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Publikacije (51)

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B. Alihodžić-Dilberović, M. Salihović, M. Pazalja, A. Osmanović, U. Glamočlija, I. Mahmutović-Dizdarević, Ajla Pediša, Monia Avdić Obučić et al.

Cornus mas L. is traditionally used for various medicinal purposes, although systematic data on its pharmacognostic properties are still limited. Considerable variation was observed among plant organs, so phenolic and flavonoid content varied by plant part, with location-related differences among samples, with the highest in leaf and fruit from Bijeljina and the lowest in leaf from Sarajevo. Antioxidant activity was much better in leaf and bark than in fruit. Extracts inhibited ESBL-producing Escherichia coli, with MICs mainly at 125 µg/mL; bark extract (Tuzla) showed 250 µg/mL and reduced biofilm formation. Leaf and bark extracts showed dose-dependent cytotoxicity against PC-9, MCF-7, and MDA-MB-231 cells, while fruit extracts were weaker. In human lymphocytes, bark (Bileća) and leaf (Tuzla) extracts decreased nuclear division and induced micronuclei at 200 µg/mL. Molecular docking indicated strong bacterial target binding for loganin and cornuside, supporting the antibacterial and antitumor potential of C. mas.

F. Skenderi, G. R. Babu, U. Glamočlija, E. Veledar, Zoran Gatalica, J. Lamovec, S. Vranić

Acinic cell carcinoma (ACC) of the breast is a very rare, primary salivary gland‐type breast malignancy, with ~100 reported cases in the literature. Limited information about the clinical features and outcomes of patients with ACC is available.

Objective This study aimed to evaluate the functional status of the urethra using uroflowmetry before surgery, as well as three and six months postoperatively in cases of distal hypospadias. Material and Methods Thirty-nine consecutive patients who underwent surgery for distal hypospadias (hypospadias group) between 2016 and 2019 were prospectively included as part of this study. The control group consisted of 40 patients with a normal urethra who underwent surgery due to conditions other than hypospadias (phimosis, undescended testis, hernia). Uroflowmetry was performed preoperatively in these patients. Postoperative uroflowmetry was performed at three and six months following hypospadias surgery. Uroflowmetric results [maximum flow rate (Qmax), average flow rate (Qave), voided volume, void duration, flow start time, time to maximum urine flow rate, post-void residual urine, flow curve] were compared between the groups. Results The mean age for the patients with distal hypospadias was 35.9±29.6 months and 40.8±26.1 months for the control group. Pre- and postoperative Qmax values (three and six months after surgery) were 6.9 mL/s (0.1-15), 6.4 (0.2-14), and 7.5 (2.5-15). Qave values were preoperatively 4.0 (0.1-12.1), 3.8 (0.3-8.1), and 4.7 (1.0-11.1) mL/s three and six months after surgery, respectively. Bell-type flow was the most frequent uroflow flow curve in the preoperative hypospadias and control groups (95% and 66.6%, respectively). Postoperatively, bell-type flow remained the most common pattern, while a significant reduction in plateau-type flow was observed. Four boys (10.3%) had symptoms of obstruction. Conclusion Surgery improved urination dynamics and partial urethral obstruction of hypospadias cases that were present from the baseline. The urinary flow rates improve over time as the reconstructed neourethra regains functionality six months after the tubularized incised plate procedure.

Maryam Golzardi, U. Glamočlija

Poor solubility remains a critical barrier in the in vitro evaluation of phytochemicals, many of which are hydrophobic and difficult to dissolve in aqueous media. This review explores the physicochemical factors influencing phytochemical solubility, emphasizing the role of solvent properties such as polarity, proximity, and cytotoxicity. Commonly used solvents—including polar protic, polar aprotic, and non-polar solvents —are discussed concerning their solubilizing capacity and compatibility with biological systems. Solvent-induced changes in membrane dynamics and cytotoxic profiles are also examined, highlighting the need for cautious selection and optimization. Several advanced strategies to enhance solubility, such as co-solvent systems, pH modulation, nanocarrier encapsulation, surfactants, and deep eutectic solvents (DESs), are reviewed. A focused case study on curcumin illustrates how different solubilization methods can significantly improve in vitro performance. The review underscores the importance of standardized solvent reporting to ensure reproducibility and reliability in phytochemical research.

