Fluorine-18-labeled estrogens, progestins and corticosteroids for receptor-based imaging of breast tumors and target areas of the brain

Estrogens can be labeled with the positron-emitting radionuclide fluorine-18 (t$\sb{1/2}$ = 110 min) by fluoride ion (n-Bu$\sb4$N$\sp{18}$F) displacement of a 16$\beta$-trifluoromethanesulfonate (triflate) derivative of the corresponding estrone 3-triflate, and purification by HPLC. That sequence has been used to synthesize the 11$\beta$-methoxy 1 and 11$\beta$-ethyl 2 analogues of the breast tumor imaging agent, 16$\alpha$-($\sp{18}$F) fluoro-17$\beta$-estradiol (FES). Tissue distribution studies of 1 and 2 in immature female rats show high selectivity for target tissue (T, uterus) vs non-target (NT, muscle and lung), with T/NT ratios being 43 and 17 at one hour after injection for 1 and 2, respectively. The parent estrogen FES has previously been shown to display an intermediate value for tissue selectivity.

Lymphadenopathy after Initiating HAART in an HIV-positive Patient with Kaposi's Sarcoma: a Case of Multicentric Castleman's Disease

We present the case of a 33-year-old lady who was diagnosed with disseminated Kaposi’s sarcoma and HIV infection. The patient improved on highly active antiretroviral therapy (HAART), however, nine days into treatment, she became febrile and dyspnoeic and developed tender cervical and axillary lymphadenopathy. Despite treatment for suspected sepsis and immune reconstitution, she died in intensive care. Lymph node biopsies revealed coexistent Castleman’s disease and Kaposi’s sarcoma. Initiation of HAART can be rarely associated with unmasking and rapid progression of Castleman’s disease, a phenomenon called immune reconstitution. Urgent investigation and treatment with agents such as steroids and cytotoxic drugs can be life-saving.

Determinação de marcadores orgânicos no perfil sedimentar do complexo estuarino de Paranaguá (PR) por CG-EM

A avaliação do aporte de matéria orgânica no ambiente aquático por atividades antrópicas pode ser realizada através da identificação e quantificação de marcadores moleculares. Diversos estudos apontam à aplicação dos marcadores moleculares com esta finalidade, no entanto, poucos avaliam a variação das concentrações desses compostos ao longo do tempo, registrada nas camadas sedimentares. O presente trabalho realiza um estudo a partir de três classes de marcadores moleculares presentes em perfis sedimentares da região do Complexo Estuarino de Paranaguá (CEP) no Paraná (PR), que nos últimos anos vêm sofrendo com o crescente desenvolvimento de atividades antrópicas. Como objetivo, tem-se identificar as principais fontes de matéria orgânica e estudar o histórico destes aportes em colunas sedimentares do CEP, relacionando as taxas de sedimentação com a deposição de origem natural e antrópica. A legislação vigente para o monitoramento ambiental, no que diz respeito à contaminação por esgoto fecal, sugere a avaliação por indicadores microbiológicos, porém, indicadores químicos como os esteróides fecais são uma alternativa bastante promissora, pois estes são persistentes, sendo menos sensíveis a variações ambientais. Outros dois marcadores moleculares de aportes antrópicos ao ambiente que foram determinados neste estudo são os alquilbenzenos lineares (LABs), presente em detergentes, que indicam aportes antrópicos oriundos de esgoto doméstico e a determinação de cafeína, tendo em vista que os esteróides fecais podem ser originários de fezes de animais de sangue quente, podendo indicar outras fontes. Para o presente trabalho foram coletados 12 testemunhos de até 1 m de profundidade em maio de 2006, totalizando 12 pontos de coleta e um montante de 121 amostras. As análises foram realizadas por cromatografia em fase gasosa com detecção por espectrometria de massas (CG-EM). Os esteróides encontrados em maior concentração foram o β- sitosterol (71,4 µg g-1), estigmasterol (8,7 µg g-1), colestanol (3,6 µg g-1) e o estigmastanol (2,8 µg g-1), todos oriundos de fonte natural, indicando que a maior contribuição para o CEP é por aporte biogênico. O coprostanol, que é um esterol fecal, foi encontrado entre as concentrações de 0,001 e 4,10 µg g-1, outros dois esteróides de origem fecal também foram detectados, coprostanona e epicoprostanol, onde as maiores concentrações foram 3,6 e 0,2 µg g-1, respectivamente, sendo encontrados em regiões próximas a centros urbanos, indicando origem antrópica. As maiores concentrações para o ∑LABs também foram encontradas em regiões próximas às cidades de Antonina e Paranaguá, sendo a maior encontrada no testemunho #3 Gererês (208 ng g-1). Para o último marcador molecular analisado, a cafeína, foi encontrada a maior concentração de 18,41 ng g-1, sendo este ponto localizado longe dos centros urbanos, porém este contaminante é bastante solúvel em água podendo ser transportado na coluna d’água e percorrer grandes distâncias. Através dos compostos analisados, pode-se perceber que a intervenção antropogênica foi mais marcante nos testemunhos coletados no eixo leste-oeste do CEP, ficando registrado nas camadas sedimentares.

