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Introduction: Oral cavity is the colonization site of most diverse microorganisms. The homeostasis of oral microbioma is affected by numerous factors. Periodontal diseases occur as a consequence of disturbed oral microbioma homeostasis, when an inflammatory reaction occurs in the periodontal tissue. The impact of parasites on periodontal pathophysiology has not been sufficiently studied, and present and future research should hopefully answer quite a few questions concerning the issue. Aim of the paper: In the light of the present knowledge of the pathogenesis, diagnosis and epidemiology of oral cavity infections caused by Entamoeba gingivalis and Trichomonas tenax, the aim of the paper was review of literature which could to point to the importance of protozoa in the practice of dentistry and to possible oral cavity manifestations of parasitic infections relevant for public health. Conclusion: Dentists have an essential role in the diagnosis of oral diseases caused by oral cavity protozoa, and protozoa relevant for public health that produce systemic infections, the pathological changes of which may manifest in the oral cavity. Their identification represents a challenge and requires multidisciplinary approach for a timely diagnosis and adequate management.

Today, we are witnessing an explosion of scientific concepts in cancer chemotherapy. It has been considered for a long time that genetic instability in cancer should be treated with drugs that directly damage the DNA. Understanding the molecular basis of malignant diseases shed light on studying phenotypic plasticity. In the era of epigenetics, many efforts are being made to alter the aberrant homeostasis in cancer without modifying the DNA sequence. One such strategy is modulation of the lysine acetylome in human cancers. To remove the acetyl group from the histones, cells use the enzymes that are called histone deacetylases (HDACs). The disturbed equilibrium between acetylation and deacetylation on lysine residues of histones can be manipulated with histone deacetylase inhibitors (HDACi). Throughout the review, an effort will be made to present the mechanistic basis of targeting the HDAC isoforms, discovered selective HDAC inhibitors, and their therapeutical implications and expectations in modern drug discovery.

Introduction. The exact prevalence of benign familial neonatal epilepsy (BFNE) is unknown due to the likelihood of overlooking the disease and not diagnosing the affected patients correctly. The rare autosomal dominant inherited disorder usually occurs within a few days after birth of an otherwise healthy newborn, and disappears after one to four months. Most patients develop no psychomotor deficiencies, nor any other forms of seizures. The disorder is most commonly linked to the KCNQ2 gene, with mutations located on the chromosome 20q13.33 which cause voltage-gated potassium channel changes. This clinically rare condition manifests itself in repeated tonic-clonic episodes of focal and generalized convulsions which are effectively treated with antiepileptic therapy. Case report. We presented a five-day old affected male infant, with genetically proven KCNQ2 gene mutation, in addition to a positive familial history of epilepsy. Seizures did not reoccur after several episodes in the fifth day of life and further psychomotor development of the child proved normal. Conclusion. Neonatal seizures have extensive differential diagnosis. However, BFNE should be suspected when the most common neonatal seizure causes have been excluded, and factors, such as the hereditary factor, in addition to the typical clinical course resembling BFNE, can be observed. Genetic identification of BFNE has resulted in easier and more specific diagnosis of this rare disorder and is therefore the gold standard in its diagnostics.

Drug discovery and development is a very challenging, expensive and time-consuming process. Impressive technological advances in computer sciences and molecular biology have made it possible to use computer-aided drug design (CADD) methods in various stages of the drug discovery and development pipeline. Nowadays, CADD presents an efficacious and indispensable tool, widely used in medicinal chemistry, to lead rational drug design and synthesis of novel compounds. In this article, an overview of commonly used CADD approaches from hit identification to lead optimization was presented. Moreover, different aspects of design of multitarget ligands for neuropsychiatric and anti-inflammatory diseases were summarized. Apparently, designing multi-target directed ligands for treatment of various complex diseases may offer better efficacy, and fewer side effects. Antipsychotics that act through aminergic G protein-coupled receptors (GPCRs), especially Dopamine D2 and serotonin 5-HT2A receptors, are the best option for treatment of various symptoms associated with neuropsychiatric disorders. Furthermore, multi-target directed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors are also a successful approach to aid the discovery of new anti-inflammatory drugs with fewer side effects. Overall, employing CADD approaches in the process of rational drug design provides a great opportunity for future development, allowing rapid identification of compounds with the optimal polypharmacological profile.

