Cranial osteology and paleoneurology of Tarjadia ruthae: An erpetosuchid pseudosuchian from the Triassic Chañares Formation (late Ladinian-?early Carnian) of Argentina.

Tarjadia ruthae is a quadrupedal terrestrial pseudosuchian from the Middle-early Upper Triassic of the Chañares Formation, La Rioja Province, Argentina. Originally, this species was identified as an indeterminate archosaur and later as a doswelliid archosauriform based on very fragmentary specimens characterized by the ornamentation of the skull roof and osteoderms. Additional specimens (including skulls and postcrania) recovered in the last decade show that Tarjadia is an erpetosuchid, an enigmatic pseudosuchian group composed of six species registered in Middle-Upper Triassic continental units of Tanzania, Germany, Scotland, North America, Brazil, and Argentina. Tarjadia ruthae from Argentina and Parringtonia gracilis from Tanzania are the best preserved and more abundant species. Although the monophyly of Erpetosuchidae is well supported, alternative high-level positions within Archosauria have been suggested, such as sister taxon to Crocodylomorpha, Aetosauria, or Ornithosuchidae. In order to improve the knowledge about the erpetosuchids, we performed a detailed description and paleoneurological reconstruction of the skull of Tarjadia ruthae, based on two articulated partial skulls (CRILAR-Pv 478 and CRILAR-Pv 495) and other fragmentary specimens. We analyzed the stratigraphic and geographic occurrence of historical and new specimens of Tarjadia and provided a new emended diagnosis (the same for the genus as for the species, due to monotypy) along with a comparative description of the cranial endocast. The skull of Tarjadia is robust, with a thick and strongly ornamented skull roof, triangular in dorsal view, with concave lateral margins at mid-length that form an abrupt widened posterior region. The external nares are the smallest openings of the skull. The antorbital fossa is deeply excavated and has a small heart-shaped fenestra with both lobes pointing anteriorly. The supratemporal fenestrae are as large and rounded as the orbits, and the infratemporal fenestrae are L-shaped with an extensive excavation along the jugal, quadratojugal and quadrate. The hemimandibles are low, slightly concave on the dentigerous region and strongly convex on the posterior region, conferring them a S-shaped profile in dorsal view. The external mandibular fenestra is small and elliptic, being twice longer than high. The maxillary dentition is restricted to the anterior to mid region of the rostrum. Since the braincase of both specimens is partially damaged, the dorsal surface of the brain could not be entirely reconstructed. As a result, the endocast is anteroposteriorly elongated and seemingly flat, and the cephalic flexure seems to be lower than expected for a suchian. The labyrinth is twice wider than high, the semicircular canals are remarkably straight, and the anterior canal is longer than the posterior one.

Flight radius and climatic conditions affect the external activity of stingless bee Melipona rufiventris (Lepeletier, 1836).

The objective of this study was to verify the flight radius and the influence of the climatic season and period of the day on the external activity of Melipona rufiventris bees. The forager bees were released at different distances to evaluate the flight radius. The following were considered for external activities in the four different seasons of the year (Winter, Autumn, Spring, Summer): the entry with no apparent load was considered as nectar/water, entry with defined and opaque mass in the corbicula was considered as pollen, the entry with undefined and shiny mass in the corbicula was considered as resin/clay or bee exit no load and removal of debris, mass trapped by the jaws. Assessments were performed between 6 am and 6 pm each month. M. rufiventris can reach distances of 2 500 meters, however the return decreases as the distance increases. The species performs all activities in and out of the colony during all seasons of the year and periods between 6 am and 6 pm but reduce nectar/water collection and exit from the box without apparent load and with debris between 6:00 am and 10 am in winter. It is concluded that distances greater than 1 500 meters hinder the external activity of bees which is influenced by air temperature, air humidity, time of day, season of the year and food availability.

Pustulosis subcórnea: a propósito de un caso / Subcorneal pustulosis: a case report

Resumen La dermatosis pustulosa subcórnea (DPS), oenfermedad de Sneddon-Wilkinson, es una dermatosis poco frecuente, benigna, de curso crónico y recidivante. En esta oportunidad presentaremos el caso de una paciente femenina de 58 años condiagnóstico de dermatosis pustulosa subcórnea, que fue tratada con dapsona 100mg por día, con resolución de lesiones. Realizamos unarevisión bibliográfica de esta patología describiendo sus características clínicas e histológicas, sus múltiples diagnósticos diferenciales y las posibles terapéuticas.

