MLPA analysis - application in the diagnostic activity of the medical geneticist

The article is mainly focused on physicians (hospital clinicians, family doctors) without specific experience in medical genetics, whose patients present with a probable genetic condition. We present the essence, possibilities and limitations of multiplex ligase-dependent amplification (MLPA) as a method for establishing a genetic diagnosis. The article describes cases from the experience of the Laboratory of Medical Genetics, Varna in the application of the method as a target and/or screening test in children with dysmorphic features and/or mental retardation. We emphasize on the role of the medical geneticist in patient selection, the choice of analysis, and comment on the results

Design and specific features of the Programme for Early Detection and Follow-Up of Full-Term and Preterm Children, Born Small for Their Gestational Age

In 2007 the International Consensus for Management of Children Born Small for Their Gestational Age (SGA) was published. SGA birth is connected to many complications in different periods of life. Often in practice children born with small sizes are underestimated and not always referred timely to а pediatric endocrinologist. Thеse children represent а significant part of children with growth problems. In our country there is not enough information for the condition and algorithm for its follow-up. Having all this in mind, Varna Pediаtric Endocrine Society (VAPES) and Bulgarian Neonatology Association (BNА) created the Programme for Early Detection and Follow-Up of Full-Term and Pre-Term Children, Born SGA. The current publication presents the design of the study. The Programme is scientifically applied investigation for early detection of full-term and preterm SGA children, aiming to facilitate timely diagnosis of syndromes and conditions connected to SGA births and, if needed, to recommend additional testing, including genetic. Through the Programme we expect to update the data for the prevalence of SGA births and SGA children without postnatal catch-up in our country. At the end of the Programme, we will evaluate its cost-effectiveness and will create an algorithm for detection and treatment of these children

Investigations of anatomical characteristics of some wine and table - grapevine cultivars, in Skopje area of vineyards

Comparative researches of anatomical characteristics on the plant (grapevine cultivars Vitis Vinifera) are important for disposition in the area around oneself(training system). Anatomical and physiogical charateristics are genetic determinate and they indicate of the genotypical variability. In this paper are presented results from investigations of some anatomical and physiological characteristics on mature branches of some cultivars (dattier, muscat hamburg, vranec, merlot, zilavka and riezling). Anatomical characteristics are the internode length, anatomical construction of buds, a diameter etc., and they are features of cultivars. The researches were conducted during the period 2002-2005 in the grapevine plantations of the Institute of Agriculture, Skopje. The mature branches, in two variants were measured - from 1 to 8 bud, and from 1 to 10 bud. The internodes, from 4 to 10 bud, separately were measured. The anatomical construction of buds and diameter were observed with diagonal and longitudinal cuts. They were photographed, separately. Fom analysis, mean value from 30 representative samples was taken. For comparison of the analysed characteristics at investigated cultivars, the official O.I.V botanical classification (description) was used. The obtained result of the analysed parametars are of a great importance for physiological condition of plant, approprition of training system, trunk number per unit of surface, planting distance, fertility of buds an so on

Basic geotechnical parameters of metallic mineral deposits in the Republic of Macedonia

This paper deals with the analysis of basic geotechnical properties of monolithic rock samples from several metallic mineral deposits in the Republic of Macedonia. Namely, results from geotechnical investigation on samples from the deposits of Ilovica, Borov Dol, Kazan Dol, Plavica, Kadiica and Bu�im were subject of the work presented herein. Over 800 different geotechnical tests have been performed on samples from different depths and zones of these deposits. The most frequently performed basic tests during geotechnical investigation phases included:point load index tests, unconfined compression tests, unit and specific weight, porosity, shear strength along joints. All data is statistically analyzed and certain conclusions for different geotechnical parameters are achieved. Special attention is paid to the vertical distribution of the parameter’s values, since this is of greatest interest for the mining planning and processes. Differences among certain deposits are discussed and certain conclusions and recommendations for further investigations are presented. We note that this is a first attempt to analyze such amount of geotechnical data from metallic mineral deposits in Macedonia, and the herein presented correlations are to be updated as new data is collected. Key words: geotechnical properties; metallic mineral deposits; statistical analysis; vertical distributio

Recent Advances in Anti-Tuberculosis Drug Discovery Based on Hydrazide–Hydrazone and Thiadiazole Derivatives Targeting InhA

