Solid-phase peptide synthesis (SPPS)

В човешкия организъм пептидите изпълняват различни функции - биологично активни хормони, невротрансмитери и невромедиатори, растежни фактори, сигнални молекули и антибиотици. Тези разнообразни функции ги правят „интересни` за фармацевтичния пазар. През последните години световният пазар на терапевтични пептиди расте почти два пъти по-бързо спрямо пазара на другите лекарства. До момента близо 70 пептидни лекарства са одобрени от Американската агенция за контрол на храните и лекарствата (FDA). Голям брой нови пептидни молекули са в клинична (>150) и напреднали предклинични (>400) фази, което илюстрира спешната нужда от търсене и откриване на нови пептиди за лечение на различни заболявания. SPPS е метод за синтез на пептиди, при който реакцията на кондензация на отделните аминокиселини (АК) се извършва в течна среда, но полученият продукт е прикрепен към твърд полимерен носител, наречен смола. Предимството на този метод пред синтеза в разтвор е по отношение на скорост и ефективност на работа. Времето, необходимо за синтез на един продукт в разтвор, е около 6-12 месеца, докато при твърдофазен синтез - същият може да се получи за по-малко от 3 седмици. Краткото време за синтез дава възможност за получаване на голям брой пептидни аналози, което помага да се определят онези промени в молекулите, които водят до по-добре изразени ефекти. SPPS се използва успешно в лекарствения дизайн на нови молекули. Синтезирането на късоверижни пептиди с определени модификации в структурата дава възможност за комбиниране на различни фармакологични ефекти в един лиганд, което да доведе до оптимизиране на терапевтичните схеми.In the human organism, peptides perform various functions - biologically active hormones, neurotransmitters and neuromediators, growth factors, signal molecules and antibiotics. These various features make them „interesting` for the pharmaceutical market. In recent years, the world market for therapeutic peptides has grown almost twice as fast as the other medicines market. So far, nearly 70 peptide drugs have been approved by the US Food and Drug Administration (FDA). A large number of novel peptide molecules are in clinical (> 150) and advanced preclinical (>400) phases, which illustrates the urgent need to search for and discover new peptides to treat various diseases. Solid-phase peptide synthesis (SPPS) is a peptide synthesis method in which the condensation reaction of the individual amino acids (AА) is carried out in a liquid medium but the resulting product is attached to a solid polymeric carrier called a resin. The advantage of this method over solution synthesis is in terms of speed and efficiency. The time required for the synthesis of a solution in solution is about 6-12 months, whereas in solid phase synthesis - this can be achieved in less than 3 weeks. The short synthesis time allows production of a large number of peptide analogs, which helps to identify those changes in molecules that lead to more pronounced effects. SPPS is successfully used in the drug design of new molecules. The synthesis of short-chain peptides with certain modifications in the structure allows the combination of various pharmacological effects in one ligand to optimize therapeutic regimens

Analysis of factors affecting adherence to therapy in patients with chronic diseases

IntroductionTreatment of chronic diseases is a long-lasting and ongoing process that requires continuous pharmacotherapy. Adherence indicates the extent to which patient behaviour (in terms of medicine intake, diet compliance and change of life) corresponds to the advice received by a medical professional.AimThe aim of this article is to study and analyse the opinion of pharmacists, working in hospital and community pharmacies, on patients’ level of adherence to the prescribed drug therapy and to identify the leading socioeconomic, pharmacotherapeutic and pharmacoeconomic factors affecting adherence in patients with chronic diseases. Materials and MethodsThis national study was conducted in May 2020. Anonymous individual questionnaires were distributed to Masters of Pharmacy and assistant pharmacists. The survey was conducted online by a sociological method, using a Google form. Data was processed through software included in the Google forms. Charts were created with MS Excel and MS Word.ResultsThe results confirm the European and global tendency towards a low level of patient adherence to drug therapies—84.7% of pharmacists responded that only half of the patients adhered to the therapy. Respondents reported the high price and low reimbursement rate of medicines as objective reasons for non-purchasing medicinal products (79.8%). Our survey results indicate that adherence to therapy in patients with chronic diseases in Bulgaria remains a significant issue due to various socioeconomic and pharmacotherapeutic factors.ConclusionAdherence to the prescribed pharmacotherapy is crucial for achieving the therapeutic results

