Discovery Of Streptomycin Research Articles

Biotechnological potential of actinomycetes in the 21st century: a brief review.

This brief review aims to draw attention to the biotechnological potential of actinomycetes. Their main uses as sources of antibiotics and in agriculture would be enough not to neglect them; however, as we will see, their biotechnological application is much broader. Far from intending to exhaust this issue, we present a short survey of the research involving actinomycetes and their applications published in the last 23years. We highlight a perspective for the discovery of new active ingredients or new applications for the known metabolites of these microorganisms that, for approximately 80years, since the discovery of streptomycin, have been the main source of antibiotics. Based on the collected data, we organize the text to show how the cosmopolitanism of actinomycetes and the evolutionary biotic and abiotic ecological relationships of actinomycetes translate into the expression of metabolites in the environment and the richness of biosynthetic gene clusters, many of which remain silenced in traditional laboratory cultures. We also present the main strategies used in the twenty-first century to promote the expression of these silenced genes and obtain new secondary metabolites from known or new strains. Many of these metabolites have biological activities relevant to medicine, agriculture, and biotechnology industries, including candidates for new drugs or drug models against infectious and non-infectious diseases. Below, we present significant examples of the antimicrobial spectrum of actinomycetes, which is the most commonly investigated and best known, as well as their non-antimicrobial spectrum, which is becoming better known and increasingly explored.

Prevention and treatment of tuberculosis before two great discoveries of the 20th century: the Bacillus Calmette-Guérin vaccine and streptomycin

Introduction and Purpose. Fundamental milestone in fight against tuberculosis is the invention of the effective vaccine, but before Anthony van Leeuwenhoek was the first to observe the bacteria, which opened the door to the first vaccinations in the 19th century. Medicine had battled against infectious diseases in different ways. Some methods can be perceived as a kind of primitive vaccines, which couldn’t, however, considerably affect a decrease in the epidemic range, due to their uncommon use and limited effectiveness. The aim of this paper is to analyze the history of tuberculosis and the role of Poland in the fight against it.
 Materials and methods. PubMed database was used for review of the literature. The following phrases were searched in English: “tuberculosis”, “vaccination”, “BCG vaccine”, “sanatorium”.
 Description of the state of knowledge. Poland played an important role in the fight against tuberculosis. It was in the laboratory of Polish pharmacist, where Koch discovered its etiological factor. In the territory of Poland there are prototypes of modern sanatoria for tuberculosis patients. Article also presents old and modern methods of tuberculosis treatment, as the use of specific climatic conditions, which resulted in developing health-resort treatment. A breakthrough in the methods used was the discovery of streptomycin in the middle of the 20th century, which led to the development of pharmacological treatment, nowadays involving the administration of proper combinations of drugs.
 Summary. The increasingly strong anti-vaccine movement is slowly destroying what people have been fighting for the centuries. It is worth recalling how we reached milestones in this fight and why immunization is so important for all societies.

Mechanism-Based Approach to New Antibiotic Producers Screening among Actinomycetes in the Course of the Citizen Science Project

Since the discovery of streptomycin, actinomycetes have been a useful source for new antibiotics, but there have been diminishing rates of new finds since the 1960s. The decreasing probability of identifying new active agents led to reduced interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a promising reservoir for new active molecules. In this work, we present several reporter plasmids encoding visible fluorescent protein genes. These plasmids provide primary information about the action mechanism of antimicrobial agents at an early stage of screening. The reporters and the pipeline described have been optimized and designed to employ citizen scientists without specialized skills or equipment with the aim of essentially crowdsourcing the search for new antibiotic producers in the vast natural reservoir of soil bacteria. The combination of mechanism-based approaches and citizen science has proved its effectiveness in practice, revealing a significant increase in the screening rate. As a proof of concept, two new strains, Streptomyces sp. KB-1 and BV113, were found to produce the antibiotics pikromycin and chartreusin, respectively, demonstrating the efficiency of the pipeline.