Tuberculosis is an extremely serious problem of global public health. Its incidence is worsened by the presence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. More serious forms of drug resistance have been observed in recent years. Therefore, the discovery and/or synthesis of new potent and less toxic anti-tubercular compounds is very critical, especially having in mind the consequences and the delays in treatment caused by the COVID-19 pandemic. Enoyl-acyl carrier protein reductase (InhA) is an important enzyme involved in the biosynthesis of mycolic acid, a major component of the M. tuberculosis cell wall. At the same time, it is a key enzyme in the development of drug resistance, making it an important target for the discovery of new antimycobacterial agents. Many different chemical scaffolds, including hydrazide hydrazones and thiadiazoles, have been evaluated for their InhA inhibitory activity. The aim of this review is to evaluate recently described hydrazide-hydrazone- and thiadiazole-containing derivatives that inhibit InhA activity, resulting in antimycobacterial effects. In addition, a brief review of the mechanisms of action of currently available anti-tuberculosis drugs is provided, including recently approved agents and molecules in clinical trials

Zinner Syndrome-From Diagnosis to Successful Treatment-A Case Report

A seventeen-year-old boy was admitted and referred for MR evaluation of acute abdominal and pelvic irritation and discomfort, dysuria and severe pain during ejaculation, the latter symptoms coincident with puberty and the onset of sexual activity. Prior ultrasound had revealed findings consistent with a hypoplastic, hydronephrotic, ectopic left kidney and compensatory hypertrophy of the right kidney. The improved tissue resolution and more precise anatomical delineation of the genitourinary tract afforded by MRI revealed the typical triad of Zinner’s syndrome-unilateral renal agenesis, ipsilateral seminal vesical cysts and obstruction of the ejaculatory duct. MRI not only facilitated the final correct diagnosis, but also supported surgical planning and successful treatment-laparoscopic resection of the left seminal vesicle, which led to complete cure, symptomatic relief and restoration of fertility. Knowledge and understanding of the anatomy and embryology of the genitourinary tract is necessary for obtaining the accurate diagnosis by using appropriate imaging modalities

Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives

Fifteen 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives 3a–d and sulfonyl hydrazones 5a–k were synthesized. They were characterized by 1H-NMR, 13C NMR, and HRMS. Mycobacterium tuberculosis strain H37Rv was used to assess their antimycobacterial activity. All compounds demonstrated significant minimum inhibitory concentrations (MIC) from 0.07 to 0.32 µM, comparable to those of isoniazid. The cytotoxicity was evaluated using the standard MTT-dye reduction test against human embryonic kidney cells HEK-293T and mouse fibroblast cell line CCL-1. 4-Hydroxy-3-methoxyphenyl substituted 1,2,3-thiadiazole-based hydrazone derivative 3d demonstrated the highest antimycobacterial activity (MIC = 0.0730 µM) and minimal associated cytotoxicity against two normal cell lines (selectivity index SI = 3516, HEK-293, and SI = 2979, CCL-1). The next in order were sulfonyl hydrazones 5g and 5k with MIC 0.0763 and 0.0716 µM, respectively, which demonstrated comparable minimal cytotoxicity. All compounds were subjected to ADME/Tox computational predictions, which showed that all compounds corresponded to Lipinski’s Ro5, and none were at risk of toxicity. The suitable scores of molecular docking performed on two crystallographic structures of enoyl-ACP reductase (InhA) provide promising insight into possible interaction with the InhA receptor. The 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives and sulfonyl hydrazones proved to be new classes of lead compounds having the potential of novel candidate antituberculosis drugs

Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold

This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 mu M), 7o (MIC 0.15 mu M) and 7k (MIC 0.17 mu M) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established

In Vivo Toxicity, Redox-Modulating Capacity and Intestinal Permeability of Novel Aroylhydrazone Derivatives as Anti-Tuberculosis Agents

The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development. Here, we present the aroylhydrazone compounds (3a and 3b) regarding their: (i) acute and subacute toxicity in mice; (ii) redox-modulating in vivo and in vitro capacity; (iii) pathomorphology in the liver, kidney, and small intestine tissue specimens; and (iv) intestinal permeability. The acute toxicity test showed that the two investigated compounds exhibited low toxicity by oral and intraperitoneal administration. Changes in behavior, food amount, and water intake were not observed during 14 days of the oral administration at two doses of 1/10 and 1/20 of the LD50. The histological examination of the different tissue specimens did not show toxic changes. The in vitro antioxidant assays confirmed the ex vivo results. High gastrointestinal tract permeability at all tested pH values were demonstrated for both compounds. To conclude, both compounds 3a and 3b are highly permeable with low toxicity and can be considered for further evaluation and/or lead optimization