Abstract Subcorneal pustular dermatosis, or Sneddon-Wilkinson disease, is a rare, benign, chronic and recurrent dermatosis. We reportthe case of a 58-year-old female patient with subcorneal pustular dermatosis, who was treated with dapsone 100mg per day, with goodtherapeutic response. We carried out a bibliographic review of this pathology describing its clinical and histological characteristics, its multiple differential diagnoses and possible therapeutic options.

Case report of Curtobacterium isolated from a catheter tip sample misidentified as Cronobacter.

The Curtobacterium genus is a member of the family Microbacteriaceae, and Curtobacterium species are recognized as plant pathogens. The aim of this study was to investigate a dubious result of species identification for an infection located on a catheter tip of a patient with Covid-19. A strain isolated from a catheter tip sample, identified by VITEK® 2 as Cronobacter spp., was submitted to polyphasic analysis: Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) using VITEK® MS, real-time polymerase chain reaction targeting dnaG gene, and 16S rRNA full gene Sanger sequencing analysis for confirmation. The strain presented negative result using qPCR and could not identified by MALDI-TOF MS. 16S rRNA full gene Sanger sequencing analysis identified the strain as Curtobacterium spp. The Gram-variable characteristic (Gram-negative instead of Gram-positive) of the isolated strain was the responsible for the misidentification by VITEK® 2 and VITEK® MS did not identify the strain. 16S rRNA full gene sequencing analysis identified the strain as Curtobacterium genus, but other complementary techniques are necessary to identify at species level.

Assessment of the neutron radiation field with activation foils and intermittent irradiations around a PETtrace biomedical cyclotron.

This work aimed at assessing the neutron radiation field with activation foils around of the PETtrace biomedical cyclotron. Activation foils of gold, gold covered with cadmium, indium and nickel was used to evaluate the thermal, epithermal and fast neutron contributions, respectively. The irradiations of the activation foils were performed using the intermittent irradiation method to conciliate the measurements with the routine 18F production. The evaluated points showed the contributions of the thermal, epithermal and fast neutrons due to interaction with the vault room, cyclotron accelerator and main cyclotron components.

The impact of different classes of lupus nephritis on maternal and fetal outcomes: a cohort study of 147 pregnancies.

OBJECTIVE: To analyze the impact of different classes of lupus nephritis as risk variables for maternal and fetal adverse outcomes in a cohort of pregnant lupus patients. METHODS: This is a cohort study with retrospective and prospective data collection, conducted at the University Hospital of State University of Rio de Janeiro, Brazil, from 2011 to 2016. A total of 147 pregnancies of 137 systemic lupus erythematosus patients of whom 66 had lupus nephritis were included. Demographic and clinical features, as well as maternal and fetal outcomes were observed for each nephritis histological class among systemic lupus erythematosus patients and compared with those without nephritis. Categorical variables were expressed as absolute and relative frequencies and numerical variables as means and standard deviation. The chi-square test with Fisher's correction and Student's t-test were used for statistical analysis. A pvalue < 0.05 was considered statistically significant. RESULTS: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV, n = 54) presented more frequent disease flares ( p = 0.02), continuous active disease during pregnancy and puerperium ( p = 0.006), hospitalization due to systemic lupus erythematosus ( p < 0.001), hospitalization not directly associated to systemic lupus erythematosus ( p = 0.04), higher frequency of cesarean delivery ( p = 0.03) and preeclampsia ( p = 0.01) than patients without nephritis. Permanent damage measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was more frequent in classes III/IV than among the other patients. The frequency of adverse fetal outcomes such as prematurity and admission to neonatal intensive care unit were not different among systemic lupus erythematosus patients with or without nephritis. However, perinatal deaths were more frequent in patients with all classes of nephritis ( p = 0.003). CONCLUSION: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV) have a higher frequency of adverse maternal outcomes. This is probably due to the major impact of proliferative forms of nephritis on women's global heath, which is corroborated by the higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index findings, although we cannot exclude the negative influence of disease activity for the maternal adverse events. The findings indicate a need for further lupus nephritis classification beyond the nonspecific term nephritis in the context of lupus pregnancy as the impact on maternal and fetal outcomes varies according to histological class.

