Aleksandra S Orlova, Karina M Shkurlatovskaia, Ekaterina V Silina, Polina M Pyatilova, Natalya P Teplyuk, Evgeniya A Kogan, Sergej I Vorobyev, Stefani S Bolevich, Valida A Dadaeva, Bella I Tachieva and Sergej B Bolevich
Mastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs) in the skin and/or other organ systems. Mastocytosis is a rare disease. The annual incidence is 5–10 cases per 1 million people. However, the majority of cases stay undiagnosed due to the lack of specific tests and a wide variety of clinical features of the disease. In mastocytosis, somatic mutations of KIT gene lead to autocrine dysregulation and constitutive c-KIT activation in the absence of its ligand SCF. Clinical symptoms of the disease are determined by MC mediator release and/or infiltration of tissues by MCs. According to the World Health Organisation classification updated in 2016 mastocytosis is divided to cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), SM with an associated hematologic (non-MC-lineage) neoplasm (SMAHN), aggressive SM (ASM), MC leukemia (MCL) and MC sarcoma (MCS). The CM and ISM prognosis is excellent with (almost) normal life expectancy, unlike aggressive forms (ASM and MCL) with poor prognosis. In this paper the key aspects of clinical features and diagnostic criteria of mastocytosis are discussed. We present a case report of a patient with mastocytosis in the skin following psoralen plus ultraviolet A (PUVA) therapy with good response.
Branislava Draskovic, Tomislav Nikolic, Sasa Jacovic and Dejan Petrovic
Acute kidney damage associated with pregnancy occurs in 1/20.000 pregnancies. In developing countries, the main cause of the development of acute kidney damage is septic abortion, and preeclampsia in the developed countries of the world. Preeclampsia is defined as newly developed hypertension, proteinuria and swelling in pregnant women after the 20th week of gestation. It occurs due to disorders in the development of placenta and systemic disorders of the function of the endothelium of the mother. It is treated with methyldopa, magnesium sulfate and timely delivery. Urgent delivery is indicated if the age of gestation is ≥ 34 weeks. HELLP syndrome is a difficult form of preeclampsia. Its main characteristics are decreased platelet count, microangiopathic hemolysis anemia, increased concentration of aminotransferase in the serum and acute kidney damage. Severe HELLP syndrome is treated with emergency delivery, antihypertensives, magnesium sulfate, and in some cases plasmapheresis and hemo-dialysis. Acute fatty liver in pregnancy occurs because of decreased activity of the LCHAD enzyme of the fetus. Due to the reduced beta oxidation of fatty acids in the hepatocytes of the fetus, long chain fatty acids that cause damage to the mother's hepatocytes are released. Swansea criteria are used for diagnosis, and the difficult form of the disease is treated with plasmapheresis and extracorporeal liver support. Atypical HUS is due to a reduced protein activity that regulates the activity of the alternative pathway of the complement system. Its main features are thrombocytopenia, microangiopathic hemolytic anemia and acute kidney damage. It is treated with plasmapheresis, and in case of resistance with eculizumab. Thrombotic thrombocytopenic purpura is due to decreased activity of the ADAMTS13 enzyme. It is characterized by thrombocytopenia, microangiopathic hemolytic anemia, high temperature, nervous system disorders and acute kidney damage. It is treated with plasmapheresis, and severe form of disease with corticosteroids and azathioprine. Early detection and timely treatment of acute kidney damage provides a good outcome for the mother and fetus.
Rade Vukovic, Igor Kumburovic, Nemanja Jovicic, Stefan Velickovic, Aleksandra Arnaut and Dragica Selakovic
The aim of this study was to estimate a potential beneficial influence of N-acetylcysteine (NAC) in the treatment of cisplatin-induced motor impairment. We included 32 male Wistar albino rats, divided into 4 equal groups: control (received saline on the 1st and 5th day), cisplatin – CIS (received saline on the 1st and cisplatin 7.5 mg/kg i.p. on the 5th day), NAC (received NAC on the 1st and 5th day, 500 mg/kg i.p.), and CIS+NAC (received NAC on the 1st and 5th day, 500 mg/kg i.p. and cisplatin 7.5 mg/kg i.p. on the 5th day) group. Motor performance was estimated by rotarod, grip wire, open field (OF), elevated plus maze (EPM) and beam-walking (BW) tests on the 10th day. Cisplatin administration resulted in decreased motor performance in all tests, except for BW test, compared to the control group. NAC supplementation on its own had no significant effect on motor performance parameters. However, simultaneous administration of NAC along with cisplatin reversed negative impact of cisplatin in rotarod, OF and EPM tests, with no significant effect on the results obtained in grip wire test. The results of this study confirmed numerous motoric manifestations of cisplatin-induced neurotoxicity in rats. However, the decline in most of the estimated parameters was successfully prevented by antioxidant supplementation with NAC.
