Репозитарій

ЛНМУ імені Данила Галицького

Introduction. Soluble suppression of tumorigenicity 2 (sST2) and galectin-3 are considered markers of myocardial hypertrophy and fibrosis. Changes in their concentrations are observed in cardiovascular diseases, including arterial hypertension.

The aim. To determine threshold values of hypertrophy and fibrosis biomarkers, namely sST2 and galectin-3, in patients with arterial hypertension.

Materials and methods. A prospective study was conducted on 82 patients with arterial hypertension (AH). Patients were stratified into two groups based on left ventricular mass index (LVMI) values: Group 1 with left ventricular hypertrophy (LVMI > 115 g/m² for men and 90 g/m² for women, n=33) and Group 2 with normal LVMI values (n=27).

Results. Patients with left ventricular hypertrophy exhibited significantly elevated sST2 and galectin-3 levels. Direct correlations were observed between LVMI and sST2 values (r=0.6397; p=0.000) and galectin-3 (r=0.5113; p=0.001). Both biomarkers correlated with various cardiac parameters, including interventricular septal thickness at end-diastole, left atrial diameter, left ventricular end-diastolic diameter, and posterior wall thickness at end-diastole (specifically with sST2). With a selected sST2 value of 17.0 ng/ml, the diagnostic method demonstrated 88.33% accuracy, 92.59% specificity, 93.3% positive predictive value, and 83.33% negative predictive value for hypertrophy. At the chosen galectin-3 level of 29.0 ng/ml, the proposed method achieved 72.22% accuracy, 73.68% sensitivity, 70.59% specificity, 73.68% positive predictive value, and 70.59% negative predictive value.

In conclusion, measuring sST2 and galectin-3 biomarkers facilitates the evaluation of left ventricular hypertrophy, serving as an additional tool in assessing cardiac dysfunction and indicating diverse developmental pathways.

УДК 616-001.18/.19:612.56:612.115

Вступ. Значна поширеність холодових уражень, недостатня ефективність запобігання та лікування гострої холодової травми зумовлюють актуальність пошуку нових фригопротекторів, з-поміж яких значну роль відіграють протизапальні засоби. За попередніми даними, високу протизапальну активність проявляють представники нового класу сполук – похідних 5,7-діацил-3-H(алкіл)-6-арил-5Н-[1,2,4]тріазоло[3,4-b][1,3,4]тіадіазину, що може бути предиктором фригопротекторної активності.

Мета дослідження – виконати скринінг низки найактивніших сполук на фригопротекторні властивості на моделі гострого загального охолодження (ГЗО) та поглиблено дослідити сполуку-лідера за критеріями впливу на температуру тіла, стан системи гемостазу, низку показників запального каскаду та NO-синтазу.

Методи дослідження. Експерименти виконано на білих нелінійних мишах та щурах-самцях. Для скринінгу на фригопротекторну активність на мишах взято три похідні 5,7-діацил-3-H(алкіл)-6-арил-5Н-[1,2,4]тріазоло[3,4-b][1,3,4]тіадіазину (лабораторні шифри: IFT-180, IFT-247, IFT-251). Сполуки в дозі 25 мг/кг та препарат порівняння диклофенак натрію (14 мг/кг) вводили внутрішньошлунково за 60 хв до холодової експозиції тварин при -18 °С. Визначали час життя мишей. У поглибленому дослідженні на моделі ГЗО (експозиція 2 год при -18 °С) з’ясовували вплив сполуки-лідера (IFT-247) в дозі 18 мг/кг та препарату порівняння диклофенаку натрію (7 мг/кг) на ректальну температуру щурів. У найгостріший період холодової травми визначали вплив зазначеної сполуки на показники системи гемостазу. В печінці визначали вміст низки маркерів запалення з використанням видоспецифічних наборів.

