Contamination, dynamics, and health risk assessment of pesticides in seawater and marine samples from the Seto Inland Sea, Japan.

We assessed the contamination, dynamics, and health risks of the pesticides cyanazine, simetryn, fenarimol, isoprothiolane, diazinon, irgarol, fenitrothion, and diuron in marine samples (seawater, sediments, plankton, fish, and other edible organisms) at various locations in the Seto Inland Sea in Japan in 2016 and 2017. Pesticide concentrations were highest at sampling sites close to the coastline, and mean concentrations in seawater were slightly higher in surface water than in bottom water. All eight pesticides were detected in plankton. Diazinon concentrations (77-387 ng/g dw) were highest in sediments and cyanazine was the most frequently detected pesticide (88%, n = 17) in sediments. Only cyanazine (2.7-41.9 ng/g dw), simetryn (1.0-34.3 ng/g dw), and diazinon (6.3-308.8 ng/g dw) were detected in fish and other edible marine organisms. Based on the calculated bioconcentration factor, the results showed that plankton, fish, and marine animals bioaccumulated pesticides. The highest hazard quotients were calculated for diazinon in red seabream and greenling, indicating a possible risk to consumers. It is, therefore, imperative to promote strict implementation of pollution control, integrated pest management practices, and policy formulation on pesticides. Usage of diazinon must be controlled and monitored to ensure large residues do not reach aquatic ecosystems and marine coastlines.

Ecotoxicological and human health risk assessment of selected pesticides in Kurose River, Higashi-Hiroshima City (Japan).

This study conducted an integrated approach combining monitoring and risk assessment of pesticides in Kurose River and its catchment area, Japan. Water samples (n = 168) were collected every month for 1 year (March 2016 to February 2017). Pesticides (cyanazine, simetryn, fenarimol, isoprothiolane, and diazinon) were extracted by Sep-Pack C18 cartridges and analyzed using a reversed-phase HPLC-UV system. The pesticides were also determined in non-target organisms Red algae (Audouinella sp.) and diatoms (Cocconeis placentula) from the river. Based on the residual concentrations, an ecotoxicological risk assessment was conducted using the risk quotient (RQ) index. The human health carcinogenic and non-carcinogenic risk assessments were evaluated using hazard quotients (HQ). Results showed that cyanazine was the most commonly detected (64%), followed by simetryn (58%), and diazinon (57%) in all the sample sites (n = 12). Except for isoprothiolane, the pesticides were highest in spring followed by summer, autumn and winter. Based on extreme values (ex), non-acceptable ecotoxicological risk was obtained for diazinon (RQex = 21.317), cyanazine (RQex = 3.129), simetryn (RQex = 8.577) and fenarimol (RQex = 10.855), while that of isoprothiolane (RQex  = 0.013) was negligible. Based on the HQ estimates, all the pesticides were below the threshold value of 1, hence pose no significant health risks to humans. PRACTITIONER POINTS: Pesticides affect non-target organisms in rivers and other aquatic systems Pesticides were frequently detected in spring and summer and accumulated in red algae and diatom The detected pesticides posed high ecotoxicological and human health risks.

Rotor Syndrome: Glucuronidated Bile Acidemia From Defective Reuptake by Hepatocytes.

Organic anion transporting polypeptide (OATP) 1B1 (gene, solute carrier organic anion transporter family member 1B1 [SLCO1B1]) and OATP1B3 (SLCO1B3) serve as transporters for hepatic uptake of important endogenous substances and several commonly prescribed drugs. Inactivation of both proteins together causes Rotor syndrome. How this OATP1B1/1B3 defect disturbs bile acid (BA) metabolism is largely unknown. In this study, we performed detailed BA analysis in 3 patients with genetically diagnosed Rotor syndrome. We found that BAs glucuronidated at the C-3 position (BA-3G) accounted for 50% or more of total BAs in these patients. In contrast but similarly to healthy controls, only trace amounts of BA-3G were detected in patients with constitutional indocyanine green excretory defect (OATP1B3 deficiency) or sodium-taurocholate cotransporting polypeptide (NTCP; gene, solute carrier family 10 member 1 [SLC10A1]) deficiency. Therefore, substantial amounts of BA-3G are synthesized in hepatocytes. The cycling pathway of BA-3G, consisting of excretion from upstream hepatocytes and uptake by downstream hepatocytes by OATP1B1/1B3 may exist to reduce the burden on upstream hepatocytes. Conclusion: Detailed BA analysis revealed glucuronidated bile acidemia in patients with Rotor syndrome. Further exploration of the physiologic role of glucuronidated BAs is necessary.