ATP Synthase, an Emerging Target in TB Drug Discovery: Review of SAR and Clinical Pharmacology of Diarylquinoline Inhibitors.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the leading causes of mortality worldwide, with an estimated 1.5 million deaths annually. The majority of infection cases are reported from the Southeast Asian region, including India. After the discovery of Streptomycin in 1943 and its anti-tubercular activity in 1945, drug discovery efforts identified Isoniazid, Ethambutol, and Rifampin as TB-actives. However, over the years, these drugs have been rendered ineffective due to genetic mutations in mycobacterial strains. This has shifted drug discovery efforts towards identifying new targets and drugs for drug-resistant forms of bacteria. ATP synthase was identified as one of the key targets of MDR-TB. This review provides key insights into the ATP synthase target, structure activity relationship studies (SAR) of diarylquinoline class of inhibitors and their clinical relevance for treating MDR-TB.

Breme tuberkuloze kao stalni medicinski i pravni izazov čovečanstva kroz vekove

Tuberculosis (TB) is a contagious disease, and throughout human history, it has been permanently opening numerous medical and legal questions, for which the answers are implied by the current social circumstances. In ancient times, insufficient knowledge of the etiopathogenesis of TB resulted in discrimination and isolation of patients. In the Middle Ages, kings used TB as a disease to secure their political power over the citizens, while TB culturally took a romanticized form during the 19th and 20th centuries, together with a great social phobia of contagion, disease, and dying on the other hand. Stereotypes were formed around all TB victims, while society tried to understand the nature of the disease and establish a civilizational relationship with it as a health problem having numerous social implications. Modern public health measures for the control of the TB pandemic were established after the discovery of the Koch bacillus in the 19th century. The invention and mass use of the BCG vaccine, the discovery of streptomycin and isoniazid, and the new era of TB treatment, with the consequent emergence of drug resistance, coepidemic with AIDS, neglect of public health facilities and the current COVID-19 pandemics threaten many legal rights of the infected and the sick and pose new challenges in its global elimination. Numerous attempts by society over the centuries to devise preventive and therapeutic measures for TB, through different levels of social obligations and activities, have had and continue to have a profound impact on the human race, shaping its further response to the victims of this deadly disease.

Whole-genome sequence of a novel, mangrove-derived streptomycete, Streptomyces malaysiense strain MUSC 136T

Since the discovery of streptomycin from Streptomyces griseus in the early 1940s, streptomycetes from various environments have been studied thoroughly for the ability to produce bioactive compounds including antibacterial, antioxidant, anticancer, antifungal as well as immunomodulatory properties. Previously identified as a novel strain from a mangrove forest in Malaysia, Streptomyces malaysiense MUSC 136T was selected for genome sequencing to explore its genomic potential. The genomic size comprises of 7,963,326 bp with a G+C content of 72.2% and a total of 6,614 proteincoding genes. As an attempt to investigate the types of biosynthetic gene cluster present in the MUSC 136T, the whole genome sequence was analyzed with a bioinformatics tool, antibiotics & Secondary Metabolite Analysis Shell (antiSMASH). Using the “strict” prediction method, a total of seven biosynthetic gene clusters which displayed similarity of more than 80% to known gene clusters including ectoine, geosmin as well as desferrioxamine. Apart from emphasizing the importance of streptomycetes from unique environments like mangrove forest, the current study serves as a foundation for future studies on the role of specific genes present in biosynthetic gene clusters which enables the exploitation of MUSC 136T to synthesize important and valuable compounds.

A novel actinobacterium species from a mangrove ecosystem- antibacterial activity and chemical characterization

The discovery of streptomycin by Selman Waksman (1943) brought into focus a new avenue of drugs from natural products, i.e., actinobacterial secondary metabolites. It forms more than 60 % of total bacterial secondary metabolites (mostly from Streptomyces). Interestingly, rare Actinobacteria can produce novel secondary metabolites with unique chemical structures. With the rise of drug resistant microbes, focus on actinobacterial research has shifted towards exploring unusual niches such as those located along land-ocean boundary where freshwater mixes with saltwater. One such ecosystem is the Sundarbans mangrove, located at the apex of Bay of Bengal. The present study aims to identify novel actinobacterial species from Sundarbans which has the ability to produce unique secondary metabolites. Mangrove sediments were collected, overall bacterial diversity and secondary metabolites producing bacterial diversity were elucidated by 16S rRNA and polyketide synthase (PKS) clone library approaches respectively. Fifteen bacterial strains were isolated from the sediment using cultured approach, among which, an isolate I2 was identified based on polyphasic taxonomy. The I2 represents a new species, Myceligenerans indicum sp. nov. This new species also possess PKS genes which indicate ability to produce secondary metabolite(s). Promising antibacterial activity of this new species was found against Escherchia coli XL10, Bacillus subtilis and Vibrio chemaguriensis Iso1 especially for fraction prepared using acetone and dichloromethane (1 : 1). Spectroscopic approaches have revealed the presence of functional groups such as amide, allene, isothiocyanate and ketenimine groups.

