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Aim: In this study, the best corrected visual acuity (BCVA) and refraction in preterm-born infants in South-Eastern Bulgaria after 12 years of treatment for type 1 prethreshold retinopathy of prematurity were presented, and the outcomes of laser treatment and cryotherapy were compared. Materials and methods: Since 2010, we have treated 319 eyes of 164 prematurely born children for type 1 prethreshold retinopathy of prematurity and were prospectively followed up. The mean (range) gestational age was 28.6 weeks of gestation (23–33) and the mean (range) birth weight was 1143 g (570–1990). Cryotherapy was applied on 76 eyes (23.2%), laser was used in 215 eyes (65.5%), anti-VEGF – in 10 eyes (3%) and surgery – in 18 eyes (5.5%). Twelve children (24 eyes, 7.3%) were lost to the follow-up. BCVA was tested in 114 eyes and refraction in 190 eyes. Because of the small number of eyes treated surgically or with anti-VEGF (18 and 10, respectively), these children’s eyes were excluded from the statistical analysis. Results: Fifty eyes showed BCVA between 0.6 and 1.0; 25 eyes – between 0.2 and 0.5; 5 eyes – between 0.04 and 0.1; 5 eyes between light perception –0.03 and 4 eyes were totally blind. Laser-treated eyes showed statistically significantly higher BCVA compared to the cryotherapy treated eyes (Fisher’s exact test, p=0.012). Myopia (any myopic refraction) was found in 50 eyes; hyperopia (>+2 D) – in 20 eyes; astigmatism (difference between the two principal meridians >0.75 D) – in 70 eyes, and emmetropia – in 30 eyes. Although in the laser-treated group more eyes showed emmetropic and hyperopic refraction compared to cryo treated group (25 eyes vs. 7 eyes – emmetropia and 15 eyes vs. 5 eyes – hyperopia, respectively), the difference did not reach statistical significance (Fisher’s exact test, p=0.106). Conclusion: Timely treatment of type 1 prethreshold retinopathy of prematurity leads to very good anatomical and functional results. Laser treatment leads to significantly higher BCVA, compared to cryotherapy. Emmetropia and hyperopia are more commonly seen in laser-treated eyes.

Introduction: The main goal of orthodontic retention is to keep the teeth in their corrected positions. Fixed or removable retainers are the most common types of retainers used during the retention phase. For the maxilla, various types of retainers have been described, including the vacuum-formed retainers and Hawley retainers. Fixed retainers are used for the lower jaw. Aim: The aim of the present study was to assess the retention characteristics of Hawley retainers, vacuum-formed retainers, and fixed retainers in preserving dental arch dimensions and tooth alignment. Materials and methods: Seventy subjects were examined and distributed into two retention groups. One of the groups received maxillary Hawley retainers and bonded retainers in the mandible. The other group received maxillary vacuum-formed retainers and bonded retainers in the mandible. The mean retention period was two years. Maxillary and mandibular casts were analyzed at pretreatment, debonding, and two years in retention. The assessed measurements were the arch length, intercanine width, interpremolar width, intermolar width and Little’s irregularity index. Results: Vacuum-formed retainers maintained maxillary anterior teeth alignment more effectively than Hawley retainers did. No differences in transversal dimensions were found between the two retention protocols. Hawley retainers showed superior retention characteristics in maxillary arch length preservation compared to vacuum-formed retainers. Even with bonded retainers, relapse could still happen. All measured variables showed a tendency to relapse to the pretreatment values in the two groups. Conclusions: Vacuum-formed retainer maintained maxillary incisor position more effectively than Hawley retainers did. No differences were observed in the transversal dimensions between the two groups. A greater decrease in the mandibular intermolar width was measured between T1 and T2 in both groups where bonded retainers were used.

Cotinus coggygria Scop. is a valuable medicinal plant species with pronounced pharmacological potential due to its numerous biological activities. The herb is characterized by a high content of polyphenols among which is fustin. The anticancer activities of fustin, however, are extremely weakly studied. The aim of the present study was to investigate the in vitro antiproliferative potential of fustin isolated from the heartwood of C. coggygria against cell lines originating from two of the most common cancer types – breast (MDA-MB-231 and MCF7), and colon cancer (Colon 26).

