Application of Nanoparticles as Novel Adsorbents in Blood Purification Strategies.

BACKGROUND: Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles. SUMMARY: In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and good hemocompatibility shown during the treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication. KEY MESSAGES: (i) The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. (ii) Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. (iii) Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in the treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. (vi) A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.

Micro/nano-plastics and microalgae in aquatic environment: Influence factor, interaction, and molecular mechanisms.

Micro/nano-plastics, as emerging persistent pollutant, are frequently detected in aquatic environments together with other environmental pollutants. Microalgae are the major primary producers and bear an important responsibility for maintaining the balance of aquatic ecosystems. Numerous studies have been conducted on the influence of micro/nano-plastics on the growth, photosynthesis, oxidative stress, gene expression and metabolites of microalgae in laboratory studies. However, it is difficult to comprehensively evaluate the toxic effects of micro/nano-plastics on microalgae due to different experimental designs. Moreover, there is a lack of effective analysis of the aforementioned multi-omics data and reports on shared biological patterns. Therefore, the purpose of this review is to compare the acute, chronic, pulsed, and combined effect of micro/nano-plastics on microalgae and explore hidden rules in the molecular mechanisms of the interaction between them. Results showed that the effect of micro/nano-plastics on microalgae was related to exposure mode, exposure duration, exposure size, concentration, and type of micro/nano-plastics. Meanwhile, the phenomenon of poisoning and detoxification between micro/nano-plastics and microalgae was found. The inhibitory mechanism of micro/nano-plastics on algal growth was due to the micro/nano-plastics affected the photosynthesis, oxidative phosphorylation, and ribosome pathways of algal cells. This brought the disruption of the functions of chloroplasts, mitochondria, and ribosome, as well as impacted on energy metabolism and translation pathways, eventually leading to impairment of cell function. Besides, algae resisted this inhibitory effect by regulating the alanine, aspartate, and glutamate metabolism and purine metabolism pathways, thereby increasing the chlorophyll synthesis, inhibiting the increase of reactive oxygen species, delaying the process of lipid peroxidation, balancing the osmotic pressure of cell membrane.

Toxicity Evaluation, Oxidative, and Immune Responses of Mercury on Nile Tilapia: Modulatory Role of Dietary Nannochloropsis oculata.

The current study evaluated the potential ameliorative effect of a dietary immune modulator, Nannochloropsis oculata microalga, on the mercuric chloride (HgCl2)-induced toxicity of Nile tilapia. Nile tilapia (45-50 g) were fed a control diet or exposed to » LC50 of HgCl2 (0.3 mg/L) and fed on a medicated feed supplemented with N. oculata (5% and 10% (50 or 100 g/kg dry feed)) for 21 days. Growth and somatic indices, Hg2+ bioaccumulation in muscles, and serum acetylcholinesterase (AChE) activity were investigated. Antioxidant and stress-related gene expression analyses were carried out in gills and intestines. Histopathological examinations of gills and intestines were performed to monitor the traits associated with Hg2+ toxicity or refer to detoxification. Hg2+ toxicity led to significant musculature bioaccumulation, inhibited AChE activity, downregulated genes related to antioxidants and stress, and elicited histopathological changes in the gills and intestine. Supplementation with N. oculata at 10% was able to upregulate the anti-oxidative-related genes while downregulated the stress apoptotic genes in gills and intestines compared to the unexposed group. In addition, minor to no histopathological traits were detected in the gills and intestines of the N. oculata-supplemented diets. Our data showed the benefit of dietary N. oculata in suppressing Hg2+ toxicity, which might support its efficacy as therapeutic/preventive agent to overcome environmental heavy metal pollution in aquatic habitats.

Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model.

