Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity and/or essential hypertension.

Objective. The hallmarks of type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and insulin receptor substrate (IRS) proteins essential for the insulin signaling. IRS-1 gene has not only been shown to be associated with T2DM, but also has indicated that it may significantly correlate with diabetic complications, such as coronary heart disease and obesity. The aim of this study was to evaluate changes of the lipid panel data in T2DM patients with comorbid obesity and/or essential hypertension in connection with the IRS-1 (rs2943640) polymorphism. Methods. The study involved 33 T2DM patients and 10 healthy individuals. The IRS-1 (rs2943640) polymorphism was genotyped using a TaqMan real-time polymerase chain reaction method. Blood serum lipid panel data were determined with commercially available kits using a Cobas 6000 analyzer. Results. Analysis of the serum lipid panel data depending on the presence of the C/A alleles of IRS-1 (rs2943640) polymorphism in T2DM patients, regardless of the presence/absence of comorbidities, showed significantly lower level of high-density lipoprotein cholesterol (HDL-C) and significantly higher level of non-HDL-C in the carriers of C allele vs. carriers of A allele. In T2DM patients with comorbid obesity and essential hypertension, proatherogenic lipid changes were found in both C and A alleles carriers. Analysis of the effect of IRS-1 (rs2943640) genotypes on serum lipid panel data in T2DM patients, regardless of the presence/absence of comorbidities, showed that the CC genotype carriers had more pronounced pro-atherogenic changes vs. carriers of СА and АА genotypes. In the comorbid course of T2DM (both in combination with obesity and obesity and essential hypertension), pro-atherogenic changes were found in the carriers of the CA genotype of IRS-1 (rs2943640) polymorphism. Conclusions. The presence of the C allele of IRS-1 (rs2943640) polymorphism in both homo-zygous and heterozygous states indicates increased risk of pro-atherogenic changes in T2DM patients with comorbid obesity and/or essential hypertension.

Insulin receptor substrate 1 gene variations and lipid profile characteristics in the type 2 diabetic patients with comorbid obesity and chronic pancreatitis.

Objective. Type 2 diabetes mellitus (T2DM) is one of diseases that develops in a setting of polymorbid processes or more often promotes their development, forming in this spectrum the phenomenon of comorbidity. The aim of this study was to evaluate changes in the lipid panel data in T2DM patients with comorbid obesity and chronic pancreatitis (CP) taking into account the C/A polymorphism of the insulin receptor substrate 1 (IRS1) gene (rs2943640). Methods. The study involved 34 T2DM patients and 10 healthy individuals. The rs2943640 IRS1 gene polymorphism was genotyped using the TaqMan real-time polymerase chain reaction (PCR) method. Blood serum lipid panel data were determined with commercially available kits on a Cobas 6000 analyzer. Results. In patients with only T2DM and T2DM + comorbid obesity, an association between IRS1 gene polymorphism (rs2943640) and lipid profile abnormalities with maximum changes of the lipid characteristics recorded in C/C genotype carriers was found. Within the C/C genotype of the IRS1 gene (rs2943640) in type 2 diabetic patients with comorbid obesity and CP, significantly lower high-density lipoprotein cholesterol (HDL-C) levels and significantly higher levels of triglycerides (TG), non-HDL-C and remnant cholesterol (RC) in relation to type 2 diabetic patients with comorbid obesity were found. At the same time, within the C/A genotype of the IRS1 gene (rs2943640), significant changes of lipid panel data were found in type 2 diabetic patients with comorbid obesity relative to the control group (p<0.001). Conclusions. Our data indicate that the presence of the C allele of IRS1 gene (rs2943640) in both homozygous and heterozygous states may indicate increased risk of dyslipidemia in type 2 diabetic patients with comorbidities.

Comorbid overweight/obesity and chronic pancreatitis exacerbate the dyslipidemia progression in type 2 diabetic patients.

