DOI: 10.3897/folmed.68.e192711

Authors: Aglika Byandova, Blagoy Marinov

Abstract: Abstract Cardiopulmonary exercise testing (CPET) is a complex functional test that allows for dynamic monitoring of the cardiovascular and respiratory systems during progressive incremental physical activity. CPET is well-established in adult patients, as it provides diagnostic and prognostic value. Pediatric CPET proves informative, although it entails numerous challenges, stemming from the developmental characteristics of children, as well as factors regarding test conduction and interpretation. Pediatric CPET applicability ranges from estimating exercise capacity in healthy and athletic children to diagnosis and prognosis in cases of chronic disease, such as respiratory or cardiovascular conditions. It can be used as a basis for the assessment of functional capacity in cases of asthma and cystic fibrosis, as well as quality of life scoring in kids with chronic heart failure. Furthermore, exercise testing is used as part of the indirect bronchoprovocation procedures for pulmonary function testing. Main challenges include the lack of standardized reference values, protocol selection, and the need for special pediatric equipment, as well as the high cost associated with the test. CPET represents a valuable and increasingly utilized tool for assessment of the pediatric population. Future studies should focus on establishing normative datasets and improving methodological standardization.

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DOI: 10.3897/folmed.68.e173421

Authors: Pravallika Kakada, Monal Yuwanati

Abstract: Introduction: Monosodium glutamate (MSG) is extensively used in processed foods to enhance umami flavor, and its lingering presence in the oral cavity may influence salivary composition and microbial activity. Materials and methods: This pilot cross-sectional observational study was conducted at the Dental Institute, between March 2025 and April 2025. Twenty healthy participants aged 18–35 years were recruited using convenience random sampling. Unstimulated whole saliva samples were collected under standardized conditions, and salivary monosodium glutamate levels were quantified using a derivatization-based high-performance liquid chromatography (HPLC) method. Dental caries experience was assessed clinically using the Decayed, Missing, and Filled Teeth (DMFT) index and caries index (CI). Associations were explored using non-parametric correlation analysis and exploratory logistic regression. Results: Participants with higher DMFT scores showed higher salivary MSG concentrations. Salivary MSG levels showed a significant positive association with dental caries (ρ=0.62, p<0.01). Logistic regression analysis indicated that higher MSG levels were associated with increased odds of belonging to the higher caries experience group (OR=1.05, p=0.03). Conclusion: Salivary MSG concentration demonstrated an association with dental caries development. Future larger and longitudinal studies are warranted to ascertain the role of salivary MSG as a non-invasive indicator of caries risk.

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DOI: 10.3897/folmed.68.e193784

Authors: Krasimir Avramov, Snezhana Terziyska, Ivan Yakov, Todor Georgiev, Aneliya Draganova, Kiril Terziyski

Abstract: Introduction: Restless legs syndrome (RLS) is a frequent yet underrecognized comorbidity in rheumatoid arthritis (RA), potentially driven by inflammation-mediated disturbances in iron metabolism. Aim: This study investigated the relationship between inflammatory markers and iron homeostasis in RA patients with and without RLS. Methods: This monocentric cross-sectional study included 32 RA patients, 12 of whom had RLS and 20 who did not. RLS was diagnosed using ICSD-3 criteria, and severity was measured using IRLSSG scores. Clinical data, disease activity (DAS28-CRP), reported sleep parameters, and laboratory markers (IL-6, TNF-α, serum iron, ferritin, and hepcidin-25) were analyzed. Between-group comparisons and receiver operating characteristic (ROC) analyses were performed. Results: The prevalence of RLS in our cohort was 37.5%. Compared to RA patients without RLS, those with RLS demonstrated significantly prolonged reported sleep latency (42.5 vs. 25.0 min, p<0.001, δ=0.86); higher disease activity (DAS28-CRP 4.64 vs. 3.82, p=0.0029, δ=0.64); elevated IL-6 (13.55 vs. 2.84 pg/mL, p=0.0022, δ=0.66); and hepcidin-25 levels (640 vs. 455 pg/mL, p=0.0382, δ=0.48) and lower serum iron (15.35 vs. 19.30 µmol/L, p=0.0292, δ=−0.47). Ferritin and TNF-α did not differ significantly. ROC analysis showed strong discrimination for reported sleep latency (AUC 0.93), IL-6 (AUC 0.83), and DAS28-CRP (AUC 0.82). Conclusions: RA patients with RLS demonstrate a distinct biological profile characterized by heightened inflammatory activity and functional iron deficiency. The IL-6–hepcidin–iron axis emerges as a central mechanistic pathway linking systemic inflammation to RLS pathophysiology. These findings support the concept that the magnitude of inflammatory activation, rather than its mere presence, contributes to RLS development in RA and highlight potential targets for improved diagnostic and therapeutic strategies.

