Serial Blood Samples Research Articles

Pharmacokinetic Interactions Between the Fixed-Dose Combination of Ezetimibe/Rosuvastatin 10/20 Mg and the Fixed-Dose Combination of Telmisartan/Amlodipine 80/5 Mg in Healthy Subjects.

Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA). An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study. Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects. The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.

Role of Rhodomyrtus tomentosa (Aiton) Hassk. in regulating the expression of fibroblast growth factor family in the liver of rat in a breast cancer model

Context: Cellular abnormalities in the ducts and breast tissue cause breast cancer to invade nearby tissues like the liver. The fibroblast growth factor (FGF) signals are sent to its receptor and regulate various cellular processes to maintain liver homeostasis. However, this condition has few and inefficient treatments. Breast cancer is characterized by the development of cellular abnormalities within the ducts and breast tissue, leading to the invasion of adjacent tissues, such as the liver. Aims: To examine the impact of Rhodomyrtus tomentosa administration on the expression of the FGF family in cancer animal models, with a specific focus on the liver. Methods: Cancer model rats were administered at dosages of 100, 200, and 300 mg/kg BW for 30 days. Liver tissue and blood serum samples were extracted from the rat. Liver tissue was stained for immunohistochemistry using FGF1, FGF15, FGF19, and FGF21, and blood samples were collected for ELISA analysis. Results: The study found that DMBA in hepatocyte cells degrades parenchyma, making it hydrophilic and necrosating. Hepatocyte cell function improved with the greatest dose of R. tomentosa. The elevation was associated with an area around the portal vein where recently dividing hepatocytes form clusters. Conclusions: The promise of R. tomentosa as a candidate for the development of hepatoprotective medicines in cancer treatment arises from its ability to influence the expression of crucial liver health markers, including FGF1, FGF15, FGF19, and FGF21.

Ultrasensitive tadalafil detection with eco-friendly CeO2/Al-pillared clay incorporated pencil graphite paste electrode

In this study, we have constructed a novel voltammetric sensor based on montmorillonite clay (MMT) incorporated with CeO2 nanoparticles using a composite graphite paste electrode as a cross linker (MMT-CeO2NPs/GPG-PE) for the trace determination of tadalafil (TAD) drug. The characterization of CeO2 nanoparticles has been conducted using various analytical techniques, including X-ray diffraction, transmission electron microscopy, and high-resolution transmission electron microscopy. The morphology of the composite of CPG and MMT-CeO2NPs/CPG was elucidated through scanning electron microscopy (SEM). The newly developed sensor (MMT-CeO2NPs/CPG-PE) exhibited remarkable efficiency towards TAD oxidation using adsorptive stripping square-wave voltammetry (AdS-SWV) in Mcllvaine buffer solution (pH 8.0). A highly selective and sensitive method for TAD detection has been successfully applied based on MMT-CeO2NPs/CPG-PE, showing two different linear concentration ranges of 0.005−0.1 and 0.1–9.9 µM. The LOD and LOQ were determined to be 1.97 × 10−10 and 6.57 × 10−10 M, respectively, with a sensitivity of 3916 µA µM−1 cm−2. Interestingly, the sensing electrode exhibited excellent reproducibility, reusability, and stability even after 30 days. Moreover, the newly developed nano-sensor (MMT-CeO2NPs/CPG-PE) has been effectively utilized for the accurate detection of TAD in pharmaceutical formulations and spiked human blood serum and urine samples, demonstrating no interference from other substances.

