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Background. The priority of the contemporary pharmaceutical industry is to create effective, safe and inexpensive drugs to ensure the highest quality of care and optimal use of available raw materials. Objective. The aim of our study was to investigate anti-inflammatory properties of the Maitake mushrooms thick extract in the experiment on rats with paracetamol(acetaminophen)-induced hepatitis. Methods. 60 white male rats, weighing 180-210 g, randomized into 10 groups of 6 animals in each, were used for the experiment. Paracetamol hepatitis was simulated by acetaminophen intragastric administering in a dose of 1250 mg/kg 1 time per day (for 2 days) as a suspension in 2% starch gel solution. Maitake mushrooms thick extract, which was administered intragastrically 2 hours before the administration of acetaminophen and daily after the lesion in a dose of 150 mg/kg of the animal’s body weight, was used for the toxic lesion correction. “Silibor” was selected as the comparison drug, which was administered according to the same scheme as the investigated extract in a dose of 20 mg/kg of the animal’s body weight. Euthanasia was conducted on the 3rd, 7th and 10th day of the experiment with sodium barbamyl. Liver homogenate and animal serum were used for the studies. The development of inflammatory processes was studied by the content of pro-inflammatory and anti-inflammatory cytokines, as well as C-reactive protein in the serum of rats with toxic hepatitis and after the application of Maitake mushroom extract and the comparison drug. Results. It was found that the introduction of acetaminophen to animals for the acute hepatitis simulation is accompanied by changes in the cytokine profile, i.e. an increase in the level of IL-6 and a decrease in the level of IL-4 in the serum of rats. Inflammatory development is evidenced by the content of C-reactive protein increase in the blood of the affected animals. The application of Maitake mushroom extract facilitated bringing the studied indicators almost to the level of intact control. Conclusions. Reduction of inflammation signs in rats with the simulated paracetamol hepatitis under the influence of Maitake mushrooms thick extract confirms its anti-inflammatory properties. Objective. The aim of our study was to investigate anti-inflammatory properties of the Maitake mushrooms thick extract in the experiment on rats with paracetamol(acetaminophen)-induced hepatitis. Methods. 60 white male rats, weighing 180-210 g, randomized into 10 groups of 6 animals each, were used for the experiment. Paracetamol hepatitis was simulated by acetaminophen intragastric administering in a dose of 1250 mg/kg 1 time per day (for 2 days) as a suspension in 2% starch gel solution. Maitake mushrooms thick extract, which was administered intragastrically 2 hours before the administration of acetaminophen and daily after the lesion in a dose of 150 mg/kg of the animal’s body weight, was used for the toxic lesion correction. "Silibor" was selected as the comparison drug, which was administered according to the same scheme like the investigated extract in a dose of 20 mg/kg of the animal’s body weight. Euthanasia was conducted on the 3rd, 7th and 10th day of the experiment with sodium barbamyl using. Liver homogenate and animal serum were used for the studies. The development of inflammatory processes was studied by the content of pro- and anti-inflammatory cytokines, as well as C-reactive protein in the serum of rats with toxic hepatitis and after the application of Maitake mushroom extract and the comparison drug. Results. It was found that the introduction of acetaminophen to animals for the acute hepatitis simulation is accompanied by changes in the cytokine profile, namely, an increase in the level of IL-6 and a decrease in the level of IL-4 in the serum of rats. The inflammatory process development is evidenced by the content of C-reactive protein increasing in the blood of affected animals. The application of Maitake mushroom extract helped to bring the studied indicators closer to the level of intact control. Conclusions. The application of the Maitake mushrooms thick extract as a corrective factor at the simulated paracetamol hepatitis confirms its anti-inflammatory properties. KEYWORDS: Maitake mushrooms, paracetamol, hepatitis, inflammatory processes, thick extract, anti-inflammatory properties.

A bee sting can be a serious problem that affects people all over the world. Several clinical manifestations of bee sting have been described elsewhere. Furthermore, local allergic reactions are more common, causing pain, redness, and swelling of soft tissue within a few hours. In some cases, severe neurological deficits that can lead to death have been reported. According to the literature, the onset of neurological symptoms can range from 30 seconds to 96 hours. Herein, we present the case of a 48-year-old man who developed allergic encephalitis and toxic hepatitis as a result of multiple bee stings.

Background Drug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. DILI is mainly caused by painkillers and fever reducers, and it is often characterized by the type of hepatic injury (hepatocellular or cholestatic). This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease. We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases. Case summary A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test. Abdominal ultrasound and computed tomography showed no biliary obstruction or non-specific findings in the liver. Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis. Following the biopsy, steroid therapy was initiated and after 3 wk of treatment, the total bilirubin level was reduced to 7.22 mg/dL. Conclusion In patients with hyperlipidemia, treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis, warranting clinical attention.

The feature of a course of tuberculosis in adolescence is the tendency to progression, necrotic reactions. The most severe outcome of general specific process is the development of meningitis, which can often be its end stage. Objective — to study the peculiarities of a course of general tuberculosis combined with tuberculous meningitis in an adolescent on the example of a clinical case. The features of a course of general tuberculosis associated with tuberculous meningitis in an adolescent were: the development of adverse reactions to long-term combination antituberculous treatment and hormone therapy (toxic hepatitis, Cushing’s disease of secondary origin); complication of tuberculous meningitis by ischemic stroke in the subcortical regions of the left hemisphere of the great brain and descending optic nerve atrophy; a positive dynamics when the regimen of antituberculosis chemotherapy is selected properly as the manifestations of both general tuberculosis and specific meningitis., Особенностью течения туберкулеза в подростковом возрасте является склонность к прогрессированию, некротическим реакциям. Наиболее тяжелым исходом милиарного специфического процесса является развитие менингита, что нередко может быть его терминальной стадией. Цель работы — изу­чить особенности течения милиарного туберкулеза в сочетании с менингитом туберкулезной этиологии у подростка на примере клинического случая. Особенностями течения милиарного туберкулеза в сочетании с менингитом туберкулезной этиологии у подростка были: развитие побочных реакций на длительный прием комплексного противотуберкулезного лечения и гормонотерапии (токсический гепатит, болезнь Иценко — Кушинга вторичного генеза); осложнение туберкулезного менингита ишемическим инсультом в подкорковых отделах левой гемисферы большого мозга и нисходящей атрофией зрительных нервов положительная динамика при правильно подобранном режиме противотуберкулезной химиотерапии как проявлений милиарного туберкулеза, так и специфического менингита., Особливістю перебігу туберкульозу в підлітковому віці є схильність до прогресування, некротичних реакцій. Найбільш тяжким наслідком міліарного специфічного процесу є розвиток менінгіту, що часто може бути його останньою стадією. Мета роботи — вивчити особливості перебігу міліарного туберкульозу в поєднанні з менінгітом туберкульозної етіології у підлітка на прикладі клінічного випадку. Особливостями перебігу міліарного туберкульозу в поєднанні з менінгітом туберкульозної етіології у підлітка були: розвиток побічних реакцій на тривалий прийом комплексного протитуберкульозного лікування та гормонотерапії (токсичний гепатит, хвороба Іценко — Кушинга вторинного ґенезу); ускладнення туберкульозного менінгіту ішемічним інсультом у підкіркових відділах лівої гемі­сфери великого мозку і низхідною атрофією зорових нервів; позитивна динаміка при правильно підібраному режимі протитуберкульозної хіміотерапії як проявів міліарного туберкульозу, так і специфічного менінгіту.

The development of osteodystrophy in diseases of the hepatobiliary system is a known fact, but the mechanism of the formation of metabolic disorders in bone tissue in liver pathology is not fully understood. The purpose of the study was to study morphological and biochemical changes in the bone tissue of female and male rats during the modeling of chronic toxic hepatitis. Materials and methods. Modeling of toxic hepatitis was carried out on 1 month old male and female Wistar rats by intraperitoneal injection of hydrazine sulfate 50 mg / kg twice a week for 3 months. The experiment was conducted in accordance with the norms and principles of the EU Council Directive on the protection of vertebrates used for scientific purposes. Morphometric measurements (density, content of mineral-organic, mineral and organic components) were carried out on the femurs and the last lumbar vertebra. Elastase activity, acidic phosphatase (indicators of bone resorption); alkaline phosphatase activity and calcium content (indicators of the synthesis of new bone tissue) were determined in homogenates of the bone tissue of the jaws and femur. The mineralizing index was calculated from the ratio of the activities of acidic phosphatase and alkaline phosphatase. Results and discussion. A decrease in the quantities organic matrix with a preserved intensity savings of bone tissue mineral parts in females and a decrease intensity in bone tissue mineralization in males under the influence of toxic hepatitis were found. Biochemical studies of bone tissue showed the activation of the destruction of the protein matrix of the bone, the intensification of mineralization in females, as well as the activation of hydrolysis of hydroxyapatite, along with a decrease in the level of calcium in the bone tissue of animals of both sexes against the background of modeling of chronic toxic hepatitis. Conclusion. The studies carried out have established multidirectional disorders of the metabolism and structure of bone tissue in males and females, induced by prolonged administration of hydrazine sulfate: in females, suppression of the formation of an organic matrix with a preserved intensity of bone mineralization, and in males, a decrease in bone mineralization against the background of a slightly increased intensity of synthesis of the organic component. The established patterns made it possible to reduce the negative effect of Hydrazine Sulfate on the protein metabolism of rat bone tissue, indirectly through the metabolism of estrogens. The results of our study provided experimental justification for the development of a scheme for the Prevention of osteodystrophic conditions in conditions of chronic exposure to toxins or impaired liver function

