Historical Developments of Bosnia and Herzegovina Pharmaceutical Industry - the Past and the Future Perspectives of Domestic Manufacturing.

Background: History of pharmaceutical industry in Bosnia and Herzegovina (B&H) has its roots from 1951. Importance of domestic industry not just from economical aspect but also from public health perspective and as scientific base has not been evaluated previously. Objective: The aim of this article was to provide the review of the pharmaceutical industry developments in Bosnia and Herzegovina, its roots, current position and future perspectives.. Methods: Research of published scientific papers as well other documents and archives of pharmaceutical manufacturers has been conducted. We have also analysed market trends focusing on domestic producers. Results and Discussion: Over more than seventy years of B&H pharmaceutical industry has been developing. During Yugoslavia only two companies existed of which one, Bosnalijek is still present, while Sanofarm has been closed. After 1996, expansion of domestic manufacturers started and today six companies are present. They are mainly oriented to generic drugs production in different forms. Total market share of domestic producers in B&H is 20-25% which is relatively low comparing to other countries. Many of domestic manufacturers are exporting their products to some of the most demanding markets in Europe and Middle East. Conclusion: Long history of domestic drug manufacturers in B&H gives solid legacy for future developments. Importance of local producers has been confirmed during war in B&H and COVID-19 pandemic as a crisis situation, mainly from public health perspective and sustainable supply of essential medicines. Higher support by state and collaboration with academia in order to expand portfolio, especially in area of biologic medicines is required in future.

Mobile Pharmacies Throughout History.

BACKGROUND: Mobile pharmacies are special organizational units or infrastructures that serve to supply medicines to remote communities or are stationed on ships or as such exist during war conflicts on the battlefields to provide first aid to the wounded and to provide the necessary medicines. The establishment of mobile pharmacies is regulated by the law of each state and only preparations approved by law can be found in it. There are also regulations for the good storage and warehousing of these drugs. OBJECTIVE: The aim of this article was to provide an overview of the available literature on the topic "Mobile pharmacies through history", which shows the development and progress in the structure and function of mobile pharmacies throughout history. METHODS: This is an descriptive study based on the searched available literature from the on-line databases regarding to present a historical overview of mobile pharmacies during the most significant war events in Europe and the USA. RESULTS AND DISCUSSION: Mobile pharmacies were first mentioned in Egypt and the Roman Empire, but it was not until 1500 that military and ship's doctors began using them, and wealthy nobles had their own boxes of medicines, which they carried on long voyages. Mobile pharmacies became more and more popular, so in the 18th century, practical manuals on the use of the contents of the box began to be published. The importance of a mobile pharmacy was shown in the wars, where people, before their appearance, died due to the impossibility of providing first aid on the battlefield. The advanced medicine and pharmacy that developed on land, greatly affected the health care at the sea. The constant incidence of infectious diseases, poverty and inadequate nutrition, insecurity of navigation and long voyages are the main reasons why sailors often fell ill and were exposed to injuries at work. A situation like that required that the problem of health protection on ships gets solved in accordance with the then principles of medicine and pharmacy. CONCLUSION: Authors demonstrated the importance of mobile pharmacies in treating and providing medical protection on boat trips. Regarding the ship's pharmacies, pharmacists have the role of supplying ships with medicines, conducting training for captains and ship staff, advising shipping companies and captains on equipping ship pharmacies and advising on the preparation of national regulations and national ship pharmacy supply policy.

Contribution of Arabic Medicine and Pharmacy to the Development of Health Care Protection in Bosnia and Herzegovina - the First Part.

The time interval from the 9th to the 13th century remained known as the "Golden period of the Arab science", and a significant place among the taught sciences are occupied by Medicine and Pharmacy. In the history of medicine, Islamic medicine, also known as Arabic medicine, refers to the science of medicine developed in the Islamic Golden Age, and written in Arabic Arabs were able to use their cultural and natural resources and trade links to contribute to the strong development of pharmacy. After the collapse of the Arab rule, the Arab territorial expanses and cultural heritage were taken over by the Turks. Although scientific progress in the Turkish period slowed down due to numerous unfavorable political-economic and other circumstances, thanks to the Turks, Arab culture and useful Islamic principles expanded to the territory of our homeland of Bosnia and Herzegovina. Significant role in the transfer of Arabic medical and pharmaceutical knowledge was also attributed to the Sephardic Jews who, with their arrival, continued to perform their attar activities, which were largely based on Arab achievements. However, insufficiently elaborated, rich funds of oriental medical and pharmaceutical handwriting testify that Oriental science has nurtured in these areas as well, and that the Arab component in a specific way was intertwined with other cultures and traditions of Bosnia and Herzegovina.