Comparison of sodium and potassium values in arterial and venous blood samples

Abstract Background: In routine practice, electrolytes are measured in serum using an electrolyte analyzer, which takes approximately 30 min. In contrast, electrolyte measurements from arterial blood using an arterial blood gas (ABG) analyzer can be completed within 5–10 min. However, limited information compares electrolyte values between venous and arterial samples. This study aims to determine if sodium (Na) and potassium (K) test results from arterial blood and venous serum samples can be used interchangeably. Materials and Methods: An observational cross-sectional study was conducted over 2 months (July and August 2019) at a tertiary care teaching hospital and research center. Data were collected from 50 intensive care unit patients, including their ABG analysis and serum electrolyte reports. The ABG samples, collected in heparinized syringes, were processed immediately using GEM Premier 3500 Blood gas analyzer. Serum electrolytes were measured with the Roche 9180 analyzer after centrifugation. Data analyses were performed using IBM Statistical Package for the Social Sciences version 21, and Bland–Altman plots were used to compare the results. Results: The mean sodium levels in venous samples and arterial blood were statistically insignificant (P < 0.17). In contrast, a significant difference was observed in potassium measurements between the two sample types (P = 0.000, null hypothesis rejected). The mean difference in sodium (Na+) results was 2.01 mEq/L, with a limit of agreement ranging from −17.98 to 22 mEq/L. The bias in arterial potassium was 0.99 mEq/L, with a 95% limit of agreement from 0.01 to 1.97 mEq/L. Conclusions: While sodium results from arterial and venous samples were similar, potassium results differed significantly. Therefore, potassium measurements from ABG and serum electrolyte analyzers should not be used interchangeably and must be interpreted cautiously.

Virological and Serological Investigation of Feline Coronavirus Infection in Cats

Feline coronavirus infection is an important viral disease affecting feline health. In this study, feline coronavirus infection (FCoV) in cats was investigated using virological and serological methods. For this purpose, both blood and stool samples were taken from 60 cats aged six months or older with or without clinical signs in different races, sexes, ages and social environments, which were not vaccinated against the aforementioned infection, which were kept as pets at home. Collected blood samples were checked for FCoV antibodies by applying FCoV rapid test-antibody (Ab) and indirect Enzyme Linked Immunosorbent Assay (ELISA) methods. Similarly, stool samples taken from the same cats were checked for the presence of FCoV antigen using the FCoV rapid test-antigen (Ag) method. Of the 60 cat blood serum samples analyzed, 21 (35%) were determined to be seropositive by rapid test-Ab method and 41 (68.33%) by indirect ELISA method. The difference between the antibody positivity rates determined as a result of the indirect ELISA method and the rapid test-Ab method was found to be statistically significant (P˂0.001). The presence of FCoV in 60 stool samples collected was investigated by rapid test-Ag method and 1 sample (1.67%) was found to be antigen positive. As a result of this research, the presence/prevalence of FCoV infection in owned cats was revealed both virologically and serologically. In addition, the indirect ELISA method was found to be more sensitive and reliable than the rapid test-Ab method in the serological diagnosis of FCoV infection.

Seroprevalence of Maedi-Visna Infection in Sheep in the Central Black Sea Region of Türkiye

Maedi-Visna is a slowly progressive infection of sheep that affects the respiratory and nervous systems and causes significant yield losses worldwide. This study was conducted to assess the seroprevalence of Maedi-Visna infection in sheep across several provinces in the Central Black Sea region of Türkiye, namely Samsun, Sinop, Ordu, Giresun, Amasya and Tokat. A total of 476 sheep serum samples were collected for further analysis. The presence of antibodies in the sera was determined by Ab ELISA. As a result of the study, 263 (55.25%) blood serum samples were positive for the presence of MVV antibodies. Seropositivity rates by province were as follows: Samsun 45%, Sinop 80%, Ordu 58.75%, Giresun 35%, Amasya 38.75%, Tokat 75%. Notably, our findings suggest a significantly high seroprevalence of Maedi-Visna infection in this region compared to other studies conducted in different parts of Türkiye This information is pivotal for understanding the extent of the infection in the sheep population of the Central Black Sea region and can contribute to the development of strategies for disease management and control.

Adiponectin and TNFα in relation to glucometabolic control in patients with type 2 diabetes mellitus.

The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM). We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables. Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin. Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.

