Pharmaco-economic features of hospital treatment of acute community-acquired pneumonia in children

The goal. Тo analyze the features of treatment and medical expenses in children hospitalized for acute community-acquired pneumonia. Materials and methods. The study analyzed medical records and examined 51 children aged 2 to 17 months hospitalized for pneumonia. In patients studied clinical symptoms, severity, structure and duration of basic treatment measures, their cost. Results. The duration of inpatient treatment was 13.3±0.62 days with subsequent outpatient treatment and rehabilitation. Antibiotics, antipyretics, antihistamines, mucolytics and corticosteroid hormones were used in the treatment. The total cost of treatment for one case averaged 2346.9±145.7 hryvnias. The most expensive were the costs of antibiotics, and the cheapest - the antipyretics. Given the community-acquired nature of the process, the initial use of third- and fourth-generation cephalosporins was irrational and significantly increased the cost of treatment. Conclusions. The introduction of a new model of medicine focuses on the optimization of treatment tactics and the rational choice of antibiotics for acute community-acquired pneumonia. In antibacterial therapy is still inadequate, from a clinical and economic point of view, the choice of drugs. In the treatment of this disease, the role of pathogenetic therapy to restore the processes of mucociliary clearance and prevention of dysbiosis on the background of the use of antibiotics has increased.

The use of some hormonal drugs in the complex therapy of psoriasis

We used corticosteroid hormones (cortisone, prednisone) in 104 patients with psoriasis; several patients received ACTH. Of the 50 patients treated with cortisone, there were patients with a widespread process (39 people) and even a universal process (5 people).

Corticosteroid hormones in the treatment of lupus erythematosus

Corticosteroids are widely used in the treatment of acute systemic lupus erythematosus, while in the treatment of the chronic form of the disease, they are used little, and the method of treatment has not been developed.

Mineralocorticoid receptor actions in cardiovascular development and disease

Mineralocorticoid receptors (MRs) are transcriptional regulators that mediate the diverse physiological and pathophysiological actions of corticosteroid hormones across many tissues. In the kidney aldosterone control of sodium/water resorption via DNA-binding actions of the MR is established. MRs also regulate tissues not involved in electrolyte homeostasis such as the heart, adipose tissue, brain, and inflammatory cells where the MRs can respond to both aldosterone and cortisol. The pathology of inappropriate MR activation in non-epithelial tissues are well-described, and steroidal antagonists of the MR have been clinically beneficial in the management of heart failure and blood pressure for decades. However, the role of cortisol-dependent MR activation in the physiological setting is less well defined. Like other steroid hormone receptors, the MR also regulates non-DNA-binding pathways including MAPK pathways and G protein coupled receptors to provide diversity to MR signaling. Whether nonDNA binding pathways are more relevant for MR activation in non-epithelial, versus epithelial, tissues remain unclear. This review will focus on molecular regulation of ligand-dependent MR activation and the physiology and pathophysiology of MR actions in the heart with a focus on the cardiomyocyte and provide a discussion of relevant genomic and non-genomic MR pathways and potential new transcriptional partners for the MR and their relevance for health and disease. Understanding MR actions in the heart will provide new insights into cell-selective mechanisms that underpin the therapeutic benefits of MRAs, and are a critical step towards developing next-generation tissue selective MR modulators with improved safety profiles.

Experimental substantiation of the composition of the gel base with hydrocortisone for use in veterinary medicine