EXPERIMENTAL EVALUATION OF NEUTRON SHIELDING MATERIALS.

A new proposed design of neutron shielding material-based on the commercial material Borotron UH050 with an addition of Al(OH)3-is evaluated in order to determine if its neutron and gamma shielding properties match those of a reference material, NS4FR. Neutron and gamma dosimetry measurements are performed, as well as neutron spectrometry measurements and Monte Carlo simulations. Negligible differences are found between the materials for neutron shielding, while significant differences are found for gamma shielding. The effect of Al(OH)3 addition to Borotron UH050 is to reduce neutron shielding properties while increasing gamma shielding properties. The resulting material is as efficient as NS4FR for neutron shielding but less efficient for gamma shielding-thicknesses 20% higher are required to match gamma shielding properties of NS4FR. Monte Carlo models of the materials are validated based on the performed measurements of neutron spectra and neutron and gamma ambient dose equivalent.

Ramos do arco aórtico e da aorta torácica em bicho-preguiça (Bradypus variegatus) / Branches of the aortic arch and thoracic aorta of the sloth (Bradypus variegatus)

As preguiças são mamíferos arborícolas, bem específicos quanto aos hábitos e à morfofisiologia. Essa condição faz delas ainda mais vulneráveis aos impactos ambientais. Com o objetivo de fornecer informações que auxiliem na clínica médico-cirúrgica desses Xenarthras, realizou-se um estudo do arco aórtico e da artéria aorta torácica, a fim de se identificarem seus principais ramos. Foram utilizados 10 animais da espécie Bradypus variegatus, sendo uma fêmea e três machos submetidos a dissecação, por meio da qual foram obtidas medidas de diâmetro e comprimento dos vasos, enquanto três fêmeas e três machos destinaram-se à técnica de radiografia digital com contraste. Constatou-se uma sintopia uniforme do arco, bem como da porção descendente da artéria aorta no tórax. No entanto, a topografia difere consideravelmente. Com base nos ramos, percebeu-se, independentemente do sexo, uma maior variação naqueles originados do arco e dos que emergem da artéria aorta torácica e irrigam estruturas medianas e do antímero direito do tórax. Foram obtidos valores maiores para o diâmetro das artérias na fêmea do que nos machos e, para o comprimento da artéria aorta torácica, foram encontrados valores correspondentes em ambos. Toda essa variação dos bradipodídeos apresenta diferenças em relação a outros mamíferos.(AU)

Sloths are arboreal mammals, very specific, regarding their habits and morphology. This condition makes them even more vulnerable to environmental impacts. In order to provide information to assist in the medical and surgical assistance to these Xenarthras, a study of the aortic arch and thoracic portion of the descending aorta was carried out with the purpose of identify its main branches. Ten animals of the Bradypus variegatus species were used. One female and three males were submitted to dissection, where measurements of vessel diameter and length were obtained, while three females and three males were submitted to the digital contrast x-ray technique. There was a uniform syntopy of the arch, as well as of the descending portion of the aorta in the thorax. However, the topography differs considerably. Based on the branches, regardless of gender, a greater variation was observed in those originating from the arch, and those that emerge from the thoracic aorta and irrigate medial structures and the right antimere of the thorax. Greater values were obtained for the diameter of the arteries in the female than in the males and corresponding values for the length of the thoracic aorta in both. All this variation is possibly related to the adaptive processes of Bradipodidae over time.(AU)

Índice de normalidade da distância atlantoaxial dorsal em cães / Normal index of dorsal atlantoaxial distance in dogs

Foram utilizados 30 cães neurologicamente saudáveis e realizadas radiografias da coluna cervical, sendo mensurada a menor distância atlantoaxial dorsal e outros parâmetros anatômicos vertebrais. Esses dados foram avaliados por meio do coeficiente de correlação de Pearson. Após detecção do melhor parâmetro de correlação, utilizou-se a fórmula de coeficiente de correlação dimensional (CCD). Na segunda etapa desta pesquisa, foram utilizadas imagens radiográficas de 33 cães com subluxação atlantoaxial (SAA) e aplicou-se a fórmula CCD. Todas as imagens atlantoaxiais normais e subluxadas foram distribuídas aleatoriamente e submetidas à análise subjetiva. Observou-se que o parâmetro anatômico de maior correlação foi o comprimento do processo espinhoso do áxis, obtendo-se valor de índice médio de 0,056 e desvio-padrão de 0,019. O valor de índice médio obtido em cães com SAA foi de 0,287, e o desvio-padrão de 0,123. A análise subjetiva revelou acerto de 88,89% a 95,24%, enquanto a avaliação por meio da fórmula CCD demonstrou ser 100% eficiente no diagnóstico da SAA. Sugeriu-se a utilização da fórmula CCD para obtenção do índice de normalidade da distância atlantoaxial com valor de normalidade médio de 0,056 e limite máximo de 0,098, sendo esse índice eficaz no diagnóstico da subluxação entre o atlas e o áxis.(AU)