Epoch-making milestones in antibiotic exploratory researches in Japan.

Professor Satoshi Ōmura was awarded the 2015 Nobel Prize in Physiology or Medicine. He is the third to win the award for research on antibiotic, following Fleming' (UK, 1945, discovery of penicillin) and Waksman (USA, 1952, discovery of streptomycin), and the second person after Waksman to receive the award for research on actinomycetes. By focusing his research on macrolides stemming from leucomycin research rather than β-lactams like penicillin or aminoglycosides like streptomycin, Prof. Ōmura realized many scientific achievements. These efforts finally led to the discovery of avermectin and its semi-synthetic derivative, ivermectin, considered a monumental contribution to the human race. In this manuscript, I will outline the chronicles of the epoch-making antibiotic exploratory researches preceding Prof. Ōmura.

New Dimensions of Research on Actinomycetes: Quest for Next Generation Antibiotics.

Starting with the discovery of streptomycin, the promise of natural products research on actinomycetes has been captivating researchers and offered an array of life-saving antibiotics. However, most of the actinomycetes have received a little attention of researchers beyond isolation and activity screening. Noticeable gaps in genomic information and associated biosynthetic potential of actinomycetes are mainly the reasons for this situation, which has led to a decline in the discovery rate of novel antibiotics. Recent insights gained from genome mining have revealed a massive existence of previously unrecognized biosynthetic potential in actinomycetes. Successive developments in next-generation sequencing, genome editing, analytical separation and high-resolution spectroscopic methods have reinvigorated interest on such actinomycetes and opened new avenues for the discovery of natural and natural-inspired antibiotics. This article describes the new dimensions that have driven the ongoing resurgence of research on actinomycetes with historical background since the commencement in 1940, for the attention of worldwide researchers. Coupled with increasing advancement in molecular and analytical tools and techniques, the discovery of next-generation antibiotics could be possible by revisiting the untapped potential of actinomycetes from different natural sources.

The Early Challenges of Antibiotic Discovery

Professor Kim Lewis' excellent review of the status of antibiotic research (“Challenges of Antibiotic Discovery,” Microbe, September 2015, p. 363–369) unfortunately includes a common microbiological misconception that should be addressed. He comments that Selman Waksman “introduced a simple screen which essentially replicates the accidental discovery of Fleming—a Streptomyces spot-inoculated on a plate with a lawn of the test pathogen, and a zone of growth inhibition indicates the presence of an antibiotic.” However, the variety of complex twists and turns of screening for antibiotics are illustrated by the theses of the following students of Waksman's and not readily apparent from the published papers: H. Boyd Woodruff (actinomycin)(H. B. Woodruff, The production of antibiotic substances by soil microorganisms. Ph.D. Thesis, Rutgers, the State University of New Jersey, New Brunswick, N.J., 1942), Elizabeth Horning (clavacin and fumigacin)(E. S. Horning, Distribution and properties of antagonistic fungi and actinomycetes in nature. Ph.D. Thesis, Rutgers, the State University of New Jersey, New Brunswick, N.J., 1942), Doris Jones (antiviral screen)(D. Jones, The effect of micro-organisms and antibiotic substances upon viruses. M.S. Thesis, Rutgers, the State University of New Jersey, New Brunswick, N.J., 1945), Elizabeth Bugie (antibiotic production)(E. J. Bugie, Production of antibiotic substances by Aspergillus flavus and Chaetomium cochliodes, M.S. Thesis, Rutgers, the State University of New Jersey, New Brunswick, N.J., 1944), and Albert Schatz (streptomycin)(A. Schatz, Streptomycin, an antibiotic agent produced by Actinomyces griseus. Ph.D. Thesis, Rutgers, the State University of New Jersey, New Brunswick, N.J., 1945). In 1952 the Nobel Committee awarded the Nobel Prize in Physiology or Medicine to Selman Waksman for his “ingenious systematic and successful studies of soil microbes that led to the discovery of streptomycin.” Likewise, this year the Nobel Prize in Physiology or Medicine was in part awarded to Satoshi mura for the discovery of Avermectin, and the Nobel Assembly cited Dr. mura's “extraordinary skills in developing unique methods” for the isolation of Streptomyces species. Screening methodology merits focus.

