Volume 32 (2019): Issue 1 (March 2019)

Derivatives of 1,2,4-triazole are actively researched by scientists and synthetic pharmacologists. The last studies have shown that potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate with low toxicity series exhibits antioxidant and hepatoprotective properties. Therefore, the purpose of this work was to develop a method for determining the API in the potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate substance using the method of high-performance liquid chromatography with diode array detection (HPLC-DAD). As a result of this work, it is shown that the developed method is specific and meets the requirements of linearity, accuracy and precision. The results of determining the contents of the API in real samples indicate that the method can be proposed to control the quality of the potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate substance.

Histamine type 2 receptor antagonists are one of the most commonly used agents to treat peptic ulcer disease. Since patients with epilepsy may have many comorbidities, the aim of this study was to investigate the influence of one of the strongest second generation histamine type 2 receptor antagonist, famotidine, on the exploratory and spontaneous activity in mice after 1 or 7 days treatment. Additionally, the interaction between famotidine and antiepileptics: carbamazepine, phenytoin, phenobarbital or valproate and their effect on animals activity was also evaluated. Locomotor activity was monitored electronically using a Digiscan analyzer in relation to ambulatory and rearing activities, as well as total distance travelled by animals during 15 minute periods. Results of our study indicate that famotidine administered alone did not modulate three variables of exploratory motor activity (horizontal activity, total distance and vertical activity) in mice. On the other hand, famotidine co-administered with valproate (1 day) or phenobarbital (1 day or 7 days) worsened vertical activity in mice in exploratory time. Similarly, impairment in horizontal activity in mice was observed when famotidine was given with phenobarbital (1 or 7 days). An increase in total distance in mice after famotidine alone or in combination with tested antiepileptic drugs was also shown. Moreover, famotidine alone or together with antiepileptic agents significantly impaired spontaneous locomotor activity in mice. The presented results show that famotidine administration to patients with epilepsy should be considered as potentially hazardous.

Non-Hodgkin lymphomas are malignant neoplasms whose incidence rates increase each year. These also include neoplasms rare in the general population. The present case report described a patient with lymphoplasmacytic lymphoma (LPL) and rapid liver damage. In most cases, infiltration of the liver is rare in advanced stages of hematopoietic malignancies when hepatomegaly, cholestatic jaundice and organ failure are observed. The patient’s history includes non-specific abdominal pain that was accompanied by general symptoms such as nocturnal hyperhidrosis, subfibrile temperature and fever, as well as weight loss. The above complaints aggravate with an increase in organ size. The laboratory findings initially demonstrated moderately elevated concentrations of transaminases. In our case, the baseline biochemical indices of liver function were found to be normal. During the next days of hospitalisation, the features of liver damage intensified and were accompanied by liver failure. The gold diagnostic standard is a biopsy of the bone marrow and the organ affected. Since the patient’s condition deteriorated and liver failure developed, the diagnosis was established based on trephine biopsy of the bone marrow. Chemotherapy was implemented; despite the treatment applied, the patient’s clinical condition did not improve. Two months after the onset of first symptoms the patient died.

Hypoxic cancer cells are more aggressive and responsible for more efficient metastasis and recurrence. It seems worth-while, hence, to supplement current cytostatic drugs therapy (i.e. cisplatin) with hypoxia cytotoxic agents (i.e. tirapazamine), the toxicity of which is activated by hypoxia. Cisplatin and tirapazamine can change a redox equilibrium and consequently lead to changes in cell metabolism, fibrosis and apoptosis. The aim of this study was to evaluate the cisplatin/tirapazamine toxicological synergism. In doing so we tested selected kidney oxidative stress parameters, as well as nephrotoxicity markers, in plasma and urine. Once a week for 6 weeks, rats received intraperitoneally two doses of tirapazamine (5 or 10 mg/kg bw), 2 hours before cisplatin (2 mg/kg bw) was applied. Our results show that Tirapazamine (TP) had no significant adverse effect on the redox balance, oxidative stress and kidney function in rats receiving cisplatin (CP). However, TP significantly increased protein concentration in the kidneys of rats. In all tested groups, a significant decrease in NADH concentration in kidneys was recorded, which could indicate disorder in the cell metabolism. TP also was found to have prevented bacterial infection caused by CP. In summary, there was no nephrotoxic synergy of TP with CP at an unacceptable level.

This paper presents the results of a study of patients with nonalcoholic steatohepatitis, alcoholic steatohepatitis, and drug-induced liver injury with concomitant colitis and the development of biliary insufficiency that manifests as a significant decrease in the volume of bile acids and bile. In patients with liver injury and concomitant colitis, changes in intestinal microflora were marked. After a combination therapy of this pathology with phosphatidylcholine and glycyrrhizic acid, an improvement of biochemical, clinical indicators was observed, as well as a decrease in fatty degeneration and reduction of elastographic indicators of liver fibrosis. The introduction of the drug formulations phosphatidylcholine and glycyrrhizic acid in the complex of conservative treatment of liver injury with concomitant colitis helps to prevent hepatic and intestinal complications and to increase the treatment efficacy of these diseases.