In this study, UHPLC-HRMS analysis of the defatted methanol extract obtained from Inula salicina L. led to the identification of 58 compounds—hydroxycinnamic and hydroxybenzoic acids and their glycosides, acylquinic and caffeoylhexaric acids, and flavonoids and their glycosides. In addition, a new natural compound, N-(8-methylnepetin)-3-hydroxypiperidin-2-one was isolated and its structure was elucidated by NMR spectroscopy. The presence of a flavoalkaloid in genus Inula is described now for the first time. Chlorogenic acid was the main compound followed by 3,5-, 1,5- and 4,5-dicaffeoylquinic acids. The methanol extract was studied for its antioxidant potential by DPPH, ABTS, and FRAP assays and sun protective properties. In addition, a study was conducted to assess the effectiveness of the tested extract in inhibiting biofilm formation by Gram-positive and Gram-negative strains. Results from crystal violet tests revealed a notable decrease in biofilm mass due to the extract. The anti-biofilm efficacy was confirmed through the observation of the biofilm viability by live/dead staining. The obtained results showed that this plant extract could be used in the development of cosmetic products with antibacterial and sun protection properties.

Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research’s need to enhance cancer patients’ outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.

The formation of microbial biofilm is a self-organizing process among bacterial cells, regulated by quorum-sensing (QS) mechanisms, contributing to development of infections. These processes, either separately or in combination, significantly contribute to bacterial resistance to antibiotics and disinfectants. A novel approach to addressing the challenge of treating infections due to antibacterial resistance involves the use of plant metabolites. In recent years, there has been increasing recognition of different phytochemicals as potential modulators. In our study, we evaluated the synergistic effect of chloroform and methanol extracts from Inula species against key virulence factors, including biofilm formation, violacein production, and swarming motility. Each of the 11 examined plant extracts demonstrated the ability to reduce biofilms and pigment synthesis in C. violaceum. Two of the extracts from I. britannica exhibited significant anti-biofilm and anti-quorum-sensing effects with over 80% inhibition. Their inhibitory effect on violacein synthesis indicates their potential as anti-QS agents, likely attributed to their high concentration of terpenoids (triterpenoids, sesquiterpene lactones, and diterpenoids). Scanning electron microscopy revealed a notable reduction in biofilm biomass, along with changes in biofilm architecture and cell morphology. Additionally, fluorescence microscopy revealed the presence of metabolically inactive cells, indicating the potent activity of the extracts during treatment. These new findings underscore the effectiveness of the plant extracts from the genus Inula as potential anti-virulent agents against C. violaceum. They also propose a promising strategy for preventing or treating its biofilm formation.

Recent scientific interest has been directed towards age-related diseases, driven by the significant increase in global life expectancy and the growing population of individuals aged 65 and above. The ageing process encompasses various biological, physiological, environmental, psychological, behavioural, and social changes, leading to an augmented susceptibility to chronic illnesses. Cardiovascular, neurological, musculoskeletal, liver and oncological diseases are prevalent in the elderly. Moreover, ageing individuals demonstrate reduced regenerative capacity and decreased tolerance towards therapeutic interventions, including organ transplantation. Liver diseases, such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis, have emerged as significant public health concerns. Paradoxically, these conditions remain underestimated despite their substantial global impact. Age-related factors are closely associated with the severity and unfavorable prognosis of various liver diseases, warranting further investigation to enhance clinical management and develop novel therapeutic strategies. This comprehensive review focuses specifically on age-related liver diseases, their treatment strategies, and contemporary practices. It provides a detailed account of the global burden, types, molecular mechanisms, and epigenetic alterations underlying these liver pathologies.