Development of ATP-modified CoFe2O4@ZIF-8@ZIF-67 core–shell nanozyme for sensitive colorimetric detection of dopamine

Core-shell nanostructures (NSs) are a type of nanozyme broadly used in various fields due to their significant physicochemical advantages. In the present study, the CoFe2O4@ZIF-8@ZIF-67 core–shell were fabricated by a consecutive two-step synthesis method, including hydrothermal for CoFe2O4 metal spinel and epitaxial solvothermal growth of ZIFs bilayers on the metal spinel NSs. The core–shell surface was modified using ATP inspired by the active site of the natural peroxidase enzyme. The nanocomposites were characterized by XRD, FT-IR, SEM, EDX, and Dot-mapping techniques. The peroxidase-like activity of the ATP/CoFe2O4@ZIF-8@ZIF-67 was assessed by a colorimetric method. Modified nanocomposite displayed desirable peroxidase mimetic activity and could enzymatically generate hydroxyl radicals from H2O2 and oxidize TMB. The high catalytic activity of ATP-modified nanocomposite and its ability to oxidize TMB provides a rapid and sensitive platform for the colorimetric detection of dopamine. Dopamine consumes hydroxyl radicals, prevents TMB oxidation, and causes a color change in the detection solution, which the naked eye can recognize. The presented colorimetric test provided an excellent LOD for dopamine (0.4 µM) with a good linear range (0.2–18 µM) and selectivity, which was prosperously applied to dopamine assay in serum blood samples.

The synergistic effects of mechanical ventilation and intrauterine inflammation on cerebral inflammation in preterm fetal sheep.

Intrauterine inflammation and the requirement for mechanical ventilation independently increase the risk of perinatal brain injury and adverse neurodevelopmental outcomes. We aimed to investigate the effects of mechanical ventilation for 24 h, with and without prior exposure to intrauterine inflammation, on markers of brain inflammation and injury in the preterm sheep brain. Chronically instrumented fetal sheep at ~115 days of gestation were randomly allocated to receive a single intratracheal dose of 1 mg lipopolysaccharide (LPS) or isovolumetric saline, then further randomly allocated 1 h after to receive mechanical ventilation with room air or no mechanical ventilation (unventilated control + saline [UVC, n = 7]; in utero mechanical ventilation + saline [VENT, n = 8], unventilated control + intratracheal LPS [UVC + LPS, n = 7]; in utero ventilation + intratracheal LPS [VENT + LPS, n = 7]). Serial fetal blood and plasma samples were collected throughout the experimental protocol for assessment of blood biochemistry and plasma interleukin (IL)-6 levels. After 24 h of mechanical ventilation, fetal brains were collected for RT-qPCR and immunohistochemical analyses. LPS exposure increased numbers of microglia and upregulated pro-inflammatory related genes within the cortical gray matter (GM) and subcortical white matter (SCWM) (pLPS < 0.05). Mechanical ventilation alone increased astrocytic cell density in the periventricular white matter (PVWM) (pVENT = 0.03) but had no effect on pro-inflammatory gene expression. The combination of ventilation and LPS increased plasma IL-6 levels (p < 0.02 vs. UVC and VENT groups), and exacerbated expression of pro-inflammatory-related genes (IL1β, TLR4, PTGS2, CXCL10) and microglial density (p < 0.05 vs. VENT). This study demonstrates that 24 h of mechanical ventilation after exposure to intrauterine inflammation increased markers of systemic and brain inflammation and led to the upregulation of pro-inflammatory genes in the white matter. We conclude that 24 h of mechanical ventilation following intrauterine inflammation may precondition the preterm brain toward being more susceptible to inflammation-induced injury.

Interstitial electrical stimulation for middle-aged, and elderly adults with early stages of knee osteoarthritis