Objective. The aim of present study was to analyze the serum lipid profile parameters in patients with type 2 diabetes mellitus (T2DM) and comorbidities [overweight/obesity and/or chronic pancreatitis (CP)] to determine the contribution of these pathologic factors to lipid metabolism disorders in T2DM. Methods. The study involved 579 type 2 diabetic (T2D) patients with comorbid overweight/ obesity and/or CP. The serum lipid panel parameters [total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)] were determined by commercially available kits on a Cobas 6000 analyzer (Roche Hitachi, Germany). Low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and remnant cholesterol (RC) levels were calculated using formulas. The data were statistically analyzed using STATISTICA 7.0. Results. It was shown that dyslipidemia in T2D patients is characterized by unidirectional changes regardless the presence/absence of comorbid overweight/obesity or CP. At the same time, the most severe dyslipidemia was detected in T2D patients with a combination of comorbid over-weight/obesity and CP. Both the elevated body mass index (BMI) and CP can aggravate lipid metabolism disorders in T2DM. In our study, however, the BMI increase positively correlated with the number of dyslipidemia patients characterized by exceeding all target lipid levels for diabetic patients. This is in contrast to T2D patients with normal body weight and comorbid CP, in whom only LDL-C and TG exceeded the target lipid levels. Conclusions. A combination of comorbidities, such as obesity and CP in T2D patients, produced a mutually aggravating course defined particularly by common pathogenic links, insulin resistance, chronic generalized low-intensity inflammation, endothelial dysfunction, and dyslipidemia caused primarily by triglyceridemia.

SUBCLINICAL HYPOTHYROIDISM AS A CONTRIBUTOR TO MACROVASCULAR COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

This study aimed to evaluate changes of the lipid panel data in patients with comorbid type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) and to identify the probable prognostic values of the lipid profile for macrovascular complication (MVC) development. The study included 370 patients presented with only T2DM and 30 patients suffering from both T2DM and SCH. Receiver operating characteristic (ROC) analysis was used to identify prognostically significant values of the lipid profile with the optimal ratio of sensitivity and specificity for MVC development. All lipid profile values in the patients with T2DM combined with SCH were significantly higher compared to those with only T2DM. At the same time, SCH + T2DM increased the risk of exceeding target levels of triglycerides by 2.9 times and HDL-C by 4.1 times. Analysis of lipid profile values according to macrovascular involvement showed that total cholesterol, LDL-C and non-HDL-C in patients with T2DM and SCH were significantly higher compared to those with only T2DM. The levels of triglycerides >1.65 mmol/L, non-HDL-C >3.74 mmol/L and remnant cholesterol >0.74 mmol/L determined by the ROC analysis can be used for stratification of patients with T2DM combined with SCH into the category of increased risk of MVC development.

Does thyroid dysfunction influence inflammatory mediators in experimental periodontitis?

Objective. The aim of the present study was to investigate the presence of inflammatory mediators in rats with only periodontitis and periodontitis in a setting of hyper- and hypo-thyroidism and to analyze the correlative linkages between inflammatory mediators and thyroid hormones. Methods. White male 12-14 weeks old inbred rats (n=48) weighing 180-200 g were employed in the experiment. They were randomly divided into the following groups: Group I - control group, Group II - group with a model of periodontitis, Group III - group with a periodontitis in a setting of hyperthyroidism, and Group IV - group with periodontitis in a setting of hypothyroidism. The presence of tumor-necrosis factor-α (TNF-α) and interleukins IL-1ß and IL-10 in the periodontal homogenate supernatant was studied by a solid-phase enzyme-linked immunosorbent assay. Results. It was shown that experimental lipopolysaccharide (LPS)-induced periodontitis is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1ß) and reduction of anti-inflammatory cytokines (IL-10), whereas TNF-α underwent to maximum changes. Thyroid dysfunction exacerbates cytokine imbalance and severity of inflammation in experimental LPS-induced periodontitis, especially pronounced at hyperthyroidism, as evidenced by the predominance of TNF-α and IL-1ß levels in the periodontal homogenate supernatant by 38.5% (р<0.01) and 75.6% (p<0.001), respectively, hyperthyroid over the euthyroid, and by 20.1% (p<0.05) and 24.1% (p<0.05), respectively, over the hypothyroid rats. Conclusions. Thyroid dysfunction, especially hyperthyroidism, may play an important role in the pro-inflammatory response in periodontitis. Hyperproduction of inflammatory mediators in thyroid dysfunction can induce a noticeable damage in the whole apparatus of the periodontium, thereby causing progression of periodontitis.