Alcohol-induced oxidative stress is a key player in the development of liver diseases, and herbal alternatives are important means of ameliorating the hepatotoxic effects. The study aimed to evaluate the hepatoprotective potentiality of Artabotrys odoratissimus, an important medicinal shrub from the family Annonaceae. The phenolic compounds from bark ethanol extract (BEE) were detected using RP-HPLC. The in vitro hepatoprotective activity against ethanol-induced damage was studied in HepG2 cells with cell viability assays, mitochondrial membrane potential (MMP) assay, reactive oxygen species (ROS) assay, double staining assay and western blotting. The in vivo mice model was used to evaluate the alcohol-induced stress with liver function enzymes, lipid profile and histopathology. All the thirteen phenolic compounds detected with HPLC were docked onto protein targets such as aspartate amino transferase (AST), alkaline phosphatase (ALP) and inducible nitric oxide synthase (NO). The RP-HPLC detected the presence of various phenolics including rutin, chlorogenic acid and catechin, amongst others. Co-administration of BEE with ethanol alleviated cell death, ROS and MMP in HepG2 cells compared to the negative control. The extract also modulated the MAP kinase/caspase-3 pathway, thereby showing protective effects in HepG2 cells. Also, pre-treatment for 14 days with the extract in the mice model before a single toxic dose (5 g/kg body weight) reduced the liver injury by bringing the levels of liver function enzymes, lipid profile and bilirubin to near normal. In silico analysis revealed that rutin showed the best binding affinity with all the target proteins in the study. These results provide evidence that BEE possesses significant hepatoprotective effects against ethanol-induced oxidative stress in hepatic cells and in vivo models, which is further validated with in silico analysis.

Immunotoxicity of petroleum hydrocarbons and microplastics alone or in combination to a bivalve species: Synergic impacts and potential toxication mechanisms.

Both the frequent occurrence of accidental petroleum spills and the ubiquitous presence of microplastics (MPs) in the sea may pose severe threats to marine species. However, the immunotoxic impacts of these two types of pollutants and the underlying toxication mechanisms still remain largely unknown in sessile filter-feeding bivalve mollusks. Therefore, the impacts of exposure to petroleum hydrocarbons and MPs alone or in combination on the total count, cell type composition, and phagocytic activity of hemocytes were investigated in the blood clam, Tegillarca granosa. In addition, the intracellular ROS content, cell viability, degree of DNA damage, and expression levels of genes from immune-, apoptosis-, and immunotoxicity-related pathways were analyzed to reveal the potential toxication mechanisms. The results demonstrated that exposure to petroleum hydrocarbons and MPs alone or in combination at environmentally realistic concentrations could exert significant immunotoxic impacts on the blood clam, which may be caused by alterations in a series of physiological and molecular processes. In addition, the immunotoxicity of petroleum hydrocarbons could be significantly aggravated by the copresence of MPs, which suggests that coexposure to these two pollutants deserves closer attention.

Time of the day dictates the variability of biomarkers of exposure to disinfection byproducts.

Non-persistent environmental chemicals (NOPEC) are xenobiotics with short half-lives of elimination (<7h). Similar to chronopharmacokinetics, NOPEC metabolism may follow diurnal patterns of cytochrome P450 activity. The role of circadian liver clock in shaping NOPEC metabolism and their concomitant measurements of biomarkers of exposure and effect remains poorly understood in real-life human settings. Metabolic activation (toxication) by CYP2E1 converts trihalomethanes (THM) to harmful metabolites. We investigated the diurnal variation of urinary THM exposures and their metabolism patterns as catalyzed by CYP2E1 redox activity, using the surrogate marker of 4-hydroxynonenal (4HNE). We implemented three time-series trials with adult volunteers conducting specific household cleaning activities at predefined times of a day. Circadia variation of 4HNE was assessed with a cosinor model and its mesor levels increased with THM exposure. The time of exposure within the day dictated the magnitude of urinary THM levels and their toxication effect; in all three trials and relative to urinary THM levels before the activity, lower and higher median THM were measured right after the activity in morning and afternoon/night, respectively. This is consistent with higher reported CYP2E1 redox activity in light/active phase. Population health studies should incorporate time-stamped biomarker data to improve the understanding of chronic disease processes.