Гепатит касаллигида фитотерапия, яъни, гиёҳлардан фойдаланиш жигар хужайраларидаги модда алмашинувини кучайтириш ҳисобига унинг фаолиятини яхшилашга қаратилган. Алоэ ўсимлиги фитомедицинада ишлатиладиган етакчи маҳсулотлардан биридир. Алоэ жигар фаолиятига ва ўт қопи ишига ижобий таъсир қилади. Гиёҳларнинг дамламаларини ичиш антибактериал, ўт хайдовчи, яллиғланишга қарши ва спазмолитик таъсир қилиб, жигар тўқималаридаги салбий ўзгаришларнинг олдини олади. Лекин, сўнгги йилларда клиник амалиётда алоэ билан қўзғатилган токсик гепатитнинг бир нечта ҳолатлари қайд этилган. Оғиз орқали алоэ вера ва бошқа ўсимлик маҳсулотларини кенг қўллаш токсик гепатит холатига олиб келиши эхтимолини орттиради. Айниқса сурункали жигар касаллиги бор беморларни ахволини оғирлаштириши мумкин. Мазкур мақола алоэ ўсимлигини жигар фаолиятига таъсирини очиб беради.

Introduction: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. Methods: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. Results: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. Conclusion: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count.

Acute toxic hepatitis was caused by intraperitoneal administration of carbon tetrachloride in vaseline oil to white rats at the rate of 0.4 ml per 100 g of body weight for 3 days once. As a result, the animals had a violation of the cytoplasmic membranes of hepatocytes, which was accompanied by an increase in serum transamination enzymes and alkaline phosphatase, a sharp decrease in glu-cose and total protein. The use of hypoxen stopped this pathological process. After using the drug, the activity of transamination enzymes and alkaline phosphatase in the blood serum of animals de-creased to physiological values, the amount of protein and glucose increased, and the physiological state of white rats improved. Thus, hypoxen can be used in animals as a hepatoprotective agent at a dose of 50.0 mg/kg of body weight.

OBJECTIVES Paediatric acute liver failure (P-ALF) is a rare condition and is associated with a high mortality rate. Management of P-ALF aims to stabilise vital organ functions and to remove circulating toxins and provide vital plasma factors that are lacking. High-volume plasmapheresis (HVP) removes protein-bound substances and improves survival in adult ALF. It is unknown if this effect can be extrapolated to P-ALF. The aim of this study is to report the safety and feasibility of HVP in P-ALF. METHODS Children with P-ALF were offered HVP if bilirubin was higher than 200 μmol/L or if the aetiology was toxic hepatitis. HVP was performed with fresh frozen plasma corresponding to 10% of the body weight on a minimum of 3 consecutive days. Diagnostics, biochemical and clinical data during HVP as well as outcome data after 3 months were collected from 2012 to 2019 and retrospectively analysed. RESULTS Sixteen children were treated by HVP and completed at least one series of three treatment sessions with HVP. The only complication seen was an increase in pH > 7.55 in three children within the first 12 hours and was corrected with hydrochloric acid. No bleeding or septic episodes were noted during HVP. Eight children survived without liver transplantation, two survived after successful grafting and a total of six children died. The liver injury unit score between survivors with their own liver and the rest, the two groups was significantly different (P = 0.005). CONCLUSION HVP with fresh frozen plasma is feasible and well tolerated in children with P-ALF. No serious adverse events and no procedure-related mortality were observed.

Insufficient effectiveness of therapeutic interventions used to treat toxic liver lesions leads to numerous complications. Liver damage is just one manifestation of multiple organ failure. Objective: to evaluate the possibility of using the Polyoxidonium as a protector in the acute period of poisoning with a toxic chemical agent.The studies were performed on 25 rats weighing 200-300 g. Acute toxic poisoning was modeled with hepatotoxic poison polyhexamethylene guanidine hydrochloride (PHMG). Polyoxidonium was injected once in a dose of 0,1 mg/kg intramuscularly through 2 days after the injection of PHMG. The animals were euthanized by diethyl ether overdose after 1 or 3 days to study the liver and peripheral blood. Through 1 day after the injection of PHMG acute polyorganic failure with predominant damage of the liver is developed in rats. An increase in AST levels with a decrease in alkaline phosphatase indicates hepatic cell failure. Granular dystrophy of hepatocytes is observed under the organ capsule. The number of liver cells increases per unit area (1 mm2). The cell size decreases due to cytoplasm. This phenomenon may be associated with the release of various substances from the cells due to damage to their membranes. Pancreatic dysfunction manifests itself in an increase in blood levels of glucose and amylase. An increase in the de Ritis coefficient indicates damage to the heart muscle. An increase in urea without a significant change in creatinine indicates kidney damage. An increase in the number of granulocytes in peripheral blood and ESR indicates the development of the inflammatory process in damaged tissues. Polyoxidonium has a protective effect on most organs examined. This is manifested in a decrease of degenerative changes in the liver and heart, a weakening of the inflammatory reaction and functional disorders of the pancreas. Polyoxidonium can be considered as a drug for detoxification therapy.

Hepatobiliary system and biliary tract diseases are common both in the world and in Ukraine (280,000 patients). According to the ATC classification, hepatotropic drugs are divided into three subgroups: А05А, А05В и А05С. The aim of this study was to analyze the assortment of drugs for the pharmacotherapy of diseases of the liver and biliary tract and the volumes of their outpatient consumption during 2016‒2018 years in DDDs/1 000 inhabitants/day. Drugs used for toxic hepatitis and presented in the pharmaceutical market of Ukraine were analyzed. The volumes of their outpatient consumption according to the ATC/DDD methodology based on the «Pharmstandard» system of the «Morion» company were determined, which also made it possible to analyze the assortment of drugs, to determine their dosage forms and manufacturing countries, and to analyze packaging prices. ATC codes identified eight subgroups of drugs, and 158‒167 TNs represent them during 2016‒2018 years. The largest number of TNs were presented A05AA02 Ursodeoxycholic acid (27‒30 TNs, including 19‒21 of foreign origin), А05ВА03 Silymarin (21‒23 TNs, including 9‒11 of foreign origin) and А05ВА50 Different preparations (Essentiale and etc. 35, 37, 34 TNs, including 22, 23 и 20 of foreign origin). Among all drugs of hepatotropic action in Ukraine in the 2018 year, foreign drugs amounted 74 TNs (44,3%) and domestic – 93 TNs (55,7%). The drugs of this group are delivered to Ukraine from 17 countries, the largest part is delivered by Germany (32% of drugs), India (12%), Austria (9%), Italy (7%). According to dosage forms, this group of drugs in 2018 was represented by 17 forms, mainly for the oral route (12 forms), 4 forms – for intravenous injection, and one – rectal suppository. The most consumed were: Different preparations including combined 3.9 DID, Silymarin – 1.48‒1.95 DID, Different preparations (Essentiale ® N, Essentiale ® Forte N, Hofitol) – 1.84‒2.08 DID. The market of drugs used for diseases of the liver and biliary tract in Ukraine in the 2018 year was represented by eight subgroups of 167 TNs, 44.3% of which are foreign-made. Total preparations were presented in forms for the oral route (12 forms), 4 forms – for intravenous injection, and one – rectal suppository. Every year, the consumption of hepatotropic drugs increased slightly: from 8.12 DID to 9.23 DID.

In recent years, there has been a pronounced tendency to increase in the incidence of drug-induced liver damage due to the growing expansion of the pharmaceutical market, which is also observed in the case of incorrect administration of nonsteroidal anti-inflammatory drugs (NSAIDs). In this case, the violation of the functional state of the body has a negative effect on synthetic processes, which in combination with the protein system of tissues significantly affects the metabolic homeostasis of the body. Therefore, the aim of the study was to determine marker changes in the plasma protein spectrum in laboratory rats with diclofenac-induced hepatitis and the effectiveness of reparative therapy based on milk phospholipids. The drug form of toxic hepatitis in laboratory animals was induced according to the author’s model by oral administration of diclofenac sodium (NSAID group) at a dose of 12.5 mg/kg, once a day for 14 days. Thus, in rats with toxic hepatitis there was a probable decrease in plasma total protein content by 15.6% compared with control, indicating a violation of protein-synthesizing function of the liver. With the introduction into the body of clinically healthy and sick animals of the liposomal form of the bioadditive "FLP-MD" based on milk phospholipids, the level of total protein in blood plasma corresponded to control values. As a result of the study of the plasma protein spectrum of Wistar rats, the four most sensitive indicators, which undergo significant probable changes in absolute and relative units of measurement with the development of toxic diclofenac-induced hepatitis, are protein fractions with molecular weights of 180–190, 150–170, 60 and 54–58 kDa and four markers of the effectiveness of restoring the protein-synthesizing function of the liver with the use of corrective therapy, in particular, bioadditives "FLP-MD" – 900, 180–190, 68–70 kDa and the value of A/G ratio, which is important for implementation in applied veterinary medicine, especially in the diagnosis of NSAID hepatopathy, supplementing the picture of its pathogenesis at the molecular level and testing the effectiveness of newly created drugs of hepatoprotective profile.

