Chloroquine and cinchonine affect rat vascular smooth muscle tonus through calcium channels - in silico and in vitro approaches.

BACKGROUND: In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in a model of phenylephrine-induced smooth muscle contractions. METHODS: Potential mechanisms of action associated with endothelial vasorelaxant compounds, voltage-gated Ca2+ channels (LTCCs), and inositol triphosphate receptors were examined in isolated rat aortic rings. Also, an in silico approach was used to predict the activity of the two test compounds. RESULTS: Experimental results revealed that both chloroquine and cinchonine significantly decrease phenylephrine-induced smooth muscle contractions, although to a different extent. Evaluated mechanisms of action indicate that endothelium is not involved in the vasorelaxant action of the two tested alkaloids. On the other hand, voltage-gated Ca2+ channels were found to be the dominant way of action associated with the vasorelaxant action of chloroquine and cinchonine. Finally, IP3R is found to have only a small impact on the observed activity of the tested compounds. CONCLUSION: Molecular docking studies predicted that chloroquine possesses a significant activity toward a suitable model of LTCCs, while cinchonine does not. The results of the present study point to the fact that great caution should be paid while administering chloroquine to vulnerable patients, especially those with cardiovascular disorders (Tab. 3, Fig. 3, Ref. 28).

The Occurrence of Acute Pancreatitis in Adult Patients during a Measles Outbreak from November 2017 to May 2018 in Southeastern Serbia.

Background and Objectives: Although it is believed that measles infections are under control, there is a global reappearance, and their treatment has become more complex as the disease is followed by a relatively high incidence of complications. This study, conducted on patients during a measles outbreak from November 2017 to May 2018, aims to evaluate a rarely reported complication of measles, acute morbilous pancreatitis (AMP), which has been reported in several cases to date. Materials and Methods: A total of 207 patients admitted and treated at the Clinic for Infectious Diseases, Clinical Center Nis, for measles infection were included in the analysis. The data collected from the patient's medical records included the demographic characteristics, disease duration, full blood, serum, and urine biochemical analysis, general measles-associated symptoms, and disease outcome. Results: According to the serum and urine amylase activity, and some clinical symptoms AMP were diagnosed in 14% (29/207) of the studied patients. These patients had significantly higher levels of ALT and vomited more frequently than the patients without AMP. Only slight differences in measles duration, changes in RBC count, and CRP levels were found between the males and females with AMP. Conclusions: Acute morbillous pancreatitis should not be underestimated as a complication, even though according to the results of our survey, it was not associated with a fatal outcome or disease severity as the course of it can be frequently rapid and fatal.

Behavioral and Dietary Habits That Could Influence Both COVID-19 and Non-Communicable Civilization Disease Prevention-What Have We Learned Up to Now?

The massive expansion of the new coronavirus SARS-CoV-2 has urged countries to introduce lockdowns and set restrictive actions worldwide. The focus of the studies was to determine how COVID-19 induces damage to the lungs in order to find an alternative or adjuvant therapy that could lead to preventing COVID-19 or at least ameliorating it. This paper aims to survey the literature and provide new insights into behavioral and dietary habits that could influence the prevention of COVID-19. Maintaining an adequate mental health status, sleep, and taking moderate exercise are often disrupted in the conditions of lockdown and are followed by weakened immunity. Mediterranean and vegetarian diets are superior to other eating patterns in terms of immunity boosting and fighting COVID-19. Our study showed how adequate hydration, green tea intake, and supplementation with vitamins D, C, and E can increase our chances of avoiding the infection and even help us sleep better. Another focus of the research was on determining what level of hygiene really increases one's chances of not contracting SARS-CoV-2, but this seems a little counter-intuitive at first. Since an immunocompromised state is a familiar predisposing factor for all contagious diseases, maintaining healthy behavioral and dietary habits could be a crucial step in boosting immunity and preventing COVID-19.

Bilberry: Chemical Profiling, in Vitro and in Vivo Antioxidant Activity and Nephroprotective Effect against Gentamicin Toxicity in Rats.

We assessed possible protective effect of bilberry diet in rat model of nephrotoxicity. In vivo and in vitro antioxidant activity and chemical profiling of this functional food was performed. With aid of HPLC-DAD and spectrophotometric method, 15 individual anthocyanins were quantified alongside total tannin, phenylpropanoid, and anthocyanin content. The study was conducted on four groups of rats: control, treated with only gentamicin, treated with only bilberry, and treated with both gentamicin and bilberry. Kidney function was evaluated by tracking urea and creatinine. Morphology of renal tissue and its changes were recorded pathohistologically and quantified morphometrically. Bilberry (100 mg/kg daily) showed strong nephroprotective effect against gentamicin toxicity in rats (as shown through MDA, AOPP, and catalase levels). In conclusion, the demonstrated protective activity of bilberry extract matched well with the assessed in vivo and in vitro antioxidant activity as well as with its polyphenolic content, particularly with high anthocyanin levels. Copyright © 2016 John Wiley & Sons, Ltd.