Walsh McDermott and Changing Conceptions of Tuberculosis Antibiotic Therapy

Although health care reform efforts are laudably directed at promoting quality and efficiency, added bureaucracy may have the unintended consequence of constraining physicians’ creativity. This has the potential to undermine clinicians’ freedom to reframe their thinking in response to unfolding biological knowledge, a defining feature of academic medicine. In this Perspective, the authors illustrate the confluence of creativity, context, and discovery through a historical example: the evolution of tuberculosis (TB) multidrug chemotherapy as espoused by Walsh McDermott and his colleagues during the 1940s and 1950s.Before the discovery of streptomycin in 1943, clinician–researchers aimed to identify a “magic bullet” that would rapidly eradicate tubercle bacilli from the body. In the years following the discovery of streptomycin, it became clear that the biology of TB did not conform to researchers’ expectations. The recognition that treatment would neither be simple nor quick prompted further attempts to devise an optimal streptomycin regimen, which would enable the host’s immune system to suppress infection and prevent the emergence of streptomycin-resistant strains. By the late 1950s, investigators clarified the limits of streptomycin’s effectiveness, which led to combined chemotherapy. In so doing, they gained a better understanding of drug–bacilli–host interactions and shifted attention from the host to the drug-resistant microbe.The authors argue that this tale of discovery offers a latent lesson for academic medicine: As the health care system undergoes systemic restructuring, it is essential to preserve the freedom to reframe thinking and creatively solve translational problems in research and practice.

Tuberculosis: are we making it incurable?

Tuberculosis (TB) is most probably the disease that has caused more damage to the human species throughout its history in terms of number of patients and, above all, death toll. There have been thousands of years spent fighting against Mycobacterium tuberculosis in which the human species could only rely on the efficiency of the immune system [1]. We must recall its importance as, in the pre-antibiotic era, the immune system alone could ensure important achievements such as: 1) only 50% of the people exposed to M. tuberculosis contract the infection [2]); 2) only 10% of those infected progress to active disease; and 3) up to 30% of patients with advanced TB disease heal spontaneously (fig. 1]) [3, 4]. In spite of this, the fate of TB patients in the pre-chemotherapy period was very bleak, with a mortality of >50% within 5 years after the onset of disease [3, 4]. For centuries, several empirical treatments were attempted to trying to change this fateful prognosis. Additionally, sanatoriums were built throughout the world for many decades (fig. 2]). However, all these interventions were not really effective, and none of them contributed significantly to improve the doom of TB patients [4]. Then, fortunately, their fate changed dramatically with the advent of the antibiotic era. The two decades from the discovery of streptomycin in 1943 to that of rifampicin in 1963 changed a devastating disease into a relatively easy to cure one. Not only were up to 11 different drugs with activity against M. tuberculosis discovered (streptomycin, p-aminosalicylate (PAS), thiacetazone, isoniazid (H), pyrazinamide, cycloserine, kanamycin, ethionamide, ethambutol, capreomycin and rifampicin (R)), but, based on multiple randomised clinical trials, the basic fundamentals of TB treatment were also established [4, 5 …

English

Pulmonary tuberculosis is probably as old as mankind itself, still it remains the major health problem globally and specially in developing nations. It is estimated that about 40% of the Indian population is infected with Tubercle Bacillus bacteria, the vast majority of whom have latent rather than active TB.As pulmonary tuberculosis is infectious in nature, early initiation of treatment to render it noninfectious is necessary. Several laboratory investigation techniques have been devised for early and accurate detection of TB, but either they are time consuming or very expensive. Radiodiagnosis is playing an important role in the management of tuberculosis since the discovery of X-rays in 1895. With advent of newer imaging modalities such as USG, CT and MRI and their widespread availability the contribution of radiodiagnosis in management of tuberculosis has been significantly increased. Chest radiographs play a major role in the screening, diagnosis, and follow-up of the patients with TB. However, the radiographs may be normal or show only mild or nonspecific findings in patients with active disease. CT is more sensitive than chest radiography in the detection and characterization of both subtle localized or disseminated parenchymal disease and mediastinal lymphadenopathy. Familiarity with the patterns of imaging characteristics of pulmonary tuberculosis is needed for its early detection and further management. INTRODUCTION: The Pulmonary tuberculosis is probably as old as mankind itself. But it took several centuries to discover Mycobacterium tuberculosis as a causative agent by Robert Koch in 1882. The discovery of streptomycin in 1944, para-amino salicylic acid in 1946 and isoniazid in1952 led to the first effective cure for TB. And the descriptions of airborne transmission of infection and of reactivation of dormant infection in the 1960s by Riley and Stead and Colleagues respectively, furthered our understanding of the spread and pathogenesis of this disease.1 But TB still remains the major health problem globally and specially in developing nations. It is estimated that about 40% of the Indian population is infected with TB bacteria, the vast majority of whom have latent rather than active TB. India is the highest TB burden country with World Health Organization (WHO) statistics for 2011 giving an estimated incidence figure of 2.2 million cases of TB for India out of a global incidence of 8.7 million cases. The estimated TB prevalence figure for 2011 is given as 3.1 million. 2