The objective of the study:to study certain parameters of the autonomic nervous system (ANS) and cognitive functions in patients with acute alcohol intoxication of different severity degrees.Subjects and methods.312 patients with acute alcohol intoxication and chronic alcohol abuse were enrolled in the study. Manifestations, medical history, the duration of drinking bout, ethanol blood level were assessed. Blood panel included ALT, AST, LDH, and blood levels of free ammonia, lactate, and medium molecules. The subjects were divided into three groups: Group I - 78 patients with severe alcohol intoxication, Group II – 166 patients with moderate alcohol intoxication, and Group III – 68 patients with mild alcohol intoxication. The state of ANS was assessed according to the following indicators: heart rate, systolic and diastolic blood pressure, Kerdo vegetative index, and results of cardiointervalography by R.M. Baevsky (1986). The severity of intellectual impairment was assessed using the ММSE scale for 10 positions, the FAB scale for 6 positions, as well as the Reitan test in seconds on the 1st day.Results.In patients of Group I, the alcohol level was 1.5 and 1.35 times lower versus patients in Groups II and III. All patients with severe intoxication had symptoms of toxic hepatitis, which was manifested by a significant increase in ALT, AST, LDH and bilirubin, exceeding the normal limits by 5.4, 5.4, 1.8, and 1.7 times, respectively. Ammonia blood levels in patients with severe intoxication exceeded the norm by 5.6 times, in patients with moderate severity of intoxication – by 3 times, and even in patients with a mild degree – by 1.5 times. The lactic acid level in patients of Group I was 3.2 times above the norm, in patients of Groups II and III – 2.0 and 1.4 times, respectively. In patients with severe intoxication, there was an increase in blood levels of medium molecules over 0.6 units of optical density which reflected severe endogenous intoxication. Assessment of ANS parameters in patients of three groups revealed development of hypersympathicotonia due to the increased tone of the sympathetic department of ANS in proportion to intoxication severity. Cognitive functions at admission were inhibited in proportion to the severity of the patient's condition. Intelligence level as per MMSE scale: at admission, patients of Groups III and II demonstrated mild and moderate cognitive impairment (25.8 ± 2.1 and 23.31 ± 1.80 points); in Group I, indicators for all items were 1.5 times lower versus Groups II and III. Intelligence as per the FAB scale: in patients with severe intoxication, deviations in conceptualization and dynamic praxis were noted. The Reitan test results were best in patients from Group III. Subsequently, 63 (80.7%) patients with severe alcohol intoxication developed alcoholic delirium.Conclusion.Patients with alcohol intoxication demonstrated a decrease in cognitive functions and impaired intelligence proportional to the severity of intoxication and levels of lactate and free ammonia. Increased tone of the sympathetic division of the ANS is typical of acute alcohol intoxication during drinking bout. Cardiointervalography parameters can be used to assess the severity of alcohol intoxication.

The aim of the study was to study the changes in the transcriptional activity of the GSTM, GSTP and GSTT genes in acute toxic hepatitis caused by paracetamol and against the background of preliminary administration of drugs (heptor, mexidol, oxymethyluracil). Material and methods : Toxic hepatitis was modulated in male albino mongrel rats assigned to fi ve groups (control group, primed with paracetamol without subsequent administration of the drug, with the administration of heptor, mexidol and oxymethyluracil). After 24 and 72 hours of paracetamol administration, the rats were anesthetized and the mRNA levels of the GSTM, GSTP and GSTT genes in the liver homogenate were examined. Drugs were administered one hour before paracetamol administration. Results : It has been shown that with 24-hour exposure to paracetamol, the expression ratio of the GSTM gene increased from –0.37 in the control group to 1.03 in the untreated group. After 72 hours of exposure to the toxicant, it was elevated compared with the control group in all groups (paracetamol without treatment — 0.77; heptor — 1.74; mexidol — 1.51; OMU — 1.62). An analysis of the representation of GSTT gene transcripts after 72 hours of exposure showed a stepwise increase and decrease in the expression level in the groups studied. The expression of the GSTP gene with the 24-hour experiment was reduced and ranged from –0.3 to –1.51. (F = 2.916; p = 0.038), and with 72 hours of exposure to paracetamol, the results were opposite. Statistically signifi cant values (p = 0.032) were obtained by comparing the group with paracetamol without treatment and when used as the OMU drug. Conclusion : the results obtained may indicate the involvement of the given genes in paracetamol metabolism in liver cells. It was found that OMU is a hepatoprotector responsible for restoring the antioxidant defense system.

Relevance. Ozone increases the oxygen transport function of the blood. The use of ozone therapy for pulmonary pathology is promising. The effect of ozone therapy is associated with the ability of ozone to eliminate hypoxemia and tissue hypoxia, which is always present in patients with pathology of the bronchopulmonary apparatus. Objective: to study morphofunctional changes in liver tissue, in the dynamics of the use of ozonized water in rats in an experimental model of chronic purulent pneumonia.Materials and methods. Three groups were formed from 30 male white rats (180-200 g). In group 1 (n = 10) healthy rats were injected intraperitoneally with 5 ml of ozonated (0.02 mg / L) 0.9% NaCl once a day for 10 minutes. Course 10 days. Animals of the 2 (n = 10) and 3 (n = 10) groups were first modeled for chronic pneumonia. For this, under local novocaine anesthesia, a 1.5-2.0 cm long incision was made on the animal's neck. A nylon thread with a diameter of 0.4 mm and a length of 10-12 cm was inserted into the lumen of the trachea, between its rings, on a thin piercing needle. The distal end of the thread was located in the lumen of the trachea, and its proximal end was fixed on the skin. The wound was sutured tightly in layers. After 45 days, the thread was removed without opening the trachea. Subsequently, animals of group 2 did not receive treatment. And rats of group 3 were injected once a day with 5 ml of ozonized (0.02 mg / l) 0.9% NaCl for 10 minutes. Course 10 days. The animals were removed from the experiment by instant decapitation. The taken pieces of the liver were fixed in formalin. Histological sections were stained with hematoxylin and eosin. Microscopy was performed using an XS-213 light microscope and a Leica microscope. Results. With prolonged irritation of the respiratory tract, structural changes in the liver, characteristic of toxic hepatitis, were revealed. After treatment with ozonated saline, the morphological picture of the liver improved. In healthy rats, ozone therapy did not have a negative effect on the general condition and behavior of the animals. Conclusions. Treatment with ozonated saline improves the morphological picture of the liver of rats with chronic pneumonia.

We report our first case of deceased-donor liver transplantation (LT) using a reuse liver graft after the first LT. The recipient was a 38-year-old female with fulminant hepatic failure from toxic hepatitis. She had a history of herb intake and her liver function deteriorated progressively. She was enrolled as the Korean Network for Organ Sharing (KONOS) status 1 and the model for end-stage liver disease score was 34. The donor was a 42-year-old male patient who fell into brain death after LT for alcoholic liver cirrhosis. Donation of multiple organs including the transplanted liver graft was performed 10 days after the first LT operation. Since the liver graft appeared to be normal and frozen-section liver biopsy showed only mild fatty changes, we decided to reuse the liver graft. A modified piggy-back technique of the suprahepatic inferior vena cava reconstruction was used. Other surgical procedures were comparable to the standard deceased-donor LT procedures. The explant liver pathology revealed submassive hepatic necrosis, which was compatible with toxic hepatitis. The peak of serum liver enzyme levels were aspartate transaminase 1,063 IU/L and alanine transaminase 512 IU/L at posttransplant day 3. Since the pretransplant general condition of the recipient was very poor, hospital stay was prolonged and she was discharged 51 days after LT operation. She is currently doing well for 3 years to date. Experience in our case and the literature review suggest that a reuse liver graft can be regarded as one of the marginal grafts which can be transplantable to the LT candidates requiring urgent LT.

