An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure.

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.

Adsorptive therapy as a modificator for tumor-host interaction.

The potential of one of the adsorption methods, enterosorption (ES), using the new generation of carbon adsorbents to correct the negative manifestations of tumor-host interaction in the framework of paraneoplastic syndrome (PNS) as well as systemic toxicity of chemo- and radiation therapy, is discussed. The ES influence on the development of PNS was demonstrated in C57/BL6 mice with transplanted Lewis lung carcinoma. Two-week administration of carbon enterosorbents resulted in a significant suppression of metastasis and correction of tumor-related anemia, activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of its mitotic activity. ES exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, increased resistance of erythrocyte membranes and decreased ligand loading of blood plasma transport proteins. The effect of ES on anticancer activity and toxic reactions of cisplatin (CP) was evaluated in Guerin carcinoma-bearing rats. ES reduced significantly creatinine and other kidney biochemical indexes elevated in the blood plasma of rats after CP treatment. ES attenuated dystrophic changes in the histological structure of internal organs (kidney, liver, spleen), caused by tumor growth and significantly aggravated under the influence of CP. Such changes were specially traced in the kidneys and well reflect the nephroprotective potential of ES. In rats irradiated with X-ray in sublethal dose, highly activated granulated carbonic enterosorbents facilitated the restoration of white blood cells and lymphocyte count. The results obtained confirm the insights of academician R.E. Kavetsky predicting the future of adsorptive detoxification with activated carbons in the treatment of cancer patients.

Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs.

Oral intestinal adsorbents (enterosorbents) are orally administered materials which pass through the gut where they bind (adsorb) various substances. The enterosorbent Enterosgel (Polymethylsiloxane polyhdrate) is recommended as a symptomatic treatment for acute diarrhoea and chronic diarrhoea associated with irritable bowel syndrome (IBS). Since 1980's there have been many Enterosgel clinical trials, however, the detailed mechanism of Enterosgel action towards specific toxins and interaction with concomitantly administered medications has not been fully investigated. Our in vitro study assessed the adsorption capacity of Enterosgel for bacterial enterotoxins and endotoxin, bile acids and interaction with the pharmaceutical drugs; Cetirizine and Amitriptyline hydrochloride. Our data demonstrate the good adsorption capacity of Enterosgel for bacterial toxins associated with gastrointestinal infection, with a lower than the comparator charcoal Charcodote capacity for bile acids whose levels can be raised in IBS patients. Adsorption capacity for the two drugs varied but was significantly lower than Charcodote. These findings suggest that the mechanism of Enterosgel action in the treatment of gastrointestinal infection or IBS is adsorption of target molecules followed by removal from the body. This therapy offers a drug free approach to prevention and treatment of infectious and chronic non-infectious diseases, where intestinal flora and endotoxemia play a role.

Highly activated carbon enterosorbent mediates the suppression of paraneoplastic syndrome associated with Lewis lung carcinoma in mice.

AIM: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). MATERIALS AND METHODS: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. RESULTS: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. CONCLUSION: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes.

Enterosorption combined with granulocyte colony stimulating factor decreases melphalan gonadal toxicity.

UNLABELLED: Today due to improvements in cancer treatment there is an increasing number of long-term cancer survivors, many of whom suffer from infertility caused by malignancy itself and chemo- or radiotherapy. Also, anticancer therapy may cause myelosuppression. Presently granulocyte colony stimulating factor (G-CSF) is used for prevention and treatment of myelosuppression. Another treatment option used to decrease intoxication and ameliorate side effects of cancer therapy is sorption technology. The aim of our investigation was to study the efficiency of combined use of enterosorption and G-CSF to decrease gonadal toxicity of chemotherapy. MATERIALS AND METHODS: Melphalan (L-PAM) injected i.v. at a single dose of 4 mg/kg to white inbred rats was used as gonadotoxic and myelosuppressing agent. Carbon enterosorbent C2 was administered by intragastric route as a suspension in saline at a dose of 5 ml per 1 kg of rats' body weight (or 900 mg/kg of the dry mass of enterosorbent) daily for 3 days before and for 7 days after L-PAM injection. G-CSF was injected once a day for 4 days starting from the next day after L-PAM administration at a dose of 50 µg/kg. Histological preparations of testicular tissues were examined by light microscopy. RESULTS: Our findings have shown that melphalan caused marked damage of testicular tissues and seminiferous, especially spermatogenic epithelium. The most expressed protection of the histological structure of testes was observed when enterosorbent and G-CSF were used in combination. CONCLUSION: Gonadal toxicity of chemotherapy could be efficiently decreased by the combined use of enterosorption and G-CSF.