Результати й обговорення. За результатами скринінгу трьох похідних 5,7-діацил-3-H(алкіл)-6-арил-5Н-[1,2,4]тріазоло[3,4-b][1,3,4]тіадіазину, фригопротекторна активність не є загальною ознакою сполук цього ряду. Досліджено, що потужні фригопротекторні властивості на рівні препарату порівняння диклофенаку натрію проявляє лише сполука IFT-247, яка статистично значуще збільшує час життя мишей із моделлю ГЗО на рівні диклофенаку натрію. У щурів сполука IFT-247 зменшує ступінь гіпотермії за двогодинної експозиції при -18 °С (15 мг/кг), не поступаючись референс-препарату. В н D-. IFT-247 4, ;  IL1- TNF- айгостріший період холодової травми в щурів досліджувана сполука запобігає розвитку ДВЗ-синдрому і тромбозу, знижуючи вміст D-димеру та фібриногену в сироватці крові й нормалізуючи підвищений тромбіновий час на рівні диклофенаку натрію. Сполука IFT-247 при ГЗО пригнічує розвиток системної запальної реакції: попереджує збільшення вмісту лейкотриєну В4 і тотальних лейкотриєнів, поступаючись за цією властивістю диклофенаку; подібно до референс-препарату значно зменшує до субнормального рівня вміст IL1-β та до нормального – TNF-α без впливу на IL-6 і на зменшений вміст протизапальних цитокінів – IL-4 й IL-10, нормалізує збільшене співвідношення про- та протизапальних цитокінів.

Висновки. Встановлено, що (1-(5-ацетил-3-метил-6-феніл-5H-[1,2,4]тріазоло[3,4-b][1,3,4]тіадіазин-7-іл)-етанон) проявляє властивості перспективного фригопротектора, що потребує подальшого дослідження.

As a result of severe injuries and post-traumatic stress disorder, sexual dysfunction and fertility disorders are among the complications men experience. The mechanisms of the effects of combat trauma are complex and include an imbalance of the immune system, which leads to severe inflammatory reactions and other immunomodifying effects after injury. An early r e sponse to an acute inflammatory injury, such as wound healing, is the production of nitric oxide (NO) as a result of L-arginine metabolism. NO is an important regulator of cellular functions throughout the wound healing process, stimulating fibroblasts to produce collagen, promoting matrix deposition, remodeling, and angiogenesis. However, insufficient or excessive NO synthesis negatively affects wound healing. The aim of the study was to investigate the prognostic power of arginase activity parameters and individual NO synthase isoforms as potential biomarkers of nitrosative stress in men with combat trauma. The study e x amined 68 men with combat trauma, including 42 men aged 20 – 39 years and 26 men aged 40 – 53 years. Criteria for inclusion in the control groups: 30 healthy men aged 20 – 39 years and 18 men aged 40 – 53 years with normal levels of cNOs, iNOs and arg i nase activity, somatically healthy, without sexual dysfunction. In all groups, the activity of NO synthases and arginase as markers of nitrosative stress was measured spectrophotometrically in blood serum and lymphocyte samples. The prognostic power of the parameters of cNOS, iNOS and arginase activity in the combat trauma and control groups was determined by the receiver opera t ing characteristic curve (ROC curve). Based on the ROC analysis, the threshold value of cNOS activity in blood lymphocytes was determined, which is an integral highly sensitive criterion for unfavorable prognosis in combat trauma. For men aged 20 – 39 years, this figure is ≤37.5 nmol NADPH(H + )/min. mg with a sensitivity of 61.9% and a maximum specificity of 100 . 0 %, while for the group of men aged 40 – 53 years, the cutoff value is ≤38.4 nmol NADPH(H + )/min. mg with a sensitivity of 65. 4 % and a maximum specificity. In the ROC analysis of iNOS activity in lymphocytes of men with combat trauma in relation to healthy men, an excellent model quality was obtained with the maximum area under the ROC curve for patients of both age groups. The lymphocyte arginase activity in the two age groups of men with combat trauma were characterized by the very good diagnostic accuracy of the test. Thus, the parameters of oxidative-nitrosative stress, in particular the activity of constitutive and inducible isoforms of NO synthase and arginase in blood serum and lymphocytes can be potential markers in distinguishing pathological changes in men affected by combat (bullet and shrapnel wounds). The inducible isoform of NO synthase has been shown in studies to be a highly sensitive and highly specific marker regardless of the age of men.