Background/Aims Tumor necrosis factor inhibitors (TNFi) have been known to induce liver enzyme elevation, sometimes associated with viral reactivation or toxic hepatitis. We evaluated the incidence and risk factors of TNFi-associated liver enzyme elevation in Korean ankylosing spondylitis (AS) patients who previously had normal liver enzymes. Methods Retrospectively, we collected data from the records of 363 AS patients treated with TNFi at a tertiary hospital from 2003 to 2017. Liver enzyme elevation was defined as abnormal elevation of aspartate aminotransferase and/or alanine aminotransferase levels on two or more consecutive visits. Patients with previously diagnosed liver disease were excluded. Results The incidence of liver enzyme elevation was 23.7% (occurring in 86 of 363 patients). The median duration of TNFi exposure before liver enzyme elevation was 3.72 months (interquartile range, 1.77 to 12.51). There was no difference in the occurrence of liver enzyme elevation with concomitant disease-modifying anti-rheumatic drugs and TNFi compared to TNFi alone (23.9% vs. 23.6%). In multivariate analysis, the hazard ratios for liver enzyme elevation were 4.62 (95% confidence interval [CI], 1.43 to 15.01) for male sex, 4.06 (95% CI, 2.11 to 7.84) for underlying non-alcoholic fatty liver disease, and 2.53 (95% CI, 1.38 to 4.64) for hyperlipidemia. After switching to another TNFi, the liver enzyme elevation was not normalized in nine of 13 patients. Conclusions Liver enzyme elevation was observed in a quarter of patients with AS receiving a TNFi. Male sex, non-alcoholic fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNFi had a limited effect on restoring normal liver enzyme levels.

Introduction. Liver diseases and pathology of the organs of mouth cavity are interconnected. Smoking, usually increases the manifestations of the underlying disease and affects the course. The aim. To investigate the effect of chronic toxic hepatitis of nicotine-dependent patients and of patients without a bad habit on their periodontal status. Materials and methods. During the clinical examination of the oral cavity of 86 patients, the depth and incidence of inflammation of the gum were determined using the number of the Svrakov's number (SN); the conditions of hygiene of the oral cavity were estimated using the Silness-Loe (S-l) index; Periodontal Index (PMA) and Bleeding Index (PBI). General histomorphology was studied on drugs stained with hematoxilin-eosin and by the method of Gerlich and van Gieson. Results. It is established that the indicator of SN had the highest value among patients of group II (2,15±0,13), it was probably (p < 0.05) higher relatively to the group I and comparison group. In the smoking patients with chronic toxic hepatitis, in spinous layer of epithelium was determinanted karyorhexis, karyolysis with the formation of cell debris; basal layer cell proliferation, acanthosis, angiogenesis. We detected damage to collagen and elastic fibers of the periodontal, wich correlated with the intensity and duration of the bad habit. In areas of pronounced alterative changes colonies of bacteria were discovered. Conclusions. Thus, the results obtained in nicotine-dependent patients with chronic toxic hepatitis visualize damaging effect on the epithelium and weakening of the histohematic barrier of the oral cavity and promotes the reproduction and penetrationof pathogenic microflora into the underlying tissues.

OBJECTIVE The aim: To determine the pathogenetic expediency, efficiency and the place of therapeutic plasmapheresis in a complex treatment of patients with chronic hepatitis. PATIENTS AND METHODS Materials and methods: It was carried out the analysis of case histories of 77 patients. In the course of treatment, the patients were diagnosed with chronic toxic hepatitis (K.71). Diagnosis was exposed in accordance with the official documentation introduced by the Gastroenterological department of Sumy Regional Clinical Hospital CH"SRCH", Sumy Regional Infectious Diseases Clinical Hospital named after Krasovytsky ZY and Sumy Regional Center of Blood Service. RESULTS Results: It was found that total protein indicator is the normal range and albumin after plasmapheresis and during conservative treatment. Markers of cytolysis and cholestasis are have great value may. The most significant changes were observed in rates indicating lesion of the hepatic parenchyma, including ALT, AsAT and alkaline phosphatase. In conservative treatment, the percentageof the alkaline phosphatase level improved by 31%, after the course of plasmapheresis - by 58%. The obtained figures of cholestasis indexes indicate the effectiveness of both methods of treatment, but treatment with plasmapheresis has a more expressed effect on the decrease of alkaline phosphatase level. The level of bilirubin improve on 38,8% after plasmapheresis and 65% in the comparison group. CONCLUSION Conclusion: Inclusion in the complex therapy of chronic hepatitis plasmapheresis reduces the severity of cytolysis and cholestasis, increases remission and significantly improves clinical manifestations.

Objective The aim: To study the effect of drug addiction and smoking on the status of periodontal tissues in patients with hepatobiliary pathology. Patients and methods Materials and methods: 58 smokers, 63 drug addicts with hepatobiliary pathology were examined and 92 persons of comparison group (with inflammatory periodontal diseases affected by hepatobiliary pathology, without addiction). Examination of patients included determination of iodine number by Svrakov, S-L and Stallard hygiene indices, PMA index and index PBI. Results Results: The results of examination of smokers are worse in patients with cirrhosis than in patients with chronic toxic hepatitis and non-alcoholic steatohepatitis and also the results of these two groups was significantly worse than that of the comparison group (iodine number by Svrakov - 1,4 times and 1,3 times higher, PMA index - 1,7 times and 1,4 times worse, in accordance). The results of the study showed that drug addicts patients are worse values in patients with cirrhosis than in patients with chronic toxic hepatitis and non-alcoholic steatohepatitis and also the results of these two groups was significantly worse than that of the comparison group (iodine number by Svrakov - 1,5 times and 1,4 times higher, PMA index - 1,7 times and 1,5 times worse, in accordance). Conclusion Conclusions: Presence of hepatobiliary pathology in smokers and drug addicts increases the risk of periodontal diseases.

The effectiveness and quality of liver biopsy in rats are applicable to the aspiration and automatic liver biopsy system. Histological examination of 240 biopsy specimens in 100% of cases identified portal tracts. The number of portal tracts to determine the stage of liver fibrosis in rats of the 1st group who underwent liver biopsy was performed using an 18 G aspirating needle from the puncture liver set (Menghini type), which is 4-5, you have the 2nd group, which one-time guillotine soft tissue biopsy with a semi-automatic action of 16G×20 cm, Italy) - 7-8 portal tracts. The average size of the biopsy in the 1st group is 0,5 cm, in the 2nd group - 1 cm. Thus, the automatic biopsy system allows you to get liver tissue in 100% of cases. At the same time, the automatic system eliminates the additional traumatization of experimental animals, as well as minimizes efforts to separate the biopsy material from the organ. In addition, the automated system for liver biopsy allows to evaluate 7-8 portal tracts with a biopsy size of 1 cm, this provides a reliable histological assessment of pathological changes in liver tissue to assess the stage of fibrosis and the activity of the inflammatory process over time.

Acute copper toxicity is uncommon in Western countries and is often the result of accidental consumption or a suicide attempt. We report the case of a 65-year-old man presenting to the accident and emergency department after a suicide attempt with ingestion of Bordeaux mixture, ibuprofen, acetaminophen and bleach. Primary evaluation showed caustic oesophagitis, toxic hepatitis and acute renal injury, which were treated with supportive care. During admission, he developed a non-immune haemolytic anaemia associated with high levels of copper in urine and blood. Chelation treatment with penicillamine was started and evolution was favourable after 1 month of treatment. Copper poisoning can be lethal. Prompt diagnosis and treatment are key for a favourable prognosis. LEARNING POINTS Acute copper intoxication is rare and early clinical suspicion and diagnosis are essential to reduce mortality. The diagnosis of copper poisoning should be based on clinical presentation and measurement of urine and blood copper levels in addition to serum ceruloplasmin levels. Treatment includes reduction of absorption, supportive measures, management of complications and chelation therapy. Keywords: Copper poisoning, non-immune haemolytic anaemia, toxicology CASE DESCRIPTION A 65-year-old man presented to the emergency room after voluntary acute intoxication with Bordeaux mixture, 4 g ibuprofen, 8 g acetaminophen and 125 ml bleach. In the last 3 months, the patient had developed dyspnoea, fatigue and weight loss (13% of usual body weight over 3 months). He was under medical investigation for suspected lung cancer. At presentation he had nausea, blue-green vomiting and abdominal pain. He was haemodynamically stable and the physical examination was normal. Arterial blood gas analysis showed a mixed acid-base disorder (pH 7.21, paCO2 52 mmHg, paO2 68 mmHg, HCO3- 21 mEq/l, anion gap 20.3, lactate 4.06 mmol/l) with normal methemoglobinemia. Blood tests showed iron deficiency anaemia (Hb 11 g/dl, MCV 71 fl, ferritin 12 ng/ml, transferrin saturation 7%) associated with acute renal injury (creatinine 1.58 mg/dl, urea 39.2 mg/dl). Acetaminophen levels were below the toxic level in sequential measurements (highest value of 11.93 μg/ml). The first approach included gastric lavage and fluid therapy. Endoscopy confirmed caustic oesophagitis. The patient was kept fasting and pantoprazole perfusion was started. After 48 hours, liver injury was detected with elevation of aminotransferases (AST 2340 U/l, ALT 780 U/l; ratio AST/ALT of 3). The abdominal ultrasound was normal. Jaundice was detected associated with a reduction in haemoglobin levels, without gastrointestinal bleeding. High levels of lactate dehydrogenase, low haptoglobin and increased unconjugated bilirubin (maximum value of 4.5 mg/dl) confirmed haemolysis. The direct Coombs test was negative. Total serum copper (874 μg/dl) and 24-hour urine copper test (356 μg/24 h) were high. In this setting, chelation treatment with penicillamine 300 mg four times daily was started. Progressive clinical and analytical improvement was established and after 1 month, no haemolysis was present and haemoglobin levels were normal. The diagnosis of small cell lung carcinoma was confirmed during the admission. The patient attended the outpatient clinic for psychiatric and oncological follow-up, with good engagement.​engagement. Table 1 Summary of laboratory findings