Benzoxazoles possess a wide range of therapeutic activities, including antimicrobial, antitumor, anti‐inflammatory, and other. Using in silico and in vitro approaches, we determined the potential antitumor activity of benzoxazoles synthesized from thymoquinone in diffuse large B‐cell lymphoma (DLBCL) cells. Molecular docking analysis showed strong binding affinities of benzoxazoles toward Akt and nuclear factor kappa B (NF‐κB) protein targets that promote cancer cell proliferation and survival and whose expression is linked to tumorigenesis of activated B‐cell (ABC) and germinal center B‐cell (GCB) DLBCL subtypes. WST‐8 assay showed the highest inhibitory activity of benzoxazole derivative bearing thiophene substituent in both DLBCL models. Western blot analysis indicated the inhibitory activity of selected compounds in HBL‐1 cells, with decreased p‐NF‐κB and p‐Akt protein expression, whereas treatment of DHL‐4 cells stimulated the expression of p‐Akt and p‐NF‐κB protein levels. These data suggest distinct, cell line‐dependent activities of the substances that potentially act through diverse oncogenic signaling pathways in DLBCL cells and activation of compensatory cell mechanisms that could be an important step for combinatorial treatment approaches.

I. Omerhodžić, B. Rovčanin, A. Džurlić, Mirsad Hodžić, Rasim Skomorac, H. Bečulić, S. Zahirović, Fahrudin Alić et al.

OBJECTIVES Brain tumor-related epilepsy management poses significant challenge in clinical practice. Healthcare providers must tailor treatment based on each patient's unique circumstances. Different antiepileptic drugs can be used, including oxcarbazepine. Several studies show this drug's efficacy and safety in brain tumor-related epilepsy. METHODS Observational, prospective study, monitoring the efficacy and safety of the drug oxcarbazepine in the prevention of epileptic seizures, included adult patients of both sexes with a supratentorial tumor and a risk of epileptic seizures after neurosurgery. RESULTS The study included 153 hospitalized patients. The percentages of amplified waves, sharp waves, and spike waves decreased in the second and third compared with the first visit. Significantly lower percentages of sharp waves (P = 0.028) on the second compared with the first measurement and spike waves (P = 0.002) on the third compared with the first measurement were determined. Deterioration from normal to low hemoglobin concentration was observed in 40 (26%) patients at the second visit and 17 (12%) at the third visit, compared with the first visit. However, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration values did not change significantly during the 6 months of follow-up. A transient drop in the number of thrombocytes was observed on the second visit. Adverse reactions to the drug were mild. Therapeutic adherence was low, as measured by the Morisky Medication Adherence Scale (MMAS-4). CONCLUSIONS The drug oxcarbazepine has shown good efficacy and safety in the prevention of epileptic attacks after neurosurgery in patients with supratentorial tumors. Additional education of patients on the importance of taking regular therapy is crucial.

Selma Hrkić, Elvir Mehanović, Alma Tanković, A. Šukalo, Amna Tanović Avdić, M. Mehić, Saša Pilipović, Berina Pilipović et al.

OBJECTIVE This study aimed to assess the prevalence and analyze characteristics and symptoms of non-infectious sore-throat in teachers. STUDY DESIGN AND METHODS Adult persons employed as teachers were screened for non-infectious sore throat. A cross-sectional study was performed in patients with non-infectious sore throat confirmed based on clinical examination. RESULTS Out of 1008 teachers who participated in the screening, non-infectious sore throat was found in 70 respondents (6.9%). Most of the participants with non-infectious sore throat were women with a mean age of 45.5 years and a mean length of service 18.1 years. A small number of participants (n = 7, 10%) often visited a medical doctor because of throat problems. Over 80% of participants commonly used throat therapeutic agents. The most common symptoms were dry throat, tickling, and scratching in the throat. The oropharyngeal mucosa in most subjects was slightly red to red, the tonsils were normal, and there was no oropharyngeal enanthema. The median subjective assessments using the visual analog scale from zero to ten were four (interquartile range (IQR) 0-5) for pain, four (IQR 1-5) for difficulty in swallowing, and two (IQR 0-4) for swelling of the pharynx back wall. Of the analyzed risk factors, the highest percentages of participants were using air conditioning and consuming chilled and carbonated drinks, 21.4% were smokers and 10% of participants had a confirmed respiratory allergy. CONCLUSIONS The prevalence of non-infectious sore throat was 6.9% with the most common symptoms being dry throat, tickling, and scratching in the throat. While a small percentage of participants often visited a medical doctor because of throat problems, the majority of them used throat therapeutic agents. Additional multicentric prospective studies are needed to increase our knowledge about symptoms and therapeutic strategies for non-infectious sore throat and voice disorders in general.