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DOI: 10.3897/folmed.68.e166432

Authors: Victor Velyanov, Nikola Lazarov, Lubomir Lubomirov, Kameliya Bratoeva

Abstract: Recent research suggests that isoforms of myosin phosphatase target subunit 1 (MYPT1) may influence blood pressure regulation by altering smooth muscle responsiveness and, as a result, the function of vascularized tissues. Cloning and sequencing from diverse tissues and species revealed the existence of MYPT1 isoforms produced through alternative splicing, indicating their potential role in the regulation of blood pressure. Moreover, alterations in MYPT1 expression are linked to several diseases, including inflammatory bowel disease, gastric cancer, intestinal cancer, colon cancer, ovarian cancer, hypertension, and liver cirrhosis. These studies, although limited, suggest a novel role for the protein as an important diagnostic marker and a potential target for gene therapies. This review analyzes recent data about the role of MYPT1 in the regulation of vascular tone in both health and disease.

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DOI: 10.3897/folmed.68.e177549

Authors: Burim Neziri, Shqipe Devaja, Samir Durmishi

Abstract: Introduction: Nickel allergy is among the most common contact hypersensitivities worldwide. It affects women predominantly. This study examined whether female nickel-sensitized patients exhibit reversible changes in pulmonary function following a period of nickel avoidance. Aim: To evaluate pulmonary functional parameters (PFPs) in female patients with nickel sensitization and assess changes after nickel avoidance. Materials and methods: Twelve adult women with confirmed nickel hypersensitivity underwent spirometry before and after a 3‑month nickel avoidance program. Measured parameters included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and the FEV1/FVC ratio. Paired-sample tests and effect sizes were calculated. Results: All indices changed significantly after avoidance. FVC increased from 2.7±0.7 L to 3.4±0.5 L [t(11)=−5.50, p<0.001, dz=1.59]; FEV1 from 2.4±0.6 L to 2.9±0.4 L [t(11)=−4.68, p=0.001, dz=1.35]; PEF from 3.9±1.3 L/s to 6.1±0.5 L/s [t(11)=−6.81, p<0.001, dz=1.97]; and the FEV1/FVC ratio from 82.9±2.9% to 89.6±7.5% [t(11)=4.39, p=0.001, dz=1.27]. Conclusion: In women with nickel allergy, pulmonary function improves significantly after nickel avoidance. Pulmonary assessment and avoidance counseling should be integrated into the management of female nickel‑sensitized patients with respiratory symptoms.

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DOI: 10.3897/folmed.68.e166581

Authors: Georgi Nikolov, Dimitar Nikolov, Mladen Naydenov, Chavdar Stefanov

Abstract: Introduction: Septic acute kidney injury (S-AKI) is a life-threatening complication of sepsis with high mortality and limited treatment options. Emerging evidence highlights the role of microRNAs (miRNAs) as critical regulators of the key pathogenic pathways involved in S-AKI, including inflammation, apoptosis, oxidative stress, and microvascular dysfunction. Aim: To provide a comprehensive overview of the current knowledge of miRNA involvement in the pathophysiology, diagnosis, and potential treatment of S-AKI. Materials and methods: A structured literature review was conducted using recent experimental and clinical studies published in peer-reviewed journals from 2018 to 2025. Key miRNAs implicated in S-AKI were identified and analyzed for their diagnostic and therapeutic relevance. Results: Several miRNAs, such as miR-155, miR-146a/b, miR-21, miR-210, and miR-22-3p, modulate essential signaling cascades in S-AKI, either promoting or attenuating kidney injury depending on context. Circulating and urinary miRNAs demonstrate high sensitivity and specificity as early biomarkers, often outperforming traditional markers like serum creatinine. Furthermore, experimental models show that targeting specific miRNAs using mimics or antagonists can significantly mitigate renal damage in sepsis. Conclusion: miRNAs offer a promising dual application in S-AKI—as sensitive noninvasive biomarkers and as novel therapeutic targets. Future research should focus on validating their clinical utility and overcoming challenges related to targeted delivery and off-target effects. miRNA-based interventions may become integral components of personalized therapy in sepsis-related kidney injury.