Analysis of risk factors for prognosis of patients with acute paraquat intoxication / 中华危重病急救医学

Objective To explore the risk factors influencing the prognosis by analyzing clinical data of patients with acute paraquat intoxication, and to assess the prognostic values of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, and Acute Kidney Injury Network (AKIN) stage.Methods The clinical data of patients with acute paraquat intoxication admitted into the First People's Hospital of Xianyang City during October 2005 to May 2015 were retrospectively analyzed.The patients were divided into death group and survival group according to 28-day outcome after poisoning.The gender, age, body weight index, toxin dose, time elapsed from poisoning to gastric lavage, time elapsed from poisoning to hemoperfusion (HP), times of HP treatment, white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK) were determined at admission.Arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), arterial lactate (Lac), and APACHE Ⅱ score, SOFA score and AKIN stage were recorded and compared between two groups.The receiver operating characteristic (ROC) curve was plotted for APACHE Ⅱ score, SOFA score and AKIN stage to analyze the prognostic value for patients with acute paraquat intoxication.Results There were 118 cases in total,with 64 survivors and 54 deaths in 28 days, and the fatality rate was 45.76％.Compared with survival group, the toxic dose (mL: 66.29 ± 27.40 vs.29.16 ± 19.40), time elapsed from poisoning to gastric lavage (minutes: 60.37 ± 26.68 vs.41.17± 14.82), WBC count (× 109/L: 16.86±2.77 vs.10.25 ± 2.60), ALT (U/L: 53.94± 10.85 vs.36.40±9.21),SCr (μmol/L: 159.69±42.85 vs.81.73±34.40) at admission as well as Lac (mmol/L: 3.06± 1.33 vs.1.71 ±0.88),APACHE Ⅱ score (6.46±2.38 vs.3.31 ± 1.51), SOFA score (3.31 ± 1.06 vs.2.21±0.76) 48 hours after admission were significantly higher in the death group (all P ＜ 0.01).PaO2 and PaCO2 48 hours after admission were significantly lower in death group than those in the survival group [PaO2 (mmHg, 1 mmHg =0.133 kPa): 64.07± 13.04 vs.75.40 ± 13.27, PaCO2 (mmHg): 26.20 ± 8.89 vs.31.25 ± 6.29, both P ＜ 0.01].There were 18, 15, 11 and 10 patients in AKIN 0, 1, 2, 3 stage 48 hours after admission respectively in death group, and 38, 15, 7, 4 in survival group.The difference between two groups was statistically significant (P ＜ 0.01).There were no statistically significant differences in gender, age, body mass index, time elapsed from poisoning to HP, levels of HP, and AST, TBil, BUN and CK at admission between the two groups.At 48 hours after admission, the area under the ROC curve (AUC) of APACHE Ⅱ score predicting the prognosis of patients with acute paraquat poisoning was 0.875 [95％ confidence interval (95％CI) =0.814-0.935, P =0.000].When the cut-off point of APACHE Ⅱ score was 4, the sensitivity and specificity were 79.6％ and 79.7％, and the best Youden index was 0.593.The AUC of SOFA score was 0.776 (95％CI=0.692-0.859, P =0.000).When the cut-off point of FOFA score was 3, the sensitivity was 72.2％, the specificity 67.2％, and the best Youden index 0.394.The AKIN stage of ROC curve had an area of 0.656 (95％CI =0.556-0.755, P =0.004).When the cut-off point of AKIN stage was 1, the sensitivity was 66.7％, the specificity was 59.4％, and the best Youden index was 0.261.Conclusions Amount of the poison, time elapsed from poisoning to gastric lavage, and WBC, ALT, SCr at admission as well as PaO2, PaCO2 and Lac 48 hours after admission are the risk factors for prediction of the prognosis of acute paraquat intoxication.APACHE Ⅱ score, SOFA score and AKIN stage can be used to assess the prognosis of acute paraquat poisoning, and APACHE Ⅱ score is better than SOFA score and AKIN stage.