Zdenka Gojković, Jelena Rožić, N. Gašpar, A. Šukalo, M. Mehić, Amna Tanović Avdić, U. Glamočlija

Aim: The aim of this study was to examine the effectiveness and safety of lysozyme-based spray in the treatment of oral mucositis in patients undergoing head and neck radiotherapy. Methods: A prospective, open-label study was conducted on patients with ulcerative inflammation of the oral cavity and pharynx mucous membranes clinically assessed for oral mucositis according to the World Health Organization (WHO) Oral Toxicity Scale. Patients were randomly divided into a lysozyme group (using a spray containing lysozyme + cetylpyridinium + lidocaine) and a control group (using a compounded preparation containing gentamicin + dexamethasone + lidocaine). The efficacy and safety of therapy were evaluated on the baseline and three follow-up visits (7, 14, and 21 days after the baseline visit). Results: The total number of participants was 56, of which 26 were in lysozyme and 30 in the control group. The efficacy parameters were similar between the groups and there was no deterioration of symptoms during the follow-up period of 21 days. A significantly lower pain intensity when eating solid food was observed after 21 days in lysozyme compared to the control group. No adverse reactions were observed. Conclusions: This study showed the efficacy and safety of lysozyme-based spray for treating radiotherapy-induced oral mucositis. The availability of new treatment options based on lysozyme, a natural enzybiotic present in the saliva of healthy subjects, could bring added value to the treatment of oral mucositis and the prevention of its complications. However, a larger randomized, blinded study is needed to confirm our results [the study was registered at the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (https://klinicka.almbih.gov.ba/pages/klinicka-registar-javni) under the protocol number LCS-OM-01].

Milkica Glogovac-Kosanović, T. Bućma, Draško Prtina, Aleksandar Gajić, A. Šukalo, M. Mehić, Amna Tanović-Avdić, U. Glamočlija

Background/Aim: Pressure ulcers develop due to prolonged periods of increased pressure on certain parts of the skin and underlying tissue. This study aimed to evaluate the efficacy and safety estimates of lysozyme-based cream in the treatment of pressure ulcers of grade two according to Yarkony-Kirk scale. Methods: Adult patients with neurological diseases and severe functional deficits with grade-two pressure ulcers according to Yarkony-Kirk scale were included. All patients were treated with polarised light. Additionally, the patients were treated twice daily with a cream containing 20 mg/g of lysozyme chloride (lysozyme group) or with povidone-iodine dressings (control group). Visual checks of the ulcer were performed at the baseline and daily until the end of follow-up. Safety was evaluated by the presence of adverse reactions to treatment. Patients were followed for two months or less in case of withdrawal from the study, ulcer healing, or worsening. The Yarkony-Kirk scale grade was determined at the end of follow-up for each patient and one of the four categories was recorded: healed, improved, no changes or worsened. Results: A total of 48 subjects were included, 28 (58 %) in the lysozyme and 20 (42 %) in the control group. Age, sex, pressure ulcer position and duration of follow-up were similar between groups. The percentage of healed pressure ulcers was significantly higher in the lysozyme (71 %) compared to the control (35 %) group (p = 0.005). No adverse reactions to treatments were recorded. Conclusion: The lysozyme-based cream was found to be effective and safe in the treatment of grade-two pressure ulcers. Additional randomised, blinded, larger studies are needed to confirm these findings.