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DOI: 10.3897/folmed.67.e154231

Authors: Paraskevi Kollia, Konstantina Agathou, Christos Nikitas, Margarita Charalambopoulou, Dimitrios Chytas, Maria Kyriakidou, Anna Christakou

Abstract: Introduction: Peripheral vestibular disorders (PVDs) are associated with the inner ear or vestibular nerve and can occur as acute, episodic, or persistent vestibular syndromes. The symptoms are mainly vertigo and dizziness, which significantly affect kinesiophobia, quality of life, and balance. Aim: The aim of the present study was to investigate the relationship between kinesiophobia, quality of life, and balance in patients with PVDs. Materials and methods: The study’s sample population comprised 35 subjects, ranging in age from 30 to 80 years, with a standard deviation of 13.36 years. These subjects were diagnosed with PVDs. The assessment of kinesiophobia employed the Tampa Scale of Kinesiophobia (TSK-GR), while the evaluation of quality of life utilized the EuroQol (EQ-5D-5L and EQ-VAS) scale. The balance of the patient was evaluated using Romberg’s test. Spearman’s r correlation analysis was conducted to examine the relationship between the measured variables. Results: EQ-VAS showed a moderate statistically significant positive correlation with EQ-5D-5L (r=0.51, p<0.01). No statistically significant correlation was observed between kinesiophobia, quality of life, and balance. Conclusion: While a significant relationship was found between EQ-VAS and EQ-5D-5L, it is plausible that different factors contributed to the non-statistically significant correlation between the variables of kinesiophobia, balance, and quality of life in patients with PVDs. Further studies are needed to ascertain the relationship between the above variables to develop effective and individualized rehabilitation programs for patients with PVDs.

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DOI: 10.3897/folmed.67.e153005

Authors: Alyea Al-Harthy, Mohammad Arafa

Abstract: Introduction: An endometrial polyp (EP) is an abnormal growth of the endometrium inside the uterine cavity. Histologically, the polyp contains glandular, stromal, vascular (thick-walled vessels), and connective tissue elements (fibrous stroma). The most common symptoms of patients with endometrial polyps are abnormal bleeding and infertility. Aim: To assess cases of endometrial polyps received at the pathology department of a hospital by exploring the different presentations of the patients and the correlation with the clinico-pathological features. Materials and methods: This retrospective, cross-sectional study used patient data from January 2018 to December 2022. It was conducted in the pathology department of a tertiary care center. It included 180 women with endometrial polyps. Data were collected from the hospital information system’s medical records, and the Statistical Package for the Social Sciences (SPSS), version 26.0, was used to analyze the data. Results: The patients’ ages ranged from 29 to 88 years. About one-third of the patients were aged between 30 and 40 years. Patients with a single polyp were more than those with multiple polyps. Abnormal bleeding and infertility were the most prevalent symptoms. All the cases were histopathologically benign except for one who presented with malignancy. Age did not show significant association with recurrence. In more than 75% of patients, there was a consensus between the clinical assessments and pathology results. Conclusion: Most endometrial polyps are benign and single with a good concordance between the clinical suspicion and the histopathological confirmation.

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DOI: 10.3897/folmed.67.e151493

Authors: Todor Georgiev, Aneliya Draganova, Krasimir Avramov, Kiril Terziyski

Abstract: Chronic insomnia is the most common sleep disorder, affecting up to 10% of the global population, with more than one-third of the individuals worldwide reporting insufficient sleep as a common complaint. Due to its high prevalence, insomnia frequently co-exists with various somatic and psychiatric disorders, exhibiting a bidirectional relationship in which each condition influences the other. Depression, anxiety, cardiovascular diseases, and malignancies can serve as factors triggering insomnia complaints, according to the behavioral model for insomnia development. Moreover, chronic insomnia increases the risk of these diseases through several pathogenic mechanisms, including activated stress response, altered neurotransmitter signaling, and impaired emotion regulation. This interplay creates a vicious cycle of poor sleep, deteriorated health, and impaired quality of life. Recognizing the relationship between insomnia and overall well-being is essential for adopting optimal treatment methodology, as addressing insomnia can ameliorate associated mental and physical health issues. This review explores the bidirectional association of chronic insomnia with other somatic and mental diseases, illustrating how each can aggravate the other, and emphasizes the importance of effective insomnia management in improving overall health and quality of life.

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DOI: 10.3897/folmed.66.e115645

Authors: Nikola Boyanov, Vladimir Andonov

Abstract: One of the most common stressors is so-called “occupational stress.” It is defined as the sum of physical, mental and physiological responses to work in situations where the workload or stress associated with it intensifies for an extended period of time. It is a gradual process in which individual cognitive assessments of occupational stressors generate adverse health events and may lead to burnout. Since it has become a major problem in the medical field, studying, measuring and limiting it have been set as goals for the future. We present a literature review on the topic of measuring stress using non-invasive means, such as cardiac indices measured through different devices, electrodermal activity, skin temperature, and salivary biomarkers. A virtual reality simulation could be used in conducting such experiments in order to provide a standardized environment with set variables for researchers to discern the most precise indices to be used in a real-life setting.