Analysis of risk factors for prognoses of 176 patients with acute paraquat intoxication / 中国中西医结合急救杂志

Objective To explore the risk factors influencing the prognoses by analyzing clinical data of patients with acute paraquat intoxication,and provide a basis for clinical prevention and treatment of the disease. Methods The clinical data of 176 patients with acute paraquat intoxication admitted into our Hospital were retrospectively collected during the period from January 2012 to February 2013. After admission,the conventional medical treatment was given to all the patients,and according to the prognoses of 28 days after poisoning,the patients were divided into death group and survival group. The gender,age,toxic dose,time elapsed from poisoning to admission,time elapsed from poisoning to gastric lavage,number of cases treated with drug lavage,white blood cell count(WBC),alanine amino-transferase(ALT),aspartate amino-transferase(AST),blood urea nitrogen(BUN), serum creatinine(SCr),acute physiology and chronic health evaluation system Ⅱ(APACHE Ⅱ)score,carbon dioxide combining power(CO2CP),number and time of cases revealing arterial blood oxygen saturation(SaO2)0.05〕.③Multivariate logistic regression revealed poisoning doses>30 ml〔odds ratio(OR)=6.455,95% confidence interval(95%CI)3.177-13.113,P30 minutes(OR=8.639, 95%CI 4.043-18.461, P12×109/L (OR=2.745,95%CI 1.388-5.426, P=0.004),BUN>8 mmol/L(OR=6.713,95%CI 2.650-17.006,P<0.001)and CO2CP≤22 mmol/L(OR=4.737,95%CI 2.389-9.394, P<0.001) were the risk factors correlated with the prognosis of patients with acute paraquat intoxicationl. Conclusion Poisoning doses,time elapsed from poisoning to admission,BUN,CO2CP and WBC are the independent risk factors for predicting prognosis of acute paraquat intoxication.

Investigation of lipid peroxidation as probable mechanism of rifampicin toxicity in vivo.

BACKGROUND: Xenobiotics may exert their toxic effects on tissues directly or after they have been metabolized. Increased reactivity of xenobiotics owing to their conversion to electrophiles, free radicals, nucleophiles and redox-active reactants may also contribute to toxicity. PURPOSE: The present study attempts to investigate the possible "lipid peroxidation/free radical generation" mechanism behind rifampicin toxicity. METHODS: Measurement of antioxidant enzymatic activity and MDA level was done according to standard procedures. RESULTS: The results showed a low, non-significant (p > 0.05) increase in the malondialdehyde (MDA) levels of the testes, serum, brain and liver of Rif treated group compared with the control. The superoxide dismutase (SOD) results in Rif treated group also showed a low, non-significant (p > 0.05) decreased levels in the testes, serum, brain and liver when compared with the control. However, there was a significant (p ≤ 0.05) decrease in the level of catalase in the testes of Rif treated rats compared with the control. CONCLUSION: The low, non-significant (p > 0.05) increase in the Malondialdehyde (MDA) levels of the testes, serum, brain and liver suggest that Rif toxicity may also be through other mechanisms such as direct toxic effects on cells, cellular dysfunction, conversion of Rif to electrophiles, nucleophiles and redox-active reactants; other than only via lipid peroxidation. It may be concluded that just as a lot of attention is directed towards targeting drug toxicity arising due to free radical generation by the use of antioxidants, similarly other mechanisms leading to drug toxicity should also be targeted.