Introduction: The number of published biofilm studies and novel ways for studying them has risen dramatically in recent years, ow-ing to the broad application of biofilms in medicine. Some bacteria develop biofilms that are highly resistant to antimicrobial agents, resulting in persistent infections. This necessitates the development of alternative methods for combating biofilms. In this regard, the application of cationic polymers is a good candidate for realization of this strategy. Aim: The aim of our study was to investigate the potential of a newly synthesized covalently attached star copolymer of N,N’-dimeth-ylaminoethyl methacrylate and hydroxyl-bearing oligo(ethylene glycol) methacrylate [P(DMAEMA-co-HOEGMA)] to silica surfaces and its quaternized version [P(QDMAEMA-co-HOEGMA)] for destruction of biofilms formed by Bacillus subtilis or Pseudomonas aeruginosa. Materials and methods: Model strains representing different genera and taxonomic groups were selected for the study. The anti-biofilm activities of two different newly synthesized cationic polymers were investigated by observation (live/dead staining) of the viability of bacterial cells within the biofilm.Results: The results obtained by the live/dead labeling of bacterial biofilms show a substantial decrease in the viability of population in the presence of cationic polymers, better expressed at B. subtilis.Conclusions: The studied two immobilized on silica wafers newly synthesized star copolymers exhibited potential for anti-biofilm effects. The results demonstrated combined potential for reducing the viability of bacterial cells within the biofilms and probably for loosening the biofilm matrix. The effect was better expressed in B. subtilis.

The association of immunocompromised patients and severity of COVID-19 infection is not well established. According to the Centers for Disease Control and Prevention (CDC), primary immune deficiencies (PIDs) are among the conditions that can predispose to a more severe course of COVID-19. We report the clinical course and immunological evaluation of five patients with common variable immune deficiency (CVID) who have experienced SARS-CoV-2 virus. Here we assess the severity of the infection, the immunophenotypic profile of the major lymphocyte subgroups, the nonspecific T-cell functional capacity and the SARS-CoV-2 specific effector T-cell immune response. Our results showed that the course of COVID-19 infection in CVID patients was mild to moderate and none of them developed a critical form of the disease. All patients developed a specific SARS-CoV-2 T cell immune response. Lymphopenia as well as impaired T-cell response prior to COVID-19 appeared to be related to a more severe course of the infection. Data on a good specific T cell response against SARS-CoV-2 in CVID patients will help to make the right vaccination decision and establish its efficacy. Clinical outcome even in these individual cases was in agreement with the therapeutic recommendations underlining that regular maintenance with subcutaneous immunoglobulins can be beneficial against immune system overreaction and a severe disease course and convalescent plasma is a treatment option in patients with CVID and COVID-19.

Background and objectives. Though glyceraldehyde-3-phosphate dehydrogenase (Gapdh) is one of the most commonly used housekeeping genes for comparison of gene expression data, studies have revealed that Gapdh expression is not constant at different developmental stages, and is modulated by many factors including ethanol. In view of this, in the present study, we investigated the effect of ethanol on Gapdh stability and expression levels in different model systems.

The leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown to have medicinal benefits and are extensively employed in traditional folk medicine. Herein, HPLC analysis of the ethyl acetate fraction of the total methanolic extract emphasized the enrichment of both A. indica L., and M. azedarach L. leaves extracts with phenolic and flavonoids composites, respectively. Besides, 4 limonoids and 2 flavonoids were isolated using column chromatography. By assessing the in vitro antiviral activities of both total leaves extracts against Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2), it was found that A. indica L. and M. azedarach L. have robust anti-SARS-CoV-2 activities at low half-maximal inhibitory concentrations (IC50) of 8.451 and 6.922 μg/mL, respectively. Due to the high safety of A. indica L. and M. azedarach L. extracts with half-maximal cytotoxic concentrations (CC50) of 446.2 and 351.4 μg/ml, respectively, both displayed extraordinary selectivity indices (SI>50). A. indica L. and M. azedarach L. leaves extracts could induce antibacterial activities against both Gram-negative and positive bacterial strains. The minimal inhibitory concentrations of A. indica L. and M. azedarach L. leaves extracts varied from 25 to 100 mg/mL within 30 min contact time towards the tested bacteria. Our findings confirm the broad-spectrum medicinal value of A. indica L. and M. azedarach L. leaves extracts. Finally, additional in vivo investigations are highly recommended to confirm the anti-COVID-19 and antimicrobial activities of both plant extracts.