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DOI: 10.3897/folmed.65.e96691

Authors: Efstathios Kotidis, Elissavet Anestiadou, Aikaterini Karamitsou, Georgios Gemousakakis, Orestis Ioannidis, Stefanos Bitsianis, Savvas Symeonidis, Nikolaos Ouzounidis, Odysseas Lomvardeas, Stamatios Aggelopoulos

Abstract: Transposition of inferior vena cava, or, left-sided inferior vena cava (LS-IVC) is a rare clinical entity, in which the inferior vena cava ascends along the left side of the abdominal aorta. Literature contains mainly clinical case reports. Although it is usually not associated with clinical symptomatology, this anomaly should be detected during preoperative planning to avoid iatrogenic injuries intraoperatively. We present a case of left-sided inferior vena cava encountered during laparoscopic lymphadenectomy in a 45-year-old man with previous laparoscopic hemicolectomy due to colon adenocarcinoma. Preoperative CT abdomen revealed the left-sided location of infrarenal IVC and laparoscopic trans-peritoneal aortic lymphadenectomy was decided. Intraoperatively, transposition of inferior vena cava was confirmed in accordance with the CT findings. Resection of lymph node block was conducted with no complications and with minimal blood loss. The postoperative course was uneventful, and the patient was discharged from the hospital the day following surgery. In conclusion, transposition of the inferior vena cava, although rare, constitutes an anatomical variant that should be identified preoperatively to decrease intraoperative risks. Several anatomical variants have been associated with left-sided inferior vena cava.

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DOI: 10.3897/folmed.65.e100100

Authors: Teodora Yaneva-Sirakova, Galina Zlatancheva, Kiril Karamfiloff, Latchezar Traykov, Ivo Petrov, Dobrin Vassilev

Abstract: Introduction: Carotid stenting may produce significant bradycardia and/or hypotension. This may have negative short- and long-term effects for the elderly high-risk patients. Their cerebral hemodynamics is with exhausted adaptive capacity because of the multiple cardiovascular risk factors, advanced age, and significant stenosis. Aim: This was a retrospective study aimed at finding whether periprocedural hypoperfusion or hypotension at the time of carotid stenting had any significance for the acute neurological outcome and mid-term general mortality in advanced-age patients who were at high risk for surgical endarterectomy. Materials and methods: We studied 138 consecutive patients with significant carotid stenosis from January 2015 to July 2019. The mean (SD) age was 67.41 (10.70) years. The mean follow-up period was 31 months (922 days). The patients were hemodynamically monitored periprocedurally according to a local protocol. Vasopressors were added if a prolonged hypotension was measured. Statistical data were analyzed using SPSS IBM v. 19 (p=0.05, CI 95%). Results: The male patients were 94 (68%). The number of patients with hypotension periprocedurally or in the first 6 hours post-procedure was 55 (42%). The mean blood pressures were 135/83 mmHg before, 116/76 mmHg during, and 121/73 mmHg after the procedure. Kaplan-Maier analysis showed no significant differences in the mid-term general mortality rate between patients with and patients without transitory hypotension. There wasn’t any difference in the postprocedural neurological outcome either. Conclusions: The presence of hypotension during carotid stenting was not linked to a negative neurological outcome. It also did not increase mid-term all-cause mortality in elderly patients (mean age, 67 years). The finding could be attributed to the relatively brief period of hypotension, the prompt administration of vasopressors, or the prevention of brain edema and hyper-reperfusion during carotid stenting in terms of elevated blood pressure; however, this remains to be determined.

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DOI: 10.3897/folmed.65.e96012

Authors: Oliver Oey, Siaw Sze Tiong, Sze Ling Wong, Suresh Navadgi, Yasir Khan

Abstract: Cancers that develop within six months of the first primary cancer are referred to as synchronous malignancies. These malignancies are difficult to diagnose and treat, with treatment primarily based on case reports. We report here the case of a 51-year-old male with prior history of prostate cancer who presented with haematuria to the general practice. A CT pyelogram showed left bladder wall lesion that was further investigated with cystoscopy and biopsy confirmed as muscle-invasive urothelial carcinoma. Incidentally, two perigastric nodes and hepatic lesions were noted on CT. FDG-PET revealed high-grade uptake in the right lobe of thyroid gland and cervical nodes that was biopsy proven as papillary thyroid carcinoma. Subsequently, gastroscopy and a biopsy of the gastric lesion confirmed a gastric neuroendocrine tumour. The patient underwent chemoradiotherapy, total thyroidectomy, and commenced somatostatin analogue for treatment of urothelial carcinoma, papillary thyroid carcinoma, and neuroendocrine tumour, respectively. The diagnosis and treatment of synchronous malignancies is complex. A multidisciplinary team approach is required to improve treatment outcomes.