Branimir Radmanovic, Jovan Jovanovic, Natasa Djordjevic, Dejan Baskic, Jelena Cukic, Predrag Sazdanovic, Radisa H. Vojinovic, Maja Sazdanovic, Katarina Pantic and Dragan R. Milovanovic
Association of SOD2 V16A single-nucleotide polymorphism (rs4880) with drug hepatotoxicity were reported but relationships with amiodarone prescriptions remained unexplored. Research was an exploratory, controlled prospective clinical trial. Patients hospitalized and treated in Clinical Center in Kragujevac, Serbia (in year 2017) were divided into experimental (using amiodarone, having liver injury, n=29, 19 males, the mean age 66.8±10.4 years), control A (neither amiodarone use nor hepatotoxicity, n=29, 19, 66.1±10.3) and control B group (using amiodarone, not having hepatotoxicity, n=29, 19, 66.8±9.8). From blood samples, among other routine biochemistry, genotyping for SOD2 polymorphism Val16Ala was conducted using real-time PCR method with TaqMan® Genotyping Master Mix and TaqMan® DME Genotyping Assay for rs4880. Patients taking amiodarone and having liver injury were mostly carriers of Val/Val (TT) genotype (13 of 24 patients, 54.2%) while Val/Ala (TC) and Ala/Ala (CC) genotypes prevailed in control group A (19 of 40, 47.5%) and control group B (9 of 23, 39.1%), respectively (2=10.409, p=0.034). Frequency of Val (T) and Ala (C) alleles were 0.51 and 0.49, respectively in the whole study sample (Hardy Weinberg equilibrium, 2=0.56, p=0.454). Carriers of TT genotype had significantly higher ALT (437.0±1158.0 vs 81.9131.5 U/L), total bilirubin (28.320.5 vs 15.313.0 mol/L) and total bile acid concentrations (10.910.2 vs 6.45.3 mol/L) compared to carriers of TC genotype (U=2.331, p=0.020, U=3.204, p=0.001 and U=2.172, p=0.030, respectively). Higher incidence of 47T allele of SOD2 was inpatients with amiodarone-associated liver injury as compared to patients on amiodarone not experiencing hepatotoxic effects.
The discovery of an adaptive immune system especially in archae and bacteria, CRISPR/Cas has revolutionized the field of agriculture and served as a potential gene editing tool, producing great excitement to the molecular scientists for the improved genetic manipulations. CRISPR/Cas9 is a RNA guided endonuclease which is popular among its predecessors ZFN and TALEN’s. The utilities of CRISPR from its predecessors is the use of short RNA fragments to locate target and breaking the double strands which avoids the need of protein engineering, thus allowing time efficiency measure for gene editing. It is a simple, flexible and highly efficient programmable DNA cleavage system that can be modified for widespread applications like knocking out the genes, controlling transcription, modifying epigenomes, controlling genome-wide screens, modifying genes for disease and stress tolerance and imaging chromosomes. However, gene cargo delivery system, off target cutting and issues on the safety of living organisms imposes major challenge to this system. Several attempts have been done to rectify these challenges; using sgRNA design software, cas9 nickases and other mutants. Thus, further addressing these challenges may open the avenue for CRISPR/cas9 for addressing the agriculture related problems.
Sunil Das Patel, Rupak Karn, Sagar Bhusal, Sujita Balami, Prabin Adhikari and Raju Kharel
The research was conducted from January 2019 to June 2019 to study the fish production and marketing system in fish zone, Rupandehi. Altogether 95 respondents including 27 small farmers, 35 medium farmers and 33 large farmers were selected for household survey using simple random sampling for the study. Statistical tools, Ms- excel and SPSS of version 23 were used for data analysis. From the study, it was evident that, six species of carps of fingerlings size were stocked with high average number of common carps (3885.5/ha.) followed by silver carp (3880.5/ha). The average production of fish species was 6.06ton/ha which is slightly higher than the national average. The observed data revealed that, marketing of major quantity of fish was from on farm sale i.e. 55.78% followed by local market sale (18.94%), live fish sale in retailers (5.26%). Similarly, percentage of farmers selling fish to wholesaler, consumers, retailers and neighbours were 63.3%, 30.5%, 26.5% and 26.3% respectively. Cost and returns analysis showed average B/C ratio of 2.13. Problem ranking using 5 point scale value showed high cost of feed as the most serious problem with index value of 0.94 in the study area.