The association of angiotensin-converting enzyme gene insertion/deletion polymorphism with bronchial asthma.

Bronchial asthma (BA) is among the most prevalent chronic inflammatory disorders of the lung airways, and it has become clear that a mixture of genetic predisposition and environmental factors plays a critical role in its pathogenesis. The aim of presented review is to analyze the published data on the possible role of ACE gene polymorphism in BA development. The article is based on available literature found in Pubmed, Elsevier, Scopus, and Google scholar databases. We have found that ACE I/D polymorphism may contribute to an important molecular mechanisms of BA development (specially D/D genotype), and may become a useful tool in risk assessment and in designing effective treatment approaches. The difference in the literature on the role of ACE alleles and genotypes can be explained by minor influence of the investigated genetic component and contributions of other genetic variations, as well as other environmental factors, considering multifactorial causes of BA.

Reproductive hormone metabolism in women with infertility due to polycystic ovary syndrome depending on the constitutional body types.

Overweight or obesity is diagnosed in approximately 60-80% of polycystic ovary syndrome (PCOS) patients. Since obesity exacerbates the hormonal and clinical features of PCOS, and women suffering from PCOS have a high risk of obesity, we suggest that hormonal imbalance resulting in certain body features can be linked to the pathogenesis of PCOS. AIM: The aim of the study was to define the features of the reproductive hormone metabolism in women with infertility due to PCOS depending on the constitutional body types. MATERIALS AND METHODS: The present study involved 100 women aged 25-39 years with infertility due to PCOS (experimental group) and 30 women of the same age with infertility due to tubal-peritoneal causes (control group). Infertility due to PCOS was diagnosed according to the Rotterdam criteria. Waist-hip ratio (WHR) was used to characterize the distribution of adipose tissue in overweight and obese patients. Hormone levels in blood serum were determined by ELISA using the «Diagnostic Systems Laboratories, Inc.¼ test systems (USA). RESULTS: We found hormonal imbalance in women with infertility caused by PCOS: increased levels of anti-Müllerian and luteinizing hormones, estradiol and testosterone, and decreased FSH levels. Body fat distribution conformed to the gluteofemoral (gynoid) type in 6.00% of the women and abdominal (android) type in 52.00%. Analysis of the relationship between the concentration of reproductive hormones and waist-hip ratio showed a weak inverse relationship between WHR with FSH levels, as well as a direct correlation with the levels of testosterone. CONCLUSIONS: In women with infertility caused by PCOS and android type of obesity, all these changes are significant compared to the women with normal body weight. Thus, obesity exacerbates the hormonal imbalance in women with infertility caused by PCOS.

Peculiarities of arterial hypertension in postmenopausal women with bone mineral density disorders and dyslipidemia.

As a long-term multisystem disorders, cardiovascular diseases can gravely affect on bone metabolism, prompting a severe bone loss and increasing predisposition to fractures and the development of osteoporosis. AIM: The aim of the study was to analyze the peculiarities of bone mineral density (BMD), lipid spectrum, lipid peroxidation (LPO) and antioxidant system (AOS) activity in postmenopausal women with arterial hypertension (AH). MATERIALS AND METHODS: Using dual-energy X-ray absorptiometry, we measured BMD in 193 women aged 45-62 years with the Stage II of AH. Lipid profile, LPO and AOS status in blood plasma were determined. RESULTS: In postmenopausal patients with hypertension, BMD and T-score values are significantly lower in comparison with the women of control group without hypertension (by 11.3% (p<0.05) and 14.4% (p<0.05) respectively). Independent predictors of osteoporosis progression in women with AHare the duration of disease, as well as menopause onset and the duration of postmenopausal period. In postmenopausal patients with AH there is a correlation dependence between the atherogenicity index and menopause duration (r=0.40, p<0.01), as well as the inverse correlation dependence between the atherogenicity index and the age of menopause onset (r =-0.27, p<0.01), which suggests that the earlier menopause in women with AH occurs, the faster the atherogenicity of plasma lipids progresses. Postmenopausal patients with AH showed higher indices of lipoperoxidation processes and simultaneous lower indices of antioxidant defence. CONCLUSIONS: The bone mineral density in postmenopausal women with AH is significantly lower than in women of reproductive age. Independent predictors of osteoporosis progression in women with AH are the duration of disease, as well as menopause onset and the duration of postmenopausal period.