Hepatoprotective effect of lingzhi extract on chronic hepatic toxication by diethyl-nitrosamine and carbon tetrachloride

The experimental trial was conducted on bull white mice, ddY strain, weight of 18-20g, were randomly assigned to different lots, with 8-15 mice in each lot. Experimental product was total dry lingzhi extract produced by OPC Company which reached standards at basic level. Lingzhi dry powder was prepared with distilled water to make liquid extract with concentration of 15% (15g dry extract/100ml water), 30% and 75%. These liquid extracts were used to test hepatoprotective effect effect of Lingzhi extract on chronic hepatic toxication by DEN and CCl4. The results showed that lingzhi extract did not show microprotective effects. However, lingzhi extract can inhibit hyperplastic nodule formation. On the other hand, lingzhi extract also reduced abnormal cells formation

Hepatoprotective effect of Lingzhi extract on CCl4-induced hepatic lesion

Study on hepatoprotective effects of lingzhi extract on CCl4-induced hepatic lesion, lingzhi formulation produced by OPC Company which reached standards at basic level. Lingzhi dry powder was prepared with distilled water to make liquid extract with concentrations of 15% (15g dry extract/100ml water), 30% and 75%. These liquid extracts were used to test hepatoprotective effects. With low dose CCl4 (0,25%) induced hepatic toxication, 15%, 30% and 75% lingzhi extracts showed hepatoprotective effect. However, with high dose CCl4 (1%), only 30% lingzhi extract showed clear and stable hepatoprotective effects. Experimental trials on hepatic diseases as well as on hepatoprotective medications should provide necessary information on physiopathological characteristics and medicinal therapies

Electrophysiological characteristics of chronic alcoholic myopathy / 第三军医大学学报

Objective To investigate the electrophysiological characteristics of chronic alcoholic myopathy. Methods Muscle fiber conduction velocity, peripheral nerve conduction velocity, and induced potentials in 26 patients with chronic alcoholic myopathy, 13 patients with chronic alcoholic peripheral neuropathy, 21 patients with chronic alcoholic neuromuscular damage, and 20 normal subjects were detected by electromyography and single fiber electromyography. Results Electromyography revealed myogenic changes in 9 cases in the myopathy group, neurogenic changes in 7 cases in the peripheral neuropathy group, and both kind of changes in 4 cases in the neuromuscular damage group. Compared with the normal subjects, neuromuscular jitter and fiber density increased in all patients ( P 0.05). Slowed sensory nerve conduction velocity was found in 28 patients (82.35%) with peripheral neuropathy or neuromuscular damage. Conclusion Electromyography and determination of nerve conduction velocity can be used to differentiate the alcoholic myopathy from peripheral neuropathy. The abnormal muscle fiber conduction velocity can be helpful for the confirmation of myopathy.

Study on some alterations of biochemical indicators in rabbit suffered the toxicity due to the single diclodietyl or clovininyl diclorasin or their combination

Concentration of SGOT, SGPT, ure and creatinine was increased in serum of rabbits, exposed to diclodietylsulfid and clovinyldiclorasin. We realized that there were synergic effects between diclodietylsulfid and clovinyldiclorasin, caused increase of ure and creatinie in rabbits higher than effect of single agent. Concentration of glucose was increased at the third day and decreased at the 7th day in rabbits exposed to mix of clovinyldiclorasin and diclodietylsulfid.

Efficacy of unithiol and naturenze in the treatment of rabbits suffered toxicity of mixture of yperite and lewisit through some biochemical indicators

Treatment of rabbits, exposed to mix of yperite and lewisite with unithiol and naturenze showed that unithol reduced concentration of SGOT (serum glutamat-oxaloacetat-transaminase), SGPT (serum glutamat-pyruvat-transaminase), urea and creatinine in serum but concentration of these components was still high. Using unithiol in combination with naturenze for treatment, concentration of SGOT, SGPT, urea and creatinine was decreased lower than treatment of single unithiol.