Effect of enterosorption on paraneoplastic syndrome manifestations in mice with highly angiogenic variant of Lewis lung carcinoma.

AIM: To study the correcting effects of microgranulated HSGD enterosorbent on hematological, morphological and biochemical indices of paraneoplastic syndrome in mice with highly angiogenic variant of Lewis lung carcinoma LLC/R9. METHODS: The study was performed on male С57/ВL6 mice with transplanted LLC/R9. Enterosorbent HSGD was administered daily at a dose of 0.625 g/kg for 2 weeks starting from 7(th) day after tumor cell transplantation. When enterosorption was completed, an analysis of peripheral blood, biochemical indices and morphological structure of tumor, lung, liver, spleen and thymus was carried out by standard methods. RESULTS: It has been shown that administration of enterosorbent did not affect LLC/R9 growth but resulted in nearly two fold decrease of the volume of lung metastases (p < 0.05). Erythrocyte number and hemoglobin level were higher by 30.0% (p < 0.05) and 23.3% (p < 0.05), respectively, in mice treated with enterosorbents as compared to untreated animals. In addition sorbent treatment completely normalized the thrombocyte index resulting in elevation of platelet number by 54.5% (p < 0.01) up to their level in intact mice. The morphological examination of liver and biochemical analysis of peripheral blood evidenced on significant positive correcting effect of enterosorption on histological structure of this organ and its functional activity. Normalization of total proteins and serum albumin level as well as significant decrease of total lipid concentration by 29% (p < 0.01) in blood of treated mice were observed. CONCLUSION: Positive influence of microgranulated carbon sorbent on some hematological, morphological and biochemical indices of tumor associated symptoms in LLC/R9-bearing mice denotes that enterosorption-based therapy can be considered as a prospective treatment for correction of some paraneoplastic syndrome signs in cancer patients.

[Prophylaxis of adhesive process in patients with extended peritonitis].

The results of treatment of 378 patients, suffering extended peritonitis, were analyzed. For prophylaxis of adhesions formation intraoperatively an adequate surgical correction and measures, directed on elimination of endotoxicosis, were applied; postoperatively--the preparations, suppressing the adhesions formation, were applied. Conduction of intracorporeal and extracorporeal therapy extremely high frequency irradiation in complex of treatment have promoted a trustworthy improvement of motor-evacuatory function stomach and intestinal due to impact on system of coagulation and blockade of the oxidative reactions cascade, as well as due to bacteriostatic effect.

[Conservative treatment of patients with intermittent claudication].

The article deals with the analysis of the results of randomized placebo-controlled studies of various therapeutic agents currently available in Russia, as well as the results of meta-analyses and Cochrane reviews of medicamentous treatment of patients with intermittent claudication. The results of these studies gave grounds to recommend the most efficient agents in the new edition of the "National Guidelines on management of patients with lower-limb arterial disease" (2013).

Analysis of medical use of carbon adsorbents in China and additional possibilities in this field achieved in Ukraine.

The review is devoted to analysis of the use of carbon sorbents for medicinal purposes in China and description of some innovative technologies in this field in Ukraine. The review underlines the presence of common roots of sorption therapy development in these two countries determined by pioneer works of Prof. T.M.S. Chang, created to the concept of artificial cells. High level of works of Chinese scientists on sorption purification of blood and combined extracorporeal methods has been mentioned. At the same time, by author's opinion, two other methods of sorption therapy, namely enterosorption and sorption therapy of wounds and burns, has not been properly developed in China. In the review, there are also described the essential results of Ukrainian scientists in the field of blood purification from protein-bound toxins and other harmful compounds what is important for treatment of many serious human pathologies, and also the important data on the use of oral sorbents and dressings from activated carbon materials, which could be considered as a useful addition to achievements of Chinese scientists in the field of the development and use of sorbents for medicinal purposes.