Historical Contribution of Pharmaceutics to Botany and Pharmacognosy Development.

INTRODUCTION: Pharmacy and medicine belong to the oldest human activities, so the development of these sciences is closely related to the socio-economic, cultural and religious opportunities of the nations within which they have been developing. GOALS: To present the historical influence of pharmacy on the development of the human being from its very beginning; To present the historical link between pharmaceutical and medical activity, as well as early development of independent pharmaceutical activity; To present the historical influence of pharmacists on the development of botany and pharmacognosy and to present the historical influence of the first written herbarium and incunabula on the development of pharmacognosy. MATERIAL AND METHODS: The article has a descriptive character, and represents a systematic review of the literature dealing with this topic. RESULTS: The roots of pharmacy started to the very beginning of human civilization, when people collected various medicinal herbs and try to alleviate their health problems, pain and suffering. The scientific foundations of the pharmacy were set up in the antique period by the books of Dioskurides and Galen, and its further development continued in the mid-century, at the beginning by rewriting famous parts of ancient literature, and later by writing new discoveries (the base of this development was represented by South Italy) so that in 1240, for the first time in history, came the separation of doctors and pharmacists, and at the beginning of the 13th century the opening of the first pharmacy. CONCLUSION: The effort to maintain knowledge of medicinal herbs and its practical application has led to the writing of a large number of recipes books, the forerunners of today's pharmacopeia, while the aspiration to classify medicinal herbs, and the desire to present medicinal herbs to ordinary people, has led to a large number of herbaria, making the knowledge and descriptions of plants available to many, not just the nobility. Descriptions of plants in herbaria and later in incunabula lead to the development of pharmacognosy, and to the opening of the first Department for pharmacognosy, 1545 in Padua.

The Role and Characteristics of Collections of Folk Recepies in the Folk and Traditional Medicine of Bosnia and Herzegovina.

INTRODUCTION: Folk medicine represents part of the folk culture, when we first think about the rural culture with characteristic of the rural population in the pre-industrial period. The difference between official and folk medicine is manifested in the education, knowledge and social status of those practicing folk medicine as well as their patients. The most common ways of treating were the treatment by use of herbs, magic and treatments based on religious beliefs. So, it is of no surprise that folk medicine was the main form of treatment for the inhabitants of Bosnia and Herzegovina (B&H) in the past. In addition to many herbalists, quacks and religious officials who treated the patients with records, there were also spells, i.e. women who, by pronouncing various magic formulas, treated the patients. Each village had at least one person who practiced this type of treatment. DISCUSSION: Numerous, original documents and records have been stored in the archives of the monastery throughout B&H, including very valuable literature in the field of medicine and pharmacy, which testifies of the very important role of Franciscans in the treatment of the population in Bosnia and Herzegovina. The most extensive health service of the Franciscans since their arrival in Bosnia in 1291 was the decadent era of Turkish rule, mostly from the 17th century until the Austro-Hungarian occupation of Bosnia and Herzegovina in 1978. In the sources of national thought, and on the basis of professional medical books, the Franciscans created recipes for the treatment of certain diseases, which they then collected in so-called "Ljekaruse" (Collections of folk recipes), and over time there was a lot of them. Most of the ljekarusa are hand-printed booklets, for some it is known the time and place of creation, and less often the author of the text. Ljekarusa is a very important source of information about our medical past. Some of them were processed and recorded, while a significant part of these manuscripts remained unknown to the general public. They included recipes for various diseases and the names they were called by the people. Professional terms were not used, nor were the illnesses and the recipes ordered in any order or systematic manner. We learn from them that our people were once treated in the absence of doctors and pharmacists. Most commonly mentioned are various herbs, animal parts, mineral substances, and some of these recipes can be even applied today. All medicines continue to be transcribed by the people and valued as good old medical receipts. CONCLUSION: This review article presents a book (ljekaruse) that was archived in several famous monasteries in Bosnia and Herzegovina.

Influence of Arabian Pharmacy on Diseases Tretament During Ottoman's Period in Bosnia and Herzegovina.