Introduction: Neuroblastoma cells show the expression of norepinephrine transporters enabling the intercellular location of mIBG, which turned out to be ideal for the visualization of neuroblastoma, as well as for the treatment of these tumors in certain cases. Aim: The aim of this retrospective analysis is to show the possibilities of the 131/123J-mIBG scintigraphy in detecting primary tumor as well as in determining the presence and localization of metastatic lesions in children with neuroblastoma. Material and methods: The investigation was carried out in 17 subjects, 7 boys and 10 girls, aged 8.2 ± 7.8 (4 months to 16 years). In 10 of them the IV neuroblastoma was confirmed. A number of 7 children underwent only the diagnostic scintigraphy while in 10 of them 2-5 scans with 123/131J-mIBG were performed during follow-up. In total, there were 35 scintigraphy for the analysis. Results: A negative finding of 123/131J-mIBG scan was observed in 8 subjects. In one of them, neuroblastoma was histopathologically proven, but the scintigraphy was performed after the surgical removal of the tumor and after chemotherapy. In 9 children with scintigraphically confirmed neuroblastoma, apart from having the primary tumor, the metastatic spread of the disease was detected in the bone marrow during the initial staging. After the treatment, 4 children had a negative finding on mIBG scintigraphy, which indicated the remission, while in 2 children, the tumor relapsed; and in 4 of them, the regression of the tumor occurred after the treatment. Conclusion: The results showed high sensitivity of 123/131J-mIBG scintigraphy in detecting neuroblastoma, both the primary tumor and metastases in the bone marrow. This radiopharmaceutical turned out to be reliable for the treatment monitoring of children with neuroblastoma. Likewise, a high incidence of bone metastases was detected on the mIBG scintigraphy, as well as a the high rate of disease recurrence after therapy.

Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5 – methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min−1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15–35 μg mL−1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs. [ABSTRACT FROM AUTHOR]

Introduction: Differentiated thyroid carcinoma (DTC) derived from follicular cells is the most frequent endocrine malignancy, which most commonly occurs in patients with thyroid nodules. Aim: The aim of this retrospective analysis is to examine the type of scintigraphic finding of the thyroid gland obtained with 99mTc-pertechnetate in patients with DTC before tireoidectomy. Material and methods: Medical documentation comprised of 95 subjects with presurgical evaluation of thyroid nodules, including 18 men (51.5 ± 8.7 years old, range 43-68) and 77 women (48 ± 12, range 14-72 years). Other tests performed during the preoperative tests are the following: ultrasound examination of the thyroid gland, thyrotropin and thyroglobulin concentration measurement. Results: During the preoperative evaluation, thyroid ultrasound was performed in 20 (21%) out of 95 subjects with DTC, while 99mTc-pertechnetate scintigraphy was performed in 75 (79%) of patients, in addition to a clinical examination. What is the distribution of scintigraphic finding? Significantly, the highest incidence of DTC was found in the multinodular goiter: 61 (64%) subjects were diagnosed with this type of DTC, while 31 (33%) carcinomas were found in abnormal, solitary "cold" nodules. The most frequent histopathological finding amongst nodules and multinodular goiter detected by scintigraphy was papillary thyroid carcinoma. Thyroid carcinoma was found in two patients with Graves' disease and in one patient with a normal scintigraphic finding. The values of thyroid hormones were normal in 71% of DTC and elevated in fewer cases (21%). The ultrasound examination showed high-risk features in only 18 subjects (19%). Conclusion: Our results have shown that DTC is the most common finding in the multinodal goiter, and that it occurs much less often within the "cold" thyroid nodules. In a small percentage of subjects, thyroid neoplasm was found in patients with hyperthyroidism. The results of the study showed that thyroid gland scintigraphy with 99mTc-pertechnetate still has a significant diagnostic role in the examination of thyroid nodules.

The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs.