Methods To Enhance The Metabolic Stability Of Peptide Drugs

Therapeutic peptides have high selectivity, efficacy, and low toxicity. These characteristics, combined with advances in solid-phase peptide synthesis and purification methods, have led to the widespread use of peptide-based drugs. Limitations in the research and development of peptide drugs are related to their short plasma half-life, rapid metabolism, proteolytic degradation and poor penetration through biological membranes. This mini-review examines the advantages of peptide drugs over small molecule drugs and biotechnological proteins, as well as various chemical methods for peptide modifications to increase the metabolic stability, bioavailability and pharmacokinetic properties of peptides

Complementary And Alternative Medicine In The Treatment Of Cancer

В търсене на алтернативи в лечението на заболявания като рак, са насочени усилията на пациенти и учени. Лекарите често са негативно настроени, когато пациентите показват интерес към неконвенционални терапии и търсят съвет. За разлика от традиционните терапии, които обикновено са предоставени само след официално научно изследване за тяхната безопасност и ефективност, неконвенционалните терапии не са научно обосновани.Около 80% от пациентите с ракови заболявания в Съединените щати и повече от 50% от пациентите с ракови заболявания в Европа използват комплементарна и алтернативна медицина (САМ) в комбинация или вместо конвенционалната терапия. Неудовлетвореността от стандартното лечение и страничните ефекти на химиотерапевтичната терапия са най-често срещаните причини за използване на нетрадиционни методи на лечение.Амигдалин е едно от най-популярните неконвенционални противоракови средства за лечение, използвано от около 70 000 американци още през 70 години на миналия век.Тетрахидроксиканабинолът (ТХК), съдържащ се в маслото от канабис, доказано предизвиква апоптоза на ракови клетъчни линии. Канабиноидите може да намалят туморния растеж и прогресията чрез модулиране пролиферацията на ракови клетки, туморната ангиогенеза и метастазирането като характерни белези на раковото заболяване.В продължение на 40 години Рене Кайс е лекувала с Essiac стотици раково болни пациенти. Съобщава, че е прилагала една от билките чрез инжектиране, а другите като чай и е модифицирала лечебната формула няколко пъти въз основа на нейния опит. Четирите основни билки в Essiac са корен от репей (Arctium lappa), индийски ревен (Rheum palmatum), киселец (Rumex acetosella) и кора от слизест бряст (Ulmus fulva или U. rubra). Поддръжниците на Essiac твърдят, че това укрепва имунната система, подобрява апетита, облекчава болка и подобрява общото качество на живот. Те също твърдят, че това може да намали размера на тумора и да удължи живота на хората с различни видове рак.Searching for alternatives to the treatment of diseases such as cancer is where the efforts of patients and scientists are directed to. Doctors are often display a negative attitude when patients show interest in unconventional therapies and seek advice. In contrast to traditional therapies, which are usually provided only after an official scientific study of their safety and effectiveness, unconventional therapies are not scientifically justified.About 80% of cancer patients in the United States and Canada and more than 50% of cancer patients in Europe use complementary and alternative medicine (CAM) in combination or instead of conventional therapy. The dissatisfaction with standard treatment and the side effects of chemotherapy are the most common reasons for using non-traditional methods of treatment.Amigdaline is one of the most popular, unconventional anticancer treatments used by some 70,000 Americans in the 1970s.Tetrahydroxycanabinol (THC) contained in cannabis oil has been shown to cause apoptosis of cancer cell lines. Cannabinoids may reduce tumor growth and progression by modulating cancer cell proliferation, tumor angiogenesis and metastasis as characteristic features of cancer.For over 40 years Renee Kays has treated hundreds of cancer patients with Essiac. She reports that she has been using one of the herbs by injection and the others as tea and has modified the healing formula several times on the basis of her experience.The four Essiac herbs are roots of burdock (Arctium lappa), Indian rheum (Rheum palmatum), sorrel (Rumex acetosella) and Ulmus fulva or U. rubra. Supporters of Essiac say it strengthens the immune system, improves appetite, relieves pain and improves overall quality of life. They too claim that this can reduce the size of the tumor and prolong the lives of people with various types of cancer