The Arab cultural heritage was an era of invaluable preservation and development of numerous teachings, including biomedical sciences. The golden period of Arab medicine deserves special attention in the history of medicine and pharmacy, as it was the period of rapid translation of works from Greek and Persian cultures into Arabic. They preserved their culture, and science from decay, and then adopted them to continue building their science on theirs as a basis. After the fall of Arabian Caliphate, Arabian pharmacy, continued to persevere, and spread through Turkish Caliphate until its fall in the First World War. That way, Arabian pharmacy will be spread to new areas that had benefited from it, including the area of occupied Bosnia and Herzegovina. Because of the vast territorial scope of the Ottoman Empire, the focus of this paper is description of developing pharmacy in Bosnia and Herzegovina during the time of Ottoman reign.

Bosnian Franciscans and the Monasteries in Kresevo and Fojnica as Source of Scientific Bibliography.

All of these centuries-old records contain enormous treasures, and the modern medicine is increasingly searching for the sources of natural remedies. The Franciscans should be credited for carefully collecting the methods folk treatment and passed them on to future generations. In the words of Br. Marko Karamatic: "The fact that the Friars were engaged in healthcare, that they became the first graduate doctors in Bosnia and Herzegovina, that they wrote" herbal manuals " and other medical records, is the result of historical opportunities in these areas, and this activity became one of the most important tasks for the Franciscans. They performed their duties regardless of the circumstances.

Role of laboratory diagnostic medical biochemistry services -analysis of requirements for the laboratory test in the laboratory of primary health care center.

INTRODUCTION: Laboratory diagnosis of medical biochemistry activity plays a significant role in the Primary Health Care Center (PHCC), dominated by Family medicine and diagnostic services. Medical biochemical diagnosis has a visible place at all levels of health care, which shows the number of requests for laboratory diagnosis, number and type of required laboratory tests. MATERIALS AND METHODS: The study included 1000 requests for laboratory tests at the PHCC in Gracanica in primary health care units. We made an analysis of the most common laboratory tests in the requests by doctors from primary health care based on requests for laboratory diagnosis. RESULTS: The requests of primary health care units in PHCC laboratory tests are required at all levels of service: urine, WBC, SE, glucose, total bilirubin, ALT, AST, AF, CK, cholesterol, HDL cholesterol, triglycerides, creatinine, urea, uric acid, CRP, fibrinogen, calcium and phosphorus. The following requirements are the most common laboratory tests with 94% representation: urine, WBC, glucose, cholesterol, triglycerides, aminotransferases, creatinine, and urea. In 1000 requires was required total of 5333 laboratory tests. Test requirements of a general practice make 44, 1%; FM doctors account for 40% and the requirements of other specialists (pediatricians, gynecologists and specialists of occupational medicine) are 15, 3%. The doctors in family practice most often required: glucose, urine, WBC, SE, TGL., Chol., ALT, AST, creatinine and urea. General practitioners are demanding more cholesterol and triglycerides, a family medicine doctors are demanding lower cholesterol and triglycerides and higher CRP, fibrinogen, total bilirubin, ALT, AST, and other specialists the most demanded urine and WBC. DISCUSSION: Laboratory diagnosis is a common diagnosis, which shows the representation of required number and type of laboratory tests. In requirements of PHC units in PHCC laboratory tests are required at all levels of service: urine, WBC, SE, glucose, bilirubin, ALT, AST, AF, CK, cholesterol, HDLchol., triglycerides, creatinine, urea, uric acid, CRP, fibrinogen, calcium and phosphorus. The following requirements are the most common laboratory tests at the primary level: urine, WBC, glucose, cholesterol, urea, and found the secondary level of triglycerides, index levels and did not clear the number of searches required by the standards and norms of PHC.

Levels of persistent organic pollutants in the Neretva River (Bosnia and Herzegovina) determined by deployment of semipermeable membrane devices (SPMD).

The main objective of this study was to determine levels of certain persistent organic pollutants (POPs) in Neretva River, Bosnia and Herzegovina (BiH), which is currently facing implementation of the Stockholm Convention on persistent organic pollutants (POPs) and environmental protection strategies. This is the very first report on the deployment of semipermeable membrane devices (SPMDs) in BiH. SPMDs were used for continuous 3-weeks sampling of POPs at three locations, covering 220 km long stream of the Neretva River. Water concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polybrominated diphenylethers (PBDEs) were calculated using performance reference compounds (PRCs). The total OCP concentrations ranged from 40 to 140 pg L(-1) and most of compounds were detected only in lower course of the river. Total PAH ranged from 160 to 4000 pg L(-1) and show a clear spatial variation. Dominant PAHs were phenanthrene, fluoranthene, fluorene and acenaphthene. Total PCB ranged from undetectable to 120 pg L(-1). From the group of 15 PBDE congeners investigated, only PBDE-47 and PBDE-99 were detected. Since the concentrations of broad spectrum of POPs found in the Neretva River are quite low, future actions should be focused on preservation rather than on sanitation measures. Regular monitoring should anyhow be established.