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DOI: 10.3897/folmed.65.e71970

Authors: Andrii Demkovych

Abstract: Introduction: Excessive lipoperoxidation is accompanied by accumulation of peroxidation products and depletion of antioxidant reserves, which cause hyperenzymemia and the accumulation of toxic substances. The level of endotoxicosis is determined by the content of hydrophilic and hydrophobic products in the blood. Aim: To define the pathogenetic role of endogenous intoxication in the dynamics of development of experimental periodontitis of bacterial-immune genesis. Materials and methods: The experiment was conducted on rats. The animals were divided into three groups: group 1 – control group/intact; group 2 – model periodontitis at 7 days; group 3 – model periodontitis at 30 days. The experimental bacterial-immune periodontitis was induced by injection into the tissue of the periodontal complex of the microorganisms’ mixture diluted with egg’s albumin. For the study, we selected the blood serum in which the content of middle molecular weight molecules and erythrocyte intoxication index were determined. The results were statistically analyzed by means of non-parametric indices methods. Results: The development of generalized periodontitis is characterized by the occurrence of oxidative stress, which leads to violation of the metabolism in the mucous membrane of the oral cavity resulting in the accumulation of toxic products and the development of endogenous intoxication. The results show that the content of middle molecular weight molecules (aromatic amino and chain amino acids) determined on day 7 of the experiment was 1.11 times higher than that of the control group (p<0.01) and by 1.16 times (p<0.01), respectively. Comparing the levels of the above hydrophilic components of endogenous intoxication at 30 days of experimental periodontitis, we found a probable increase in these indicators compared with those at 7 days of the experiment. Studying the level of erythrocyte intoxication index, we found that at 7 days of experimental periodontitis this index was 1.28 times higher (p<0.01) than that of the intact group and continued to increase at 30 days. Conclusions: The dynamics of experimental periodontitis of bacterial-immune genesis show that the highest rates of endogenous intoxication are found in the late stages of the dynamics of the inflammatory process in the periodontium, namely at 30 days of the experiment, which may indicate chronic inflammation.

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DOI: 10.3897/folmed.65.e71368

Authors: Başak Büyük, Yasemen Adali, Ebru Karakoç, Hüseyin Avni Eroğlu, Cemre Aydeğer

Abstract: Introduction: One of the most important factors influencing post-transplant success in kidney transplantation is preserving the viability of the organ from removal to transfer into the recipient. Aim: This study aimed to reduce the energy requirement with thiopental doses administered before organ transplantation, and to increase the organ viability by minimizing the tissue damage during the cold ischemia process. Materials and methods: Twenty female Wistar albino rats were divided into two groups: control group (group C), and thiopental group (group T). In group C, a midline incision was performed, and the renal artery was isolated under ketamine and xylazine anesthesia. A standard organ storage solution (cooled to +4°C) was used for kidney perfusion. Nephrectomy was applied, and the removed kidneys were placed into +4°C standard organ storage solution and stored at +4°C for 12 hours. Animals in group T were subjected to the procedures explained above under 85 mg/kg thiopental sodium anesthesia. After 12-hour storage, samples from the kidney tissues were fixed in 10% neutral buffered formalin. Histopathological evaluation and apoptosis detection via TUNEL method were performed. Results: Tubular necrosis was more extensive in group C compared with that in group T and this difference was statistically significant. Similarly, vacuolization was widely observed in group C, and this increase was also statistically significant. For the ‘dilatation of Bowman’s space’ parameter, a significant decrease was observed in group T compared with group C. When the apoptotic index values of both groups were examined, it was seen that they were lower in group T than those in group C. This result was statistically significant. Conclusions: These data suggest that thiopental provides protection to the kidney tissue during the cold storage process. Thiopental has been shown to decrease the number of apoptotic cells in the kidney tissue when administered to the donor before organ transplantation, increasing the organ viability.