The limitation in bone tissue engineering is the lack of available natural or synthetic biomaterials to replace bone tissue under need. Carbon nanotubes have great potential as bone tissue scaffolds because of their remarkable mechanical and electrical properties combined with high aspect ratio. In this work, we demonstrated for the first time a novel approach based on the sol-gel technique for functionalization of multi-walled carbon nanotubes (MWCNTs) with two amino acids: L-arginine, L(+) Arg and L-aspargine, L(+) Asp. We have examined the effect of both functionalities on physico-chemical properties of MWCNTs, cytotoxicity in osteosarcoma MG63 and normal fibroblastic BJ cells and the ability to induce nucleation and growth of hydroxyapatite (HA) crystals in vitro under physiological concentrations of Ca2+ and PO4+ (SBF). The scaffolds were characterized using Fourier transform infrared spectroscopy (FTIR-ATR), dynamic light scattering technique (DLS), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The results showed that both functionalized MWCNTs have a particle size of 269 and 411 nm, a zeta potential of –12.8 and –8.8 mV, respectively, high colloidal stability, enhanced biocompatibility, and enhanced formation of an apatite layer on the scaffolds surface in comparison to ox-MWCNTs. Altogether, the results confirmed the important role of the amino acids L(+) Arg and L(+) Asp in ox-MWCNTs-based composites for bone tissue engineering applications.

Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into first-line defense mechanisms against bacterial infections of the lung.

Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the Cryptococcus neoformans and Cryptococcus gattii species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the C. gattii species complex. There is an increase in resistance to fluconazole for yeasts of the C. gattii species complex and the virulence is variable according to the genotype. In the present study, (i) we explored and compared the mechanisms of resistance to fluconazole between C. deuterogattii clinically resistant strains and induced fluconazole-resistant strains by exposure to fluconazole in vitro, and (ii) we studied their virulence in the Galleria mellonella study model. We demonstrated that the fluconazole resistance mechanisms involved were different between clinically resistant strains and induced resistant strains. We also demonstrated that fluconazole-induced resistant strains are less virulent when compared to the original susceptible strains. On the contrary, the clinically resistant strain tested maintains its virulence compared to fluconazole-susceptible strains of the same sequence type.

Background: Cross-resistance to medical azoles by exposure to azole pesticides is well documented for Aspergillus family fungi but is poorly evaluated for other environmental pathogen fungi, particularly for yeasts belonging to the Cryptococcus neoformans/Cryptococcus gattii species complexes. Methods: One thousand C. neoformans yeast were exposed to various concentrations of seven different commonly used azole pesticides. Clones surviving exposure were picked randomly, and their minimal inhibitory concentrations (MICs) of fluconazole, voriconazole, posaconazole, itraconazole and isavuconazole were assessed. Results: Depending on the pesticide used for exposure, up to 13.3% of selected Cryptococcus colonies showed a phenotype of resistance to fluconazole, and among them, several showed cross-resistance to another or several other medical azoles. Molecular mechanisms involved in the resistance setups seem to be dependent on ERG11 and AFR1 gene overexpression. Conclusion: Exposure to any of the seven azole pesticides tested is capable of increasing the MIC of fluconazole in C. neoformans, including up to the level of the fluconazole-resistant phenotype, as well as generating cross-resistance to other medical azoles in some cases.

Introduction: Nosocomial infections (NI) are frequent complications in neonatal intensive care units (NICU) which result in high morbidity and mortality.Aim: To determine and analyze the incidence, risk factors and etiologic agents of NI in newborns admitted in the NICU to help plan-ning future surveillance and prevention strategies.Materials and methods: A prospective cohort study was carried out at the NICU of St George University Hospital, Plovdiv, Bul-garia from January 1, 2017 to June 31, 2018. The number of neonates included in the study was 507. Descriptive statistics such as count, percent, mean and standard deviation was used. Chi-square test was performed to prove associations. Odds ratios, with 95% confidence intervals, were computed from the results of the binominal logistic regression analyses.Results: Of the 507 hospitalized newborns in NICU, 48 presented with 54 NI. The incidence and the density incidence rates were 9.5% and 7.67 per 1,000 patient-days, respectively. Nosocomial infections were detected in neonates from all birth weight (BW) classes, but it was low BW and premature neonates that were at major risk to acquire them. The most common infection sites were ventilator-asso-ciated pneumonia (VAP) (67.27%), bloodstream infection (23.64%) and conjunctivitis (9.09%). Major pathogens were Gram-negative such as Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa and Acinetobacter baumannii. In the multivariate logistic regression analysis NIs were strongly associated with intubation, presence of a venous catheter, the duration of antibiotic treatment and increased CRP> 10 mg/l.Conclusions: This report highlights the burden of NIs, identifies the major focus for future NI control and prevention programs.