[Peculiarities of enterosorption via nasointestinal probe using sorbent diosmectite].

Peculiarities of conduction of enterosorption, using sorbent diosmectit via nasointestinal probe, were analyzed in patients, suffering peritonitis in acute ileus. The data obtained witness positive dynamics of indices of endogenic intoxication and antiendotoxic immunity while application of sorbent.

Optimization of physico-chemical properties of carbon enterosorbents and evaluation of their sorption activity for use in the treatment of paraneoplastic syndrome and other endogenous intoxications in cancer patients.

AIM: Development of carbon enterosorbents with optimal physical-chemical properties and high adsorptive capacity for their usage in the treatment of paraneoplastic syndrome and other endogenous intoxication in cancer patients. METHODS: physical-chemical and biochemical methods of investigation. RESULTS: In the work it has been shown that performance of additional steam activation on pilot plant developed in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, allows produce highly active granulated and fibrous carbon enterosorbents which possess well developed porous surface providing potent sorption potential toward compounds of hydrophilic and hydrophobic nature. Being placed in gastro-intestinal tract lumen these sorbents may cause certain effect on functional activity of detoxifying body systems and regeneration potential of many organs and tissues. CONCLUSION: The usage of carbon enterosorbents with optimal physical-chemical properties and high adsorptive capacity could be very perspective for correction of biochemical, immunologic, morphologic and hematological manifestations of paraneoplastic syndrome.

[Possibility of the liver ultrastructure recovery in intoxication with heavy metals salts].

Experimental studies helped to reveal ultrastructural changes in hepatocytes, caused by prolonged exposure to heavy metals salts taken in combination and ratios characteristic to soil contents near Almalyk mining and smelting enterprise. The authors demonstrated possibility of liver structural recovery via enterosorption with additional antioxidant therapy.

[Experimental study of the effect of detoxification with enterosorbents on the function of irradiated myocardium].

Increase in intoxication products, such as medium size peptides, indole and myoglobin, in urine was observed in Wistar rats after exposure of their chest to gamma-radiation at a dose of 6 Gy (dose rate 4 Gy/min). The rats exhibited moderate ischemic ECG. Administration of enterosorbents, such as Smekta and Clay of Kaluga deposit, to the irradiated rats resulted in the decrease of the toxicant content in the animals and the recovery of the cardiac function on the 28th day. These sorbents had practically a similar efficacy.

[Changes of micellarity and lithogenicity of bile under conditions of transcutaneous electrostimulation and enterosorption in patients with obturation jaundice of nontumoral genesis].

The conduction of pathogenetically substantiated treatment--enterosorption together with procedures of electrostimulation--in patients, suffering obturation jaundice of nontumoral genesis, secures favorable course of postoperative period, the hepatorenal insufficiency prophylaxis, and postcholecystectomy syndrome occurrence as well.

[Diagnostics and treatment approach for abdominal ischemic syndrome].

During 2005-2009 years 150 patients aged between 45-90 years were investigated at the department of general surgery (Rostov medical university) for abdominal ischemic syndrome (AIS). 70 patients were found to have AIS. 4 stages of this syndrome were determined. According to Doppler evaluation of abdominal vessels, an algorithm for the differential treatment approach at various stages of AIS was worked out. The critical level of pathological changes in abdominal vessels and optimal terms for surgical operation were estimated.

[Opportunities of the enterosorption and evolution of the enterosorbent for surgical treatment of endotoxicosis].

In this article was shown the efficiency of enterosorbtion in various departments of medicine. You can find a comparative assessment of different enterosorbents. Were presented results of own using of pectin containing sorbents for enterosorbtion and nutritional support in surgical treatment of endotoxemia on the background of intestinal insufficiency syndrome in 161 patients. Application of the PCD had reduced bed-day in 1,4 times and mortality--a 2.05-times in compare with conventional treatment in the control group of 171 patients of the paired samples.