Heavy metals in urban dusts from Alexandria and Kafr El-Sheikh, Egypt: implications for human health.

A total of 23 road-dust and 9 house-dust samples were collected from Alexandria and Kafr El-Sheikh cities, Egypt in 2016 to investigate heavy metal (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) contamination, spatial distribution, sources, and health risks. The mean concentrations (mg kg-1) of Cd (road-dust (RD) = 0.33, house-dust (HD) = 0.77), Cu (RD = 80, HD = 141), Pb (RD = 70, HD = 260), and Zn (RD = 169, HD = 771) in Alexandria and Zn (RD = 192, HD = 257) in Kafr El-Sheikh were higher than corresponding background (background refers to generic earth crust shale values given in the literature) levels. Whereas average concentrations (mg kg-1) of Co, Cr, Mn, and Ni (Alexandria: RD = 2.7, 24.3, 251, 14.4; HD = 3.2, 29.2, 237, 25.1 and Kafr El-Sheikh: RD = 6.6, 31.9, 343, 20.2; HD = 8.6, 33.4, 438, 23.2) in both cities were much lower than their background values. Spatially, for most heavy metals, the high concentrations were observed in areas characterized with increased anthropogenic activities, heavy traffic, and high population density. Contamination indices revealed moderate contamination (Cd and Cu) to high contamination (Pb: only house-dust from Alexandria), which posed low (most metals) to moderate ecological risk (Cd and Pb). Correlation analysis and factor analysis classified the studied metals in two groups as: natural input (Co, Cr, Mn, Ni, and Fe) and anthropogenic sources (Cd, Cu, Pb, and Zn). The noncancerous risks posed by studied metals ranged from 0.0001 (Cd) to 0.15 (Pb) and were insignificant. The cancerous risk of Pb (1.4 × 10-4) for children on exposure to house-dust form Alexandria exceeded the guideline values and was considered unacceptable, whereas the cancerous risks of other studied metals were acceptable for both subpopulations. The results of health risk revealed that children are facing higher risk than adults.

A simple, inexpensive method for gas-phase singlet oxygen generation from sensitizer-impregnated filters: Potential application to bacteria/virus inactivation and pollutant degradation.

Airborne infectious diseases such as the new Coronavirus 2019 (COVID-19) pose serious threat to human health. Indoor air pollution is a problem of global environmental concern as well. Singlet oxygen (1O2) is a reactive oxygen species that plays important role in bacteria/virus inactivation and pollutant degradation. In this study, we found that commercially available filters typically deployed in air purifier and air conditioning units, when impregnated with Rose Bengal (RB) as a 1O2 sensitizer, can be used for heterogeneous gas-phase generation of 1O2. It was confirmed that irradiation of the RB filter under oxygen gas stream produced 1O2, which was measured using furfuryl alcohol trapping method followed by HPLC analysis. It was also observed that the amount of 1O2 generated increases as the light intensity increased. Similarly, the sensitizer loading also positively influenced the 1O2 generation. The heterogeneous gas-phase generation of 1O2 can find potential applications in air purifier and air conditioning units for the purpose of bacteria/virus inactivation and/or pollutant degradation thereby improving indoor air quality.

Temporal trends in organophosphorus pesticides use and concentrations in river water in Japan, and risk assessment.