Background: Botulinum toxin type A has become an increasingly used tool in the preoperative management of giant abdominal wall hernias. Its primary objective is to “downstage” the hernia by inducing temporary paralysis of the lateral abdominal wall muscles, thereby increasing their compliance and enabling safer fascial closure. While the muscular and anatomical benefits of this approach are well documented, the potential effects on pulmonary function remain poorly studied, despite the involvement of the targeted muscles in the process of breathing.

Objective: This study aimed to evaluate the impact of botulinum toxin type A on respiratory system function, using spirometry to assess whether any observed changes reflect true improvement, mechanical compensation, or potential impairment.

Methods: This prospective, observational study included 37 patients with large abdominal wall hernias and a Loss of Domain component. All patients received 300 units of botulinum toxin type A injected bilaterally into the external, internal oblique, and transversus abdominis muscles under ultrasound guidance. Spirometry was performed before the injection and again on the day of surgery. Evaluated parameters included forced vital capacity, forced expiratory volume in one second, the ratio of forced expiratory volume to forced vital capacity, peak expiratory flow, maximum mid-expiratory flow, maximal expiratory flow at 75, 50, and 25 percent of forced vital capacity, forced inspiratory vital capacity. Results were analyzed using paired statistical tests with a significance threshold of p < 0.05.

Results: No statistically significant changes were observed in forced vital capacity or forced expiratory volume in one second. However, statistically significant increases were recorded in maximum mid-expiratory flow and maximal expiratory flow at 50 percent of lung volume. Peak expiratory flow showed a trend toward improvement but did not reach statistical significance. These changes appear to reflect altered expiratory dynamics due to increased diaphragmatic excursion, rather than improved ventilation. Forced inspiratory vital capacity decreased slightly. Only two patients reported subjective changes in breathing.

Conclusion: Botulinum toxin type A does not impair core lung volumes but induces mechanical changes that may affect airflow velocity. Standard spirometry may not fully reflect these dynamics, and further investigation is warranted to better understand respiratory outcomes in this patient group.

Introduction: Incisional hernias are prevalent complications, with significant recurrence rates and associated surgical wound complications. Giant hernias, classified by the European Hernia Society (EHS) as exceeding 10 cm (width dimension), pose a challenge due to the “loss of domain” effect. Component separation techniques (CST), including anterior component separation (ACS) and transversus abdominis release (TAR), are established interventions but have drawbacks related to the irreversible alteration of abdominal wall anatomy and associated risks. An alternative approach involves the preoperative application of Botulinum Toxin A (BTA) to reduce lateral abdominal muscle tension, facilitating hernial defect closure.

Aim: The aim was to assess the impact of BTA on reducing the necessity for CST, the occurrence of surgical site complications, and the need for further interventions.

Materials and methods: A retrospective cohort study was conducted across two reference centers specializing in hernia treatment in Poland and Ukraine. The study compared outcomes between patients undergoing elective abdominal wall reconstruction surgery for giant hernias, specifically looking at the requirement for CST following preoperative BTA application. Patients were divided into two groups – those who received BTA injections 3–4 weeks prior to surgery (BOTOX group) and those who did not (NON-BOTOX group).

Results: The study found that in the BOTOX group, a significantly lower proportion of patients required CST compared to the NON-BOTOX group (46 vs 84%, P-value = 0.000124). Additionally, the BOTOX group experienced fewer postoperative complications, suggesting a beneficial effect of BTA in simplifying surgical procedures and enhancing patient outcomes.

Conclusions: The findings support the use of preoperative BTA injections as a valuable adjunct in the management of giant abdominal hernias. This approach not only facilitates fascial closure without the need for extensive CST but also potentially reduces perioperative trauma and postoperative complications. Preoperative BTA injections significantly reduce the need for CST in giant incisional abdominal hernia repairs, offering a less invasive and more effective approach to fascial closure. The most important role of BTA is "downstaging" the hernia before surgery. This study highlights the importance of considering BTA injections in preoperative protocols, advocating for broader acceptance and reimbursement to improve surgical outcomes and patient care in hernia surgery.

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