A comparative study of oral microbiocenosis structure in experimental comorbidity-free periodontitis and in periodontitis combined with thyroid dysfunction.

Thyroid hormones regulate numerous metabolic processes. Therefore, any alteration in their synthesis or function has important health implications. However, limited data are available regarding the relationship between thyroid hormone imbalance and periodontal health. AIM: The aim of the study was to perform a comparative analysis of qualitative and quantitative structure of oral microbiocenosis in rats with comorbidity-free periodontitis and in animals with periodontitis in a setting of hyper- and hypothyroidism. MATERIALS AND METHODS: Inbred white male rats (n=48) were randomly divided into the following groups: I - control animals, II - animals with a model of periodontitis, III - rats with periodontitis in a setting of hyperthyroidism, IV - rats with periodontitis in a setting of hypothyroidism. Samples for microbiological investigations were taken from dental surfaces (on the border between hard tissue and gums in the interdental spaces). The isolated pure cultures were identified by their morphological, tinctorial, cultural and biochemical properties. RESULTS: The oral dysbiosis occurring in a setting of periodontitis in rats is chiefly characterized by increased quantity of coccal forms and by increased candidal inoculation; these organisms cumulatively inhibit the growth of normal microbial flora, such as Lactobacilli, bacteroids and Bifidobacteria. The periodontitis in a setting of thyroid dysfunction increases both the species variety and the quantitative counts of oral microbial flora, with predominance of such microbial organisms as Staph. aureus, E. coli, E. faecalis, Candida albicans and P. aeruginosa. Comparative assessment of intensity of oral microbial colonization in hyper- and hypothyroid animals with periodontitis has demonstrated significant changes only for the strains of S. aureus, yeast-like fungi and Candida albicans, which were predominant in hyperthyroid rats. CONCLUSIONS: Both hyperthyroidism and hypothyroidism exacerbate changes in the qualitative and quantitative structure of oral microbiocenosis in case of experimental periodontitis.

The role of Candida spp. contamination and efficacy of camphorated oil in skin care of incontinent associated dermatitis patients.

Candida albicans is the most prevalent human fungal commensal organism and is reported to be the most frequent aetiological factor responsible for infection associated with incontinence-associated dermatitis (IAD). AIM: The aim of the study was to investigate the Candida spp. colonisation and efficacy of camphorated oil in the skin care of the patients with incontinence-associated dermatitis. MATERIALS AND METHODS: In patients of the study group (n=104), a local application of camphorated oil was used to clean and protect their skin from urine and/or faeces. In 30 patients of the control group routine wet wipes 3 in 1 or a combination of cleansing foam with protective cream were used. Pre-treatment (day 1) and post-treatment (day 30±1) study evaluations included detailed description of eruption, assessment by evaluation tools, and mycological culture for Candida spp. from sites with fungal-appearing rash. RESULTS: Fungal-appearing rash was found in almost a half (51.0%) of patients at pre-treatment examination and in less than one-third (31.7%) of the patients after the course of application of camphorated oil. Candida spp. was cultivated in 39 (37.5%) patients. Fungal-appearing rash was approved by mycological culture in 56.6%. In patients with urine incontinence, Candida spp. negative cases (43.3%) were significantly prevalent over Candida spp. positive (22.1%). At post-treatment, this prevalence become more noticeable, accordingly obtaining 62.5% of negative and 2.9% of positive results. In patients with double incontinence, Candida spp. negative cases (19.2%) were almost equal to the number of Candida spp. positive (15.4%). After a course of study treatment, Candida spp. negative cases (26.0%) significantly overpassed Candida spp. positive level (8.7%). At an early and moderate grade of IAD Candida spp. negative cases were prevalent, but at severe grade did not differ from the number of positive mycology cultures. CONCLUSIONS: The topical use of camphorated oil in skin care of the incontinence-associated dermatitis significantly decreases the severity of disease, reduces fungal appearing rash and Candida spp. colonisation. Camphorated oil was superior to routine products in the controlling of yeast colonisation of the skin in incontinence-associated dermatitis, especially in cases with double incontinence.