Current trends in the prevention and treatment of liver diseases with phytopreparations

The liver is a dynamic, heterogeneous organ, which is under heavily regulated physiological control. The various types of liver pathologies are a global health concern with a significant mortality rate.The unhealthy lifestyle leaves its mark on the liver. The toxins in the environment, medications and alcohol are merely a sample of the factors, which could negatively affect the basic functioning and self-recovery of the liver.Along the conventional treatment, there is a widely spread application of phytopreparations as an accompanying therapy, and more commonly in the cases of less severe liver diseases they may be the main therapy. A number of medicinal plants are also used, such as milk thistle (Silybum marianum), dandelion (Taraxacum officinale), burdock (Arctium lappa), artichoke (Cynara scolymus), curcuma (Curcuma longa). They arе taken in the form of tinctures, extracts or tea and the extracted biologically active ingredients of the plants are part of the composition of various capsules and tablets

In vitro study of antimicrobial activity of essential oils of Origanum vulgare against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922

INTRODUCTION: Essential oils are aromatic and volatile liquids, extracted from different plant parts with antibacterial, antifungal, antiviral, antioxidant, and biological properties. For example, the essential oil of oregano presents antioxidant and antimicrobial activities.AIM: The aim of this study is to evaluate the potential antimicrobial activity of two (for external and internal use) commercial essential oils of Origanum vulgare against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922.MATERIALS AND METHODS: The study was conducted in Medical College, Varna, Bulgaria. The antimicrobial activity of oregano essential oils was determined by the use of the Kirby-Bauer disk diffusion susceptibility test.RESULTS: Antimicrobial activity of oregano essential oils (for external and internal use) was efficient in the control of Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922. This inhibitory effect was observed by the inhibitory diameters above 21 mm.CONCLUSION: The future evaluation of natural essential oils with a relatively high in vitro activity could be researched in the treatment of various infectious diseases.

Immunomodulating and antitumor effect of Agaricus blazei, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa

Лечебното използване на гъби има много дълга традиция в азиатските страни, докато използването им в западните страни постепенно се увеличава в последните десетилетия. Някои от проучените гъби са едни от най-мощните стимулатори и модулатори на имунната система. Техните лечебни свойства се ценят високо и са обект на множество изследвания. Те понижават холестерола, подпомагат здравословното отслабване и спомагат за контрол над диабета. Ползите от тях са щателно проучени и документирани. Най-много внимание привличат техните противоракови свойства. Има много гъби с мощни противоракови свойства, но най-добри резултати се получават при употреба на препарати, съдържащи екстракти от повече от един вид гъби. Някои от проучванията показват, че полизахарид е главният компонент с противотуморен ефект.Молекулното тегло, степента на разклоняване, броят на заместителите, както и ултраструктурата, включително наличие на единични и тройни спирали, значително повлияват биологичните активности на бета-глюканите. По-високата антитуморна активност изглежда е корелирана с по-високото молекулно тегло, по-ниско ниво на разклоняване и по-голямата разтворимост във вода на бета-глюканите.The curative use of mushrooms has a long tradition in Asian countries, whereas their use in the Western countries has gradually increased in recent decades. Some of the studied mushrooms are among the most powerful stimulators and modulators of the immune system. Their healing properties are highly valued and subject to many studies. They lower cholesterol, help reduce weight loss, and help control diabetes. Their benefits are thoroughly researched and documented. Most attention is attracted by their anticancer properties. There are many mushrooms with powerful anticancer properties, but the best results are obtained with the use of preparations containing extracts from more than one type of fungus. Some studies have shown that polysaccharide is the main component with an antitumor effect.The molecular weight, branching rate, number of substitutions as well as ultrastructure, including the presence of single and triple helices significantly affect the biological activities of beta-glucans. Higher antitumor activity appears to be correlated with higher molecular weight, lower branching, and greater water-soluble beta-glucans