Biodiscovery from rare actinomycetes: an eco-taxonomical perspective

Microbial natural products, in particular, the ones produced by the members of the order Actinomycetales, will continue to represent an important route to the discovery of novel classes of bioactive compounds. As a result, the search for and discovery of lesser-known and/or novel actinomycetes is of significant interest to the industry due to a growing need for the development of new and potent therapeutic agents, mainly against drug resistant bacteria. Current advancements in genomics and metagenomics are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes. New discoveries, however, will only stem from a sound understanding and interpretation of knowledge derived from conventional studies conducted since the discovery of streptomycin, on the ecology, taxonomy, physiology and metabolism of actinomycetes, and from a combination of this knowledge with currently available and continuously advancing molecular tools. Such a powerful information platform will then inevitably reveal the whereabouts, taxonomical and chemical identities of previously undetected bioactive actinomycetes including novel species of streptomycetes as potential producers of novel drug candidates.

Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis.

Background:Pulmonary tuberculosis (PTB) is an age old disease described in Vedic Medicine as ‘Yakshma’. Later on, in Ayurveda it earned a prefix and found way into mythology as ‘Rajayakshma’. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947.Objectives:To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs.Materials and Methods:In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera) and a multi-herbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profile, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment.Results:The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and significantly increased bioavailability of isoniazid and pyrazinamide were recorded.Conclusion:This innovative clinical study coupled with empowered research may turn out to be promising in finding a solution for the treatment of PTB.

A high G418-resistant neoR transgenic mouse and mouse embryonic fibroblast (MEF) feeder layers for cytotoxicity and gene targeting in vivo and in vitro

Aminoglycoside antibiotics have been in use since 1944 with the discovery of streptomycin. The aim of this study was to derive a new, highly resistant multicopy neoR transgenic mouse strain, named TgN3Ems, by random insertion of the plasmid, pPGKneobpA, and compare the level of drug resistance of wild-type and transgenic mice in vivo and corresponding primary mouse embryonic fibroblasts (MEFs) in vitro to a model neomycin analog, G418. The expression neoR in transgenic animals caused a 5-fold increase in the approximate lethal dose of G418, compared to wild type. No adverse pathological changes were found for the transgenic mice treated with G418, as they all died within minutes after injection. In contrast, the G418 treatment of wild-type mice resulted in a marked liver and kidney toxicity detected microscopically and via increases of serum biomarkers for liver and kidney damage. In addition, there was a mild bone marrow and lymphoid depletion. In in vitro studies, the transgenic MEFs survived 20-fold higher G418 levels, compared to the wild-type MEF cells. Therefore, TgN3Ems transgenic mice could be used as a source of G418-resistant feeder cells for gene targeting. Since the expression of drug-resistance genes in transgenic animals confers resistance to toxicity, the TgN3Ems mice might serve as a tool applicable in drug design.

Chemotherapy for tuberculosis; yesterday, today, and tomorrow--basic and clinical studies

The discovery of streptomycin in 1944 had given rise to great flowering of chemotherapy for tuberculosis. The times which triple treatment of SM.PAS.INH after the temporal time of SM.PAS had been standard regimens on initial treatment had continued for more than twenty years. The shortening of duration for chemotherapy had become possible by the introduction of RFP, and the duration had reduced to one fourth compared with that of the regimens till then by the addition of PZA for two months at the beginning of treatment on the initial treatment cases. In this paper, historical aspects of early and present-day chemotherapy of tuberculosis and the reports of main studies have been summarized, and pharmacokinetics of INH, action of antituberculous drugs in short-course chemotherapy, MDR-TB and biological response modifiers for treatment of tuberculosis, etc. has been reviewed. It is urgently awaited that more new drugs without cross resistance to previous drugs will be developed for the more shortening of the duration and the improvement of the treatment for MDR-TB.