The specific features of free radical oxidation in patients with chronic obstructive pulmonary disease and arterial hypertension.

The pathogenesis of both chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH) is closely related to oxidative stress, which is characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense. AIM: The aim of the study was to assess the parameters of free-radical oxidation and to establish their correlation to spirogram findings in patients with COPD without comorbidity and in patients with COPD and AH. MATERIALS AND METHODS: Detection of intracellular ROS levels was performed by EPICS XL cytometer (Beckman Coulter, USA) with DCFH-DA and DHE. Serum levels of 8-isoprostane were assayed with ELISA, Cayman Chemicals (USA). RESULTS: Intracellular ROS levels suggest a probable increase in production of O2•- in patients with COPD and in patients with COPD+AH vs control. The direction of changes in production of H2O2 in the assessed patients was also identical. Serum levels of 8-isoprostane were found to be significantly increased in patients with COPD and in patients with COPD+AH. High levels of H2O2, O2•- and 8-isoprostane were significantly associated with low values of spirometry parameters in patients of both test groups, which suggested bronchial obstruction. In this respect, oxidative stress parameters were significantly negatively correlated with the values characteristic of impaired patency of largeand medium-sized bronchi. CONCLUSIONS: Oxidative stress is playing an important role in the mechanisms of COPD/AH comorbidity, since intracellular ROS levels were found to increase, leading to destruction of cell membrane. In the meantime, the degree of oxidative stress correlates with the severity of bronchial obstruction.

Glutathione antioxidant system of lymphocytes in the blood of patients in a setting of concomitant chronic obstructive pulmonary disease and arterial hypertension.

The pathogenesis of both chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH) is closely related to oxidative stress, which is characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense. AIM: The aim of the study was to assess the status of glutathione-based antioxidant protection system in lymphocytes of blood in patients with associated COPD and AH. MATERIALS AND METHODS: Lymphocytes were isolated from peripheral blood using A. Boyum technique. The quantification assay for reduced glutathione (GSH) level, glutathione reductase (GR), glutathione peroxidase (GP) and glutathione S transferase activities were assessed with spectrophotometry method. RESULTS: The study population included 73 patients admitted to the Ternopil University Hospital. The subjects were distributed across three groups: group 1 (25 patients with COPD), group 2 (28 patients with COPD and AH) and the group 3 (control group of 20 healthy subjects). The analysis of parameters of lymphocytic glutathione system has not revealed any significant changes in GSH in patients with COPD only and a significant (20.5%) decrease in reduced glutathione in a COPD + AH combination. The group of patients with COPD was found to have decreased GP and GST activities, as well as increased GR activities. Patients with concomitant COPD and AH had uniform changes in the enzymes of the glutathione system. These changes were seen as significant decreases in GP activity (by 31.6%), GST activity (by 28.4%) and GR activity (by 18.8%). In patients with COPD+AH, positive correlations were found between GSH and GR/GST. In this respect, GST activity was directly correlated with GR activity and inversely correlated with GP activity. CONCLUSIONS: Overall, the results of our research suggest the glutathione-based antioxidant protection system to change differently in patients with COPD (GR activity increases, GP and GST activities decreases, GSH level does not change) and in patients with COPD+AH (GSH level and activities of glutathione-based antioxidant enzymes [GR, GP and GST] decreases). The changes found in the glutathione redox system suggest an important contribution of arterial hypertension to adverse course of COPD.