Low molecular weight compounds from mushrooms as potential Bcl-2 inhibitors: docking and virtual screening studies

Mushrooms have the ability to promote apoptosis in tumor cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the ability to inhibit Bcl-2 is an ongoing research topic in drug discovery. In this study, we started by analyzing Bcl-2 experimental structures that are currently available in Protein Data Bank database. After analysis of the more relevant Bcl-2 structures, 4 were finally selected. An analysis of the best docking methodology was then performed using a cross-docking and re-docking approach while testing 2 docking softwares: AutoDock 4 and AutoDock Vina. Autodock4 provided the best docking results and was selected to perform a virtual screening study applied to a dataset of 40 Low Molecular Weight (LMW) compounds present in mushrooms, using the selected Bcl-2 structures as target. Results suggest that steroid are the more promising family, among the analyzed compounds, and may have the ability to interact with Bcl-2 and this way promoting tumor apoptosis. The steroids that presented lowest estimated binding energy (ΔG) were: Ganodermanondiol, Cerevisterol, Ganoderic Acid X and Lucidenic Lactone; with estimated ΔG values between -8,45 and -8,23 Kcal/mol. A detailed analysis of the docked conformation of these 4 top ranked LMW compounds was also performed and illustrates a plausible interaction between the 4 top raked steroids and Bcl-2, thus substantiating the accuracy of the predicted docked poses. Therefore, tumoral apoptosis promoted by mushroom might be related to Bcl-2 inhibition mediated by steroid family of compounds.

Investigating mushroom LMW compounds as potential Bcl-2 inhibitors: docking studies using AutoDock4

The B cell CLL/lymphoma-2 (Bcl-2) family is functionally classified as either anti-apoptotic or pro-apoptotic, and the regulation of its interactions dictates survival or commitment to apoptosis. Bcl-2 family is also implicated in a wide range of diseases. In some types of cancers, including lymphomas and epithelial cancers, protein overexpression of anti-apoptotic Bcl-2 family, such as the Bcl-2 protein is indicative of cancer in an advanced stage, with a poor prognosis and resistant to chemotherapy [1]. Several reports indicate that mushrooms have the ability to promote apoptosis in tumour cell lines, but the mechanism of action is not fully understood. Inhibition of the interaction between Bcl-2 (anti-apoptotic protein) and proapoptotic proteins could be an important step in the mechanism of mushroom induced apoptosis. Therefore, the discovery of compounds with the capacity to inhibit Bcl-2 is an ongoing research topic on cancer therapy. In this work, docking studies were performed using a dataset of 40 low molecular weight (LMW) compounds present in mushrooms. The docking software AutoDock 4 was used and docking studies were performed using 5 selected Bcl-2 crystal structures as targets. Compounds with the lowest predicted binding energy (predΔG) are expected to be the more potent inhibitors. Among the tested compounds, steroids presented the lowest predΔG with several exhibiting values below -9 kcal/mol. The results are corroborated by several reports that state that steroids induce apoptosis in several tumor cells. It is thus feasible that they might act by preventing Bcl-2 from forming complexes with the respective proapoptotic protein interaction partners, namely Bak, Bax, and Bim. Moreover, previous studies on our research group demonstrated that 48 h treatment of MCF-7 cells (breast carcinoma) with Suillus collinitus methanolic extract caused a decrease in Bcl-2, highlighting the antitumor potential of this mushroom species [2]. In conclusion, the process of apoptosis promoted by mushroom extracts may be related to the inhibition of Bcl-2 by the steroid derivatives herein studied. However, further studies are needed to confirm this hypothesis.