Introduction The adequate, pathogenetically substantiated pain management is essential for treatment of early stages of deforming osteoarthritis of the knee joint. There is a need to explore the effectiveness and mechanisms of modern methods of electrical therapy and their impact on the quality of life due to close cause-and-effect relationship between the pain, inflammatory and destructive components of osteoarthritis (OA) as one of the most common conditions.The objective was to evaluate the effect of interstitial electrical stimulation (IES) as a monotherapy in the course of conservative treatment of early stages of gonarthrosis based on clinical and biochemical findings.Materials and methods Radiographic findings, skin electrometry (objective parameters of pain intensity), limb weight-bearing capacity, biochemical parameters of connective tissue matrix degradation in blood serum and 24-hour urine samples, and treatment satisfaction were explored in 43 patients. Patients who received a course of IES were assigned to the treatment group (n = 22) and patients who received standard treatment without IES constituted the control group (n = 21).Results Electrometric analysis showed a higher effectiveness of pain relief in the treatment group compared to the controls with asymmetry coefficient measuring 3.2 ± 0.31 versus 1.9 ± 0.4 at p &gt; 0.05. The weight‑bearing scored 3.59 ± 0.34 versus 3.26 ± 0.2 at p &gt; 0.05. The treatment group showed shorter treatment length with 13.21 ± 1.2 days versus 18.3 ± 1.2 days in the control group at p &gt; 0.05 and a higher degree of satisfaction with outcomes scored 96.2 ± 2.59 in the treatment group versus 86.2 ± 3.17 in the control group. A statistically significant difference (p &gt; 0.05) was established in the levels of free and total hydroxyproline characterizing the different intensity of collagen breakdown in the groups at the end of treatment.Discussion The IES used as an analgesic and anti-inflammatory therapy was shown to be highly effective with changes in the hydroxyproline level in the media suggesting a chondroprotective effect. The analysis and comparison of objective parameters demonstrated high effectiveness of IES in the treatment of early stages of gonarthrosis in middle-aged and elderly adults.Conclusion The IES used for treatment of early stages of gonarthrosis helps pain reducing the intensity of collagen destruction and improving weight-bearing.

Nanoengineered plasmonics-enhanced photothermal tags for sensitive detection of cardiac biomarker troponin I using lateral flow immunoassay

In recent years, photothermal lateral flow immunoassay (LFIA) has gained widespread use as a point-of-care testing (POCT) technique because of its cost-effective portable instrumentation and easy-to-handle procedures. However, developing a highly sensitive photothermal LFIA platform with high photothermal efficiency remains challenging. In this study, we developed a portable smartphone-based plasmonics-enhanced photothermal LFIA (PPh-LFIA) platform to improve the photothermal LFIA sensitivity by engineering plasmonic-active gold nanostars (GNS) having large-sized sharp branches. We investigated the photothermal effect using various GNS engineered to have different sizes and spike lengths of GNSs (GNS-1, GNS-2, GNS-3, and GNS-4) in order to exhibit optimal plasmonics properties. The results showed that the GNS-3 having a broad plasmon band with a plasmon maximum band at 995 nm exhibited the strongest photothermal efficiency (80 %). As a proof-of demonstration, we have employed GNS-3 for the detection of the cardiac biomarker, troponin I (cTnI), used as the model system. The results show high sensitivity with a detection limit (LOD) of 5.5 pg/mL, which was around 1000 times more sensitive than traditional colorimetric LFIA based on gold nanospheres (GNSP). To verify the applicability of the PPh-LFIA platform, cTnI was spiked into human blood serum samples, enabling the detection of cTnI with an LOD of 6.7 pg/mL. Overall, this study offers insights for nanoengineering and fine-tuning the GNS morphology to increase the photothermal efficiency, consequently improving the PPh-LFIA detection sensitivity, which makes it suitable for use as a sensitive and portable POCT tool.

The potential of five c-miRNAs as serum biomarkers for Late-Onset Alzheimer’s disease diagnosis: miR-10a-5p, miR-29b-2-5p, miR-125a-5p, miR-342-3p, and miR-708-5p

The nervous system is rich in miRNAs, indicating an important role of these molecules in regulating processes associated with cognition, memory, and others. Therefore, qualitative and quantitative imbalances involving such miRNAs may be involved in dementia contexts, including Late-Onset Alzheimer’s Disease (LOAD). To test the viability of circulating miRNAs (c-miRNAs) as biomarkers for LOAD, we proceed accordingly to the following reasoning. The first stage was to discover and identify profile of c-miRNAs by RNA sequencing (RNA-Seq). For this purpose, blood serum samples were used from LOAD patients (n = 5) and cognitively healthy elderly control group (CTRL_CH) (n = 5), all over 70 years old. We identified seven c-miRNAs differentially expressed (p ≤ 0.05) in the serum of LOAD patients compared to CTRL_CH (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p, miR-380-5p and miR-340-3p). Of these, five (p ≤ 0.01) were selected for in silico analysis (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p), for which 44 relevant target genes were found regulated by these c-miRNAs and related to LOAD. Through the analysis of these target genes in databases, it was possible to observe that they have functions related to the development and progress of LOAD, directly or indirectly connecting the different Alzheimer’s pathways. Thus, this work found five promising serum c-miRNAs as options for biomarkers contributing to LOAD diagnosis. Our study shows the complex network between these molecules and LOAD, supporting the relevance of studies using c-miRNAs in dementia contexts.