Effects of the therapy combining calcium and vitamin D3 supplement with calcitonin on bone tissue density in patients with coronary heart disease complicated with chronic heart failure.

As a long-term multisystem disorder, chronic heart failure (CHF) can gravely affect on bone metabolism, prompting a severe bone loss and increasing predisposition to fractures and the development of osteoporosis. AIM: The aim of the study was to investigate whether in patients with CHF a therapy combining calcium and vitamin D3 supplement (Calcemin Advance) and calcitonin (Miacalcic) can help to prevent and treat osteopenia and osteoporosis. MATERIALS AND METHODS: Using dual-energy X-ray absorptiometry, we measured bone mineral density (BMD) in 59 patients with coronary heart disease (CHD) complicated with chronic heart failure. RESULTS: Our results suggest that following the standard treatment protocol of CHD complicated with CHF resulted in significant BMD loss in the lumbar vertebrae, approaching the level of osteopenia. After taking a calcium and vitamin D3 supplement, patients with this heart disorder had significant increase of BMD in the lumbar vertebrae and in the femoral bone. Patients with CHD complicated with CHF and diagnosed osteoporosis taking Calcemin Advance did not experience osteoprotection outcome, rather their BMD continued to decrease. However, combined therapy with Miacalcic and Calcemin Advance was effective in significantly increasing L1, L2 - L4 BMD in these patients. CONCLUSIONS: We demonstrated effectiveness of using a calcium and vitamin D3 supplement, for patients with CHD complicated with CHF and diagnosed osteopenia. Patients with CHD complicated by CHF and diagnosed osteoporosis did not experience osteoprotective action when using Calcemin Advance. However, in these patients L1 lumbar vertebra BMD significantly increased after the combined therapy.

The effect of flavonoid quercetine on the indices of nitric oxide system in rats with chronic enterocolitis combined with streptozotocin-induced diabetes.

OBJECTIVE: Introduction: Chronic hyperglycemia is accompanied by significant physiological, biochemical, and histological changes, e.g. development of oxidative and nitrosative stress that affects the motor activity of the intestine. The aim: The present study was designed to evaluate the indices of nitric oxide (NO) system in blood serum and a colon tissue supernatant of rats with chronic enterocolitis combined with streptozotocin-induced diabetes. PATIENTS AND METHODS: Materials and methods: The total NOS activity was performed by monitoring the rate of conversion of L-arginine into citrulline. The total contents of NO metabolites was assessed by evaluation of their amount, which included nitrite ions that were previously presented in the sample (NO2-) and also nitrate ions reducted to nitrites (NO3-). RESULTS: Results and conclusions: Thus, in rats with modeled chronic enterocolitis activation of nitroxydergic process in blood serum and colon tissue has been established. Herewith more pronounced intensification of nitroxydergic processes was observed in rats with chronic enterocolitis combined with streptozotocin-induced diabetes. The liposomal form of quercetin - Lipoflavon significantly reduces nitrosative stress in rats with chronic enterocolitis combined with streptozotocin-induced diabetes.

Charlson comorbidity index and the severity of community-acquired pneumonia caused by SARS-CoV-2: A retrospective analysis.

BACKGROUND: The Charlson comorbidity index (CCI) has been considered as a valid and reliable tool for predicting poor clinical outcomes and mortality in patients with coronavirus disease 2019 (COVID-19). However, its relationship with the severity of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been thoroughly explored. OBJECTIVES: The aim of the present study was to identify the impact of the comorbidity burden, quantitatively assessed by applying CCI, on the severity of inpatient community-acquired pneumonia (CAP) caused by SARS-CoV-2. MATERIAL AND METHODS: The study was conducted using the medical records of 208 patients with CAP who had an epidemiological history of a plausible SARS-CoV-2 infection, with positive polymerase chain reaction (PCR) confirmation no later than 1 month before being admitted for inpatient treatment. The CCI was calculated using a custom computer program. The statistical analysis of data was carried out using Statistica, v. 7.0. RESULTS: Our study found a significant correlation between the comorbidity burden and the severity of CAP caused by SARS-CoV-2. Specifically, we observed a low CCI score in the majority of patients in the pneumonia risk class II and III groups, and a high CCI score ≥3 in the majority of patients in the pneumonia risk class IV group. Moreover, a direct correlation between CCI and age was established. The comorbidities most commonly associated with CAP caused by SARS-CoV-2 were congestive heart failure, moderate to severe liver diseases and diabetes mellitus (DM) with chronic complications. CONCLUSIONS: The use of CCI to evaluate comorbid pathology in hospitalized patients with CAP caused by SARS-CoV-2 can assist the medical staff in developing timely preventive and therapeutic strategies, leading to improved patient prognosis.