We reviewed organophosphorus pesticide use in Japan between 1982 and 2016 using data from the National Institute of Environmental Studies. Organophosphorus pesticide concentrations in river water throughout Japan were taken from the literature, and risk assessments were performed for some organophosphorus pesticides based on risk quotients and hazard quotients. Assessments were performed for 20 common pesticides, including insecticides, fungicides, and herbicides. The amounts used decreased in the order: insecticides > herbicides > fungicides. Organophosphorus insecticide and fungicide use have decreased over the last four decades, but organophosphorus herbicide use has increased. During this period, annual organophosphorus pesticide use was the highest for chlorpyrifos (105,263 tons/year) and the lowest for glyphosate-sodium (8 tons/year). The ecotoxicological risk assessment indicated that diazinon and fenitrothion posed strong risks to the Japanese aquatic environment, and chlorpyrifos and malathion have moderate risks. None of the pesticides that were assessed posed significant risks to humans. Continued use of organophosphorus pesticides in Japan may cause strong risks to aquatic environments. These risks should be reassessed periodically.

Polycyclic aromatic hydrocarbons in urban road dust, Afghanistan: Implications for human health.

Polycyclic aromatic hydrocarbons (PAHs) were analyzed in road and aerial dust to assess their concentration, composition profile, distribution, emission sources, and potential human health risks. Sixteen priority PAHs and Benzo [e]pyrene (BeP) were analyzed in 13 aerial dust samples from Jalalabad, and 78 road dust samples from Kabul and Jalalabad cities, Afghanistan. The mean concentration of ∑17PAHs in road dust from Kabul and Jalalabad were 427  µg kg-1 and 288  µg kg-1, respectively whereas ∑17PAHs in aerial dust from Jalalabad averaged 200  µg kg-1. Fluoranthene (Flu), Chrysene (Chr), Benzo [b]fluoranthene (BbF), Benzo [k]fluoranthene (BkF) and BeP were major individual PAH species. The composition patterns of the PAHs were dominated by 5-6-ring PAHs (51% in road dust from Kabul; 44% in road dust from Jalalabad; and 44% in aerial dust) followed by 4-ring and 2-3-ring PAHs. Source apportionment of the road dust PAHs by the molecular diagnostic ratios (MDR) and principal component analysis (PCA), indicated signatures of PAHs sources (including vehicular exhaust, coal/wood combustion and oil spill). The Benzo [a]pyrene (BaP) toxicity equivalent values (BaPeq17PAHs) for road dust were 75  µg kg-1 (Kabul) and 36 µg kg-1 (Jalalabad); and 35 µg kg-1 for aerial dust (Jalalabad). BaP and Dibenz [a,h]anthracene (DahA) together contributed > 50% of the BaPeq associated cancer risk. All incremental lifetime cancer risk (ILCR) due to human exposure to road and aerial dust PAHs were in the order of 10-7, which is one-fold lower than the threshold (10-6). The noncancerous risk (Hazard Index < 1) on exposure to dust was also negligible for both subpopulations.

Evaluation of Levels, Sources and Health Hazards of Road-Dust Associated Toxic Metals in Jalalabad and Kabul Cities, Afghanistan.

This study was designed to investigate selected road-dust associated heavy metals, their relations with natural and anthropogenic sources, and potential human and environmental health risks. For this purpose, 42 and 36 road-dusts samples were collected from Jalalabad and Kabul cities (Afghanistan), respectively. The following elements were found in descending concentrations: Mn, Zn, Pb, Ni, Cu, Cr, Co, and Cd in Jalalabad; and Mn, Zn, Ni, Cu, Cr, Pb, Co, and Cd in Kabul. Except for Ni, all the elemental contents were less than the Canadian permissible limits in residential/parkland soils. Principle Component Analysis and enrichment of Cd, Cu, Ni, Pb, and Zn pointed to anthropogenic sources, whereas Co, Cr, and Mn indicated crustal inputs. Broadly, Cd monomial risk index ([Formula: see text]) was considerable; however, one site each in both cities showed high risk ([Formula: see text] ≥ 350). The potential ecological risk (RI) is mostly low; however, at some sites, the risk was considerable. Ingestion appeared to be the main exposure route (99%) for heavy metals and contributed > 90% to noncancerous (all residents), as well as 92% (children) and 75-89% (adults) cancerous risks. The noncancerous risks of all metals and their integrated risks for all residents were within acceptable levels. Moreover, potential cancer risks in children from Ni and Cr were slightly higher than the US-EPA safe levels but were within acceptable levels for adults. This study found higher risks to children and therefore recommends proper management and ways to control metals pollution load in these areas to decrease human health and RIs.