Background and objectives. Though numerous studies have shown that the dysregulation of the epigenetic control is involved in disease manifestation, limited data is available on the transcriptional activity of DNA methylation related genes in alcohol and drug addiction. With regard to this, in this study we analyzed the expression levels of genes involved in DNA methylation, including DNMT1, DNMT3a, MeCP2, MBD1, MBD2, MBD3 and MBD4, in blood samples of alcohol and drug dependent persons in comparison to healthy abstainers.

Multiple myeloma is a clonal proliferation of the plasma cell line that accounts for approximately 10% of all hematological malignancies. It is characterized by abnormal growth of plasma cells producing monoclonal immunoglobulin or light chain (paraprotein), with subsequent development of osteolytic bone lesions, anemia, hypercalcemia, and renal failure. In 3-6% of myeloma patients, more than one monoclonal protein (usually two) is discovered, with different heavy or light chain or both. These additional monoclonal proteins may be identified at the time of diagnosis or appear later during an observation or therapy. The authors describe two patients with biclonal myeloma, one diagnosed during evaluation for newly discovered renal failure, and one identified in the course of treatment of monoclonal gammopathy. The discussion of the diagnosis, natural history, and prognosis in patients with biclonal myeloma are also reported.

Abstract Background Since the early days of PCR techniques, sex identification, “sex-typing,” of genomic DNA samples has been a fundamental part of human forensic analysis but also in animal genetics aiming at strategic livestock breeding. Most analyses are employing the AMELX/AMELY gene loci on the X and Y chromosomes present in most mammals. We hypothesize that sex-typing in humans is also possible based on the genes NLGN4X and NLGN4Y, which represent X and Y chromosome-specific copies of a common ancestral neuroligin-4 orthologue. Methods Genomic DNA was isolated from human blood and buccal cell samples (total n = 111) and submitted to two different strategies: (a) a traditional two-primer PCR approach detecting an insertion/deletion (indel) polymorphism immediately upstream of the translational start on exon 1 and (b) detection of a single nucleotide polymorphism, SNP, on the translational stop carrying exon 7. The SNP detection was based on a quantitative PCR approach (rhAMP genotyping) employing DNA/RNA hybrid oligonucleotides that were blocked and which could only be activated upon perfect annealing to the target DNA sequence. Results All indel PCR-tested human DNA samples showed two bands for males representing X- and Y-specific copies of NLGN4 and a single band for female samples, i.e., homozygosity of NLGN4X and absence of NLGN4Y, in accordance with the self-reported sex of the donors. These results were in perfect agreement with the results of the rhAMP-based SNP-detection method: all males were consequently positive for both alleles, representing either SNP variant, and females were interpreted as homozygous regarding the SNP variant found in NLGN4X. Both methods have shown reliable and consistent results that enabled us to infer the sex of donor DNA samples across different ethnicities. Conclusions These results indicate that the detection of human NLGN4X/Y is a suitable alternative to previously reported methods employing gene loci such as AMELX/Y. Furthermore, this is the first report applying successfully the rhAMP-genotyping strategy as a means for SNP-based sex-typing, which consequently will be applicable to other gene loci or different species as well.