As veterinary practice shows, most often atopic dermatitis in animals manifests itself in the form of a rash (in the ears, muzzle, paws, etc.), which in turn is accompanied by itching. First of all, prescribe a single injection of glucocorticoids, or short-term therapy. Corticosteroid hormones (glucocorticoids) are one of the most powerful antiallergic drugs. They are effective in treating almost all types of allergic reactions. An appropriate dose of glucocorticoids is required to obtain a rapid effect, and the form of the drug should be convenient to use. The aim of the research. The aim of our study was experimentally substantiate the choice of the optimal gelling agent when developing a gel composition with hydrocortisone for use in veterinary medicine. Materials and methods. Physical, physico-chemical and pharmaco-technological methods were used during the experimental study. Studies were performed according to the method described in the SPhU. The rheological properties of the samples were determined using a rotary viscometer type Brookfield HB DV (USA) with spindle SC4-21. Results. As a result of the research, it was found that Aristoflex as a gelling agent in the development of a veterinary drug of local action will ensure the availability of appropriate extrusion properties (namely, easy and uniform application of animal skin, ease of use). Gels with hydrocortisone based on Aristoflex gave stable performance, which was confirmed by the results of mechanical and colloidal stability. Conclusions. The composition and technology of a hydrocortisone gel for local therapy of atopic dermatitis in animals has been developed. Aristoflex at a concentration of 1.5 % on the basis of a set of physicochemical, structural-mechanical and biopharmaceutical studies was selected as the optimal gelling agent in the drug

EVALUATION OF THE CORTICOSTEROID RECEPTORS’ LEVEL IN THE KIDNEYS OF RATS AFTER SYSTEMIC ISCHEMIA-REPERFUSION

Background: With disturbance of the systemic blood supply, the body experiences hypoxia and stress. Under stress of any etiology, there is a non-specific rearrangement of physiological and biochemical processes. These processes occur under the influence of corticosteroid hormones. Aim: To determine the level of corticosteroid receptors in the kidneys of rats at different times after systemic ischemia-reperfusion. Methods: The study included 80 male white rats. All the animals were divided into 2 groups. A model of systemic ischemia-reperfusion was created in the main group (n=70). Further, on 1, 3, 5, 7, 14, 21 and for 35 days, we determined the level of gluco - and mineralocorticoid receptors in the kidneys. Results: In the animals of the main group, we observed a short-term period (during the first 3 days) of a decrease in the content of both glucorticoid (p<0.05) and mineralocorticoid (p<0.01) receptors. The dynamics of recovery of the level of corticosteroid receptors was 3 times faster than that of mineralocorticoid receptors. Conclusions: The dynamics of corticosteroid receptors’ level in the kidneys of rats after ischemia caused by an arrest of systemic circulation show the recovery time after ischemia-reperfusion injury, which ensures the stability of an individual to hypoxia.

Aldosterone: Implications in Diabetic Nephropathy

Objective: The focus of this review is to summarize the recent advancement to understand the molecular pathogenesis of diabetic nephropathy (DN). Also, to highlight the role of abnormal aldosterone secretion on the development and progression of diabetic nephropathy. Background: Diabetic Nephropathy (DN) is a progressive disease of nephron due to slow progressive failure of kidney tubule to perform its filtration process. It is often associated with proteinuria and glomerular stiffening which eventually leads to low glomerular filtration rate, finally succumbs the patient toward the end stage of kidney disease. The abnormal level of aldosterone in diabetes mellitus is a fatal combination to combat because of progressive development of diabetic nephropathy. Methods: We reviewed the literatures for implications of aldosterone in diabetic nephropathy. The literatures that were related to different aspects of diabetic nephropathy in relation to aldosterone were analyzed and summarized in this review article. Result & Conclusion: Aldosterone, a mineralocorticoid of corticosteroid hormones releases under the influence of adrenocorticotrophic hormone (ACTH) from zona glomerulosa of adrenal gland of kidney. In normal physiological condition it regulates the renin-angiotensin system of kidney, which regulates the resorption and conservation of sodium (Na+), potassium (K+) ions and water (H2O) from distal tubule. Aldosterone secretion, despite an important regulator to maintain the equilibrium of water and ions in the body, its non-regulated higher secretion gives rise to various pathological conditions. Additionally, we also discuss the risk factors associated with the use of mineralocorticoid receptor antagonist and renin-angiotensin-aldosterone therapy, and suggesting the need of robust and controlled methods to administer these drugs. Keywords: Aldosterone, Diabetic nephropathy (DN), Diabetes mellitus, Mmineralocorticoid receptor antagonists, Renin angiotensin system

Role of insulin-like growth factor 1, sex and corticosteroid hormones in male major depressive disorder

Background Hormones of the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–adrenal (HPA), and hypothalamic–pituitary–somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1). Methods Serum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated. Results Patients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 μg/dL vs. 307.4 ± 131.2 μg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls. Conclusion Estradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.

