Sex differences in the hepatotropic effects of antiulcer drugs and placenta cryoextract in an experimental rat liver injury model

Background/Aim: Sex-related variances in drug metabolism provide a foundation for refining treatment protocols for prevalent conditions based on the patient's sex. Tailoring treatment strategies based on sex is particularly noteworthy among patients with comorbid illnesses due to the potential for drug interactions and the impact of concurrent diseases on clinical outcomes. Aim of this study was to assess the hepatotropic effects of antiulcer drugs (esomeprazole, clarithromycin and metronidazole - E/C/M) and placenta cryoextract (CEP) within a simulated model of tetrachloromethane (CCl4 )-induced hepatitis combined with underlying ethanol-induced liver cirrhosis (EILC), with a focus on the role of subjects' sex. Methods: Using 112 male and female rats, the research explored the effects of different sex hormone levels. Chronic EILC was induced by administering a 50.0 % CCl4 oil solution (8 mL/kg) twice a week, combined with a 5.0 % ethanol solution, over 45 days. Total protein (TP) levels and alkaline phosphatase (AP) activity were measured spectrophotometrically. Results: The research findings indicate that the onset of EILC and the administration of E/C/M resulted in a significantly greater 10.8 % (p = 0.03) reduction in TP levels among females compared to males, without altering hormonal status. Introducing CEP led to a noteworthy (p < 0.001) rise in TP levels, by 30.8 % in males and 33.9 % in females, in the context of EILC and E/C/M administration, while maintaining hormonal status. Among male rats, the most elevated AP activity was observed with excess testosterone propionate administration (5.0 [5.0; 5.9] mmol/L), while the lowest level was recorded in rats after testectomy, measuring 3.8 [2.5; 4.7] mmol/L, exhibiting a significant 20.8 % decrease (p < 0.05) compared to male rats without hormonal status changes. In female rats, the study revealed that against the backdrop of EILC and E/C/M administration, the highest AP level was seen in ovariectomised females, reaching 5.8 [5.1; 6.2] mmol/L, reflecting a substantial 9.4 % increase compared to rats without hormonal status changes. Conclusions: The administration of CEP under similar experimental conditions led to the recovery of the liver's protein-synthesising function in both male and female rats. When female sex hormones were introduced to sham-operated female rats, a significant 20.8 % greater reduction in AP levels was observed. Additionally, gonadectomy led to a more pronounced decrease in this enzyme's levels in male rats compared to female rats, indicating the cytoprotective properties of female sex hormones

Development of Green Production TECHNOLOGY and Research of Harpagophytum Procumbens Root Dry Extract

The aim of this work is to study of standardization parameters and pharmacological properties of Harpagophytum procumbens (H. procumbens) root dry extract. Materials and methods – obtaining of H. procumbens root dry extract was performed in accordance with developed scheme that is characterized by simplicity and cost-effectiveness of technology compared to analogous scheme. Study of standardization parameters of obtained extract was performed in accordance with the requirements of the monograph «Harpagophyti extractum siccum» of the State Pharmacopoeia of Ukraine 2.2., harmonized with the monograph «Harpagophyti extractum siccum» of the European Pharmacopoeia 9.5. Pharmacology study of analgesic and anti-inflammatory activities were conducted on the rat paw formalin-induced&nbsp;edema model. Results. Obtained H. procumbens root dry extract is a free flowing, non-hygroscopic, light brown powder with taste and odor that is specific to raw material of H. procumbens. Determined loss on drying was 3.2±0.18 %. Content of heavy metals in dry extract was not more than 0.01 % (100 ppm). Harpagoside was identified by TLC method. Chromatographic zones on the obtained chromatograms of the reference solution and test solutions are the same in intensity of a color, cross-over and sharpness of development. Based on the results of the research performed by HPLC method, it has been established that content of harpagoside in investigated H. procumbens root dry extract is 2.50±0.02 %. According to the results of pharmacological research it was found that investigated dry extract (the content of harpagoside is not less than 37.0 mg/kg) showed a higher activity compared to reference drug («Phong Te Thap»). Conclusions. A new method of obtaining dry extract of H. procumbens (3.5:1) was proposed. The developed green production technology is simple; it does not require special equipment and expensive solvents. A correspondence of quality parameters with the requirements of State Pharmacopoeia of Ukraine and European Pharmacopoeia: appearance, identification of harpagoside and fructose, loss of drying, content of heavy metals, assay of harpagoside (2.50±0.02 %) was set. Analgesic and anti-inflammatory activities of H. procumbens dry extract has been establishe