CD11c+ resident macrophages drive hepatocyte death-triggered liver fibrosis in a murine model of nonalcoholic steatohepatitis.

Although recent evidence has pointed to the role of organ- and pathogenesis-specific macrophage subsets, it is still unclear which subsets are critically involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Using melanocortin-4 receptor-deficient (MC4R-KO) mice fed Western diet (WD), which exhibit liver phenotypes similar to those of human NASH, we found a histological structure, termed hepatic crown-like structure (hCLS), in which CD11c+ macrophages surround dead/dying hepatocytes, a prominent feature of NASH. Here, we demonstrate that hCLS-constituting macrophages could be a novel macrophage subset that drives hepatocyte death-triggered liver fibrosis. In an "inducible NASH model," hepatocyte death induces hCLS formation and liver fibrosis sequentially in the short term. In combination with the long-term WD feeding model, we also showed that resident macrophages are a major cellular source of CD11c+ macrophages constituting hCLS, which exhibited gene expression profiles distinct from CD11c- macrophages scattered in the liver. Moreover, depletion of CD11c+ macrophages abolished hCLS formation and fibrogenesis in NASH. Our clinical data suggest the role of CD11c+ macrophages in the disease progression from simple steatosis to NASH. This study sheds light on the role of resident macrophages, in addition to recruited macrophages, in the pathogenesis of NASH.

Concentrations of polycyclic aromatic hydrocarbons: Their potential health risks and sources at three non-urban sites in Japan.

This investigation was undertaken to monitor particulate polycyclic aromatic hydrocarbons (PAHs) concentrations in order to determine their emission sources and potential human health risks in remote and rural areas of Japan. Seventeen PAHs in aerosol samples collected in remote (Kamihaya), coastal (Hiki) and inland (Higashi-Hiroshima) areas of Japan during 2013-2014 were analyzed using gas chromatography/mass spectrometry. Total PAH (Σ17PAH) concentrations in aerosol samples were in the range of 0.08-6.51 ng m(-3), 0.09-4.74 ng m(-3), and 0.21-6.53 ng m(-3) at Kamihaya, Hiki, and Higashi-Hiroshima sites, with mean concentrations of 1.63, 1.18, and 2.43 ng m(-3), respectively. Significant seasonal variation in concentrations occurred at Hiki and Higashi-Hiroshima, while no significant variation occurred at Kamihaya. Ambient air temperature greatly affected PAH concentrations in Higashi-Hiroshima, but had only moderate effects in Kamihaya and Hiki. Wind direction also influenced the concentrations of PAHs. Vehicle exhaust, industrial emissions, biomass combustion, and domestic heating and cooking were identified as the main PAH emission sources using principal component analysis. Backward trajectory calculations showed that domestically generated PAHs were significant in Kamihaya and Hiki, while in Higashi-Hiroshima concentrations were mainly influenced by long-range transport. The incremental lifetime lung cancer risk had values of 3.38 × 10(-5) and 1.84 × 10(-5) at Higashi-Hiroshima and Hiki, which are greater than the US EPA acceptable level (10(-6)). Typically, 5-6-ring PAHs contributed 95% to this overall health risk, of which benzo(a)pyrene was the largest contributor, followed by dibenz(a,h)anthracene at both residential sites. Clearly, stricter guidelines for PAHs need to be implemented at these sites to protect the population.

Recessive inheritance of population-specific intronic LINE-1 insertion causes a rotor syndrome phenotype.

Sequences of long-interspersed elements (LINE-1, L1) make up ∼17% of the human genome. De novo insertions of retrotransposition-active L1s can result in genetic diseases. It has been recently shown that the homozygous inactivation of two adjacent genes SLCO1B1 and SLCO1B3 encoding organic anion transporting polypeptides OATP1B1 and OATP1B3 causes a benign recessive disease presenting with conjugated hyperbilirubinemia, Rotor syndrome. Here, we examined SLCO1B1 and SLCO1B3 genes in six Japanese diagnosed with Rotor syndrome on the basis of laboratory data and laparoscopy. All six Japanese patients were homozygous for the c.1738C>T nonsense mutation in SLCO1B1 and homozygous for the insertion of a ∼6.1-kbp L1 retrotransposon in intron 5 of SLCO1B3, which altogether make up a Japanese-specific haplotype. RNA analysis revealed that the L1 insertion induced deleterious splicing resulting in SLCO1B3 transcripts lacking exon 5 or exons 5-7 and containing premature stop codons. The expression of OATP1B1 and OATP1B3 proteins was not detected in liver tissues. This is the first documented case of a population-specific polymorphic intronic L1 transposon insertion contributing to molecular etiology of recessive genetic disease. Since L1 activity in human genomes is currently seen as a major source of individual genetic variation, further investigations are warranted to determine whether this phenomenon results in other autosomal-recessive diseases.

An inflammatory polyp in the colon caused by the migration of a Kirschner wire following fixation of a pelvic fracture.

The migration of Kirschner wires (K-wires) is a rare complication. We herein present a case of an inflammatory polyp in the colon caused by the migration of a K-wire following fixation of a pelvic fracture. Surgery was carried out to remove the K-wire through an incision at the level of the left iliac bone. Simultaneous endoscopic clipping of the colonic wound was also performed. The patient's postoperative course was uneventful. Although very rare, migration of devices should be considered in patients with a previous history of orthopedic surgery.

Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS)" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

[A rare case report of incarceration of Lambl's excrescence of aortic valve resulting in myocardial infarction].

We report a rare autopsy case of Lambl's excrescence of the aortic valve resulting in myocardial infarction. A 50-year-old female patient was referred to our hospital, but she died 4 hours after admission due to myocardial infarction. Autopsy disclosed Lambl's excrescence of the aortic valve, which obstructed the main branch of the left coronary artery. Histologically, fibrin thrombus and bacterial flora were found on surface of Lambl's excrescence. Differential diagnosis of infected Lambl's excrescence, so called endocarditis with infected vegetation, and papillary fibroelastomais discussed with a literature review.

Automobile exhaust gas as a source of aqueous phase OH radical in the atmosphere and its effects on physiological status of pine trees.

Free radical generation potential of automobile exhaust gas was examined by measuring hydroxyl (OH) radical photo-formation rates in exhaust gas-scrubbing water. Effects of automobile exhausts on physiological status of Japanese red pine trees (Pinus densiflora Sieb. et Zucc.) were also investigated to elucidate the mechanism how the free radicals derived from exhaust gas damage higher plants. Gasoline and diesel exhaust gases were scrubbed into pure water. Potential photo-formation rates of OH radical in aqueous phase (normalized to sun light intensity of clear sky midday on May 1 at 34°N) for gasoline and diesel cars were ave. 51 and 107 µ Mh⁻¹ m⁻³ of exhaust gas, respectively. Nitrite was a dominant source (ca. 70-90%) of photochemical formation of OH radical in both gasoline and diesel car exhausts. The scrubbed solution of diesel car exhaust gas was sprayed for six times per week to needles of pine tree seedlings in open top chambers. Control, exhaust+mannitol (added as OH radical scavenger), and nitrite+nitrate standard solution (equivalent levels existed in the exhaust gas) were also sprayed. Two months sprays indicated that the sprayed solutions of diesel exhaust and nitrite+nitrate caused a decrease of maximum photosynthetic rate and stomata conductance in pine needles while the control and exhaust+mannitol solution showed no effects on photosynthetic activities of pine needles. These results indicated that OH radicals generated mainly from photolysis of nitrite occurring in the scrubbing solution of exhaust gas are responsible for the decrease of photosynthetic activities of pine needles.

Transesterification of soybean oil using combusted oyster shell waste as a catalyst.

Transesterification of soybean oil catalyzed by combusted oyster shell, which is waste material from shellfish farms, was examined. Powdered oyster shell combusted at a temperature above 700 degrees C, at which point the calcium carbonate of oyster shell transformed to calcium oxide, acted as a catalyst in the transesterification of soybean oil. On the basis of factorial design, the reaction conditions of catalyst concentration and reaction time were optimized in terms of the fatty acid methyl ester concentration expressed as biodiesel purity. Under the optimized reaction conditions of a catalyst concentration and reaction time of 25wt.%. and 5h, respectively, the biodiesel yield, expressed relative to the amount of soybean oil poured into the reaction vial, was more than 70% with high biodiesel purity. These results indicate oyster shell waste combusted at high temperature can be reused in biodiesel production as a catalyst.