Ethanolic extracts from three commercial edibe mushrooms: determination of ergosterol contente and evaluation of bioactives properties

Mushrooms are rich in several bioactive metabolites among them are phenolic compounds, terpenoids, polysaccharides, lectins, and steroids including mycosterols, namely ergosterol [1]. Ethanolic extracts prepared by maceration of several mushroom species have been recently described as having antiinflammatory properties [2]. In the present work, ethanolic extracts of Agaricus bisporus L., Lentinus edodes (Berk.) Pegler and Pleurotus ostreatus (Jacq. ex Fr.) P.Kumm., purchased from a local supermarket in the Northeast of Portugal, were obtained by Soxhlet and chemically characterized in terms of ergosterol content by HPLC-UV. The antioxidant properties of these extracts were evaluated through DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity (RSA), reducing power (RP), p. carotene bleaching inhibition (CBI) and lipid peroxidation inhibition in TBARS (thiobarbituric acid reactive substances) assay (LPI); the antioxidant activity of ergosterol was also evaluated by the DPPH assay. The anti-inflammatory activity of the same extracts and ergosterol was evaluated in LPS (lipopolysaccharide) stimulated RAW 264.7 macrophages, through the inhibition of NO production. A. bisporus revealed the highest content in ergosterol (44.8 ± 0.4 mg/ g extract) followed by P. ostreatus (34 ± 3 mg/ g extract) and finally L. edodes (8.9 ± 0.1 mg/ g extract). A. bisporus showed the highest RSA, RP and CBI (EC50 values= 7.0 ± 0.8, 2.3 ± 0.1 and 1.4 ± 0.1 mg/mL, respectively), while L. edodes presented the highest LPI (2.5 ± 0.1 mg/mL ); ergosterol revealed higher RSA (0.46±0. 0 I mg/mL) than the extracts. Concerning the anti-inflammatory potential, the most efficient species was L. edodes (lC50 value = 164 ± 16 J.lg/mL), followed by A. bisporus (185 ± 16 J.lg/mL) and finally P. ostreatus (290 ± 10 J.lg/mL). However, ergosterol presented lower activity (338 ± 23 J.lg/mL) due to its low solubility in the culture medium. The higher antioxidant properties displayed by A. bisporus can be related with its higher ergosterol content, while in the anti-inflammatory activity this relation cannot be established also due to the low solubility of ergosterol in the cells culture medium, decreasing the ergosterol availability. More studies are being conducted regarding the ergosterol solubility. Several compounds have been implicated in the bioactivity of mushrooms and in this study we have found that ergosterol can give an important contribution.

Anti-inflammatory potential of mushroom extracts and isolated metabolites

Background: In the recent years natural resources are being in focus due to their great potential to be exploited in the discovery/development of novel bioactive compounds and, among them, mushrooms can be highlighted as alternative sources of anti-inflammatory agents. Scope and approach: The present review reports the anti-inflammatory activity of mushroom extracts and of their bioactive metabolites involved in this bioactive action. Additionally the most common assays used to evaluate mushrooms anti-inflammatory activity were also reviewed, including in vitro studies in cell lines, as well as in animal models in vivo. Key findings and conclusions: The anti-inflammatory compounds identified in mushrooms include polysaccharides, terpenes, phenolic acids, steroids, fatty acids and other metabolites. Among them, polysaccharides, terpenoids and phenolic compounds seem to be the most important contributors to the anti-inflammatory activity of mushrooms as demonstrated by numerous studies. However, clinical trials need to be conducted in order to confirm the effectiveness of some of these mushroom compounds namely, inhibitors of NF-κB pathway and of cyclooxygenase related with the expression of many inflammatory mediators.

Elastic Computing - a novel paradigm for distributed systems

This talk, which is based on our newest findings and experiences from research and industrial projects, addresses one of the most relevant challenges for a decade to come: How to integrate the Internet of Things with software, people, and processes, considering modern Cloud Computing and Elasticity principles. Elasticity is seen as one of the main characteristics of Cloud Computing today. Is elasticity simply scalability on steroids? This talk addresses the main principles of elasticity, presents a fresh look at this problem, and examines how to integrate people, software services, and things into one composite system, which can be modeled, programmed, and deployed on a large scale in an elastic way. This novel paradigm has major consequences on how we view, build, design, and deploy ultra-large scale distributed systems.

Penile Skin Involvement as the First Presentation of Henoch-Schonlein Purpura Report of Nine Cases and Review of Literature

Introduction: Involvement of penis is a rare presentation in henoch-schonlein purpura (HSP). The presentations are mainly due to the deposition of immunoglobulin A (IgA) into the vessel walls. In this report, we present the clinical history of nine HSP cases that presented with penile skin involvement. Case Presentation: All patients were referred in the acute phase of HSP. Penile skin involvement was evident as erythema, edema, ecchymosis, or induration of prepuce and/or penile shaft, that appeared simultaneously with skin rash in seven patients. Gastrointestinal involvement was positive in six patients. Patients were treated with steroids and follow up visits were normal except for one patient that developed crescentic glomerulonephritis. Conclusions: We present nine cases of HSP with penile involvement in order to indicate another rare aspect of HSP and its possible complications as well as its appropriate treatment.