Oxidised Albumin Levels in Plasma and Skeletal Muscle as Biomarkers of Disease Progression and Treatment Efficacy in Dystrophic mdx Mice.

Redox modifications to the plasma protein albumin have the potential to be used as biomarkers of disease progression and treatment efficacy in pathologies associated with inflammation and oxidative stress. One such pathology is Duchenne muscular dystrophy (DMD), a fatal childhood disease characterised by severe muscle wasting. We have previously shown in the mdx mouse model of DMD that plasma albumin thiol oxidation is increased; therefore, the first aim of this paper was to establish that albumin thiol oxidation in plasma reflects levels within mdx muscle tissue. We therefore developed a method to measure tissue albumin thiol oxidation. We show that albumin thiol oxidation was increased in both mdx muscle and plasma, with levels correlated with measures of dystropathology. In dystrophic muscle, albumin content was associated with areas of myonecrosis. The second aim was to test the ability of plasma thiol oxidation to track acute changes in dystropathology: we therefore subjected mdx mice to a single treadmill exercise session (known to increase myonecrosis) and took serial blood samples. This acute exercise caused a transient increase in total plasma albumin oxidation and measures of dystropathology. Together, these data support the use of plasma albumin thiol oxidation as a biomarker to track active myonecrosis in DMD.

Evaluation of effects of Tempol on testicular ischemia/reperfusion injury

AimTempol, a synthetic antioxidant compound, has received significant attention for its potential therapeutic applications in recent years, especially against ischemia/reperfusion (I/R) injury. The aim of the present research was to assess the protective effects of Tempol on testicular I/R injury caused by testicular torsion and detorsion (T/D) in rats. MethodsThe subjects were divided into five groups: sham, testicular T/D, testicular T/D with Tempol treatment at 50 and 100 mg/kg, and healthy rats treated with Tempol at 100 mg/kg. Testicular torsion was induced by rotating the left testicles for 2 h, followed by detorsion for 24 h. Testicular tissues were evaluated for gene expression, oxidative stress markers, and histopathology, epididymal sperms were stained and analyzed, and blood serum samples were collected to measure the testosterone hormone. ResultsThe results showed that testicular I/R caused a significant decrease in sperm velocity parameters, viability, and count, as well as an increase in abnormal sperms (p < 0.05). However, treatment with Tempol significantly improved these parameters (p < 0.05). Histopathological analysis revealed severe damage to the testicular tissues, but treatment with Tempol improved the structural integrity of the seminiferous tubules. Testicular I/R also resulted in increased oxidative stress index and decreased testosterone levels significantly (p < 0.05), but Tempol administration mitigated these effects significantly (p < 0.05). Furthermore, the expression of Bax and Bcl2, genes associated with apoptosis, were significantly altered by testicular I/R (p < 0.05), but Tempol prevented these changes significantly (p < 0.05). ConclusionThese findings provide strong evidence that Tempol can effectively prevent testicular I/R injury.

Novel method of phosphorous doped bismuth oxide with carbon aerogel for a selective voltammetry quantification of anti-cancer drug: Regorafenib

Regorafenib (REG) is an oral multikinase inhibitor derived from diphenylureas. This drug is prescribed to treat colorectal and gastrointestinal stromal tumors and hepatocellular carcinoma. Our present study demonstrates the non-enzymatic electrochemical determination of REG in human blood serum at low concentrations by applying phosphorous-doped bismuth oxide (P-BiO) and porous graphene oxide (PGO)/protonated graphitic carbon nitride (PGCN) combined Aerogel form a P-BiO/Aerogel nanohybrids fabricated glassy carbon electrode (GCE). The property of our proposed electrocatalyst was characterized using several spectroscopic techniques. Utilizing cyclic voltammetry and differential pulse voltammetry techniques the electrochemical performance of this designed sensor was analyzed. Our P-BiO/Aerogel/GCE sensor exhibited a lower detection limit (LOD) of 0.1 nM with a high sensitivity of 1.433 µA µM-1cm−2. As a part of the real-time functionality, our fabricated sensor quantified the trace levels of REG in the consumed patient’s blood serum samples at the recovery range of 99–103 %. Therefore, our P-BiO/Aerogel nanohybrid electrocatalyst is a promising electrocatalyst for the real-time monitoring of REG.