СТАТЕВІ ВІДМІННОСТІ ВПЛИВУ ПРОТИВИРАЗКОВИХ ЗАСОБІВ ТА КРІОЕКСТРАКТУ ПЛАЦЕНТИ НА ІНТЕНСИВНІСТЬ ПЕРЕКИСНОГО ОКИСЛЕННЯ ЛІПІДІВ ТА АКТИВНІСТЬ АНТИОКСИДАНТНОЇ СИСТЕМИ ЗА ЕКСПЕРИМЕНТАЛЬНОГО ГЕПАТИТУ ТА ЕТАНОЛ-ІНДУКОВАНОГО ЦИРОЗУ

Introduction. It is well recognized that drug metabolism products in the liver can induce oxidative stress and mitochondrial dysfunction, leading to the development of hepatocellular injury. As a potential agent capable of counteracting the hepatotoxic effects of drugs, we focused our attention on a domestic biotechnological preparation – cryopreserved placental extract (CPE). The aim. To characterize gender differences in the effect of esomeprazole, clarithromycin, metronidazole (E/C/M), and CPE on the intensity of lipid peroxidation and the activity of the antioxidant system in tetrachloromethane (CCl4) hepatitis with a background of ethanol-induced cirrhosis (ETCM). Materials and methods. The study was conducted with varying levels of sex hormones on 112 male and female rats. Chronic ETCM was induced by administering a 50.0% oil solution of CCl4 at a dose of 8 ml/kg body weight of the animals twice a week, in combination with a 5.0% ethanol solution for drinking over a period of 45 days. The content of TBA-RP in liver homogenates was determined spectrophotometrically by the method described by Asakawa T. et al. Catalase activity in liver homogenates was determined spectrophotometrically according to the method of Korolyuk M.A. and co-authors. Results. The most pronounced increase in lipid peroxidation processes was observed in females with chronic ETCM-induced liver damage and administration of antiulcer drugs following ovariectomy, resulting in a TBA-RS content of 36.1±2.79 μmol/kg of tissue. Administration of E/C/M in animals with chronic liver damage led to a suppression of the antioxidant system, as evidenced by a decrease in catalase activity in liver tissues. Conclusion. The combined use of anti-ulcer drugs and CPE on the background of chronic ETCM mitigated the activation of lipid peroxidation processes, which was indicated by a statistically significant (p &lt; 0.001) 2.7-fold lower content of TBA-RP in liver homogenates. Additionally, it was established that the administration of CPE was accompanied by a statistically significant increase in catalase activity in females, more prominently than in males. In females without changes in hormonal status, the introduction of CPE resulted in a growth (p &lt; 0.001) of catalase activity by 75.0%, with the most significant increase observed in females after ovariectomy – catalase activity statistically significantly (p &lt; 0.001) increased by 2.6 times compared to the indicators of females not administered with CPE. The administration of CPE in female rats without altering hormonal status was accompanied by a twofold (p &lt; 0.01) increase in the antioxidant-prooxidant index compared to male rats, indicating more pronounced antioxidant properties of CPE in female rats.ВСТУП. Добре відомо, що продукти метаболізму лікарських засобів у печінці можуть спричинювати окислювальний стрес та мітохондріальну дисфункцію, призводячи до розвитку гепатоцелюлярного ушкодження. У якості потенційного засобу, спроможного нівелювати гепатотоксичні ефекти лікарських засобів нашу увагу привернув вітчизняний біотехнологічний препарат – кріоекстракт плаценти (КЕП). Мета роботи. Охарактеризувати статеві відмінності впливу езомепразолу, кларитроміцину і метронідазолу (Е/К/М) та КЕП на інтенсивність перекисного окислення ліпідів та активність антиоксидантної системи при тетрахлорметановому (CCl4) гепатиті з фоновим етанол-індукованим цирозом (ЕТХМ). Матеріали та методи. Дослідження проведено за різного вмісту статевих гормонів на 112 самцях та самицях щурів. Хронічний ЕТХМ відтворювали шляхом введення 50,0 % олійного розчину CCl4 у дозі 8 мл/кг маси тіла тварини двічі на тиждень в комбінації з 5,0% розчином етанолу для пиття впродовж 45 днів. Вміст реактантів з тіобарбітуровою кислотою (ТБК-РП) у гомогенатах печінки визначали спектрофотометрично за методом Asakawa Т. et al. Активність каталази у гомогенатах печінки визначали спектрофотометрично за методом Королюка М.А. та співав. Результати та обговорення. Найвиразніша активація процесів перекисного окислення ліпідів відмічена у самиць на тлі хронічного ЕТХМ-індукованого ураження печінки та введення противиразкових препаратів після оваріектомії, у яких вміст ТБК-РП становив 36,1±2,79 мкмоль/кг тканини. Введення Е/К/М при хронічному ураженні печінки у тварин супроводжувалось пригніченням антиоксидантної системи, на що вказувало зниження активності каталази у тканинах печінки. Висновки. Комбіноване застосування противиразкових препаратів та КЕП на тлі хронічного ЕТХМ нівелювало активацію процесів перекисного оксиення ліпідів, на що вказувало статистично вірогідно (р &lt; 0,001) нижчий вміст ТБК-РП в гомогенатах печінки у 2,7 рази. Крім того, встановлено, що введення КЕП супроводжувалось статистично вірогідним зростанням активності каталази у самиць виразніше ніж у самців. Так у самиць без зміни гормонального статусу введення КЕП викликало зростання (р &lt; 0,001) активності каталази на 75,0 %, а найвиразніше вказаних показник збільшився у самиць після оваріектомії – активність каталази статистично вірогідно (р &lt; 0,001) зросла у 2,6 рази відносно показників самиць, яким КЕП не вводили. Введення КЕП у самиць щурів без зміни гормонального статусу супроводжувалось вдвічі більшим (р &lt; 0,01) зростанням антиоксидантно-прооксидантного індексу, ніж у щурів-самців, що вказує на виразніші антиоксидантні властивості КЕП у щурів-самиць

Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

Aiming to reduce the potential in vivo hepato-and neph‐ rotoxicity of Ag/Au bimetallic nanoparticles (NPs) stabi‐ lized by sodium dodecyl sulphate (SDS), an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp) as a reduc‐ ing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5-15 nm sized) were able to form stable aggregates with an average size of 370-450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical param‐ eters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application

Establishing Changes in the Technical Parameters of Nipple Rubber for Milking Machines and Their Impact on Operational Characteristics

Nipple rubber is an important part of a milking machine, one of its key elements. This is the only component of a milking plant that has direct contact with the surface of a cow udder. In addition, nipple rubber is the most loaded component of a milking machine. During the milking process, it is compressed and unclenched more than 400 times. In order to maximize the effect of the use of rubber, it is necessary to calculate the conditions of its use correctly, to monitor technical parameters in due time. The task of the study is to establish changes in the technical parameters of the nipple rubber of milking machines and their impact on the performance of the article.In the course of the research, it was established that the service life of all kinds of nipple rubbers was 1,000 hours, which, if used for 8 hours a day, corresponds to 125 days or 4 months of operation. When used for 1,000 hours, the rubber stiffness varies within significant limits and an average is: for products made of silicone 2,849.61±52.23–3,343.76±51.26 N/m; made of the material of rubber mixtures – 2,597.76±78.26–2,821.43±55.24 N/m. The readiness coefficient of all products is 1. Using electron microscopy, it was possible to establish the changes of the inner surface of nipple rubber after operating for 125 days/1,000 hours and after operating for 250 days/2,000 hours. It is proved that all its basic parameters change during operation. The weight of an article changes by 8.5 %, the depth – by 37 %, the wall thickness – by 2.5 %, and the stretching length – by 27 %. The high positive correlation dependence (r=+0.939) between the nipple rubber stiffness and milking intensity was found.The studied indicators are important for determining the performance and nipple rubber suitability for use. The conducted research offers a real possibility of taking into consideration the qualitative parameters of nipple rubber during their selection and subsequent operatio

Chronic coronary syndromes without standard modifiable cardiovascular risk factors and outcomes: the CLARIFY registry

Background and Aims: It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs—diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD). Methods: CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE—CV death, non-fatal MI, or non-fatal stroke). Results: Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08–7.19] vs. 7.68% [95% CI 7.30–8.08], P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women. Conclusions: SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors