YasuhiroRegeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Fas(lpr/lpr) and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1(+) neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3(+) T cells was remarkably higher in MRL/MpJ-Fas(lpr/lpr) than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220(+) B cells. The numbers of IBA1(+) macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7(+) satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Fas(lpr/lpr).Lead concentrations and isotope ratios in blood, breastmilk and feces : contribution of both lactation and soil/dust exposure to infants in a lead
http://hdl.handle.net/2115/90474
Title: Lead concentrations and isotope ratios in blood, breastmilk and feces : contribution of both lactation and soil/dust exposure to infants in a lead
Authors: Toyomaki, Haruya; Yabe, John; Nakayama, Shouta M. M.; Yohannes, Yared B.; Muzandu, Kaampwe; Mufune, Tiza; Nakata, Hokuto; Ikenaka, Yoshinori; Kuritani, Takeshi; Nakagawa, Mitsuhiro; Choongo, Kennedy; Ishizuka, Mayumi
Abstract: Lead (Pb) poses a serious public health concern. Breastmilk may be a possible source of Pb exposure in infants, as Pb can be transferred from the maternal blood to breastmilk. The present study was undertaken to determine the Pb exposure and the contribution of lactation as one of the exposure pathways to infants in a Pb mining area, Kabwe, Zambia. Blood, breastmilk and infants' feces were collected from 418 pairs of infants and mothers. The Pb concentrations, isotope ratios in the samples, and biochemistry in mothers' plasma were analyzed. The overall mean of blood lead levels (BLLs) in infants and mothers were 18.0 and 11.3 mu g/dL, respectively. High Pb concentration in breastmilk (range: 0.4-51.9, mean: 5.3 mu g/L) above the WHO acceptable level between 2 and 5 mu g/ L were found and could be one of the sources of Pb exposure in infants. The Pb isotope ratios in infants' feces were the most similar to Pb ratios in the soil samples. The results suggest that infants are also exposed to Pb from the environment. Pb exposure in infants through breastfeeding and soil ingestion could potentially exceed daily intake of Pb which causes neurodevelopmental toxicity. In contrast to the high BLLs in mothers, the plasma biochemical profiles of most analyzed parameters were interestingly within, or close to, the standard reference values. Our data suggest that environmental remediation is urgently needed to reduce the Pb exposure in infants and mothers from the environment in Kabwe in parallel with chelation therapy.2021-09-30T15:00:00ZToyomaki, HaruyaYabe, JohnNakayama, Shouta M. M.Yohannes, Yared B.Muzandu, KaampweMufune, TizaNakata, HokutoIkenaka, YoshinoriKuritani, TakeshiNakagawa, MitsuhiroChoongo, KennedyIshizuka, MayumiLead (Pb) poses a serious public health concern. Breastmilk may be a possible source of Pb exposure in infants, as Pb can be transferred from the maternal blood to breastmilk. The present study was undertaken to determine the Pb exposure and the contribution of lactation as one of the exposure pathways to infants in a Pb mining area, Kabwe, Zambia. Blood, breastmilk and infants' feces were collected from 418 pairs of infants and mothers. The Pb concentrations, isotope ratios in the samples, and biochemistry in mothers' plasma were analyzed. The overall mean of blood lead levels (BLLs) in infants and mothers were 18.0 and 11.3 mu g/dL, respectively. High Pb concentration in breastmilk (range: 0.4-51.9, mean: 5.3 mu g/L) above the WHO acceptable level between 2 and 5 mu g/ L were found and could be one of the sources of Pb exposure in infants. The Pb isotope ratios in infants' feces were the most similar to Pb ratios in the soil samples. The results suggest that infants are also exposed to Pb from the environment. Pb exposure in infants through breastfeeding and soil ingestion could potentially exceed daily intake of Pb which causes neurodevelopmental toxicity. In contrast to the high BLLs in mothers, the plasma biochemical profiles of most analyzed parameters were interestingly within, or close to, the standard reference values. Our data suggest that environmental remediation is urgently needed to reduce the Pb exposure in infants and mothers from the environment in Kabwe in parallel with chelation therapy.Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors
http://hdl.handle.net/2115/90384
Title: Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors
Authors: Morimoto, Kohei; Ouchi, Mai; Kitano, Taisuke; Eguchi, Ryota; Otsuguro, Ken-ichi
Abstract: Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 mu M) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 mu M) were inhibited by a beta-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 mu M) promoted process formation, which was inhibited by a beta-antag-onist and enhanced by both an alpha-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and beta-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and beta-adrenoceptors. Further-more, bidirectional regulation exists; namely, the effects of D1-like receptors and beta-adrenoceptors were nega-tively regulated by D2-like receptors and alpha(2)-adrenoceptors.2022-08-04T15:00:00ZMorimoto, KoheiOuchi, MaiKitano, TaisukeEguchi, RyotaOtsuguro, Ken-ichiDopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 mu M) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 mu M) were inhibited by a beta-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 mu M) promoted process formation, which was inhibited by a beta-antag-onist and enhanced by both an alpha-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and beta-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and beta-adrenoceptors. Further-more, bidirectional regulation exists; namely, the effects of D1-like receptors and beta-adrenoceptors were nega-tively regulated by D2-like receptors and alpha(2)-adrenoceptors.Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid
http://hdl.handle.net/2115/90325
Title: Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid
Authors: Nimako, Collins; Ikenaka, Yoshinori; Akoto, Osei; Fujioka, Kazutoshi; Taira, Kumiko; Arizono, Koji; Kato, Keisuke; Takahashi, Keisuke; Nakayama, Shouta M. M.; Ichise, Takahiro; Ishizuka, Mayumi
Abstract: This study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were >= 70% for most compounds), sensitive (LODs <= 0.47 ng/mL and LOQs <= 1.43 ng/mL were recorded for all detected compounds, R-2 >= 0.99) and precise (RSDs <= 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitroIMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios >= 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Sigma 6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species. (C) 2021 Elsevier B.V. All rights reserved.2021-08-29T15:00:00ZNimako, CollinsIkenaka, YoshinoriAkoto, OseiFujioka, KazutoshiTaira, KumikoArizono, KojiKato, KeisukeTakahashi, KeisukeNakayama, Shouta M. M.Ichise, TakahiroIshizuka, MayumiThis study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were >= 70% for most compounds), sensitive (LODs <= 0.47 ng/mL and LOQs <= 1.43 ng/mL were recorded for all detected compounds, R-2 >= 0.99) and precise (RSDs <= 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitroIMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios >= 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Sigma 6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species. (C) 2021 Elsevier B.V. All rights reserved.Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites
http://hdl.handle.net/2115/90295
Title: Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites
Authors: Torimoto, Ryouta; Ishii, Chihiro; Sato, Hiroshi; Saito, Keisuke; Watanabe, Yukiko; Ogasawara, Kohei; Kubota, Ayano; Matsukawa, Takehisa; Yokoyama, Kazuhito; Kobayashi, Atsushi; Kimura, Takashi; Nakayama, Shouta M. M.; Ikenaka, Yoshinori; Ishizuka, Mayumi
Abstract: Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure. 0 2021 Elsevier Ltd. All rights reserved.2021-08-14T15:00:00ZTorimoto, RyoutaIshii, ChihiroSato, HiroshiSaito, KeisukeWatanabe, YukikoOgasawara, KoheiKubota, AyanoMatsukawa, TakehisaYokoyama, KazuhitoKobayashi, AtsushiKimura, TakashiNakayama, Shouta M. M.Ikenaka, YoshinoriIshizuka, MayumiLead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure. 0 2021 Elsevier Ltd. All rights reserved.