Thirty healthy dogs had their cervical spines radiographed, and the dorsal atlantoaxial distance and others vertebral anatomical parameters were measured. These data were assessed using the Pearson correlation coefficient. After detection of the best correlation parameter, we used the dimensional correlation coefficient of formula (CCD). In the second stage of the study, radiographs of the 33 dogs with atlantoaxial subluxation (SAA) were used. In each radiographic image, the CCD formula was applied. All normal and subluxation radiographic images were randomized, and submitted to subjective analysis. It was observed that the anatomical parameter with the highest correlation is the length of the spinous process of the axis, obtaining a mean value of 0.056 index and 0.019 standard deviation. Index mean value obtained in dogs with the disease of 0.287 and standard deviation of 0.123. The subjective analysis revealed 88.89% to 95.24% agreement, while the result obtained by the CCD formula was shown to be 100% effective in the diagnosis of SAA. We suggest the use of the CCD formula to obtain the index of normality of the atlantoaxial distance with a mean value of 0.056 and maximum of 0.098, and it is concluded that the index is highly effective in the diagnosis of subluxation between the atlas and the axis.(AU)

Use of a GnRH synthetic analog (buserelin) for estrous induction in female dogs / Utilização de análogo sintético de GnRH (buserelina) na indução do estro em cadelas

The aim of this study was to evaluate the effectiveness of a GnRH synthetic analog, as an estrous inducer in female dogs when administered during the anestrous phase, and to evaluate the pregnancy rate achieved through natural copulation. For this purpose, ten female dogs of different breeds were used. The subjects received buserelin by intramuscular injections at a dose of 2,1mcg when female dogs weighed up to 10kg (Group 1) and of 4,2mcg when the dogs weighed above 10kg (Group 2). Of the ten subjects, only three presented estrus after a single injection of buserelin: two dogs from Group 1 and one dog from Group 2 on average 7±1.29 days. The remaining seven dogs were given a second dose of buserelin, equal to the first administration. Of these, three belonged to Group 1 and four to Group 2. Four of these dogs exhibited clinical signs of estrus within, on average 9±7.3 days from the second injection. The seven female dogs that did enter estrus were fertilized successfully through natural copulation. The administration of buserelin was effective in inducing estrus in female dogs during the anestrous phase, with a maximum of two administrations.(AU)

Objetivou-se avaliar a eficácia de um análogo sintético ao GnRH como indutor de estro em cadelas em anestro e a taxa de prenhez por meio de cópula natural. Para isso, foram utilizadas 10 fêmeas caninas de diferentes raças. Cadelas de até 10kg de peso (grupo 1) foram submetidas à administração de buserelina por via intramuscular, na dose de 2,1mcg, e cadelas acima de 10kg (grupo 2) foram submetidas à mesma medicação, porém na dose de 4,2mcg. Das fêmeas em anestro, apenas três apresentaram estro com apenas uma aplicação, sendo duas do grupo 1 e uma do grupo 2, em 7±1,29 dias, em média. Em sete cadelas foi administrada mais uma dose de buserelina; destas, quatro eram pertencentes ao grupo 2 e três eram do grupo 1. Os sinais de estro ocorreram, em média, após 9±2,73 dias da segunda aplicação. As sete cadelas que manifestaram estro foram fertilizadas por meio de cópula natural. A administração de buserelina é eficiente para a indução de estro, em cadelas em anestro, em, no máximo, duas aplicações.(AU)

Gestational outcomes in patients with neuropsychiatric systemic lupus erythematosus.