Larvicidal, pupicidal and insecticidal activities of Cosmos bipinnatus , Foeniculum vulgare and Tagetes minuta against Culex quinquefasciatus mosquitoes

Purpose: To evaluate the larvicidal, pupicidal and insecticidal activities of Cosmos bipinnatus , Foeniculum vulgare and Tagetes minuta against Culex quinquefasciatus mosquitoes. Methods: The leaves of the plants were extracted with distilled water, ethanol (95 %), and hexane and the extracts screened for their phytochemical profile. While larvicidal and pupicidal activities were assayed at concentrations ranging from 0.1 - 10 mg/mL, insecticidal property was tested at varying amounts (0.25 - 2 g) of the plant sample. The respective larval mortality was thereafter evaluated using Probit analysis. Results: Saponins, terpenoids, flavonoids and steroids were detected in the plant extracts. The ethanol extracts of F. vulgare, T. minuta and C. bipinnatus exhibited larvicidal activity half-maximal lethal concentration (LC50) of 0.10, 1.17 and 1.18 mg/mL, followed by hexane extracts with LC50 value of 1.03, 1.01 and 1.27 mg/mL, respectively, against the larvae of C. quinquefasciatus mosquito. Hexane extracts displayed pupicidal activity with LC50 of 1.07, 1.12 and 1.16 mg/mL against F. vulgare, T. minuta and C. bipinnatus, respectively, while the ethanol extracts of T. minuta, C. bipinnatus and F. vulgare displayed pupicidal activity at LC50 of 1.11, 1.14 and 1.31 mg/mL respectively, against pupa of C. quinquefasciatus mosquito. The aqueous extracts had no (p > 0.05) lethal effects on both larvae and pupa of C. quinquefasciatus at all evaluated concentrations. F. vulgare had the highest (p < 0.05) half-maximal knock-down effect (KD50 = 7.52 min-1), followed by T. minuta (KD50 = 8.64 min-1) on adult C. quinquefasciatus mosquitoes after 6 h of exposure. F. vulgare and T. minuta killed all evaluated mosquito adults within 12 h with LD99 = 0.25 g/air, while the leaves of C. bipinnatus had no (p > 0.05) knock-down or lethal effects on the adult mosquito. Conclusion: C. bipinnatus, F. vulgare and T. minuta possess larvicidal and pupicidal properties against C. quinquefasciatus, whereas only F. vulgare and T. minuta displayed insecticidal properties. Consequent upon these findings, all the plants can be considered naturally potent larvicidal and pupicidal agents against C. quinquefasciatus.

Antibacterial and cytotoxic properties of isoprenoids from the red sea soft coral, Lobophytum sp

Purpose: To evaluate the antibacterial and cytotoxic activities of the secondary metabolites of Lobophytum sp. Methods: Maceration with methanol: chloroform (1:1) was applied to extract the coral material. Chromatographic and spectroscopic techniques were employed for fractionation, isolation and elucidation of pure compounds. Antibacterial activities were performed by well diffusion method against three Gram-positive and four Gram-negative bacteria. Brine shrimp lethality test was employed to predict toxicity, while antitumor activity were tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) method against Ehrlich carcinoma cells. Results: Four sesquiterpenes, one cembranoid type diterpenes and two steroids were isolated. 1 exhibited significant antibacterial activity against four tested bacteria (P. aeruginosa, S. aureus, S. epidermis, and S. pneumonia) with MIC value of 15 μg/mL. Moreover, 1 showed high diameter zone of inhibition ranging from 16 - 18 mm against test bacteria. Compounds 4 and 5 displayed moderate antibacterial activity against all test bacteria with inhibition zone diameter (IZD) ranging from 11 – 15 mm and MIC values of 30 μg/mL. 2, 3, 6 and 7 exhibited weak antibacterial activity (IZD, 7 - 11 mm; MIC ≥ 30 μg/mL). In addition, only diterpene compound (4) showed high toxicity against A. Salina and antitumor activity against Erhlich carcinoma cells with the LD50 of 25 and 50 μg/mL, respectively. Conclusion: This study reveals the strong antibacterial activity of sesquiterpene alismol (1) and the potential antibacterial and antitumor activity of cembranoid type diterpene, cembrene A (4).