Low expression of the CCL5 gene and low serum concentrations of CCL5 in severe invasive group a streptococcal disease.

Our objective was to elucidate host dependent factors of disease severity in invasive group A Streptococcal disease (iGAS) using transcriptome profiling of iGAS cases of varying degrees of severity at different timepoints. To our knowledge there are no previous transcriptome studies in iGAS patients. We recruited iGAS cases from June 2018 to July 2020. Whole blood samples for transcriptome analysis and serum for biomarker analysis were collected at three timepoints representing the acute (A), the convalescent (B) and the post-infection phase (C). Gene expression was compared against clinical traits and disease course. Serum chemokine ligand 5 (CCL5, an inflammatory cytokine) concentration was also measured. Forty-five patients were enrolled. After disqualifying degraded or impure RNAs we had 34, 31 and 21 subjects at timepoints A, B, and C, respectively. Low expression of the CCL5 gene correlated strongly with severity (death or need for intensive care) at timepoint A (AUC = 0.92), supported by low concentrations of CCL5 in sera. Low gene expression levels and low serum concentration of CCL5 in the early stages of an iGAS infection were associated with a more severe disease course. CCL5 might have potential as a predictor of disease severity. Low expression of genes of cytotoxic immunity, especially CCL5, and corresponding low serum concentrations of CCL5 associated with a severe disease course, i.e. death, or need for intensive care, in early phase of invasive group A Streptococcal disease.

Study of the bioequivalence of drugs for veterinary use «Avecardit» and «Vetmedin S» in the body of dogs

This article reflects the results of a pharmacokinetic comparison of the reproducible drug based on pimobendan «Avecardit» with the reference drug «Vetmedin S» when used in dogs. The experiment used a sequential study design. A group of experimental dogs was formed, consisting of 7 animals (6 main and 1 reserve animal). Blood sampling was carried out before administration and after 10, 20, 40 min; 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12 and 24 hours after drug administration. Key parameters assessed during the study: maximum concentration (Cmax) and time to reach it, area under the concentration-time curve (AUC) of the active substance of the drug in the blood serum of dogs. The article describes the main stages of the experiment, reagents and standard samples, the process of sample preparation of blood serum samples and HPLC-MS/MS analysis, and presents the results of a study of the bioequivalence of the drugs «Avecardit» and «Vetmedin S».The time to reach the maximum concentration of pimobendan (Tmax) in the blood serum averaged 0.67–1 hour for the drug «Avecardit», 1–1.5 hours for the drug «Vetmedin S».Maximum blood serum concentrations (Cmax) of pimobendan were in the range of 53,995–62,873 ng/ml for the study drug and 49,956–61,108 ng/ml for the reference drug. The 90% confidence intervals for the CmaxT/CmaxR and AUC0-tT/AUC0-tR ratios of pimobendan were within the range of 80–125%. The obtained results of the research work, from a scientific point of view, are a sufficient basis for recognizing the pharmacokinetic equivalence of the reproduced drug to the reference one.