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DOI: 10.3897/folmed.64.e70074

Authors: Asparuh G. Nikolov, Nikola K. Popovski, Svetla Blazheva

Abstract: Introduction: Podocalyxin (PCX) is an indicator of glomerular injury. Aside from the kidney, it is expressed in the endothelial cells of various organs. Echographic examinations are useful in assessing the alterations in cardiovascular structure and function during pregnancy. Aim: The aim of the present study was to evaluate PCX concentrations in preeclampsia (PE) and to investigate the existence of association between PCX levels and maternal echocardiographic and Doppler ultrasound parameters. Materials and methods: Fifty-five women with PE were examined. The mean age of patients was 24.9±6 years; and the mean age of the control group of 35 women with normal pregnancies was 24.7±5.4 years. ELISA was used to determine concentrations of PCX. Echocardiographic assessment of all subjects was performed. In addition, umbilical (UmA) and uterine (UtA) artery pulsatility indices (PI) were evaluated. Results: The levels of serum PCX in PE women were statistically significantly higher than those in women with normal pregnancy: 2.66±0.67 vs. 2.40±0.33 ng/ml (p=0.03). Cut-off value at 3 ng/ml was obtained for podocalyxin in order to discriminate between PE and healthy pregnancy. Logistic regression model was statistically significant: OR=3.226, (95% CI 1.084–9.599); (p=0.019). PCX correlated with systolic blood pressure (r=0.30; p=0.004), diastolic blood pressure (r=0.35; p=0.0007), UtA PI (r=0.30; p=0.004), UmA PI (r=0.21; p=0.047), IVS (r=0.32; p=0.002), and LVPWD (r=0.28; p=0.007). Conclusions: Healthy pregnant women with PCX levels above the cut-off value of 3 ng/ml are at a higher risk for developing preeclampsia. Elevated PCX levels indicate three times higher probability for PE development than women with values below the cut-off value. PCX might be a promising marker for diagnosis and prognosis of PE.

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DOI: 10.3897/folmed.64.e68349

Authors: Eka Prasetya Budi Mulia, Kartika Afrida Fauzia, Rerdin Julario

Abstract: Introduction: Patients with chronic renal disease (CKD) are at a significantly elevated risk for ventricular arrhythmia. Several electrocardiographic (ECG) methods can be used to assess the ventricular arrhythmia risk on the standard 12-lead ECG. Aim: This study aimed to evaluate the ECG parameters of ventricular repolarization abnormalities, such as QT, QTc, Tp-e, and Tp-e/QT ratio, Tp-e/QTc ratio, and their predictors in hemodialytic end-stage renal disease (ESRD) patients. Materials and methods: Fifty-three patients with hemodialytic ESRD and 32 pre-dialytic CKD patients were enrolled in the study. ECG parameters were measured manually using calipers. The independent samples t-test was used for comparative analysis. The multivariate linear regression analysis was used to distinguish the independent predictors of each ECG parameters and variables correlating significantly in bivariate analysis. Results: Mean ages of hemodialytics and pre-dialytics were 47±11 and 51±7 years, respectively. Ventricular repolarization abnormalities in the hemodialytic compared to the pre-dialytic group were found to be significantly different [QTc (448±34 vs. 428±31 ms, p=0.007), Tp-e (81±20 vs. 71±19 ms, p=0.025), Tp-e/QT (0.23±0.06 vs. 0.20±0.05, p=0.043)]. QTc interval was positively correlated with sodium (p=0.001) and age (p=0.007). Tp-e/QT ratio was the ECG parameter correlated to most of variables including eGFR (p=0.003), creatinine (p=0.040), potassium (p=0.009), chloride (p=0.048), and glucose (p=0.041). Conclusions: Ventricular repolarization was found to be increased in patients with hemodialytic ESRD. Hence, observation ECG parameters of ventricular repolarization should be performed in the hemodialytic patients for early detection of ventricular arrhythmia.

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DOI: 10.3897/folmed.64.e65507