Production of prebiotic enriched maple syrup through enzymatic conversion of sucrose into fructo-oligosaccharides.

Maple syrup, a popular natural sweetener has a high content of sucrose, whose consumption is linked to different health issues such as obesity and diabetes. Hence, within this paper, the conversion of sucrose to prebiotics (fructo-oligosaccharides, FOS) was proposed as a promising approach to obtaining a healthier, value-added product. Enzymatic conversion was optimized with respect to key experimental factors, and thereafter derived immobilized preparation of fructosyltransferase (FTase) from Pectinex® Ultra SP-L (FTase-epoxy Purolite, 255 IU/g support) was successfully utilized to produce novel functional product in ten consecutive reaction cycles. The product, obtained under optimal conditions (60 °C, 7.65 IU/mL, 12 h), resulted in 56.0% FOS, 16.7% sucrose, and 27.3% monosaccharides of total carbohydrates, leading to a 1.6-fold reduction in caloric content. The obtained products` prebiotic potential toward the probiotic strain Lactobacillus plantarum 299v was demonstrated. The changes in physico-chemical and sensorial characteristics were esteemed as negligible.

Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats.

Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic effects often characterized by both morphological and functional alterations of kidney leading to acute renal failure. The aim of this study was to examine the effect of dietary calcium supplementation on GM-induced nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats divided into three groups of 10 animals each. G-group received GM intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as control, received 1 mL/day of normal saline. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural and functional changes of kidney was performed by histopathological, morphometrical, and biochemical analyses. Compared with control, G-group of rats were found to have diffusely and unequally thickened glomerular basement membrane with neutrophil cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule cells with coagulation-type necrosis was observed. These GM-induced pathological lesions were significantly reduced in the rats of GCa-group. Morphometric analysis revealed statistically significant differences in the size of glomeruli (area, major and minor axes, perimeter), optical density, and roundness of glomeruli (p < 0.05) between G and GCa groups. Biochemical analysis showed significant elevation in blood urea and serum creatinine concentrations, whereas potassium concentration was lowered in G-group compared with the other groups (p < 0.01). It is concluded that oral supplementation of calcium during treatment with GM resulted in significant reduction of morphological and functional kidney alterations.

Influence of different wild-garlic (Allium ursinum) extracts on the gastrointestinal system: spasmolytic, antimicrobial and antioxidant properties.

OBJECTIVES: As there are no previous studies of the European wild-garlic (Allium ursinum) effects on the gastrointestinal system, despite its traditional applications in gastrointestinal disorders' treatment and regular use in the human diet, we have quantified and compared spasmolytic, antimicrobial and antioxidant activities of its different leaf extracts. METHODS: Wild-garlic extracts were tested for spasmolytic activity on isolated rat ileum, antimicrobial activity on selected Gram-positive and Gram-negative bacteria and fungi by microdilution method and antioxidant capacity by DPPH radical-scavenging assay. KEY FINDINGS: Wild-garlic extracts were found to decrease ileal basal tone. As the relaxation of K+ -induced contractions was similar to one caused by papaverin, the observed spasmolytic effect was most likely mediated through Ca2+ -channel inhibition. Ethanolic extract (with the highest phenolic and high alk(en)yl cysteine sulphoxides' levels) produced the strongest spasmolytic activity. In case of acetylcholine-induced contractions, only hydromethanolic extract showed no statistical difference in comparison with positive control. All samples exhibited certain antioxidant potential and strong antimicrobial activity against tested enteropathogenic strains (Salmonella enteritidis was the most sensitive, followed by Escherichia coli, Proteus mirabilis and Enterococcus faecalis). CONCLUSION: Besides other already established health-promoting effects, wild garlic could be useful in treatment of mild gastrointestinal disturbances.

Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats.

AIMS: One of the most popular beverages worldwide, green tea, was investigated for its potential protective effect in a rat model of gentamicin-induced nephrotoxicity by monitoring functional and morphological changes in kidneys. MAIN METHODS: The study was conducted on four groups of rats: control group (C), treated with only gentamicin (GM), treated with only green tea (GT) and treated with both gentamicin and green tea (GT+GM). Kidney function, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Morphometric analysis was used to quantify these histopathological changes. KEY FINDINGS: Gentamicin caused significant elevations in serum creatinine and urea and oxidative stress parameter (AOPP), while antioxidative enzyme catalase was significantly decreased. Histological sections of kidneys in GM group revealed necrosis of proximal tubules, vacuolation of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin histologically showed renoprotective effect. Histological results were confirmed and quantified by morphometric analysis. Also in this group we measured ameliorated parameters of renal functions and antioxidative defense. SIGNIFICANCE: Regenerative potential of green tea after renal injury induced by gentamicin could be explained through the decrease of oxidative stress and lipid peroxidation. Green tea is a natural antioxidant, with many health promoting effects, widely available and in accordance to that affordable. Because of the established habits, people largely consume it as a beverage. It could be beneficial in the reduction of oxidative stress and changes caused by it primarily in renal tubules and interstitium.