Influence of chronic hyperhomocysteinemia on the features of bone metabolism in the case of lipopolysaccharide-induced periodontitis.

BACKGROUND: Periodontal disease is the second most common oral health problem after dental caries. This increasing prevalence makes it not only a health problem, but also a social issue. The pathogenesis of periodontal disease is associated with a number of adverse exogenous and endogenous factors, including hyperhomocysteinemia (HHcy). OBJECTIVES: This study aimed to determine the features of bone metabolism in rats with lipopolysaccharide (LPS)-induced periodontitis combined with chronic thiolactone HHcy. MATERIAL AND METHODS: Forty-eight white, non-linear, mature rats were divided into 4 groups: control (n = 12); LPS­induced periodontitis (n = 12); chronic thiolactone HHcy (n = 12); and periodontitis combined with HHcy (n = 12). The rats were sacrificed the day after the last LPS injection or the day after the last homocysteine (Hcy) thiolactone administration. Bone metabolism was determined based on the activity of alkaline phosphatase (ALP) and acid phosphatase (AP) in blood serum and periodontal homogenate. RESULTS: A decrease in ALP activity (by 40.1%; р = 0.001) and the mineralization index (MI) (3.5 times; р < 0.001) with an increase in AP activity (2.0 times; р < 0.001) was observed in the periodontal homogenate of rats with LPS­induced periodontitis. In the case of LPS­induced periodontitis combined with chronic thiolactone HHcy, more pronounced changes in the activity of phosphatases and in MI were established as compared to rats with LPS­induced periodontitis only. CONCLUSIONS: Chronic thiolactone HHcy enhances disturbances in bone metabolism in LPS­induced periodontitis. The osteotoxic effect of HHcy is associated with the activation of osteoclastogenesis and enhanced bone resorption. However, further research is required on the subject.

Insulin Receptor Substrate 1 Gene and Glucose Metabolism Characteristics in Type 2 Diabetes Mellitus with Comorbidities.

BACKGROUND: Genetic variants that affect insulin signaling play an important role in insulin resistance (IR) in type 2 diabetes mellitus (T2DM). This study aimed to evaluate changes of the glycemic profile and IR in T2DM with comorbid obesity and chronic pancreatitis (CP) considering the allele status of the IRS1 gene (rs2943640). METHODS: The study involved 33 type-2 diabetic patients and 10 healthy individuals. The IRS-1 gene rs2943640 C>A polymorphism was genotyped using the TaqMan real-time PCR method. RESULTS: In type 2 diabetic patients regardless of the presence/absence of comorbid obesity and CP glycemic profile parameters significantly did not differ between carriers of allele C or allele A of the IRS1 gene (rs2943640). At the same time significantly higher HOMA-IR (by 2.25 times) was established in carriers of the C allele. In type 2 diabetic patients with both comorbidities (carriers of the C allele) the maximum HOMA-IR was established, which significantly differed from the data of patients with only T2DM and patients with comorbid obesity. In carriers of the A allele significantly higher level of HOMA-IR was found in patients with comorbid obesity and CP vs patients with only T2DM, and also in patients with comorbid obesity vs patients with only T2DM. CONCLUSIONS: Presence of the C allele of the IRS1 gene (rs2943640) may indicate risk of high IR in type 2 diabetic patients regardless of the presence/absence of comorbid obesity and CP; here with CP is a more important factor in IR progression then obesity.