A rare case of asymptomatic traumatic neuroma, triggered by the performed amputation within the right thigh due to the osteosarcoma is reported. The MRI examination has shown a focal lesion at the end of the sciatic nerve, with isointense signal and weak contrast enhancement on T1-, high signal on T2-weighted images, without restriction diffusion on DWI. The morphology did not significantly change after 12 months, which confirms the primary diagnosis. The main limitation of the case is the lack of histological confirmation, since the lesion was not removed.

Given the increase in global mortality rate due to various types of cancer, the present study aimed to develop optimal conditions for the synthesis of cellulose-magnesium oxide nanocomposite with favorable anticancer activity. For this purpose, the Taguchi method was used to design nine experiments with varied ratios of cellulose biopolymer, magnesium oxide nanoparticles and different stirring times. The scanning electron microscopy (SEM) images confirmed the formation of cellulose-magnesium oxide nanocomposite. The anticancer activity level of nine nanocomposites studied was evaluated using MTT assay on Michigan Cancer Foundation-7 (MCF-7) cell line. The nanocomposite synthesized in experiment 9 (8 mg/ml of magnesium oxide, 2 mg/ml of cellulose and stirring time of 60 min) showed the highest growth inhibitory activity on the cancer cells. Based on the attained results,e cellulose-magnesium oxide nanocomposite synthesized in optimal conditions can be used as an eligible anticancer agent.

Patulin is a mycotoxin produced by many species of the fungi. The toxic action of patulin mainly affects the gastrointestinal tract and the immune system. The aim of our work was to assess the toxic effect of patulin, based on the analysis of interleukin IL-6 concentrations in the liver of test animals loaded with different doses of this mycotoxin. The research was conducted on mice which were assigned to 6 groups receiving different doses of active substances. After decapitation, their livers were taken for laboratory testing.

Our studies have shown that chronic intoxication with patulin at 0.1 LD50 leads to a statistically significant increase in IL-6 concentration in the liver of the animals. We also found that the loading of experimental animals with a single dose of patulin in the amount of 0.5 LD50 and 0.2 LD50 also leads to a statistically significant increase in this interleukin in the examined organ. There was no difference in its concentration compared to the control group only after the single dose of the lowest concentration of patulin, while the highest average IL-6 concentration was recorded in the liver of animals loaded with the highest single dose of patulin. After applying, one-time doses of this mycotoxin in the amount of 0.2 LD50 and 0.1 LD50, the mean concentrations of IL-6 in the liver in animals from these groups were statistically significantly lower.

In conclusion, the analysis of the obtained results confirms the fact of the hepatotoxic effect of patulin.

Chikungunya virus is an Alphavirus that possesses characteristics similar to that of an arthropod-borne virus. Chikungunya virus has been one of the major concerns for the last few decades due to its nature of explosive spreading throughout the world. This article is intended to give detailed information about Chikungunya virus, and includes its pathogenesis, origins, diagnosis, treatment and prevention. Although, recent researches suggests various approaches to treating Chikungunya virus, extensive literature search on Chikungunya virus has revealed that, currently, there is no effective treatment available and the virus is greatly dependent on its vectors. Patients affected by Chikungunya virus mainly show symptoms of fever, arthralgia, joint pain and skin rash. Since there is no effective treatment available, public awareness is the most significant factor for potential prevention against Chikungunya virus.

The aim of the study was to evaluate experimentally, the myoprotective effect of new chromone-3-aldehyde derivatives in conditions of muscular dysfunction and to establish a potential mechanism of myoprotective activity – the blockade of the function of sirutin 2. Materials and methods. The effect of new chromone-3-aldehyde derivatives on the development of muscular dysfunction under the conditions of an electromiostimulation test, was studied. The degree of muscle fatigue was evaluated in the «grip-strength» and through test biochemical assays (determination of the activity of lactate dehydrogenase, creatine kinase, concentration of lactic and pyruvic acids, creatinine, myoglobin, and total protein) to determine the possible mechanism of action of the test compounds (5 new derivatives of chromone-3-aldehyde) and their effect on the function of sirtuin 2 was evaluated.

Results. The study showed that chromone-3-aldehyde derivatives have a pronounced myoprotective effect associated with low toxicity (class 5 toxicity according to the GHS classification), which was confirmed by the results of the «grip-strength» test and biochemical tests data. Test compounds under the X3AC1, X3AOAC and X3AN codes evince sirtuin 2 inhibitory activity, which was reflected in a decrease in its concentration by 63.6% (p <0.05); 130.2% (p <0.05) and 218.8% (p <0.05).

Conclusion. The study showed that chromone-3-aldehyde derivatives are promising subjects for further study with the goal of creating a drug with a high myoprotective effect and an optimal safety profile.