Coping with stress and hypertension-mediated organ damage

Aim of the study: Chronic exposure to high blood pressure may lead to the development of hypertensionmediated organ damage (HMOD). This study compares styles and strategies of coping with stress in hypertensive patients with arterial stiffness or left ventricular hypertrophy (LVH) and in individuals with hypertension, but without HMOD. Material and methods: Each study participant (n=93) underwent the following procedures: clinical assessment, echocardiography, pulse wave velocity measurement and psychological testing. Blood pressure in the study group was measured using ABPM method. Carotid-femoral pulse wave velocity (PWV) was assessed to identify patients with arterial stiffness. Left ventricular mass index was measured to diagnose LVH. Each patient was also assessed using three psychometric tools: PSS-10, CISS and Brief COPE. Results: Subjects with arterial stiffness (increased PWV) scored significantly lower than patients with normal PWV in three scales: CISS Avoidance-oriented coping (median values: 39 vs. 41.5; p=0.042), Brief COPE Self-distraction (median values: 1.5 vs. 2; p=0.013) and Brief COPE Venting (median values: 1 vs. 1.5; p=0.037). Individuals with LVH had significantly lower results in Brief COPE Use of emotional support scale than hypertensive subjects with normal left ventricular mass index (median values: 1.5 vs. 2; p=0.041). Discussion: In our study group, hypertensive patients with HMOD preferred different coping styles and strategies than individuals with hypertension, but without vascular and cardiac damage. The mechanism underlying these differences is probably complex. Conclusions: HMOD may be associated with coping styles and strategies, but further research is necessary to fully understand the results of this study

Improved pharmacokinetics and tissue uptake of complexed daidzein in rats

The pharmacokinetic profile and tissue uptake of daidzein (DAI) was determined in rat serum and tissues (lungs, eyes, brain, heart, spleen, fat, liver, kidney, and testes) after intravenous and intraperitoneal administration of DAI in suspension or complexed with ethylenediamine-modified γ-cyclodextrin (GCD-EDA/DAI). The absolute and relative bioavailability of DAI suspended (20 mg/kg i.v. vs. 50 mg/kg i.p.) and complexed (0.54 mg/kg i.v. vs. 1.35 mg/kg i.p.) was determined. After i.p. administration, absorption of DAI complexed with GCD-EDA was more rapid (tmax = 15 min) than that of DAI in suspension (tmax = 45 min) with a ca. 3.6 times higher maximum concentration (Cmax = 615 vs. 173 ng/mL). The i.v. half-life of DAI was longer in GCD-EDA/DAI complex compared with DAI in suspension (t0.5 = 380 min vs. 230 min). The volume of distribution of DAI given i.v. in GCD-EDA/DAI complex was ca. 6 times larger than DAI in suspension (38.6 L/kg vs. 6.2 L/kg). Our data support the concept that the pharmacokinetics of DAI suspended in high doses are nonlinear. Increasing the intravenous dose 34 times resulted in a 5-fold increase in AUC. In turn, increasing the intraperitoneal dose 37 times resulted in a ca. 2-fold increase in AUC. The results of this study suggested that GCD-EDA complex may improve DAI bioavailability after i.p. administration. The absolute bioavailability of DAI in GCD-EDA inclusion complex was ca. 3 times greater (F = 82.4% vs. 28.2%), and the relative bioavailability was ca. 21 times higher than that of DAI in suspension, indicating the need to study DAI bioavailability after administration by routes other than intraperitoneal, e.g., orally, subcutaneously, or intramuscularly. The concentration of DAI released from GCD-EDA/DAI inclusion complex to all the rat tissues studied was higher than after administration of DAI in suspension. The concentration of DAI in brain and lungs was found to be almost 90 and 45 times higher, respectively, when administered in complex compared to the suspended DAI. Given the nonlinear relationship between DAI bioavailability and the dose released from the GCD-EDA complex, complexation of DAI may thus offer an effective approach to improve DAI delivery for treatment purposes, for example in mucopolysaccharidosis (MPS), allowing the reduction of ingested DAI doses

The use of liposomes for daidzein delivery - in vitro studies

Celem pracy jest zbadanie układów liposomalnych do dostarczania daidzeiny (DZ) oraz stabilności takich formulacji w warunkach fizjologicznych (izotoniczny bufor fosforanowy o pH 7,4 oraz symulowany kwas żołądkowy). Otrzymano dwie serie materiałów liposomowych zawierających DZ stosując kalibrator i homogenizator. Zbadano stabilność układów liposomowych w czasie mierząc zmiany promieni hydrodynamicznych za pomocą metody Dynamicznego Rozpraszania Światła (Dynamic Light Scattering – DLS). Wykorzystując hydrofobową sondę fluorescencyjną sprawdzono dystrybucję liposomów w fibroblastach. Zbadano także wpływ liposomów zawierających DZ na komórkowy poziom glikozaminoglikanów (GAG) i żywotność fibroblastów w kontekście ich zastosowania w leczeniu mukopolisacharydoz.The aim of the study was to examine the liposomal systems for daidzein (DZ) delivery and the stability of such formulations under physiological conditions (in phosphate buffer solution with pH=7,4 and in simulated gastric acid). Two methods of liposome preparation were used, i.e., sonification and extrusion. Liposomal hydrodynamic diameter after 72 hours was measured using Dynamic Light Scattering (DLS) method. The effect of liposomal daidzein on glycosaminoglycans (GAGs) level in human skin fibroblasts (HSF) in vitro was determined. HSF were subjected to fluorescence staining using Nile Red delivered in liposomes. Liposomal daidzein significantly reduced the amount of glycosaminoglycanes in cultured cells in a dose-dependent manner without inhibition of cell growth. In conclusion, liposomal daidzein systems may be considered as a candidate for supportive drug therapy in patients with mucopolysaccharidoses

Adverse events associated with analgesics : a focus on paracetamol use

Acetaminophen is one of the most commonly used analgesics worldwide. It can induce toxic liver injury and hypersensitivity reactions. Toxicity may occur after an acute or chronic overdose. The mechanism is mainly associated—in contrast to nonsteroidal antiinflammatory drugs—with the presence of a toxic metabolite. N-Acetyl-p-benzoquinone imine is a product of acetaminophen oxidation via cytochromes and it is directly responsible for hepatotoxicity. Excessive production of this toxic agent, with reduced ability to neutralize it with glutathione, leads to clinically significant liver damage. First line treatment for acetaminophen toxicity is N-acetylcysteine. The criteria for this antidote treatment are based on Rumack-Matthew nomogram, the dose of paracetamol taken and symptoms of liver injury. Early administration of N-acetylcysteine significantly reduces risk of hepatoxicity. Hypersensitivity to paracetamol involve immediate reactions such as urticaria, bronchospasm, anaphylaxis and delayed reactions, including the most the most severe one—SJS/TEN. The majority of patients hypersensitive to NSAIDs tolerate paracetamol up to 500mg. Management of paracetamol hypersensitivity is based on long-term drug avoidance and finding a safe alternative antipyretics