Statistical evaluation of olanzapine efficacy in catamnesticly investigated patients.

The aims of this research are: a) To compare GAF (Global Assessment of Functioning) score after the olanzapine treatment with the GAF score recorded after the treatment conducted by typical antipsychotics; b) To compare CGI (Global Clinical Impression) score after the treatment with CGI subsequent to treatment by typical antipsychotics; c) To compare number of hospitalizations of patients during the treatment with olanzapine with the number of hospitalizations during previous treatment; and 4. To monitor and record the possible weight gain of patients who were taking olanzapine. The research was conducted in the period from 2004 to 2007 in the Department of Psychiatry of the University Clinical Center in Sarajevo. Research subjects were patients with diagnosed schizophrenia who did not have expected response to the treatment with conventional antipsychotics, or who experienced serious adverse effects in the course of this treatment. Daily dosage of olanzapine was adjusted to the clinical condition of the patient and it varied from 5 to 20 mg a day. Clinical assessment is done once a month with CGI scale and GAF scale. During follow-up the possible weight gain was also followed. Statistically significant difference was found (p<0.001).

Transplantation of organs: one of the greatest achievements in history of medicine.

The history of transplantation is a scientific journey describing the medical community's effort to understand how the human body works. Humans have long realized the possibilities which transplantation of organs and tissue provides. Throughout history people have always been intrigued by the possibilities of the transplantation of organs and tissues. In the 6th Century BC Indian surgeons described how to reconstruct facial wounds by transplanting skin from one place on the body to the other. During the middle age there were many references in historical medical literature of attempted blood transfusions as well as the transplantation of teeth. A skin transplant and a corneal transplant were reported in medical journals dating as far back as 1880. These early attempts were usually unsuccessful. Early in the twentieth century transplantation started to offer the promise of restored health and life. One of the exceptional medical advances of the twentieth century, organ transplantation has become a routine treatment for patients with organ failure which was a goal.

QSAR study of antimicrobial activity of some 3-nitrocoumarins and related compounds.

A new class of antimicrobial agents, 3-nitrocoumarins and related compounds, has been chosen as a subject of the present study. In order to explore their activity and molecular properties that determine their antimicrobial effects, QSAR models have been proposed. Most of the 64 descriptors used for the development were extracted from semiempirical and density functional theory (DFT) founded calculations. For this study literature data containing results of microbiological activity screening of 33 coumarin derivatives against selected clinical isolates of C. albicans (CA) and S. aureus (SA) have been selected. Multivariate predictive models based on random forests (RF) and two hybrid classification approaches, genetic algorithms (GA) associated with either support vector machines (SVM) or k nearest neighbor (kNN), have been used for establishment of QSARs. An applied feature selection approach enabled two-dimensional linear separation of active and inactive compounds, which was a necessary tool for rational candidate design and descriptor relevance interpretation. Candidate molecules were checked by cross-validated models, and selected derivatives have been synthesized. Their antimicrobial activities were compared to antimicrobial activities of the representative derivatives from the original set in terms of minimal inhibitory concentration (MIC) against chosen SA and CA ATCC strains. High ranking of descriptors consistent with the degree of hydrolytic instability of selected compounds is common to models of antimicrobial activity against both microorganisms. However, descriptor ranking indicates different antimicrobial mechanisms of action of chosen coumarin derivatives against selected microbial species.

[Pharmaco-economic analysis of NSAID usage in Gastroenterology Department of Tuzla Clinic]. / Farmakoekonomska analiza primjene nesteroidnih antireumatika na odjelu za gastroenterologiju Klinickog centra u Tuzli.

Pharmacoeconomics is young rapidly developing science that uses economic, clinical and epidemiologic methods. It studies adequate use of therapeutics giving guidelines towards rational utilization of the resources in health care. Pharmacoeconomics indentifies estimates and compares costs and clinical outcomes of different strategies giving the best solution: optimal cost/benefit ratio. These studies can be used to estimate existing programs and plan the new ones. The aim of this paper was to carry out pharmacoeconomic study on the non-steroid anti-inflamatory drugs (NSAID) use in canton Tuzla, to compare costs of medication with highly selective cyclooxygenase 2 (COX-2) inhibitors and nonselective NSAIDs and to calculate medication costs of the bleeding from upper parts of gastrointestinal tract. Study covers period from January to April 2004. Meta-analysis of selected clinical studies on safe and efficiency of NSAIDs was simultaneously conducted. Our results show that hospital treatment costs of the high-risk patients group significantly exceeds their potential medication costs with highly selective COX-2 inhibitors. Simultaneous use of non-selective NSAIDs with antacids has justification only in the low-risk group with mild gastrointestinal disturbances.