The influences of energy transitions on social inequity are multidimensional in their attributes and connections. For adequate accountability of their social correlates, policies aiming to implement a transition towards sustainable energy supply and demand have also to be evaluated regarding their influences on social inequalities, namely in terms of energy access and consumption. A capability-based and relational approach is used to monitor the social correlates of the governance of energy transitions. This accountability model is applied to three different European countries: Austria, Belgium, and Bulgaria. They have different characteristics in terms of levels and inequalities regarding material deprivation and energy access as well as patterns of energy transitions. The proposition here is that the capability approach could be usefully adopted to evaluate future implementation of energy transitions and to assess how they could influence inequalities in various aspects of citizen’s daily life. In such a framework, the focus is on potential links between energy transitions and energy inequalities that can be channelled by their respective relations to the capabilities. Data used to quantify the inequalities regarding various capabilities are from the Generations and Gender Programme (GGP). Keywords: Energy transitions, Social inequalities, Capability, Accountability, Energy poverty

Abstract Sudden onset of disturbed consciousness, neurocognitive deficits, and weakness of the proximal limbs are typical findings of a watershed stroke. Occurrence after an intense emotional experience and electrocardiogram changes are hints toward the rare cause of stroke of a takotsubo cardiomyopathy, even more if the stroke pattern is embolic.

Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4–/–) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling, and electrophysiological characterization, we detected TRPV4 in bronchial epithelium, alveolar epithelial type I (ATI), and alveolar epithelial type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of the water-conducting aquaporin-5 (AQP-5) channel in ATI cells. Migration of TRPV4–/– ATI cells was reduced, and cell barrier function was impaired. Analysis of isolated primary TRPV4–/– ATII cells revealed a reduced expression of surfactant protein C, and the TRPV4 activator GSK1016790A induced increases in current densities only in WT ATII cells. Moreover, TRPV4–/– lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared with WT lungs. Therefore, our data illustrate essential functions of TRPV4 channels in alveolar epithelial cells and in protection from edema formation.

Rhabdomyolysis (RM) is defined as striate muscle-cell damage with disintegration of skeletal muscles and release of intracellular constituents to the circulation, with or without subsequent kidney injury. RM is one of the leading causes of acute kidney injury and is associated with substantial morbidity. The major signs of acute kidney injury in rhabdomyolysis are: pain, weakness and swelling of the injured muscle or muscle groups and myoglobinuria with reddish discoloration of the urine and decrease in urine output to anuria. The authors describe three cases of rhabdomyolysis with acute renal injury and discuss the current knowledge on the etiopathogenesis, clinical manifestations, diagnosis and treatment of this condition.

Abstract The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3−/− intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states.

Cotinus coggygria Scop. leaf aqueous ethanolic extract was examined for its in vitro antiproliferative and antioxidant activity. Antiproliferative effect was assessed on four human gynecological cancer cell lines: breast (MCF7, T47D), cervical (HeLa) and ovarian (A2780) and compared to the cell growth inhibitory effect on non-cancerous breast epithelial cell line MCF10A using MTT cell proliferation assay. Radical scavenging assay with DPPH was applied to evaluate antioxidant potential of the extract. The obtained results showed that the herb inhibited cell growth of all of the tested cancer cell lines and the highest was the cytostatic effect on A2780 cells with a half maximal inhibitory concentration (IC50) value of 30.8 μg/ml. For the other cell lines the IC50 values were in the range of 55-122.7 μg/ml. Additionally, the extract exerted considerably weaker reduction in cell proliferation of the non-cancerous cell line MCF10A compared to cancer cells, which indicates for antiproliferative selectivity. C. coggygria extract showed high free radical scavenging activity with an IC50 value of 11.2 μg/ml. The obtained data provide evidence for pharmacological potential of the tested extract and future more detailed studies concerning the molecular mechanisms of the anticancer effect of the herb are needed.

Horseshoe kidney is an inborn renal fusion anomaly. It is frequently associated with renal stones and infections. The diagnosis is made using imaging methods - ultrasound, X-ray of the abdomen and intravenous pyelography, computed tomography (CT), magnetic resonance imaging (MRI) and radionuclide investigations. The diagnosis sometimes is hard, especially when other abnormalities are present, i.e. hydronephrosis, nephrolithiasis, stenosis of the ureteropelvic junction, etc. The authors present a male patient with horseshoe kidney and unilateral hydronephrosis due to obstruction of the ureteropelvic junction and discuss the diagnosis of horseshoe kidney and the diagnostic approach in such patients.

Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.