Background:Acute rheumatic fever in childhood continues to cause serious morbidity despite all developments. The objective of this study was to evaluate the clinical and laboratory characteristics of patients with acute rheumatic fever and to determine the frequency of subclinical carditis and the side effects of the drugs used in the treatment.Methods:The data of patients hospitalised between 2008 and 2018 with the diagnosis of acute rheumatic fever were included in the study. The relationship of gender and age with the frequency of major symptoms and the distribution of the drugs used in the treatment and their side effects were evaluated.Results:Medical records of 102 patients with complete data were reviewed. 56.9% of the patients were male and the mean age was 10.7 ± 1.9 years. The most common distribution of complaints found were arthritis (51%), arthralgia (25.5%) and fever (16.7%). 10.8% of all patients (n = 11) were diagnosed subclinical carditis via echocardiographic evaluation. The frequency of carditis was higher in female patients with a borderline statistical significance (p = 0.05). However, there was no statistically significant difference between gender and arthritis (p = 0.22) and carditis (p > 0.05). Anti-congestive therapy was required in 22% and inotropic treatment was needed in 6.1% cases. Toxic hepatitis developed in four cases during the acetylsalicylic acid treatment.Conclusions:In a 10-year period, detection of subclinical carditis in 10.8% cases supported that echocardiography should be performed as a standard method for the diagnosis of acute rheumatic fever. Patients should be followed closely in terms of hepatic toxicity due to acetylsalicylic acid used in the treatment.

Drug-induced liver injury is hardly diagnosed, considering not only the wide range of hepatotoxic substances but also the diversity of associated phenotypes and the absence of specific biomarkers. Symptom chronology, drug or toxic exposure, and temporal association help to establish the diagnosis. Exposure to isopropanol has known but rare toxic effects. We report the clinical case of a 33-year-old female hairdresser admitted to the hospital with fatigue, epigastric pain, and jaundice. She presented the following values: aspartate aminotransferase, 485 U/L; alanine transaminase, 908 U/L; ALP, 240 U/L; GGT, 370 U/L; total bilirubin, 3.5 mg/dL; and direct bilirubin, 2.1 mg/dL. Albumin, platelet, and INR values were normal. Structural, infectious, immune, and vascular causes were excluded. Liver biopsy was suggestive of toxic hepatitis. A possible association with ibuprofen intake was considered. The patient resumed professional activity, with fatigue and jaundice relapse, as well as a new liver enzyme increase, despite ibuprofen withdrawal. It was concluded that a new hair product containing isopropanol had recently been introduced. As soon as its professional use was discontinued, there was no recurrence of the symptoms. Given the temporal association between the development of acute hepatitis and the use of an isopropanol-containing product, liver toxicity by exposure to isopropanol was assumed. This substance is metabolized in the liver and toxicity may occur by ingestion, skin exposure, or inhalation, and it is described in cases of occupational or accidental exposure. The treatment is symptomatic and comprises toxic suspension.

43 yaşında kadın hasta acil servise karın ağrısı, sarılık ve idrar renginde koyulaşma şikâyeti ile başvurdu. Hastanın adet düzensizliği nedeniyle bir ay didrogesteron preperatı aldığı öğrenildi. Labaratuar değerlerinde karaciğer enzimlerinde yükseklik saptanan ve diğer etyolojik faktörler dışlanan hastada ilaca bağlı toksik hepatit düşünüldü. Hastaya karaciğer biyopsisi yapıldı, biyopsi sonucu toksik hepatit ile uyumlu gelen hastanın ilacı kesildi ve hastaya destek tedavisi başlandı. Takipte enzimleri ve kliniği düzelen hasta önerilerle taburcu edildi. Didrogesteron her ne kadar güvenli bir ilaç olarak bilinse de ilaç kullanımında sarılık gelişen hastalarda ilacın indüklediği toksik hepatit akla gelmelidir., 43 years old female patient admitted to our clinic with icter, abdominal pain and darkness in urine. It was learned that she used a didrogesterone preparation for one month due to menstrual irregularity. Drug-induced toxic hepatitis was considered in the patient whose liver enzymes were increased and other etiological factors were excluded. Liver biopsy was performed and the biopsy was compatible with toxic hepatitis. The drug was discontinued and supportive treatment was initiated. At follow up liver enzymes regressed and patient discharged. Although didrogesterone is known to be a safe drug, drug-induced toxic hepatitis should be considered in cases of jaundice.

Background Dimethylacetamide (DMAc) exposure has been associated with toxic hepatitis, and no clinical treatment has been reported. Aim To investigate the clinical manifestations of DMAc-induced symptoms and how to rescue the functional loss due to occupational exposure. Design Clinical observations of 60 spandex factory workers with the exposure to DMAc from January, 2017–19. Methods Chinese drugs (reduced glutathione, polyene phosphatidylcholine, glycyrrhizin compound, Hugan tablets and ornithine aspartate) were used to evaluate the therapeutic improvements in DMAc-exposed patients. Results Our data found that 58.3% patients had no distinct clinical symptoms, but 41.7% patients felt fatigue, and 21.7% patients suffered abdominal discomfort and appetite loss, and 8.3% patients had yellow skin and sclera. The ultrasonic and CT imaging revealed that some patients have fatty livers, intrahepatic calcifications, hepatomegaly, gallbladder wall edema and abdominal effusions. Biochemical analysis showed that the alanine aminotransferase (ALT) (P 0.05) and glutamyl transpeptidase (P> 0.05) did not decrease. Twenty-nine out of the thirty-one patients’ abnormal blood ammonia recovered. The risk factor of ALT on hospitalization time was significantly related (P Conclusions The drugs above are sufficient to rescue functional loss in DMAc-induced toxic hepatitis, in part via the regulations of ALT, AST, LDH, bilirubin and ammonia. Workers with the exposure to DMAc should receive specific drugs to maintain the health and prevent functional loss in the long term.

Energy drinks are widely used and very popular. They are touted as "harmless" energy boosters for use in professional, recreational and domestic settings. They are typically high in monosaccharides, and caffeine with other assorted products like ginseng. Careful study of the potential risks of their use is nonexistent while rigorous documentation of their touted energy boosting capacity is also meagre. We present the cautionary case of a 46-year-old Caucasian man with well-controlled type 2 diabetes and nonalcoholic fatty liver disease who developed a toxic triad syndrome of gastritis, hepatitis and pancreatitis within 4 months of commencing daily consumption of 2-3 160z cans of the energy drink Monster Energy. His clinical symptoms and biochemical derangements promptly resolved with stopping the beverage. We discuss the potential risks inherent in unsupervised liberal consumption of energy drinks and the need for both caution and vigilance among clinicians and patients.