Authors: Deyana Vankova, Yoana Kiselova-Kaneva, Diana Ivanova

Abstract: Introduction: Elevated plasma levels of uric acid (UA) are considered an independent risk factor for hypertension, diabetes, cardiovascular disease, endothelial and vascular damage, obesity, and metabolic syndrome. Even physiological concentrations of soluble UA have been proved to induce gene expression of macrophage-secreted inflammatory cytokines and stimulate production of reactive oxygen species in mature adipocytes. UA is also described as a powerful endogenous plasma antioxidant, which reveals a paradox of duality for this parameter. Aim: The aim of this study was to investigate the effect of UA on expression of antioxidant defense related enzymes in cultured J744A.1 macrophage cell line. Materials and methods: Mouse macrophage J744A.1 cells were treated with uric acid at increasing concentrations of 200 to 800 μM. Changes in expression levels of genes related to the metabolism of glutathione – glutamate-cysteine ligase, catalytic subunit (GCLc), glutathione peroxidase 1 (GPx1), glutathione reductase (GR) and glutathione synthetase (GS) were analyzed. Gene expression levels were calculated using the 2-ΔΔCt method. Results: When UA is applied in concentrations of 200 µM and 400 µM, cell viability did not change significantly. Higher, pathophysiological concentrations of 600 μM, 800 μM UA, and 1000 μM of UA caused significant decrease in cell viability to 95.81% (p<0.01), 76.22% (p<0.001), and 18.01% (p<0.001), respectively. UA treatment in concentrations of 200 μM, 400 μM, 500 μM, and 800 μM induced significant transcription levels of glutathione reductase – 8.14 (p<0.05), 7.15 (p<0.01), 22.07 (p<0.001), and 27.77 (p<0.01), respectively, and of glutathione synthetase – 13.71 (p<0.01), 13.05 (p<0.05), 18 (p<0.01), and 48.60 (p<0.01) folds, respectively. GCLc and GPx1 genes were transcriptionally activated by higher (500 μM and 800 μM) concentrations of UA. For these UA concentrations the measured levels of mRNA were 7.51 (p<0.05) and 12 fold (p<0.05) higher than the non-treated control for GCLc and 1.90 (p<0.05) and 1.93 (p<0.01) for GPx1. Significant difference in the GCLc expression was found between the 200 μM and 500 μM (p<0.05) and 800 μM (p<0.01) treated cells. mRNA levels were significantly different between 400 μM and 800 μM (p<0.05) for both GCLc and GR genes. Very strong correlation was found between GCLc and GR (0.974, p=0.005) and GS (0.935, p=0.020) expression and between GS and GR (0.886, p=0.045) expression levels. Conclusions: It appears that 500 μM and pathophysiological concentrations (800 μM) of UA induce antioxidant cell response in J744A.1 macrophages proved by the indicative elevation GCL, GPx1, GR, and GS transcription. GR and GS can be stimulated even by lower concentrations (200 μM and 400 μM) indicating that glutathione metabolism in macrophages is tightly regulated in order to keep adequate GSH levels.

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DOI: 10.3897/folmed.64.e77713

Authors: Oliver Oey, Pravin Viswambaram, Andrew Moe, Nicole Swarbick, Dickon Hayne

Abstract: BK polyoma virus (BKV) is a known risk factor for the development of urothelial carcinoma. There is currently limited data on the management of BKV-induced urothelial carcinoma (BUC) of the bladder, with available data limited to case reports. It remains debatable whether radical cystectomy (RC) with removal of the native urinary tract or RC alone is the most optimal management for BUC of the bladder. BKV-induced urothelial carcinoma is rare, and its management is challenging in immunocompromised patients such as that of post-transplant patients. This case report provides additional insight into a rare disease, the management of which still lacks established guidelines and remains debatable. We present a unique case of BKV-induced muscle-invasive urothelial carcinoma of the bladder in an immunosuppressed renal transplant patient who underwent open radical cystectomy, anterior pelvic exenteration, bilateral native nephroureterectomy and ileal conduit formation to transplant kidney. The patient remains recurrence-free with preserved graft function 2 years since surgery. An aggressive management approach which involves anterior pelvic exenteration with removal of the native urinary tract may be favoured in young patients with BUC of the bladder with minimal comorbidities. However, treatment should be individualised for each individual patient.

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DOI: 10.3897/folmed.64.e61539

Authors: Sergey Pavlov, Nataliia Babenko, Marina Kumetchko, Olga Litvinova, Mykyta Valilshchykov

Abstract: Introduction: Treatment of chronic wounds is an urgent worldwide problem for medicine. Among the many efforts in wound healing techniques, photobiomodulation therapy has shown promising results. Aim: To study the effect of photobiomodulation therapy on optimisation of the regulation of reparative processes in chronic wounds by cytokines (through the example of interleukin-1β, tumour necrosis factor-alpha, interleukin-6, interleukin-4, interleukin-10, and granulocyte macrophage colony stimulating factor). Materials and methods: The study involved 12 Wistar rats. A trophic wound was modelled in the animals. After the operation, the animals were divided into two groups of 6 animals each. The wound defects of animals in the experimental group were exposed to low-intensity laser radiation. Photobiomodulation therapy was applied once a day for 5 days, starting the day after wound modelling. The device Lika-therapist M (Ukraine) was used in a continuous mode at a wavelength of 660 nm, an output power of 50 mW, and an energy density of 1 J/cm², and 60 s exposure time. Results: The study showed the following changes in the expression of intercellular mediators in the blood serum of animals with chronic wounds when using photobiomodulation therapy: a decrease in the levels of interleukin-1β (p>0.05) and tumour necrosis factor-alpha (p<0.05); increased concentrations of interleukin-4 (p<0.05); the concentrations of interleukin-6, granulocyte macrophage colony stimulating factor, and interleukin-10 were not significantly changed. The histological study showed better organization of collagen fibers in the experimental group. Conclusions: Photobiomodulation therapy can be an instrument for optimizing the reparative process by correcting the regulation by intercellular mediators.