Phytopharmacological and ethnomedicinal uses of the Genus Berberis (Berberidaceae): A review

Plants belonging to Berberis are reported in several folklore medicinal pharmacopeias and are used in traditional medicines in Asia and European countries. The plants have been used in the preparation of various traditional and synthetic medicines since pre-historic times for wound healing, fever, eye disease, jaundice, vomiting during pregnancy, rheumatism, kidney and gall balder stones, and several other illnesses. Their healing properties are appear to be due to the presence of secondary metabolites and important alkaloids with different pharmacological activities. Their antibacterial, antifungal, antiviral, anti-diabetic, and anti-tumor activities as well as positive effects on the cardiovascular and body immune systems have been reported. Root extracts of some species of the plant genus contain quinine which acts as a powerful anti-malarial agent. The main chemical constituents of Berberis plants are alkaloids, steroids, glycosides, flavonoids, saponins, terpenoids and reducing sugars. Of these alkaloids, berberine is the most important. The present review focuses on recent advances in phytopharmacological and ethnomedicinal uses of plants belonging to Berberis genus.

Effect of supraphysiological dose of Nandrolone Decanoate on the testis and testosterone concentration in mature and immature male rats: A time course study

Background: Most studies on anabolic-androgenic steroids abuse have been done in adult rats, but few data are available to immature. Objective: This study was conducted to assay the effect of Nandrolone Decanoate (ND) on the testis and testosterone concentration in male immature rats compare with mature ones in short and long time. Materials and Methods: 40 mature rats were divided into 4 groups: group A (short term) and group B (long-term) received 10 mg/kg/day ND interaperitoneally for 35 and 70 days, respectively. Group C (control) without any treatment, and group D (vehicle) received dimethyl sulfoxide (DMSO) solution in two periods 35 and 70 days. 40 immature rats were divided into 4 groups same as mature ones. After surgery body weight, testis size, histomorphometry of testis, and serum testosterone level were evaluated. Results: Our results showed that ND decreased the number of Leydig cells in group B (39.9 ±. 919), group A (43.4 ±. 120), and long term (40.6 ±. 299) immature rats, which could result in a reduction of testosterone concentration significantly in all experimental groups except short term mature group. Number of sertoli cells, testis size, and diameter of seminiferous tubules decreased in the long-term immature group. Eventually, the number of sperm was decreased in mature and immature groups, but a severe depletion of sperm was occurred in both mature and immature in long time in comparison to the control group (p< 0.05). Conclusion: This time course study showed that supraphysiological dose of ND may negatively affect the number of Leydig cells, sperm cell, and testosterone concentration of immature rats in the same matter of mature rats. However, the number of sertoli cell, testis size, and seminferous diameter were decreased only in the long immature rats.

Exploring judicial opinion on the relationship between anabolic-androgenic steroid use and violent offending

Research suggests that there is a link between the use of anabolic-androgenic steroids (AAS) and violence, though this link may be moderated by other substance use such as alcohol. Violent acts in the nighttime economy in recent times has led to governments adopting a law enforcement approach. This study sought to investigate whether the judicial system considers that there is a link between AAS use and violence. Sentencing decisions in Victoria, Australia, were identified using three publically available case law databases. Of the six cases identified, three cases had some mention of a potential link between AAS use and violent offending; however, it appears that evidence of AAS use had neither an aggravating nor mitigating effect on sentencing. In all six cases, a history of other substance use had more of an impacting upon sentencing. Harm reduction approaches should be adopted to reduce violence related to any substance use, including AAS.

Sex steroid profiles in zebra finches : effects of reproductive state and domestication

The zebra finch is a common model organism in neuroscience, endocrinology, and ethology. Zebra finches are generally considered opportunistic breeders, but the extent of their opportunism depends on the predictability of their habitat. This plasticity in the timing of breeding raises the question of how domestication, a process that increases environmental predictability, has affected their reproductive physiology. Here, we compared circulating steroid levels in various "strains" of zebra finches. In Study 1, using radioimmunoassay, we examined circulating testosterone levels in several strains of zebra finches (males and females). Subjects were wild or captive (Captive Wild-Caught, Wild-Derived, or Domesticated). In Study 2, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined circulating sex steroid profiles in wild and domesticated zebra finches (males and females). In Study 1, circulating testosterone levels in males differed across strains. In Study 2, six steroids were detectable in plasma from wild zebra finches (pregnenolone, progesterone, dehydroepiandrosterone (DHEA), testosterone, androsterone, and 5α-dihydrotestosterone (5α-DHT)). Only pregnenolone and progesterone levels changed across reproductive states in wild finches. Compared to wild zebra finches, domesticated zebra finches had elevated levels of circulating pregnenolone, progesterone, DHEA, testosterone, androstenedione, and androsterone. These data suggest that domestication has profoundly altered the endocrinology of this common model organism. These results have implications for interpreting studies of domesticated zebra finches, as well as studies of other domesticated species.