17-SUBSTITUTED STEROIDAL TETRAZOLES – NOVEL LIGANDS FOR HUMAN STEROID-CONVERTING CYP ENZYMES

In animal and human organisms, there are many enzymes, members of the family of heme- containing proteins, cytochromes P450 (CYPs), included in the biosynthesis and metabolism of many biomolecules, as cholesterol, bile acids, sex, and corticosteroid hormones, as well as in metabolism of drugs and xenobiotics. It is also well-known that different imidazole and triazole derivatives are efficient inhibitors of CYPs activity. In this study, we present in vitro screening of binding of novel androstane derivatives with tetrazole- containing substituents in position 17 to human recombinant steroid-converting CYP enzymes: CYP7A1, CYP7B1, CYP17A1, CYP19, and CYP21. Initial screening was performed using a high throughput screening approach, while the affinity of the ligands was analyzed using spectrophotometric titration. For some among tested compounds type I spectral response (substrate-like binding) for CYP7A1 selectively, while for one compound type II spectral response (inhibitor-like binding) for CYP21 were detected, with micromolar values of Kds. Interestingly, one compound with mixed spectral response was found to bind for CYP7B1, which means that there are two optimal positions of the ligand inside the protein active site. Such results could be useful in CYP-inhibiting drug development, during a fast, high-throughput screening of pharmacological potential of novel compounds, as well as in side- effects recognizing.

Transfusion surgeries and infusion therapy in patients with malignant non-Hodgkin’s lymphoma after splenectomy

Objective. To present the immediate results of the splenectomy and preferable variants of transfusion therapy performance in patients with malignant non-Hodgkin’s lymphoma (MNHL). Materials and methods. 109 splenectomies were performed in patients with MNHL at the Department of General and Hematological Surgery of the institute from 1987 to 2020. The surgery was conducted by upper middle laparotomy under general anesthesia with intubation and, in particular cases, under spinal anesthesia. Results and discussion. The indications for splenectomy in patients with MNHL were as follows: massive splenomegaly, abdominal syndrome, associated hemocytopenia, inefficacy of cytostatic therapy, absence of diagnosis. All patients underwent vaccination against capsular bacteria for prevention of post-splenectomy infection in 10-14 days prior to the surgery. In case of anemia, which has been observed in 55 % of patients, the RBC concentrate was applied. All the patients, who received corticosteroid hormones prior to splenectomy, were administered prednisolone and hydrocortisone in the amount of 3 mg/kg of body mass at similar doses in an hour before the surgery for prevention of adrenal insufficiency during the surgery. The patients, who did not receive those medications, were also intramuscularly administered prednisolone at a dose of 0.5 mg/kg of body mass in an hour before the surgery for the same aim. The patients with PLT value <150.0×109/L were administered 1-2 doses of PLT concentrate immediately before the laparotomy. M-gradient was found in blood serum of 3 patients prior to the surgery. They underwent courses of therapeutic plasmapheresis due to the risk of intraoperative hemorrhage. 2 patients with hyperleukocytosis (WBC >80.0×109/L) underwent two courses of leukapheresis. The patients with concomitant regional portal hypertension and in case of manipulations close to the pancreatic tail were administered somatostatin drugs in the course of the splenectomy. The splenectomy proved to be effective in 100 (92 %) of patients with MNHL: the great tumor mass was removed, the abdominal syndrome and concomitant hemocytopenia were neutralized, the signs of hypersplenism ceased, the hemolysis ceased, the cytostatic therapy became less necessary or unnecessary, the final diagnosis was established. The most serious postsurgical complications were acute adrenal failure (n=3), postsurgical intra-abdominal hemorrhage (n=2), pancreonecrosis (n=6). The postsurgical lethality was 2.7 %. Conclusions. The splenectomy proved to be effective in 92 % of patients with MNHL. The infusion therapy is individual for each patient and may include transfusion surgeries if indicated. The main objective of the infusion therapy in patients with MNHL is prevention and elimination of intra- and postsurgical complications.