Цель работы – определить взаимосвязи между ультразвуковыми и иммунологическими изменениями при прогрессировании стеатоза и фиброза печени у больных с хроническими диффузными заболеваниями печени (ХДЗП) различной этиологии.Материалы и методы. Обследовали 120 больных ХДЗП в возрасте от 19 до 78 лет (средний возраст – 47,91 ± 1,23 года): 77 женщин (64,2 %) и 43 мужчины (35,8 %). Пациентов поделили на группы в зависимости от этиологического фактора развития стеатоза и фиброза печени: І – 24 больных с неалкогольной жировой болезнью печени (НАЖБП); ІІ – 37 обследуемых с неалкогольным стеатогепатитом (НАСГ); ІІІ – 21 человек с хроническим вирусным гепатитом, ассоциированным с вирусом С; ІV группу составили 18 пациентов с алкогольной болезнью печени (АБП); V – 20 пациентов с токсическим гепатитом (ТГ) (медикаментозным). Выполнены сонографические исследования брюшной полости, определение коэффициента затухания ультразвука и сдвиговолновую эластографию (СВЭ) печени/селезенки. Определены содержание показателей клеточного иммунитета, уровень интерлейкина (ИЛ)-6 и ИЛ-10, фактора некроза опухоли альфа (TNF-α), инсулина и индекс HOMA-IR. Проведен корреляционный анализ между ультразвуковыми и иммунологическими показателями у обследованных больных.Результаты. У больных ХДЗП изменение структуры печени в виде неоднородности установлено в 97 (80,8 %) случаях (p < 0,001). Максимальные значения СВЭ печени отмечены у пациентов с АБП (18,10 ± 2,68 кПа), минимальные – с НАЖБП. Жесткость селезенки наибольшая у пациентов с АБП (24,09 ± 3,68 кПа). Уровень TNF-α достоверно выше контрольных значений при НАСГ в 11,6 раза (р < 0,05), ХГС в 13,9 раза (р < 0,05), АБП в 9,4 раза (р < 0,05) и ТГ в 9,5 раза (р < 0,05). Концентрация ИЛ-6 выше в 2,1 раза (р < 0,05) у больных НАСГ и ХГС, в 2,5 раза (р < 0,05) у пациентов с ТГ. Коэффициент TNF-α/ИЛ-10 возрастает в 7,1 раза (р < 0,05) у больных НАЖБП, в 19,3 раза (р < 0,05) у больных НАСГ, в 14,4 раза (р < 0,05) у пациентов с ХГС, в 14,0 раза (р < 0,05) у больных АБП и в 8,4 раза (р < 0,05) у больных ТГ.В ходе корреляционного анализа установлено, что у больных НАЖХП уровень TNF-α имел положительную связь с жесткостью селезенки (r = +0,601, р < 0,01). У больных ХГС уровень ИЛ-6 ассоциирован с жесткостью селезенки (r = +0,680, р < 0,05), жесткостью печени (r = +0,618, р < 0,05) и степенью фиброза (по METAVIR) (r = +0,573, р < 0,01). У больных АХП увеличение жесткости печени сопровождается достоверным повышением индекса НОМА (r = +0,843). У больных ТГ отмечена отрицательная связь между уровнем Т-хелперов и жесткостью селезенки (r = -0,577, р < 0,05) и печени (r = -0,522, р < 0,05).Выводы. Прогрессирование стеатоза печени сопровождается недостаточностью клеточного звена иммунитета и повышением уровня провоспалительных цитокинов. Увеличение структурных изменений печени и селезенки, а также возрастание степени стеатоза сопровождается активацией провоспалительных цитокинов, истощением противовоспалительного ответа и ростом инсулинорезистентности., Objective. To determine the relationships between ultrasound and immunological changes in the progression of steatosis and liver fibrosis in patients with chronic diffuse liver diseases (CLD) of various etiologies.Materials and methods. We examined 120 patients with CLD. Patients were distributed according to the etiological factor of the development of steatosis and liver fibrosis: Group I – 24 patients with non-alcoholic fatty liver disease (NAFLD), ІІ – 37 patients with non-alcoholic steatohepatitis (NASH); Group III – 21 people with chronic viral hepatitis associated with the C virus (HCV). Group IV consisted of 18 patients with alcoholic liver disease (ALD), group V – 20 patients with toxic hepatitis (TG). Sonographic abdominal examination, ultrasound attenuation coefficient (UAC) and shear wave elastography (SWE) of the liver / spleen were performed. The content of cellular immunity parameters, the level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), insulin and HOMA-IR were determined. A correlation analysis was made between ultrasound and immunological parameters in the examined patients.Results. In patients with CLD, changes in liver structure in the form of heterogenety were detected in 97 (80.8 %) (P < 0.001). The maximum values of SWE of the liver were observed in patients with ALD (18.10 ± 2.68) kPa, minimal – with NAFLD. The stiffness of the spleen was highest in patients with ALD 24.09 ± 3.68 kPa. TNF-α was significantly higher than the control values with NASH by 11.6 times (P < 0.05), HCV by 13.9 times (P < 0.05), ALD by 9.4 times (P < 0.05) and TG by 9.5 times (P < 0.05). The concentration of IL-6 was 2.1 times higher (P < 0.05) in patients with NASH and CHC, 2.5 times higher (P < 0.05) in patients with TG. The TNF-α / IL-10 ratio was increased by 7.1 times (P < 0.05) in patients with NAFLD, by 19.3 times (P < 0.05) in patients with NASH, by 14.4 times (P < 0.05) in patients with chronic hepatitis C, by 14.0 times (P < 0.05) in patients with ALD and by 8.4 times (P < 0.05) in patients with TG.When conducting a correlation analysis, it was revealed that in patients with NAFLD, the level of TNF-α had a positive relationship with the spleen stiffness (r = +0.601, P < 0.01). In patients with HCV, the level of IL-6 was associated with spleen stiffness (r = +0.680, P < 0.05), liver stiffness (r = +0.618, P < 0.05) and the degree of fibrosis (according to METAVIR) (r = +0.573, P < 0.01). In patients with ALD, an increase in liver stiffness is accompanied by a significant increase in the NOMA index (r= +0.843). In patients with TG, a negative relationship was found between the level of T-helper cells and stiffness of spleen (r = - 0.577, P < 0.05) and liver (r = -0.522, P < 0.05).Conclusion. The progression of liver steatosis is accompanied by a lack of cellular immunity and an increase in the level of pro-inflammatory cytokines. An increase in structural changes of the liver and spleen, as well as the increase in the degree of steatosis, is accompanied by activation of pro-inflammatory cytokines, depletion of the anti-inflammatory response and increased insulin resistance., Мета роботи – визначити взаємозв’язки між ультразвуковими та імунологічними змінами при прогресуванні стеатозу та фіброзу печінки у хворих на хронічні дифузні захворювання печінки (ХДЗП) різної етіології.Матеріали та методи. Обстежили 120 хворих на ХДЗП віком від 19 до 78 років (середній вік – 47,91 ± 1,23 року): 77 жінок (64,2 %) та 43 чоловіки (35,8 %). Хворих поділили на групи залежно від етіологічного фактора розвитку стеатозу та фіброзу печінки. У І групу ввійшли 24 особи, які хворі на неалкогольну жирову хворобу печінки (НАЖХП) зі стеатозом; ІІ – 37 хворих на неалкогольний стеатогепатит (НАСГ); ІІІ – 21 пацієнт із хронічним вірусним гепатитом, що асоційований з вірусом С (ХГС); ІV – 18 осіб з алкогольною хворобою печінки (АХП), V група – 20 пацієнтів із токсичним гепатитом (ТГ) (медикаментозним). Контрольну групу становили 30 практично здорових осіб.Здійснили сонографічні дослідження органів черевної порожнини, визначення коефіцієнта затухання (КЗ) амплітуди ультразвуку (стеатометрію) та зсувнохвильову еластометрію (ЗХЕ) печінки, селезінки. Визначили вміст основних показників клітинного імунітету й рівень інтерлейкіну (ІЛ) 6, ІЛ-10, фактора некрозу пухлини альфа (TNF-α), інсуліну та індексу HOMA-IR. Виконали кореляційний аналіз між ультразвуковими та імунологічними показниками в обстежених хворих.Результати. У хворих на ХДЗП зміни структури печінки у вигляді неоднорідності виявили в 97 (80,8 %) випадках (p < 0,001). Максимальні показники ЗХЕ печінки спостерігали в пацієнтів з АХП (18,10 ± 2,68 кПа), найнижчі – у хворих на НАЖХП. Жорсткість паренхіми селезінки найбільша в пацієнтів з АХП (24,09 ± 3,68 кПа).Рівень TNF-α вірогідно перевищує контрольні значення при НАСГ в 11,6 раза (р < 0,05), ХГС у 13,9 раза (р < 0,05), АХП у 9,4 раза (р < 0,05) і ТГ у 9,5 раза (р < 0,05). Концентрація ІЛ-6 вірогідно вища у 2,1 раза (р < 0,05) у хворих на НАСГ і ХГС, у 2,5 раза (р < 0,05) у хворих на ТГ. Коефіцієнт TNF-α/ІЛ-10 зростає в 7,1 раза (р < 0,05) у хворих на НАЖХП, у 19,3 раза (р < 0,05) у пацієнтів із НАСГ, в 14,4 раза (р < 0,05) у хворих на ХГС, у 14,0 раза (р < 0,05) у пацієнтів з АХП і в 8,4 раза (р < 0,05) у хворих ТГ.Під час кореляційного аналізу виявили, що у хворих на НАЖХП рівень TNF-α мав позитивний зв’язок із жорсткістю селезінки (r = +0,601, р < 0,01). У пацієнтів із ХГС рівень ІЛ-6 асоційований із жорсткістю селезінки (r = +0,680, р < 0,05), жорсткістю печінки (r = +0,618, р < 0,05) та ступенем фіброзу (за METAVIR) (r = +0,573, р < 0,01). У хворих на АХП збільшення жорсткості печінки супроводжується вірогідним підвищенням індексу НОМА (r = +0,843). У пацієнтів із ТГ виявили негативний вірогідний зв’язок між рівнем Т-хелперів і жорсткістю селезінки (r = -0,577, р < 0,05) та печінки (r = -0,522, р < 0,05).Висновки. Прогресування стеатозу печінки супроводжується недостатністю клітинної ланки імунітету й підвищенням рівня прозапальних цитокінів. Збільшення структурних змін печінки та селезінки, а також збільшення ступеня стеатозу супроводжується активацією прозапальних цитокінів, виснаженням протизапальної відповіді та зростанням інсулінорезистентності.

