Recent Patents on Endocrine, Metabolic & Immune Drug Discovery - Volume 11, Issue 1, 2017

Background: The red propolis (RdProp) is a resin produced by Apis mellifera bees, which collect the reddish exudate on the surface of its botanic source, the species Dalbergia ecastophyllum, popularly known in Brazil as “rabo de bugio”. Considered as the 13th type of Brazilian propolis, this resin has been gaining prominence due to its natural composition, rich in bioactive substances not found in other types of propolis. Objective: This review aims to address the most important characteristics of RdProp, its botanical origin, the main constituents, its biological properties and the patents related to this natural product. Method: By means of the SciFinder, Google Patents, Patus® and Spacenet, scientific articles and patents involving the term "red propolis" were searched until August 2017. Results: A number of biological properties, including antimicrobial, anti-inflammatory, antiparasitic, antitumor, antioxidant, metabolic and nutraceutical activities are attributed to RdProp, demonstrating the great potential of its use in the food, pharmaceutical and cosmetics industries. Conclusion: The available papers are associated to pharmacological potential of RdProp, but the molecular mechanisms or bioactive compounds responsible for each activity have not yet been fully elucidat ed. The RdProp patents currently found are directed to components for the pharmaceutical industry (EP2070543A1; WO2014186851A1; FR3006589A1; CN1775277A; CN105797149A; CN1879859A), cosmetic (JP6012138B2; JP2008247830A; JP6012138B2) and food (JP5478392B2; CN101380052A; WO2006038690A1).

Background: The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Objective: Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and autologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Conclusion: Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use.

Background: Uncontrolled thyrotoxicosis, especially in early infancy, may cause irreversible damage to the central nervous system as well as profound effects on the function of many organs. Thyrotoxicosis has multiple etiologies and treatment depends on the underlying etiology. An accurate diagnosis is essential so that appropriate treatment can be initiated without undue delay. Objective: To review in depth the evaluation, diagnosis, and treatment of children with thyrotoxicosis. Methods: A PubMed search was completed in Clinical Queries using the key terms "thyrotoxicosis" and “hyperthyroidism”. The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key terms "thyrotoxicosis" and “hyperthyroidism” from www.freepatentsonline.com and www.google.com/patents. Results: Graves' disease accounts for approximately 96% of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma, pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug-induced thyrotoxicosis. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. The underlying cause of thyrotoxicosis should be treated if possible. Treatment options for Graves' disease include antithyroid medications, radioiodine therapy, and surgery. Recent patents related to the management of thyrotoxicosis are discussed. Conclusion: Currently, antithyroid medications are considered to be the initial treatment of choice for Graves' disease in the pediatric age group. Radioactive iodine treatment is generally used for children with poor compliance with antithyroid medications, children not in remission after 1 to 2 years of antithyroid medications, and children with a major adverse effect while receiving an antithyroid medication. Total or near-total thyroidectomy should be considered in children younger than 5 years of age who do not respond to or experience a major adverse effect to antithyroid medications. Surgery should also be considered in those with very large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in spite of treatment with antithyroid medications and radioactive iodine, and personal preference.

Background: Microdialysis is a minimally invasive technique that allows direct in situ and in vivo sampling, studies and manipulations of the interstitial/extracellular fluid/space. It has been shown to be of use mainly in acute brain injury/neurocritical care. Methods: Microdialysis has been used to study obesity, diabetes mellitus, inflammation and pharmacokinetics at the adipose tissue level. In critically ill patients (and particularly in those with sepsis or septic shock), within days to weeks, adipose tissue shows profound alterations; under such conditions, the implementation of microdialysis can provide researchers with interesting findings. Results: The well-known association between lipolysis and cortisol has been verified at the tissue level with microdialysis. Specific metabolic aberrations in critically ill patients with septic shock have been noted in adipose tissue - assessed with microdialysis before becoming evident in the systemic circulation. Measurement of the lactate to pyruvate ratio in adipose tissue - also assessed with microdialysis - in patients with septic shock has prognostic value equal to that of universally accepted clinical severity scores. Conclusion: Microneedle arrays have been already used to assess interstitial fluid glucose. Possibly, the implementation of microneedle and lab-on-a-chip technology, might complement the current use of microdialysis in the study of the interstitial space/adipose tissue metabolism in health and disease.