Objective: The objective of the study was to determine the differences in selected clinical variables and self-image in people with alcohol dependence differing in severity of physical, emotional and sexual abuse experienced before age 18.
Method: The study included 90 people with alcohol dependence. The following research tools were used: Early Trauma Inventory (ETI), Adjective Check List (ACL), MAST, SAAD, and a questionnaire designed by the authors. In order to identify groups with varying indices of physical, emotional and sexual childhood abuse, a cluster analysis method was used.
Results: Two groups of subjects with alcohol dependence were identified: Group 1 with high indices of physical, emotional and sexual childhood abuse and Group 2 with low indices. In terms of self-image the subjects in Group 1 compared to subjects in Group 2 were characterized by a lower self-esteem, self-acceptance, resistance to stress, less intense needs for achievement, endurance, order, nurturing others, interaction with opposite-sex partners, subordinations but more intense need for change. The age of alcohol use initiation and the onset of regular alcohol drinking was statistically significantly lower in Group 1. The severity of alcohol dependence was significantly lower in Group 2. The subjects in Group 1 significantly more frequently confirmed the history of a hereditary predisposition to alcohol dependence, suicidal ideation, suicide attempts and self-harm.
Discussion: The obtained results closely correspond to the data available in the literature.
Conclusions: An assessment of exposure to various forms of childhood abuse appears to be an indispensable element of collecting medical history of people with alcohol dependence.
Simon Fletcher, Steve Chaplin, Cathy Harrison, Kristian Juusola and Norma Collins
Background: Guidance from the European Association for Haemophilia and Allied Disorders (EAHAD) sets out the educational milestones haemophilia nurses should aim to achieve. However, little is known about the resources nurses use for education and current awareness.
Aims: To assess the current educational level of haemophilia nurses, how and where they access ongoing education, where they feel they need extra support, and how best this teaching could be delivered.
Methods: Haemophilia nurses in the Haemnet Horizons group devised and piloted a questionnaire. This was distributed in hard copy to nurses attending the 2019 EAHAD Congress and promoted as an online survey hosted by Survey Monkey.
Results: Seventy-five replies were received from nurses in Europe (46 in the UK), and two from nurses in Chile and the Philippines. Most described their role as ‘specialist nurse’, with the majority having worked in haemophilia care for up to ten years. Half had a nursing degree and one quarter had a nursing diploma. Three quarters had attended at least one course specifically related to haemophilia nursing. Almost all used academic sources, study days and the websites of health profession organisations as information sources. Most also used Google or Wikipedia, but fewer used Twitter. Patient association websites were more popular among non-UK nurses. About half attended sponsored professional meetings and three quarters reported that educational meetings were available in their workplace. A clear majority preferred interactive and face-to-face activities using patient-focused content.
Conclusions: The study shows that nurses, predominantly in Western Europe, access a range of educational resources, most of which are ‘traditional’. Use of online sources is high, but social media are less popular than Google or Wikipedia. Further research is needed to explore the potential of new media for haemophilia nurse education, and whether the current educational levels and needs highlighted in the survey remains the same across the whole of Europe.
Dragana Djordjevic, Jelena Milovanovic, Milena Jurisevic, Bojana Stojanovic, Olga Cvetkovic, Marija Pergal, Elizabeta Ristanovic, Danilo Vojvodic, Milos Simic, Dragan Manojlovic, Marija Milovanovic and Nebojsa Arsenijevic
Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.
The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin.
Dragce Radovanovic, Mladen Pavlovic, Dragan Canovic, Dejan Lazic, Aleksandar Cvetkovic, Marko Spasic, Bojan Stojanovic and Bojan Milosevic
One of the most intriguing problems in modern esophageal surgery is the acquired short esophagus. While some authors recognize this entity, others deny its existence. There is a consensus about types of the short esophagus, its etiology and pathophysiology. Definitive diagnosis can be established only intraoperatively. There are a few surgical procedures for this problem, and most frequently is used Collis gastroplasty with fundoplication. In this review we emphasize recent literature data and further perspectives of the Collis procedure.