The correlation of serum cholinesterase and clinical signs in acute organophosphate poisoning

30 acute organophosphate poisoning patients admitted in our department were classified into three groups of severity based on serum cholinesterase level and clinical syndromes of cholinergic crisis. Atropine was given at dose of 2-5mg every 10-15 minutes until the atropinisation reached then the doses of atropine were adjusted to maintain it. Pralidoxime was administered according to severity and its dosages were titrated as serum cholinesterase levels and clinical changes. Data was analyzed by SPSS for Windows. (1) The patients had good outcome with short duration of hospitalization (5.73.8) and low mortality (3.3%). (2) Serum cholinesterase was correlated with number of clinical symptoms (r=-0.613); clinical score (r=-0.580); number clinical syndromes (r=-0.515); total dose of atropine (-.714) severity of poisoning (r=-0.928) and total dose of PAM (r=-0.721). All correlation was significantly at the 0.01 level. (3) Total dose of PAM was correlated with clinical symptoms (r=0.625); clinical score (r=0.596); clinical syndromes (r=0.658); severity of poisoning (0.695); duration of hospitalization (0.889)

Study on utilization of gel activated charcoal in the management of acute poisoning

The combinations of gel activated charcoal and sorbitol in rational proportion (product name: Antipois- Bachmai) were given for 91 patients with ingestion-induced poisoning as protocol of Bachmai Poison Control Center. 76 cases (83.5%) were admitted before 6 hours and 85 cases (93.4%) before 12 hours. 66 patients (72.5%) were given 1 dose, 93.4% were given less than 3 doses, and in 2 patients (2.2%), 6 doses have been used. Antipois-Bachmai was used conveniently. Deposit was not observed in gastric sonde, so this drug prevented from obstruction due to charcoal. Almost patients had charcoal loose stool within first 12 hours.

Improved gastric lavage with close system

Method: 73 patients were performed gastric lavage by an improved technique with new equipment. All of the patients were monitored clinical signs (pulse rate, blood pressure, respiratory rate, SpO2, lung sound...) and tested (blood count, electrolyte, ECG, chest X-ray, toxic screening...) before and after doing gastric lavage. The results were compared to a retrospective study in 1998-2000 we found that complications are reduced significantly from 6.21% to 2.74%. In addition, there was not any severity complication; we only met two cases hypokalemia after doing gastric lavage. Conclusion: the improved technique with new equipment of gastric lavage would be safe for the patients, reduce significantly complication, and easy to implement.

Titrate pam dosage according to serum cholinesterase level in the management of acute organophosphate poisoning

20 patients hospitalized from 1998 to 2000 due to acute organophosphate poisoning were treated by intravenous infusion of PAM at dose of 0.25g - 1g per hour. The dosage of PAM was adjusted according to concentrations of serum cholinesterase tested every 12 hours. The results of study showed that the clinical status was significantly improved: in-hospital stay time was shorter, dose of atropine was lower, severe complications such as paralysis, respiratory failure were decreased in comparison to previous studies. Thus, the level of serum cholinesterase is correlated to poisoning severity and is good indicator for adjustment of PAM dosage in the management of acute organophosphate poisoning.

Contribution to study on pregnancy intervention in severe pregnancy toxicity

A restrospective study on the 30 patients with severe pregnancy toxicity in Hanoi hospital of Gynaecology and Obstetrics during 1995-1996 was implemented aiming to determination of the time for pregnancy intervention which prevent the pregnant women from the bad complications and finding the experiences in the diagnosis and management. Conclusions: the indication depends on the condition of eclampsia such as blood pressure; nervous symptoms and evaluation of renal functions (with or without complication in the process of treatment). The edema is reference symptom

Changes of morphological structure and ability of regeneration of the rat's kidney after poisoning the pesticide Bassa

A study on 41 white male rats with ages of 2 - 2.5 months, weight of 130-150g was carried out. Materials included the sun oil and Bassa 50EC of Novatis. The authors found that renal lesions occurred in some positions and become more severe after 7 days of poison. The lesions included early and long lasting vasodilative congestion in the glomerular and interstitial tissues, cellular proliferation, basement tissular proliferation in glomeruli of kidney cavity and plasma surrounding the cellular nuclear in the renal tubular cells. The images of regeneration of the parenchyma appeared after 7 days of poison