Purpose.To compare the efficacy of metabolic hepatoprotectors at an early stage of acute alcohol poisoning complicated by toxic hepatitis.Material and methods.80 patients with acute alcohol poisoning complicated by toxic hepatitis who received medical treatment in the toxicology unit of the Republican Research Center of Emergency Medicine during 2015–2017 were examined. The patients were split into 3 groups. At the background of backbone therapy, patients of group I (n=30) received a hepatoprotectors on the basis of inosine, meglumine, methionine, nicotinamide, and succinic acid; patients of group II (n=20) were prescribed to receive drugs based on betaine glucuronate (glucomethamine), diethanol amine (glucodiamine), and nicotinamide ascorbate. Patients of group III (n=30) received the backbone therapy. In all patients, the concentrations of liver enzymes, bilirubin, free ammonia, blood lactate, the condition of vegetative nervous status were analyzed. Psychoastenics was examined using the MMSE score, FAB score and Reitan test.Results.After 48 hours, in group I patients, the concentration of blood lactate became almost normal, in group II patients it decreased to 2.6Ѓ}0.9 mmol/l, and in group III patients it was equal to 2.7Ѓ}0.9 mmol/l. On day 5, in patients of groups I and II the cognitive deficit was almost absent, in patients of group III the MMSE scores were 1.3-fold and 1.4-fold lower than in patients of groups I and II, respectively.Conclusion.The drug used in group I possessed increased antihypoxant properties but smaller hepatoprotective properties than the drug used in group II. When signs of toxic hepatitis are predominant it would be more preferable to use the drug applied in group II and when the signs of tissue hypoxia are predominant the drug applied in group I should be used.

Problem: impact of liver malfunction on the condition of hard and soft tissues of the oral cavity. Aim: to study the condition of the dentoalveolar system in rats at the background of experimental dysbiosis and toxic hepatitis. Methods. The research was carried out in 1-month old male rats. Intact animals served as the control group. Hepatitis modelling (group 2) was performed by intra-abdominal introduction of hydrazine sulphate (50 mg/kg twice a week) for 5 weeks, dysbiosis (group 3) was formed by adding lincomycin (70 mg/kg into potable water), rats from group 4 were given lincomycin at the last week of hepatitis formation to model dysbiosis. Estimation of caries process was performed by the method of A. P. Levytskyi, the activity of elastase and acid phosphatase was determined in the tissues of gums, and the activity of alanine aminotransferase, acid phosphatase and amount of cholesterol – in the serum. Main results. Experimental modelling in rats of both hydrazine hepatitis and dysbiosis resulted in the liver malfunction. Simultaneously, pathological changes in the oral cavity, namely increase of caries process intensity and growth of activity of inflammation markers (elastase and acid phosphatase) in the rats’ gums were observed. The most expressed inflammation of gums was observed when the pathologies were combined. Simultaneous modelling of dysbiosis and hepatitis was accompanied by increase in the activity of “liver” markers of inflammation (alanine aminotransferase and acid phosphatase) and increase of the amount of cholesterol in blood. Conclusions: dysbiosis enhances the liver pathology and increases the degree of inflammation in rats’ gums.

Estimation of the bone marrow haemopoietic status depending on the reasons and duration of breaks in a standard chemotherapy (BFM-ALL protocol) to predict the course of acute lymphoblastic leukemia (ALL) in chil- dren exposed to low doses of ionizing radiation after the Chornobyl accident.The ALL patients (n = 34) were examined within 5 stages of a program chemotherapy. The clinical symptoms, hemogram and myelogram data were analyzed. The radiation dose on bone marrow, initial leuko- cyte count, variants and prognosis of ALL course were accounted. Days of the stopped chemotherapy, type and fre- quency of complications (septic processes, febrile neutropenia, toxic hepatitis, granulocytopenia degree), and the prognosis of disease course (child living status, i.e. alive or died) were estimated.There were abnormal differentiation processes and high percentage of lymphoblasts (86.2 ± 3.3) % in bone marrow in the 1st acute period. Hematological remission was established in all patients on the 33rd day of chemothe- rapy. In a half of cases the haematopoietic recovery occurred by a granulocyte-monocyte type. One third of patients presenting an erythroid type of haemopoiesis died later. The inverse correlation was found between the number of myelocaryocytes and disease prognosis (rs = -0.49). Breaks in chemotherapy for various reasons were recorded. The number of patients with granulocytopenia was greater at the phase 1 and 2 of protocol I and protocol M application, coinciding with a higher incidence of complications. An inverse correlations between the prediction of ALL course and sum of days of breaks between the protocol M and phase 1 of protocol II (rs = -0.56), as well as the duration of the phase 2 of protocol II (rs = -0.62) were found. The radiation dose on bone marrow was (5.37 ± 1.23) mSv. No relationship was found between the radiation doses, ALL variants and disease course.Prognosis of ALL course in children depends on the type of haemopoietic recovery and reasons of breaks in a standard chemotherapy. Interaction between the haemopoiesis functioning and microenvironment and that of their regulation are the key mechanisms of above-mentioned abnormalities, which is the basis for further research.Meta: otsinyty stan kistkovomozkovogo krovotvorennia zalezhno vid prychyn i tryvalosti pererv pry provedenni standartnoï khimioterapiï za protokolom BFM-ALL dlia prognozu perebigu gostrykh limfoblastnykh ley̆kemiy̆ (GLL) u ditey̆, iaki zaznaly vplyvu malykh doz ionizuiuchogo vyprominiuvannia vnaslidok avariï na ChAES.Materialy i metody. Obstezheno 34 khvorykh na GLL na 5 etapakh programnoï khimioterapiï. Vyvchaly klinichnu symp- tomatyku, pokaznyky gemogram i miielogram. Vrakhovuvaly dozy oprominennia na kistkovyy̆ mozok, initsial'ne chys- lo ley̆kotsytiv, varianty ta prognoz perebigu GLL. Otsiniuvaly kil'kist' dniv zupynok pry provedenni khimioterapiï, vyd i chastotu uskladnen' (septychni protsesy, febryl'nu ney̆tropeniiu, toksychnyy̆ gepatyt, stupin' granulotsyto- peniï) ta prognoz perebigu zakhvoriuvannia (zhyva zhytyna chy pomerla).Rezul'taty. V I gostryy̆ period u khvorykh v kistkovomu mozku maly mistse zminy protsesiv dyferentsiiuvannia i vy- sokyy̆ vidsotok limfoblastiv (86,2 ± 3,3) %. Na 33-y̆ den' khimioterapiï u vsikh khvorykh bulo konstatovano gemato- logichnu remisiiu. U polovyny khvorykh krovotvorennia vidnovliuvalos' za granulotsytarno-monotsytarnym typom. Tretyna khvorykh, u iakykh sposterigavsia erytroïdnyy̆ typ gemopoezu, v podal'shomu pomerly. Vstanovleno zvorot- nyy̆ koreliatsiy̆nyy̆ zv'iazok mizh kil'kistiu miielokariotsytiv i prognozom perebigu zakhvoriuvannia (rs = -0,49). Pry provedenni khimioterapiï u ditey̆ buly perervy v likuvanni z riznykh prychyn. Chyslo khvorykh z granulotsytopeniieiu bulo bil'shym na 1-y̆ i 2-y̆ fazi protokolu I ta protokoli M, i tse spivpadalo z bil'shoiu chastotoiu uskladnen'. Vsta- novleno zvorotni koreliatsiy̆ni zv'iazky mizh prognozom perebigu GLL i sumoiu dniv pererv mizh protokolom M ta 1-iu fazoiu protokolu II (rs = -0,56), a takozh tryvalistiu 2-ï fazy protokolu II (rs = -0,62). Doza na kistkovyy̆ mozok u ditey̆ dorivniuvala (5,37 ± 1,23) mZv. Ne vyznacheno zv'iazku mizh dozamy oprominennia khvorykh, variantamy GLL i perebigom zakhvoriuvannia.Vysnovky. Prognoz perebigu GLL u ditey̆ zalezhyt' vid typu vidnovlennia krovotvorennia ta prychyn pererv pry provedenni standartnoï khimioterapiï. V osnovi vyznachenykh zmin lezhat' mekhanizmy vzaiemodiï mizh funktsionuvan- niam gemopoezu, mikrootochenniam ta ïkh reguliatsiieiu, shcho ie pidgruntiam dlia podal'shogo vyvchennia.

Epidemiological and clinical-laboratory features of the course of drug-induced and viral liver damage are considered. Clinical observation of severe toxic liver damage in a patient suffering from chronic viral hepatitis “C” is given. The authors share the experience of successful therapy.

The liver is the largest gland in the human body and it is situated in the right side of the upper abdominal cavity. Liver damage can be generally caused by drugs, particularly antitubercular, paracetamol, general anesthetics, and some anticancer drugs. Toxic hepatitis is the most common severe adverse reaction caused by antituberculosis drugs. It mostly starts in the first few weeks of treatment accompanying liver necrosis, which may unfold to neurological disorder and death. Apart from synthetic drugs, many agents such as alcohol consumption also play a significant role in liver damage. Although many synthetic drugs are available to treat hepatotoxicity, still natural product-based drugs such as silymarin are among the favorable choices for hepatotoxicity.