COVID-19-associated acute respiratory distress syndrome versus classical acute respiratory distress syndrome (a narrative review).

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), led to the ongoing global public health crisis. Existing clinical data suggest that COVID-19 patients with acute respiratory distress syndrome (ARDS) have worse outcomes and increased risk of intensive care unit (ICU) admission. The rapid increase in the numbers of patients requiring ICU care may imply a sudden and major challenge for affected health care systems. In this narrative review, we aim to summarize current knowledge of pathophysiology, clinical and morphological characteristics of COVID-19-associated ARDS and ARDS caused by other factors (classical ARDS) as defined by Berlin criteria, and therefore to elucidate the differences, which can affect clinical management of COVID-19-associated ARDS. Fully understanding the characteristics of COVID-19-associated ARDS will help identify its early progression and tailor the treatment, leading to improved prognosis in severe cases and reduced mortality. The notable mechanisms of COVID-19-associated ARDS include severe pulmonary infiltration/edema and inflammation, leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis, endothelial inflammation and vascular thrombosis. Despite some distinct differences between COVID-19-associated ARDS and classical ARDS as defined by Berlin criteria, general treatment principles, such as lung-protective ventilation and rehabilitation concepts should be applied whenever possible. At the same time, ventilatory settings for COVID-19-associated ARDS require to be adapted in individual cases, depending on respiratory mechanics, recruitability and presentation timing.

Arterial Hypertension as a Risk Comorbidity Associated with COVID-19 Pathology.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an ongoing global public health challenge. Current clinical data suggest that, in COVID-19 patients, arterial hypertension (AH) is one of the most common cardiovascular comorbidities; it can worsen outcomes and increase the risk of admission to intensive care unit (ICU). The exact mechanisms through which AH contributes to the poor prognosis in COVID-19 are not yet clear. The putative relationship between AH and COVID-19 may be linked to the role of angiotensin-converting enzyme 2 (ACE2), a key element of the AH pathophysiology. Another mechanism connecting AH and COVID-19 is the dysregulation of the immune system resulting in a cytokine storm, mediated by an imbalanced response of T helper cells subtypes. Therefore, it is essential to optimize blood pressure control in hypertensive patients and monitor them carefully for cardiovascular and other complications for the duration of COVID-19 infection. The question whether AH-linked ACE2 gene polymorphisms increase the risk and/or worsen the course of SARS-CoV-2 infection should also receive further consideration.

A Comparative Study of Connective Tissue Metabolism Indices in Experimental Comorbidity-Free Periodontitis and Periodontitis Combined with Thyroid Dysfunction.

Periodontal disease is a chronic bacterial infection characterized by persistent inflammation, connective tissue breakdown, and alveolar bone destruction. The current study aimed to compare the connective tissue metabolism indices in rats with comorbidity-free periodontitis and in animals with periodontitis in a setting of hyper-and hypothyroidism. 12-14-week-old inbred white male rats (n=48) were included in the experiment. They were randomly divided into the following groups: control, animals with a model of periodontitis, animals with periodontitis in a setting of hyperthyroidism, animals with periodontitis in a setting of hypothyroidism. Serum levels of free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were assayed using ELISA kits manufactured by Vector Best (Russia) to confirm the hyper- and hypothyroid status. Collagenolytic activity, the content of glycosaminoglycans, free hydroxyproline, and fucose, unbound with proteins in blood serum were assayed using the spectrophotometric method. We have found the increasing of collagenolytic activity by 46.1% (р<0.001), the content of free hydroxyproline by 74.1% (р<0.001), the content of glycosaminoglycans by 1.8 times (р<0.001), the content of fucose, unbound with proteins by 2.8 times (р<0.001) in rats with periodontitis vs. the control group. The development of periodontitis in a setting of thyroid dysfunction leads to an even more significant increase in the destruction of connective tissue, which is confirmed by a significant increase in the content of studied indices vs. euthyroid animals, both in hyperthyroidism and hypothyroidism.