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DOI: 10.3897/folmed.63.e57713

Authors: Devaraja Sannaningaiah, Ashwini Shivaiah, Jayanna Kengaiah, Chandramma Srinivasa, Sharath Kumar M. Nandish, Chethana Ramachandraiah, Sujatha Hanumegowda, Bhagyalakshmi Manjappa, Sebastin Santosh Martin, Ramesh Komalapura Laxmaiah, Manohar Shinde

Abstract: Introduction: Oxidative stress plays a critical role in the progression of diabetes, arthritis, cancer, eryptosis, cardiovascular disease, and thrombosis. Currently, antioxidants from natural sources are in high demand due to their beneficial role in the management of said diseases.Aim: The purpose of the study was to evaluate the protective effect of sorghum protein buffer extract (SBE) on sodium nitrite-induced oxidative stress and thrombosis.Materials and methods: Protein characterization of SBE was done using SDS-PAGE. Oxidative stress in RBC was induced using sodium nitrite (NaNO2) and the key stress markers such as lipid peroxidation (LPO), protein carbonyl content (PCC), and the level of antioxidant enzymes (SOD and CAT) were measured. The anticoagulant effect of SBE was identified by employing in-vitro plasma recalcification time, activated partial thromboplastin time (APTT), prothrombin time (PT), and in-vivo mouse tail bleeding time. SBE antiplatelet activity was examined using agonist adenosine diphosphate (ADP) and epinephrine-induced platelet aggregation. Non-toxic property of SBE was identified using in-vitro direct haemolytic, haemorrhagic, and edema forming activities using experimental mice.Results: SBE revealed similar protein banding pattern under both reduced and non-reduced conditions on SDS-PAGE. Interestingly, SBE normalized the level of LPO, PCC, SOD, and CAT in stress-induced RBCs. Furthermore, SBE showed anticoagulant effect in platelet rich plasma by enhancing the clotting time from the control 250 s to 610 s and bleeding time from the control 200 s to more than 500 s (p<0.01) in a dose dependent manner. In addition, SBE prolonged the clot formation process of only APTT but not PT. SBE inhibited the agonists ADP and epinephrine induced platelet aggregation. SBE did not hydrolyze RBC cells, devoid of edema and haemorrhage properties.Conclusions: This study demonstrates for the first time the anticoagulant, antiplatelet, and antioxidant properties of SBE. Thus, the observed results validate consumption of sorghum as good for health and well-being.

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DOI: 10.3897/folmed.62.e50410

Authors: Tsvetelin K. Georgiev, Anna N. Tolekova, Nikolay V. Genov, Lilia Zh. Pashova-Stoyanova, Zhivka I. Tsokeva, Krasimira G. Nancheva, Rositsa V. Sandeva, Galina S. Ilieva, Maria G. Ganeva, Petya V. Hadzhibozheva

Abstract: Introduction: The high-fructose diet in rats has been reported to cause metabolic disorders such as impaired fasting glucose levels, in-sulin resistance, dyslipidemia, and dysregulation of the renin-angiotensin system. This could lead to further complications, for instance, to the smooth muscle dysfunction.Aim: The present study aimed at developing fructose-induced metabolic perturbations in rats and the investigation of their impact on angiotensin II-induced smooth muscle intestinal motility. Materials and methods: Mature Wistar rats were randomly divided into two groups (9 rats per group): control group (drinking tap water) and fructose-drinking group (15% fructose, dissolved in tap water). At the end of the experimental period (11 weeks), the plasma levels of insulin, renin, angiotensin II and creatinine, as well as the lipid profile were assessed. Morphometric analysis and lipid index calculation were also performed. The contractile properties of ileum, colon and rectum were studied using stimulation with angiotensin II in the isolated tissue bath system. Results: Our experiment showed that drinking 15% fructose solution induced dyslipidaemia accompanied by elevated lipid indexes as well as an increase in creatinine and renin plasma levels in the rats. Conclusions: Fructose drinking and consequently the developed metabolic disorders modified the Ang II-induced intestinal activity causing a gradual alteration in the distal direction with the rectum being the most strongly affected organ.

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