Background: In 1994, International Organizations: WHO, UNICEF and ICCIDD indicat ed salt Natrium Chloride as the main carrier of iodine in the prophilaxis systems in the iodine deficient areas over the world. Following this recommendation, 24 European countries introduced the model of iodine p rop hylaxis based on the salt iodization. However in 7 European countries only - among tchem in Poland - salt iodization is mandatory as the most effective mode lon the population level. Objective: Presenting the method for the reduction of the consumption of iodized salt and supplement ation of iodine by other iodine carriers. Methods: Concentration of iodine in the salt has been calculated according to the daily salt consumption and WHO recommendation on the daily dose of iodine that should be supplied in different groups of age and in pregnant and breast feeding women. No relevant recent patents were available for this WHO report. Results: Consumption of salt in European countries is from 8 to 11g/day/person. In Poland, it is very high 11.5g/day/person. WHO in 1996 introduced recommendation on reducing daily salt intake to 5g/day/person as Natrium is a risk factor of hypertension and some neoplastic processes. Conclusion: When iodized salt is the main carrier of iodine in the prophylaxis systems, additional carriers of iodine should be introduced in the food market for instant -iodized mineral water. A very important factor is the proper information and education on the population level. This action is under control of the Polish Council for Control of Iodine Deficiency Disorders [PCCIDD] established in 1991 following the example of the International Council for Control of Iodine Deficiency Disorders [ICCIDD].

Background: On 26th April, 1986 the greatest accident of nuclear plant in Czernobyl occured and isotopes with high percentage of release were erupted: 33-Xe, 131-I, 132-Te, 134-Cs and 137-Cs. The radioactivity of the isotopes was very high - for instance: 33-Xe 6500 PBq, 131-I 1760 PBq. Rest of the 15 isotopes represented similar radioactivity with shorter percentage of release. The most exposed group of people were 237 liquidators, and 11600 people living around had to be evacuated when the limit dose for a person (5mSv) was crossed. Ionizing radiation on the molecular level produces high energy radicals, water radiolysis and ionization of the atoms leading to damage of the enzymes activity centers and receptors, cell membranes DNA, intracellular lysosomes, and especially important for ATP synthesis - mitochondria. These destructions lead to tissue and organs damage. Objective: The aim of this article is the presentation of the protective property of iodine application in the case of nuclear accident. Methods: In Poland at that time, effective iodine prophylaxis did not exist. In the face of such exposition, a special Governement Commission was appointed. When permissioned maximal dose for children and adolescents 50mSv appeared in some areas of the country, the Commission made a decision about obligatory administration of a single pharmacological dose of potassium iodide for all children and adolescents till age 16. No relevant recent patents were available for this WHO report. Results: In this way, the dose of 131-I to thyroid for inhabitants in high, moderated, and low contaminated regions were reduced by about 45%. However, from 1987 to 1997 increase in prevalence of the differentiated thyroid cancer in adults in Polish population especially in women over 40 years old in the southern part of Poland was observed. Conclusion: Actually in European countries work 185 nuclear power plants and to 2045 another 100 is planned. In 1999, WHO issued recommendations on iodine prophylaxis in the case of nuclear accident.

Background: Ligaria cuneifolia (Lc) (R. et P.) Tiegh. (Loranthaceae) (Argentine mistletoe) is usually used in local folk medicine. Objective: We studied the effect of treatment with the Lc proanthocyanidin-enriched fraction (PLc) in rats fed with Cho-enriched diet on plasma lipids levels, the hemorheological parameters, and biliary secretion. Method: Adult male Wistar rats were fed ad libitum with a Cho-enriched diet (Cho (97% purity) 8 g/kg of diet and corn oil 280 g/kg of diet) during 28 days. Then, were separated in six experimental groups (n=5 each one), which were injected ip every 24 h with: 1) saline solution (control group, C) and 2) PLc, 3 mg/100 g body weight (treated group, C+PLc), during 3, 7 and 10 days. Group C presented an increase in plasma levels of Cho and Triglycerides (TG), and also, accumulation of hepatic lipid droplets. Also, cell shape and their corresponding morphological index (MI) were altered too. Results: The treatment with PLc at 3, 7 and 10 days produces a diminution in the plasma Cho, LDL-Cho and serum TG levels, accompanied by a diminution of the lipid accumulation in the liver. The rates of bile acid output in bile can explain the diminution of plasma Cho, evidencing that some of the enzymes involved in the cholesterol conversion into bile acids could be up regulated by the treatment with PLc, leading to the observed increase bile flow. PLc treatment leads to a diminution of plasma levels of Cho and TG. Conclusion: Essentially, the treatment with PLc, despite the duration produces a modification in hemorheological parameters approaching the values of the experimental group with standard diet. Plasma levels of Cho, LDL-Cho and TG represent selected markers to evaluate the effect of enriched extract from Ligaria cuneifolia. Further work is necessary to better evaluate the mechanisms by which PLc induces modifications in the lipids metabolism.