[Criteria of differential assignment of drugs with sorptive and disintoxication properties to patients with obturative icterus of non-tumoral genesis].

The article defines criteria of differential assignment of drugs with sorptive and disintoxication properties according an analysis of clinical signs of a mechanical icterus, results of biochemical, immunologic, biophysical, crystal optics methods. The results were assessed by points (high--a score 98-65; average--64-32 a point; low--not higher 31 points) that allowed to judge severity level of a patient condition with obturative icterus not tumoral genesis. Positive efficiency of treatment was defined by point estimation which was not lower than 10 times (severe and moderate degrees; moderate and mild degrees). The study has shown that consideration both clinical and laboratory characteristics of the course of obturative icterus allows raising results of the treatment due to individual therapy and to predict its efficiency based on dynamic definition of point assessment of severity level.

[Change of humoral immunity under influence of enterosorption in presurgery period in the treatment of patients with mechanical jaundice of non-neoplastic genesis].

The authors have studied indices of the humoral immunity with mechanical jaundice of nonneoplastic genesis. Disorders of immune status of patients with bilious ways obturation, which were characterized by concentration increase IgG in 1,6 times, IgA--in 1,3 times and IgM--in 1,7 times of the level of circulating immune complexes--in 1,6 times and decrease in fractional index and fractional number in 2 and 1,7 times accordingly. The study has shown principle efficiency of enterosorption in patients with mechanical jaundice in restoration of indices of the humoral immunity. It was seen more considerably with application of chitin-contained active substance, mycotin. It has allowed improving functional ability of the liver, especially its synthesizing function and hydroxylation processes in hepatic cells.

[Experimental and clinical evaluation of a modified pectin-containing drugs in the treatment of intestinal insufficiency in peritonitis].

Experimental studies on 26 rats showed a stimulating effect of beet pectin at small intestine with paresis, mucosal repair, and bactericidal action on intestinal microflora. In comparison of activity intensity of small intestine solder at 1 day was 2.5-1.75 times less than 3 days and it is not reached. In the experimental group at 1 day solder activity was lower than the norm for the divisions in the 1.7-1.64--1.53-fold, and by 3 days, respectively, exceeded the norm of 0.8-2.4--2.25 times. We examined 150 patients aged 19 to 86 years with poured peritonitis primarily toxic (85.3%). III. The main causes of peritonitis were acute appendicitis (24.0%) and perforation of gastroduodenal ulcers (21.3%). For a comparative analysis of results of treatment were formed 3 patient groups using paired sample. Control group patients received conventional treatment. Enterosorption conducted through nazointestinalny probe known carbon sorbent UAO-A and pektincontents products (SAPs) the dining beet sublimate materials. The results are compared. Reducing the time used to resolve paresis of intestine and nazointestinal intubation in 1,3 times, reducing the severity of the patient on a scale of SAPS is already at 2 hours improving immunity more rapid decline in toxicity of blood plasma and leukocyte index of intoxication, reduction of postoperative pneumonia in 12% and postoperative mortality from 14% to 6.6% showed the advantages enterosorption modified pectin contents drug.

[Early postoperative enteral immunocorrection using modified pectin containing drugs in peritonitis].

Surgical endotoxicosis entails dysfunction of all organs and systems including immune system that considerably aggravates severity of current disease and slows down a recovery in the postoperative period. Searching of various ways of immunocorrection in peritonitis of various etiology is the actual commitment of the contemporary surgery. The complex method of simultaneous enterosorbtion and immunocorrection with the modified pectin contained specimen in patients with a peritonitis is offered. In study the role natural enteral sorbents in optimization of the immune answer due to restoration of microbiocenosis sorbtion and immunocorrection modified with the modified pectin contained intestines is proved. Entero specimen provide decreasing of medium molecular weight substances' level to 89.0% in reactive stage of a peritonitis and to 69.0%--in toxic stage during 3 days. By 5th day of treatment the level of medium molecular weight substances and leucocyte intoxication index were already reached to the normal parameters. It allows us to recommend this introducted method in a complex of medical treatment in postoperation period in peritonitis.