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Abstract

Allergic rhinitis (AR) is a common disease that causes severe inflammation and even disabilities. Previous studies have reported baicalein to have an anti-inflammatory effect. However, the pharmacological action of baicalein on anaphylaxis has not been clarified yet. This study assessed the in vivo protective effect of baicalein post-treatment in an ameliorating ovalbumin (OVA)-sensitized AR rat model. Baicalein attenuated histological alterations, aberrant tissue repair and inflammation after OVA-induced AR. Baicalein reduced the frequency of nasal/ear rubs and sneezes in rats, and inhibited generation of several inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both blood and nasal lavage of rats. Infiltrations of eosinophils, lymphocyte, and neutrophils were decreased in baicalein-administered rats. Furthermore, baicalein inhibited the expression of STAT3 phosphorylation in the nasal mucosa. In summary, baicalein attenuated OVA-induced AR and inflammation, which suggests it as a promising therapeutic agent for the alleviation of AR-associated inflammation and pathology.

Abstract

Liver damage is a common problem all over the world. To optimize the drug provision in the limited financing of the Health Care System, it is necessary to develop new drugs with hepatoprotective properties that are highly effective and of low cost. That is why we developed the original drug Lavaflam. Lavaflam is a combination of the following substances: dry concentrate of Helichrysum arenarium and Lavender oil. The purpose of the research was to assess the biochemical evidence of the hepatoprotective properties of the drug Lavaflam on the experimental model of subchronic hepatitis in rats. Construction of an experimental model of subchronic hepatitis in rats, comparison of hepatoprotective properties of Lavaflam and Carsil preparations on the basis of biochemical research. The subject of the study was to determine the hepatoprotective properties of Lavaflam tablets. Experimental subchronic hepatitis induced in rats by way of intragastrical introduction of tetrachlormethane. The study drug Lavaflam in this experimental model of subchronic tetrachlormethane hepatitis in rats showed a positive effect on oxidant processes by increasing the compensatory mechanisms of antioxidant systems; inhibiting free radical pathology; having positive effect on the processes of biliary excretion, cholestasis, reduction of infiltrative, destructive and inflammatory process in the liver; decreasing the cytolytic process; restoring the structure of the membrane components of hepatocytes; stabilizing and enhancing functional activity of the liver; restoring its protein-synthetic function; and increasing the ability of the drug Lavaflam to restore metabolic and liver damage.

As a result of the performed biochemical study of the hepatoprotective action of Lavaflam, it has been found that in the developed drug Lavaflam, the level of hepatoprotective action corresponds with the reference drug Carsil.

Abstract

Despite several shortcomings such as extreme hydrophobicity, low drug capacity, characteristic triphasic drug release pattern with a high burst effect, poly(lactic-co-glycolic acid derivatives are widely used in drug delivery. Most frequent attempts to improve their properties are blending with other polymers or synthesis of block copolymers. We introduce a new class of branched poly(lactic-co-glycolic acid) derivatives as promising biodegradable carriers for prolonged or targeted drug release systems, employed as thin adhesive films, solid dispersions, in situ forming implants or nanoparticles. A series of poly(lactic-co-glycolic acid) derivatives with lower molar mass and star or comb architecture were synthesized by a simple, catalyst free, direct melt polycondensation method not requiring purification of the obtained sterile product by precipitation. Branching monomers used were mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and polyacrylic acid. The products were characterized by molar mass averages, average branching ratio, rheological and thermal properties.

Abstract

Aseptic meningitis is one of the most common inflammatory disorders of the meninges of the central nervous system (CNS). The aim of our study was to investigate the cytokine profiles in the CSF and in the serum of children with aseptic meningitis to determine their role in CNS inflammation. Sixty-eight (68) children were kept under observation. Cytokine profile of CSF and blood (based on the results of determining of IL-1β, IL-4, IL-10, TNF-α levels) and procalcitonin in children were revealed, meningitis severity were estimated by AMSS score. It was found that in the majority of patients with aseptic meningitis, the levels of IL-1β, TNF-α, IL-10 in CSF were increased and exceeded the serum cytokines levels. The severe course of meningitis was characterized by significantly higher concentrations of IL-1β and TNF-α in CSF, which was confirmed by positive correlation between AMSS score and IL-1β concentration (r=0.46, p<0.01), IL-10 (r=0.32, p<0.01), TNF-α (r=0.62, p<0.05). The IL-10/TNF-α ratio was – 17.8. PCT level in CSF was within normal limits in the majority of patients with meningitis. Increasing of anti-inflammatory cytokine levels in aseptic meningitis contributes to preventing of excessive inflammatory/immune responses in the brain. This can cause a longer diseases course and a longer recovery period. This can an indicate active production of cytokines in the central nervous system due to intrathecal inflammation and activation of immune responses caused by viral infection, but not due to penetration across the blood-brain barrier.

Abstract

A UPLC-MS method for the estimation of atazanavir sulfate was developed using the “analytical quality by design” approach. The critical chromatographic quality attributes identified were retention time, theoretical plates and peak tailing. The critical method parameters established were percent of organic modifier, flow rate and injection volume. Optimization performed using Box-Behnken Design (BBD) established 10 % organic modifier, 0.4 mL min−1 flow rate and 6-µL injection volume as the optimum method conditions. Atazanavir sulfate eluted at 5.19 min without any interference. Method validation followed international guidelines. The method has proven linearity in the range of 10–90 µg mL−1. Recovery was between 100.2–101.0 % and precision within the accepted limits (RSD 0.2–0.7 %). LOD and LOQ were 2.68 and 8.14 µg mL−1, resp. Stress testing stability studies showed atazanavir sulfate to degrade under acidic and basic conditions. The suggested technique is simple, rapid and sustainable. It is, therefore, suggested for routine analysis of atazanavir sulfate.