Phytotoxicities of fluoranthene and phenanthrene deposited on needle surfaces of the evergreen conifer, Japanese red pine (Pinus densiflora Sieb. et Zucc.).

Polycyclic aromatic hydrocarbons (PAHs) have been widely studied with respect to their carcinogenic and mutagenic effects on animals and human cells. Phenanthrene (PHE) and fluoranthene (FLU) effects on the needle photosynthetic traits of 2-year-old Japanese red pine (Pinus densiflora Sieb. et. Zucc.) seedlings were investigated. Three months after fumigation of foliage with solutions containing these PAHs (10 microM each), FLU had negative effects on net photosynthesis at near-saturating irradiance, stomatal conductance, initial chlorophyll fluorescence, and the contents of total chlorophyll, magnesium, and ribulose 1,5-bisphosphate carboxylase (rubisco) of current-year needles. PHE had similar negative effects to FLU but in lesser magnitude. The effects of the PAHs were mitigated by the addition of an OH-radical scavenger (mannitol) into the PAH solutions. PAHs deposited on the surface of pine needles may induce the generation of reactive oxygen species in the photosynthetic apparatus, a manner closely resembling the action of the herbicide paraquat.

Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3.

BACKGROUND: Interferon regulatory factor (IRF)-3 plays an important role in initiating cellular interferon-stimulated gene-mediated antiviral responses. In the present study, we evaluated the effects of IRF-3 expression and activation on intracellular hepatitis C virus (HCV) replication using an HCV replicon system. METHODS: An HCV replicon was constructed that expressed a neomycin-selectable chimeric firefly luciferase reporter protein. A small interfering (si) RNA oligonucleotide directed against IRF-3 mRNA was designed and synthesized. A eukaryote expression plasmid vector was constructed that expressed IRF-3 mRNA under control of the cytomegalovirus early promoter/enhancer. To evaluate transcriptional activity of the interferon-stimulated genes, a reporter vector was used that expressed firefly luciferase under control of the interferon-stimulated response element (ISRE). RESULTS: The baseline expression of IRF-3 did not significantly differ between cells with and without expression of the replicon. Transfection of an IRF-3 expression plasmid into the cells raised the ISRE-luciferase activities. The increase of ISRE activity was significantly more potent in the replicon-expressing cells than in cells without replicon expression. Concomitantly, the overexpression of IRF-3 suppressed HCV replication levels. In contrast, siRNA knockdown of IRF-3 suppressed ISRE activity by 38% +/- 2%. Interestingly, the suppression of IRF-3 resulted in a significant increase of HCV replication, by up to twofold, depending on the IRF-3 suppression levels. CONCLUSIONS: IRF-3 negatively regulated intracellular HCV replication, and was partially activated in cells that expressed the HCV replicon. Thus, IRF-3 is a key molecule controlling HCV replication through modulation of host interferon gene responses.

Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.

The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 +/- 16.3 vs. 36.0 +/- 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.

Impairment of host immune response against strongyloides stercoralis by human T cell lymphotropic virus type 1 infection.

A large-scale study was undertaken to clarify the prevalence rate of strongyloidiasis in Okinawa, Japan and to evaluate the relationship between strongyloidiasis and infection with human T cell lymphotropic virus type 1 (HTLV-1). The prevalence rate of Strongyloides stercoralis and HTLV-1 infection were 6.3% and 14.0%, respectively. Among 2,185 patients more than 50 years of age, the rate of S. stercoralis infection was significantly higher in patients with HTLV-1 infection compared with patients without HTLV-1 infection. In 252 patients treated with ivermectin, serum IgE levels and peripheral eosinophil counts were significantly lower in HTLV-1 co-infected patients compared with patients without HTLV-1 infection. In addition, the anthelmintic effect was significantly lower in patients with HTLV-1 infection compared with patients without HTLV-1 infection. Our prospective study demonstrated a prevalence rate for strongyloidiasis and HTLV-1 infections, and clearly demonstrated that co-infection with HTLV-1 impaired the immune response against S. stercoralis.