Electrochemical sensor based on reduced graphene oxide paste electrode for detection of gemcitabine as a chemotherapy drug in breast cancer

The development of a precise and sensitive electrochemical sensor is essential in the field of medical diagnostics in order to identify gemcitabine, a chemotherapy drug that is commonly used to treat breast cancer. This work presents a novel electrochemical sensor based on a reduced graphene oxide (rGO) nanocomposite and a zirconium-based metal-organic framework (Zr-MOF) with terephthalic acid as a ligand. Gemcitabine (GEM), a chemotherapy medication used to treat breast cancer, is detected with remarkable sensitivity and selectivity by the Zr-MOF-rGO modified graphene paste electrode (GrPE) sensor. By combining the strong structure and active sites of Zr-MOF with the large surface area and electrical conductivity of rGO, the sensor's design maximizes electron transfer rates and GEM adsorption capacity. The sensor outperforms current GEM sensors with its wide linear detection range (0.5–490 μM) and low detection limit (0.008 μM). The sensor's long-term analytical applicability is confirmed by stability and reusability studies, which produced accuracy rates surpassing 94 % and RSD values below 4.21 % in recovery trials using spiked human blood serum and urine samples. Overall, the results of this investigation show that the Zr-MOF-rGO/GrPE electrode has the potential to be a useful platform for the detection of gemcitabine in patients with breast cancer.

The Relationship of Mitochondrial-derived Peptide (MOTS-c) and Brain Mitochondrial Carrier Protein 1 (BMCP1) Response in Sheep with Some Physiological Parameters

Background: Mitochondria are organelles called power plants of the cell, which are found in eukaryotic cells and are responsible for the production of energy needed by the cells through aerobic respiration. Mitochondrial dysfunction causes endocrinological, cardiovascular, metabolic and neurodegenerative diseases. The aim of this study was to examine the effects of body condition score (BCS), lactation, pregnancy, age and gender on Mitochondrial-Derived Peptide (MOTS-c) and Brain Mitochondrial Transporter Protein 1 (BMCP1) levels in Akkaraman sheep. Methods: Sheep are classified into 3 categories according to BCS (BCS less than 2, BCS=3-3.5, BCS≥4). In creating groups in terms of BCS, it was determined by the palpation method applied to the waist area. The sheep included in the study were divided into 4 groups: early lactation, early pregnancy, late pregnancy (dry period) and age (female and male sheep).1st group, ewes in the first period of pregnancy (on the 100th day of the first pregnancy) (n = 30), 2nd group, ewes in the early lactation period (n = 30), 3rd group, ewes in the dry period (the last two months of pregnancy) (n = 30) and in the 4th group, less than 2 (young) (n=30), 2-8 (adult) (n=30), 8 greater than (old) (n=30), male and female sheep (n=30) of different ages. =180) total of 270 animals. Blood samples were taken from the jugular vein of the sheep before the morning feeding. MOTSc and BMCP1 levels were determined in blood serum samples by ELISA method. Result: In the study, serum MOTS-c and BMCP1 levels in sheep during lactation and pregnancy were determined to be lowest in the VKS less than 2 group and highest in the VKS≥4 groups. Likewise, in age and gender groups, the highest level was detected in young lambs and yearlings in the VKS less than 2 group, while the highest level was detected in old sheep and rams in the VKS≥4 group. As a result, it was determined that different age, gender, pregnancy and lactation periods affected serum MOTS-c and BMCP1 levels depending on the change in BCS (P less than 0.05). It was concluded that MOTS-c and BMCP1 may be useful parameters in the evaluation of mitochondrial function, energy metabolism and metabolic profile.

Devoting turbidity measurements via absorptiometry: glutathione determination

The study included estimation of glutathione (GSH) as an important biomarker using turbidimetric method based on reaction of GSH with Ce(IV) in acidic medium to form turbid solution. More than twenty metal ions were used to test their interaction with GSH in acidic medium, it was obtained that only Ce(IV) forms turbid product. Instead of using turbidimeter to conduct measurements, a single beam spectrophotometer was used for this purpose. The measurements were studied at three wavelengths via 500, 700 and 900nm, but a near infrared wavelength, i.e. 900nm, shows the best results. In addition, the effect of temperature, time, type of acid, sequence addition as an optimum conditions required for the product to form were studied. Then the effect of the interferences was studied at two concentrations. A calibration curve in µg.mL-1 was constructed and its trending lies on points of concentrations ranged from 20 to 180µg.mL-1 with a correlation coefficient of 0.9994, and detection limit of 0.0005 µg.mL-1 and slope is (0.0014). The analytical method was applied on samples of human blood serum. The obtained results were compared with the results of the referenced (kit) method. The results obtained by the method followed, some of them were close and the others were far.