[Classification of drugs using the ATC system (Anatomic, Therapeutic, Chemical Classification) and the latest changes]. / Klasificiranje lijekova po ATC sistemu i najnovije izmjene.

World Health Organization (WHO) established ATC system of drug classification. All drugs are grouped in five levels (anatomical main group, therapeutic subgroup, pharmacological subgroup, chemical subgroup and chemical substance). Alterations in ATC classification are made only by experts in WHO centre in Oslo, Norway. Changes are made in assigned new international generic names (INN), in ATC levels likes in changes of Defined Daily Doses (DDD) once a year. Changes are made following current scientific articles and international pharmacopeas, as well as the guideline.

[Effect of alcohol on aminotransferase activity in adolescents]. / Uticaj alkohola na aktivnosti aminotransferaza u adolescenata.

The objective of research were consolidate the correlation the greatest values ALT and AST, and consummation alcohol. To the group of 302 adolescents, male sex of 18, 19 and 20 years is measured the activity of ALT and AST. The examines are questionned to the consummation of alcohol. Had to the significant increased values AST, and only mildly increased values in relation to the upper referent values.

[Kinesitherapy in the treatment of muscle spasm]. / Kineziterapija u tretmanu misicnog spazma.

Muscular spasm is type of the increased muscle tone which is common in the upper motor neuron lesion and it can be developed due to disease (stroke, MS, tumors, infection, intoxication) and trauma. This research included 30 patients with muscular spasm after upper motor neuron lesion. All of the patients were treated by passive exercises and stretching of agonists and antagonists. All patients were males, with age between 25 and 45 years (average 26.9 years). Applying t-test, in testing significant differences in changing muscular spasm, in relationship to the length of the kinesitherapy treatment, there were no significant differences between 1st and 15th day of treatment. Significant difference in spasm grades was after 30th day of treatment compare to 1st and 15th day. This research showed that decreasing muscle spasm we could be expected by applying the kinesitherapy procedures for a longer time.

Co-relation between risk factors of falls down and the Berg balance scale in elderly people (third age).

This study encompassed 77 randomly assigned participants of both sexes and older than 65 of age. Every participant was questioned in his/her own house and completely familiarized with the methodology and the aims of the questionnaire. Out of 27 men, data on falls down were provided by 4 participants (14.81%): one of them lived alone while three of them lived in their families. Out of 50 women, data on falls down were provided by 17 (34%) participants: 9 of them lived in their families and 8 lived alone. Out of all living alone women 44% fell down twice or more during this study in comparison to 20% of living alone men. Regarding the values of the score of risk factors obtained throughout the questionnaire and the Berg balance scale, there are statistically significant differences between men and women (p < 0.005, i.e. p < 0.01), as well as participants that have never fallen down (p < 0.001, i.e. p < 0.01), while regarding the life style (living alone or in the family) there are no statistically significant differences (P > 0.05). Nowadays, the Berg balance scale is the most frequently used questionnaire that is, in total, significantly superior to other ever utilized tests. Average values of results obtained throughout the Berg balance scale in this study are statistically significantly higher in men and those participants who did not provide data on falls down, while regarding the life style there are no statistically significant differences.

[Pharmacoeconomic evaluation of use of ciprofloxacin and norfloxacin with cost-benefit analysis]. / Farmakoekonomska procjena potrosnje Ciprofloksacina i Norfloksacina metodom analize troska i dobiti (CBA--cost-benefit analysis).

Pharmacoeconomics is application of economical principles in health and pharmaceutical care sector. This is comparative analysis of treatment e.i. therapeutic alternatives (drugs), which takes into consideration both their costs and their health repercussions. Cost-benefit analysis (CBA) has been used where effectiveness of cost was calculated by calculating the sum of costs for urinary infections treatment which include the cost of examinations, the costs of therapy with ciprofloxacin and norfloksacin, other costs associated with treatment and total benefit for both of treatments. CBA of costs are pointing out that it is economically justified to prescribe both drugs, ciprofloxacin and norfloksacin, due the costs-benefit are the quite equal for both.