The Future of Melanoma Therapy is the Combination Approach

From a historical point of view, treatment of neoplastic disease can be considered one of the clearest example of the importance of combination strategies. In fact, a combination of surgery, radiotherapy and chemotherapy, is the best approach for the treatment of certain cancers such as breast cancer, ovarian and head and neck cancer. However, not only cancer may benefit from combination therapy. Tubercolosis is a classical example of this concept [1]. After the discovery of Streptomycin in 1944, a new era for the treatment of tubercolosis dawned with further detection of Isoniazid, the first oral mycobactericidal drug in 1952 and Rifamycins in 1957. Sanatoria closed and truly effective public health measures became possible. Treatment was also increasingly expanded to include those with latent tuberculous infections. Furthermore, the introduction of Rifampicin in 1970 revolutionized the treatment of tuberculosis as, with its use in the context of combination strategies, the therapy of this infectious disease changed. In fact, use of antituberculosis drugs in monotherapy, including those of first choice, is strictly proscribed, since it might be easy to select spontaneously resistant germs. For this reason, drug regimens include associations of 3 or more drugs, variously alternated in relation to the clinical and developmental stages of tuberculosis (Table 1). Another aim of using drugs in combination was to eliminate bacterial subpopulations in various stages of metabolic activity and at different locations.

Medicinal Chemistry of Aminocyclitols

Aminocyclitols comprise an important group of compounds with remarkable biological activities. From a structural standpoint, aminocyclitols are amino polyhydroxy cycloalkanes that can be found in nature in several families of natural products. Among them, the aminoglycoside antibiotics, since the discovery of streptomycin, have become particularly relevant at the forefront of the antibacterial treatment. Another group of aminocyclitols, generally referred to as aminocarbasugars, have been found as key structural components of some families of alkaloids that have evolved as suitable leads for the development of potent glycosidase inhibitors with a vast array of applications in medicinal chemistry, both as therapeutically useful agents as well as valuable pharmacological tools. On the other hand, the aminocyclitol moiety has been used by medicinal chemists as a versatile scaffold in drug design. Thus, in the antiviral arena, it is found as the key component of several families of carbocyclic nucleoside analogues, designed as metabolically stable surrogates of the natural nucleosides. Finally, in a still relatively unexplored area, some aminocyclitol derivatives are being used as key components of artificial receptors for which promising applications in drug research can be envisaged. In all cases, the development of the modern regio- and stereoselective synthetic methodologies enables a large variety of stereochemically defined aminocyclitol analogues in order to study in depth the influence of this moiety on the structure-activity relationships from a given lead.

Retrospecto do controle da tuberculose no Brasil

The aim of the study was to look back on the course of action involving measures of tuberculosis control in Brazil since the end of the 19th century, covering the history of social struggles and pointing out institutions and people that have dedicated themselves to looking for solutions to these issues. The Brazilian response to tuberculosis started in society with the Ligas Contra a Tuberculose (Leagues Against Tuberculosis), promoting scientific advances, such as the BCG vaccination, which begun in 1927. From the public power, the Inspetoria de Profilaxia da TB (TB Prophylaxis Inspection Service - 1920), the Serviço Nacional de Tuberculose (National Service of Tuberculosis - 1940), and the Campanha Nacional Contra a Tuberculose (National Campaign Against Tuberculosis - 1946), coordinated national policies such as chemotherapy, beginning with the discovery of streptomycin in 1944. The emergence of bacterial resistance led to the development of several therapeutic schemes. The Scheme 1 (rifampycin, hydrazide and pyrazinamid), which was the main one in 1979 and is still used nowadays, had a great epidemiological effect. The WHO declared TB a public health emergency in 1993. In response, Brazil developed some strategies; the first one was the Plano Emergencial para Controle da Tuberculose (Emergency Plan for Tuberculosis Control - 1994), prioritizing 230 municipalities. The current prospects are an effective municipalization of actions and their greater integration with the Programas de Agentes Comunitários e Saúde da Família (Humanitarian Agents and Family Health Programs).