Analysis of the Results of a Survey Among Healthcare Professionals Working with Electronic Medicine Lists

In the current information society, electronic communication technologies are the basis of the most successful economic, administrative, health, and other organizations. A number of countries in Europe and around the world have successfully implemented the model of electronic management and the large-scale use of electronic services. Already in 2017, based on detailed analysis and technological recommendations, the project for the implementation of the first two parallel stages of the construction of the National Health Information System (NHIS) was launched. It covers all participants and main flows of information in the healthcare sector, including: -          Electronic health record (patient file);-          Eluctronic recipe (e-recipe);-          Electronic referrals (e-referrals); The aim of this study is to summarize the opinions of healthcare professionals about working with an electronic medicine list. 87 health professionals (midwives) from a total of 128 states who were directly engaged in the activities of the hospital wards of SHOGAT Prof. Dr. D. Stamatov, Varna, were interviewed during the period May–June 2022. More than half of the respondents (66.7%) prefer the electronic form for prescribing drug therapies. 57.5% believe that the process of work is facilitated by the introduced amendments regarding the work with electronic databases compared to paper media. In conclusion, in the current information society, electronic communication technologies are the basis of the most successful economic, administrative, and health activities that support the processes of diagnosis and treatment in hospital structures. They save time and resources, ensure patient safety, and improve the quality of service

The opportunities of kinesitherapy to keep elderly people independent

The opportunities of kinesitherapy to keep elderly people independent Recent social and demographic studies show considerable changes in the age structure of the population of our country. The percentage of the grown-up and elderly people is significantly increasing. Most important from health point of view is the high morbidity and pathology domination mostly of degenerative type, which necessitates diversity of health services and social care with the aim to improve quality of life. As the age goes on, chronic motive changes pile up and people need more and more support to keep adequate their motive activity.Aim: To study and analyze the opportunities of the active kinesitherapy and the rehabilitation therapist role in helping elderly people stay independent.Conclusion: it is essential for elderly people to maintain their abilities for doing the basic everyday activities like feeding, hygiene, getting dressed, moving, shopping. The kinesitherapy can contribute for bigger self-dependence and independence of the elderly

Review on the pharmacological activities of lactoferricin and lactoferricin analogues

INTRODUCTION: Antimicrobial peptides (AMPs) are a growing class of natural and synthetic compounds with a wide spectrum of targets including viruses, bacteria, fungi, and parasites.AIM: The aim of the present review was to make an overview of the available literature on the pharmacological activities of these peptides, focusing on lactoferricin and lactoferricin analogues.MATERIALS AND METHODS: To achieve this aim, information from databases, such as PubMed, Google Scholar and ResearchGate was searched and summarized.RESULTS: Antimicrobial peptides (AMPs) are considered a promising alternative to the antibiotics used nowadays. They have drawn a special attention in the fight against infections caused by antibiotic-resistant bacterial strains. Lactoferricin is the most studied AMP derived from milk protein. Lactoferricin (Lfcin) is a fragment of the ferro-chelate complex of the bovine protein lactoferrin (Lf). The amphipathic and cationic properties of Lfcin account for its broad spectrum antimicrobial activity. Lfcin also manifests potential antiviral, immunomodulatory, antitumor and anti-inflammatory properties. Shorter analogues of Lfcins have been synthesized with a broad spectrum of activities and enhanced pharmacokinetic properties.CONCLUSION: Lactoferricin and its analogues are a good demonstration that it is possible to design and obtain synthetic peptides with enhanced pharmacological activities