OBJECTIVES Testicular torsion (TT) is an emergency requiring timely surgery to prevent testicular loss. There is a lack of reports on the clinical significance of the time of admission (on-hours vs. off-hours) on the long-term surgical outcome of TT. METHODS We retrospectively reviewed all consecutive patients <18 years who were admitted to the hospital and treated for TT during the ten years. Patients were classified according to their admission time: weekday (on-hours), outside working hours, and weekends (off-hours). They were also classified based on their testicular outcome: salvaged and non-salvaged testis. RESULTS Seventy-two patients were included. Their median age was 14.2 years. Thirty-three patients (46 %) were admitted during on-hours, whereas 39 patients (54 %) were admitted during off-hours. Forty-three patients (59.7 %) required orchidopexy and, out of those, during the long-term follow-up, only 27 (37.5 %) had definitive testicular salvage. Forty-five patients (62.5 %) were with no testicular salvage. On-hours vs. off-hours admission had no impact on the clinical outcome (p = 0.25). However, significant differences in the duration of symptoms (DoS) between the orchidopexy and orchidectomy groups were observed (p < 0.001). CONCLUSION Testicular torsion is a time-dependent diagnosis, and any delay in treatment could cause testicular loss. Our data suggest that the DoS before admission, rather than the admission time, influences the testicular outcome. The efficient management of emergencies regardless of the time of day is a key factor for the reduced probability that admission timing affects outcomes.

U. Glamočlija, Lejla Mahmutović, Esma Bilajac, V. Šoljić, Katarina Vukojević, Abas Sezer, M. Suljagić

Diffuse large B cell lymphoma (DLBCL) is classified into Germinal Center B‐cell (GCB) and activated B‐cell (ABC) subgroups originating from different stages of lymphoid differentiation. Cell of origin dictates the behavior and therapeutic response of DLBCL. This study aimed to evaluate single and combinatorial effects of metformin and thymoquinone (TQ) in two DLBCL cell lines belonging to GCB and ABC subtypes. Metformin and TQ caused dose‐dependent responses in both ABC and GCB DLBCL subtypes. Metformin had a greater impact on the ABC subtype while TQ demonstrated more pronounced effects on the GCB subtype. Synergistic effects were observed in the DHL4 (GCB subtype) but not in the HBL1 (ABC subtype) cell line. This is the first study to compare the effects of metformin and TQ in ABC versus GCB subtype of DLBCL. It brings valuable results that could be utilized in further research aimed at reshaping treatments for subtype‐specific lymphomas.

Lejla Brigić, Ehlimana Mušija, Faris Kadić, M. Halilčević, A. Durak-Nalbantić, L. Dervišević, U. Glamočlija

Background: Lactate dehydrogenase (LDH) isoenzyme assay was used widely in the past to diagnose myocardial infarction (MI). Recent studies show that lactate dehydrogenase seems to be a promising biomarker of adverse left ventricular remodeling. Objectives: Higher levels of these biomarkers were associated with lower odds for favorable reverse remodeling in patients with MI. Methods: The study was performed on patients with the first occurrence of acute myocardial infarction (ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI)), aged 34 to 80 years who underwent catheterization at the admission or during their hospital stay depending on indications. In this study, we compared peak levels of lactate dehydrogenase (LDH) and left ventricular ejection fraction (LVEF). Peak values of LDH were used from the second to the fourth day of hospitalization. Echocardiography has been done in the first 72 hours, which represents an early phase of cardiac remodeling. The ejection fraction was evaluated using the Simpson method. Results: Spearman's rank test showed a negative, statistically significant correlation between LDH and ejection fraction ρ(80)=−0.543, p<0.001. Weighted least squares regression model included LDH concentration, age, and type of myocardial infarction (STEMI/NSTEMI), and the slope coefficient for the LDH level was −0.010 (95% confidence interval (CI): −0.013 to −0.006). With each unit of LDH increase, there was a decrease of 0.01% in left ventricular ejection fraction when age and type of myocardial infarction were held constant. Conclusion: The increased LDH level could be a new predictor for early myocardial remodeling after the first occurrence of myocardial infarction independent of age and type of myocardial infarction.

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