All tested compounds show agonistic activity onserotonin5-HT2areceptors, which activation causes neuronal excitations, behavioral changes and platelet aggregation. The main aims of this study were to create 3D-QSAR(3D-Quantitative structure-activity relationship)model, analyse 3D-structure of the pharmacophore, validate the 3D-QSARmodel, and propose structural modification for novel 5-HT2aagonists.3D-QSAR modeling was applied to 51 agonists of 5-HT2areceptors. Dominant forms at physiologic pHof the examined compounds were optimized using the PM3 method and used for QSAR modeling. Data set was divided in two groups, training set of38 compounds, and test set of 13 compounds. Training set was used to build 3D-QSAR model, while test set was examined for the model validation. PLS (Partial Least Square Regression)method was used to develop 3D-QSAR model. Statistical parameters of the created and validated 3D-QSAR model,R2= 0.93, Q2=0.72, RMSEE=0.178, RMSEP=0.190 and R2 pred=0.63, indicate good prognostic capacity of the model.The3D-QSAR model was applied to analyse pharmacophore and to predict activity of other agonists of serotonin 5-HT2areceptors. Information obtained from the 3D-QSAR study indicated that presence of hydrogen bond donor and steric hot spot at a distance 14.80-15.20Å (v477:O-TIP), hydrophobic region and hydrogen bond donor at a distance of 2.40-2.86Å (v226:DRY-O), hydrogen bond donor and hydrogen bond acceptor at a distance of 1.60-2.00Å (v389:O-N1) and two hydrophobic regions at a distance 9.20-9.60Å (v23:DRY-DRY) are essential for agonistic activity on 5-HT2aserotonin receptors.

Creation of a statistically reliable 3D-QSAR (Quantitative Structure Activity Relationships) model enables definition of the structure of the pharmacophore for antagonists of serotonin 5-HT2A receptors and selection of the key molecular determinants for the design of new antagonists. A 3D-QSAR study was applied on a series of 50 antagonists of 5-HT2A receptors. The data set is divided into the training set, composed of 33 compounds, and test set containing 14 molecules. The training set was used to build the 3D-QSAR model, while test set was used for model validation. This 3D-QSAR study was performed by use of the Pentacle 1.07 programs. Obtained statistical and validation parameters for training set (R²= 0.96; Q²=0.75, RMSEE= 0.211); and for test set (R²pred=0.51; RMSEP= 0.558); indicate on reliability and good predictive potential of the 3D-QSAR model. Based on the most influential variables of the selected 3D-QSAR model, the molecular determinants for the antagonistic effect on the 5-HT2A receptors were selected: hydrogen bond acceptor and hydrogen bond donor at a distance of 10.4A-10.8A (v495: O-N1); carbonyl oxygen and a steric hot spot at a distance of 14.8A-15.2A (v640: N1-TIP); hydrophobic domain and hydrogen bond acceptor at a distance of 3.2A-3.6A (v276: DRY-O); two steric hot spots at a distance of 18.8A-19.2A (v248: TIP-TIP) .

Introduction/Aim. Psoriasis is a chronic, relapsing, non-infectious dermatosis, affecting patients quality of life. There is still insufficient evidence from routine clinical practice on how the biological therapy improves the quality of life of patients with psoriasis. The aim of our study was to examine the effectiveness of biological therapy, regardless of the drug type, on health-related quality of life (HRQoL) in patients with psoriasis. Methods. We performed a prospective observational pilot study at the Clinic of Dermatovenerology, University Clinical Center Niš in the period from from October 1, 2019 to March 1, 2020. The study involved 29 patients with psoriasis vulgaris (11 females, 18 males) on biological therapeutics regardless of the type of the drug. The severity of psoriatic lesions and the patient's response to treatment was assessed using the Psoriasis Area and Severity Index (PASI) before the treatment with secukinumab and ustekinumab and after 10 weeks. Dermatology Life Quality Index (DLQI) was determined at the beginning of biological treatment as well as after 10 weeks. Results. The average age of participants was 49.69 ± 12.75 years and the sample consisted mainly of men (62.1%). The average disease duration among men was 16.44 ± 10.05 years, and among women 17.82 ± 12.79 years. The mean DLQI decreased from 15.62 ± 7.79 to 6.34 ± 7.19 after biological treatment. The initial mean PASI and DLQI scores differed significantly from the average control scores (t-test for paired samples, p < 0.0001). Conclusion. Biological therapies of psoriasis, in addition to improving the clinical picture, demonstrated an improvement in the patients' HRQoL very quickly and they should be considered during evaluating the benefits and risks of this type of therapy. [ABSTRACT FROM AUTHOR]