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l-1 vs. 37.49 (27.41-52.00) nmol*min*l-1; p=0.098, respectively], whereas the peak cortisol Cmax was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l-1 vs. 227.73 (200.10-280.52) nmol*min*l-1; p≤ 0.001, respectively], and peak cortisone Cmax was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement.

Neutron spectra due (13)N production in a PET cyclotron.

Monte Carlo and experimental methods have been used to characterize the neutron radiation field around PET (Positron Emission Tomography) cyclotrons. In this work, the Monte Carlo code MCNPX was used to estimate the neutron spectra, the neutron fluence rates and the ambient dose equivalent (H*(10)) in seven locations around a PET cyclotron during (13)N production. In order to validate these calculations, H*(10) was measured in three sites and were compared with the calculated doses. All the spectra have two peaks, one above 0.1MeV due to the evaporation neutrons and another in the thermal region due to the room-return effects. Despite the relatively large difference between the measured and calculated H*(10) for one point, the agreement was considered good, compared with that obtained for (18)F production in a previous work.

High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa.

BACKGROUND: Cisplatin is administered as the first-line treatment of soft-tissue cancers. It has a reported cure rate of up to 85%, but is associated with a high incidence of ototoxicity, characterised by irreversible bilateral hearing loss and affecting 23 - 50% of adults who receive the drug. OBJECTIVES: To determine the incidence of cisplatin-induced ototoxicity at Groote Schuur Hospital (GSH), Cape Town, South Africa. METHODS: retrospective cross-sectional study of cisplatin-receiving cancer patients attending GSH between January 2006 and August 2011. RESULTS: A total of 377 patients were recorded as receiving cisplatin therapy during the study period. A 300% increase in new cisplatin-receiving patients receiving audiological monitoring was observed between 2006 and 2010. However, only patients with all clinical data as well as baseline and follow-up audiometric analyses were investigated. One hundred and seven such patients were identified, 55.1% of whom developed cisplatin-induced ototoxicity while receiving high-dose (> or = 60 mg/m2) cisplatin treatment. Higher cumulative cisplatin dosages were associated with development of significant hearing loss (p = 0.027). The odds of developing cisplatin-induced hearing loss were elevated for patients with head and neck tumours and lymphoma (p = 0.0465 and p = 0.0563, respectively) and were significantly lower for those with reproductive cancers (p = 0.0371). CONCLUSION: Comprehensive audiological monitoring should be available for every patient during cisplatin treatment to minimise the development of disabling hearing loss.

Use of the MCNPX to calculate the neutron spectra around the GE-PETtrace 8 cyclotron of the CDTN/CNEN, Brazil.

The Monte Carlo code MCNPX was used to calculate the neutron spectra in 4 points around the targets of the CDTN/CNEN cyclotron, Belo Horizonte, Brazil, during the production of the (18)FDG. Simulated data were compared with experimental data obtained with a Bonner multisphere spectrometry system (BSS) using TLD-600 and TLD-700 and the unfolding codes BUNKIUT, BUMS and NSDUAZ. In general, simulated spectra disagreed with those obtained by experimental means by a factor as high as 14. Measurements performed with a doserate meter in other 3 more shielded points, showed also an overestimation of the ambient dose equivalent rate by a factor as high as 20 in comparison with simulated results. Results are not conclusive and a more refined study is necessary. However, neutron emission rate of the source-term of radiation must be investigated and an special caution must be taken in the experimental measurements, by discriminating of the target selected for the irradiations and utilizing a matrix response suitable for the passive detectors (e.g. TLD) utilized in the experiments, instead of a matrix response (e.g. UTA4) developed for scintillation detectors.

Use of a TLD-based multisphere spectrometry system to measure the neutron spectra around a not-self-shielded PET cyclotron: Preliminary results.

In the present work, we utilized the BSS system with TLD-600 and TLD-700 to measure the neutron spectra around the GE-PETtrace 8 cyclotron of the Development Centre of Nuclear Technology (CDTN/CNEN) in Belo Horizonte, Brazil. The cyclotron is capable of accelerating protons up to 16.5 MeV, to production of fluorine-18. Four points inside the bunker of the cyclotron were studied. Two points in front of the primary radiation beam and other two opposed to the primary radiation beam. The measurements were unfolded with the BUMS and the NSDUAZ computer codes. The dosimetric quantities obtained were in agreement with the other published data and were coherent with the expected from theoretical estimates obtained from source term informed by the manufacturer of the cyclotron.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.