Liver problems among troops and civilians during conflicts is not new as evident from the rise in Hepatitis A and E viruses in troops during the World War 2. The liver is the primary site for xenobiotics clearance and metabolism and in a position to be exposed to potentially toxic chemicals. In toxic hepatitis, reactive metabolites of a drug tend to cause toxicity. The deleterious effect of the drugs and chemicals on liver structure and functions can be prevented and treated through the administration of healthy nutrition, plant foods, hepatoprotective medicinal plants, antioxidant supplements, and Unani dietotherapy in risky individuals and patients. This chapter particularly updates information about the effects of dietary intake of healthy food and botanicas on liver health, with a specific focus on the possible beneficial effects of dietary and medicinal plants on protection from liver damage induced through drugs and chemicals.

Tamoxifen (TAM) is commonly used for breast cancer treatment. It is considered non-steroidal antiestrogen agent. Toxic hepatitis, significant hepatic steatosis, and cirrhosis have been reported to be caused by TAM. Stem cells (BM-MSCs) are used for regenerative medicine and therapy. Aim of the work: to know how BMMSCs can improve tamoxifen induced damage in the liver of female albino rats. Materials & Methods: Ten female albino rats of average 200 gm were served as a donor for stem cells. Thirty female adult albino rats of 200-240 gm were randomly divided to three equal groups (10 animals each). Group I (Control group): provided ordinary diet. Group II (tamoxifen treated group): rats were orally given TAM with a dosage 20 mg per kg body weight daily for nine weeks consecutively. Group III (TAM & BM-MSCs group): animals were given TAM with a dosage 20 mg per kg body weight daily for nine weeks consecutively as in group II then received single intraperitoneal injection of 2×106 BM-MSCs suspended in PBS per rat then scarified after another four weeks. Biochemical studies were done, and liver sections were processed for histological, immunohistochemical and electron microscopic studies. Results: Sections of the animals’ liver taking TAM showed disturbance of the normal structure, showing cytoplasmic vacuolation, leukocytic infiltration, pyknotic nuclei, dilated cisternae of rough endoplasmic and dilated blood sinusoids also excessive collagen fibers, as well as increased expression of caspase 3. The levels of liver enzymes((AST), (ALT) and (ALP)) were elevated, On the other hand, animals’ liver sections treated with TAM followed by BM-MSCs showed improvement of the disturbed structure. In conclusion, BM-MSCs revealed ameliorative effect against TAM toxicity in rats.

Lung damage is a characteristic feature of paraquat intoxication; most deaths resulting from ingesting paraquat are due to progressive respiratory failure. Liver failure caused by paraquat intoxication is rare. A case of orally ingested paraquat intoxication is reported in which serious liver injury and toxic encephalopathy were observed, but little lung damage was found. The principal systemic symptom was severe liver injury, characterized by cholestasis, that gradually became aggravated. In addition to standard treatment, aggressive treatment through liver protection and cholestasis was administered. Finally, liver function returned to normal and central nervous system symptoms were controlled. The patient was successfully discharged. This case suggests that the hepatotoxicity of paraquat intoxication is possibly characterized by cholestasis, and the treatment of cholestasis promotes recovery of severe hepatocyte damage.

The objective of this study was to investigate the prevalence of pathologies of the hepatobiliary system in dogs, and the spectrum of hepatoprotective medications. It was generated from information gathered from study patient records of veyterinary hospital and analyzed of veterinary drugs market. It was determined that a large part of hepatopathies in dogs is secondary diseases – 81.8 %. It was found that the chronic heart failure and toxic stress in pets are the main causes of a liver pathology. Hepatopathies, as individual diseases, were registered in 18.2 % of dogs. Hepatosis predominates in the pathology of the hepatobiliary system in dogs – 54.6 %. Also, there was an increase in the incidence of toxic hepatitis in dogs – 27.3 %, as a result of acute and chronic poisoning. No liver tumors were registered in pets during the study period. The results of this study showed that the dependence of the manifestation of hepatopathies on the breed and sex of dogs was not observed. The average age of dogs with hepatopathies was 5.5 years. Also, hepatodystrophies are often subclinical or have no signs of high diagnostic value. The most informative symptoms of hepatosis are depression, hyporexia, diarrhea, urge to vomit, and abdominal pain, but they are common symptoms of most diseases of the gastrointestinal tract in dogs. Biochemical parameters of blood in dogs with hepatodystrophy are characterized by hyperbilirubinemia and hyperenzymemia, which indicates cholestasis, hepatocellular damage and disorders of pigment metabolism. In particular, in the serum of patients registered dogs increased activity of AST and ALT respectively 3.5 and 1.6 times compared to that of normal. It has been observed that the level of elevated transaminases is often not directly correlated with the severity of the pet's clinical condition. It was found that the structure of hepatoprotectors for animals is most formed by combined drugs – 71.4 %. It was determined that most of the plant species in hepatotropic preparations for dogs is traditional for our country and common in South Asian countries. The most common plant species in traditional preparations for dogs hepatoprotective action appeared to milk thistle, artichoke seeds and everlasting sand (everlasting) which belonged to the family Asteraceae (Asteraceae).

BACKGROUND: Identification of risk factors for drug-induced liver injury (DILI) has been hindered by the unpredictable incidence and idiosyncratic nature of DILI. The aim of this study was to identify characteristic host risk factors for DILI. METHODS: A retrospective cohort study was performed examining all patients admitted with a diagnosis of DILI over a 5.5-year period. Cases were compared to a control group non-exposed to DILI using propensity score-derived inverse probability weights. Patients with DILI due to alcohol or paracetamol were excluded from analysis. RESULTS: Seventy-two cases of DILI admitted to hospital were identified. Antimicrobials caused 56.9% of cases, with amoxicillin-clavulanate the single most common agent, responsible for 13.9% of cases. DILI cohort median age (50.2±36 years) was significantly younger than controls (65.0±38 years) (P

Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India. We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases. Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15–34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265–6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%. Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this.

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy., Graphical Abstract

The liver performs a number of functions that may be broadly classified as synthetic, excretory, or metabolic in nature. Measurement of albumin, bilirubin, and ammonia can be used to evaluate the synthetic, excretory, and metabolic functions of the organ, respectively. However, due to the extensive reserve capacity of the liver, laboratory tests that directly assess hepatic function are largely insensitive in the identification of liver damage. Further, abnormal values may be observed in extra-hepatic disease states. Therefore, markers of hepatocyte or canalicular injury are more reflective of hepatitis or liver damage. The clinical specificity of liver injury markers is dependent on sites of expression, protein half-lives, and subcellular localization. Liver injury markers are helpful both in the recognition and the differential diagnosis of hepatic pathologies, including viral, alcoholic, and toxic hepatitis, as well as biliary tract obstruction and acute liver failure. This chapter discusses hepatic physiology, as well as laboratory methodologies used for the assessment of liver function and injury, and typical laboratory patterns observed in the background of acute and chronic organ injury.

An herbaceous suckering plant, that is found in the Himalayas (India, Nepal), and China. It is called White Christmas Rose because the flowers appear in winter during Christmas time. In Unani medicine, the rhizomes/root are considered stomachic, carminative, anthelmintic, and laxative; purgative in high doses. It is used to strengthen stomach function in cases of indigestion, in ascites due to hepatic involvement, to kill and expel intestinal worms, and especially useful for brain ailments. In small doses, it is a bitter, stomachic and laxative, and in large doses, a cathartic, and used in the treatment of epilepsy, paralysis, as an emmenagogue, emetic, abortifacient, and antidote to dog bite. It is also used in chronic dysentery, asthma, hepatic derangement, jaundice, and as a valuable antiperiodic in low continued fevers. It is one of the most commonly used drugs in polyherbal preparations clinically used in India for their potent antihepatotoxic activity in various liver disorders. Hepatoprotective effects of P. kurroa are similar and superior to the effect of Silybum marianum in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis, due to its antioxidative, antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects. Iridoids: pikuroside, picroside I, picroside II, and 6-feruloyl catalpol, iridoid glycosides: 6-feruloylcatalpol, veronicoside and minecoside, and two phenol glucosides, picein and androsin, cucurbitacine glycosides, and apocynin have been isolated from the rhizomes. Aqueous extract significantly reduced TC, LDL-C, and TGs of hyperlipemic mice. Hydroalcohol extract, methanol extract, and picroliv are protective against various hepatotoxic agents, and picroliv is also a potent choleretic and anticholestatic agent than silymarin. Alcohol extract lowers blood glucose in basal conditions and after a heavy glucose load in normal rats, and in diabetic rats; aqueous extract also significantly reduces diabetic hyperglycemia and nephropathy, and a standardized aqueous extract significantly lowered blood glucose and the lipids (TC, LDL-C and TGs). Ethanol rhizome extract enhanced healing rate of gastric ulcers in rats, with significant elevation of antioxidant enzymes; and picroliv methanol and aqueous extracts demonstrated significant free radical scavenging capacity.