Abstract

The study was conducted on seventy individuals of both genders who have been exposed to human cytomegalovirus, a common illness in Iraq. Total cases of human cytomegvirus associated with malignant brain tumors were detected by a real time PCR technique. This resulted in only thirty-six cases of true infection. Of these 24 cases were female, while 12 cases of male infected. The titer to assay the presence of anti- and pro-inflammatories was assessed in sera of all patients by using ELISA kits to evaluate cytokines. This indicated that the pro-inflammatory IL12, after seven days increased (1.67±0.23 pg/ml), while IL4, an anti-inflammatory, decreased to reach (0.39±0.16 pg/ml) (at p<0.05) in the plasm of the experimental patients compared with the control group.

Abstract

Our interest has focused on the investigation of the anti-obese potential of kidney beans (P. vulgaris) pods extract. In the course of the study, obesity development in rats was induced with high-calorie diet. Control and obese rats then have consumed with aqueous kidney beans (P. vulgaris) pods extract during 6 weeks (200 mg/kg). Results show that the long-term consumption of P. vulgaris pods extract can lead to the reduction of hyperglycemia and insulin resistance development. Furthermore, we saw a normalization of lipid peroxidation parameters and oxidative modification of protein due to the consumption of the kidney beans (P. vulgaris) pods extract. Our experimental data demonstrate the ability of the kidney beans (P. vulgaris) pod extracts to mitigate obesity development but the details of this mechanism remains to be not fully understood.

Abstract

To research and deepen the understanding of the links between morphological tubular kidney lesion parameters and serum markers – neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18), in patients with chronic glomerulonephritis (CGN) with saved renal function, as well as to estimate therapeutic correction of identified changes using ACE inhibitor ramipril. The diagnosis of “chronic glomerulonephritis” was verified based on clinical, laboratory and morphological data. Patients were divided into 2 clinical groups: patients with CGN and arterial hypertension (AH) and without AH. We used the data of renal biopsies to analyze the indicators of tubular kidney lesion in patients with CGN. Levels of serum NGAL and IL-18 were measured by means of ELISA kits. Treatment of patients was carried out over 24 weeks using the ACE inhibitor ramipril. The average daily dose of ramipril for the entire treatment period for patients with AH was 12.8±5.6 mg, patients of the second group – without AH, were treated with ramipril at a dose of 2.5 mg. On the basis of rank correlation analysis, we demonstrated that the level of serum NGAL is directly correlated with interstitial fibrosis (r=0.65; p<0.05), serum IL-18 – with dystrophic changes in the epithelium of renal tubules (r=0.81; p<0.05).

Conclusion. Serum levels of NGAL and IL-18 are one of the most sensitive markers of tubular kidney lesion and have diagnostic efficiency up to 97%. A 24-week treatment with ACE inhibitor ramipril in patients with CGN with and without AH leads to a decrease in the levels of tubular kidney lesion markers.

Abstract

Modified release of furosemide from tablet formulations is preferred by patients, because of physiological problems, acute diuresis being the most serious, compared to the forms designed for immediate release. With this in view, we aimed at achieving furosemide’s longer gastric retention and waste minimization by preparing matrix and compression coated tablets incorporating different grades of Eudragit® and poly(ethylene oxide) (PEO), polyvinylpyrrolidone (PVP) and lactose monohydrate. Dissolution profiles of the new formulations were compared with that of the main stream drug Lasix®, 40 mg tablets. The results indicate that the use of Eudragit® in conjunction with either PVP or lactose monohydrate led to a slower release rate in the intestinal fluids compared to Lasix®. Moreover, furosemide release in the intestinal pH from matrix tablets and compression coated tablets was not noticeably different. Formulations incorporating PEO led to sustained release, in intestinal fluids, which depended on the molecular weight of PEO.

Abstract

Doxorubicin cardiotoxicity is caused by various mechanisms, most importantly by oxidative stress originating in the mitochondria. Tirapazamine is a hypoxia-activated anticancer experimental drug. Both drugs in normoxia conditions undergo univalent reduction, thus tirapazamine may compete with doxorubicin in univalent reduction enzyme uptake. Herein, tirapazamine derivatives consisted of drug molecules and alkyl chain-connected triphenylphosphine cations that bring about an accumulation in mitochondria. The aim of this study was to evaluate the interaction of newly synthesized tirapazamine derivatives with doxorubicin in rat cardiomyocytes via an vitro model. In the work, H9C2 cells were incubated with combinations of doxorubicin, tirapazamine and seven variants of tirapazamine derivatives. After 24 hours, cell viability was assessed using MTT assay and the results were confirmed by microscopic observation. Tirapazamine in all tested concentrations did not revealed significant protective activity to cardiomyocytes treated with doxorubicine. However, tirapazamine derivatives diminished the cytotoxic effect of doxorubicin regardless of concentration and alkyl chain length. Tirapazamine derivatives have shown protective effects in relation to cardiomyocytes treated with doxorubicin and the mechanism of this phenomenon must be confirmed.