Synthesis of a new allelopathic agent from the biotransformation of ent-15α-hydroxy-16-kauren-19-oic acid with Fusarium proliferatum.

The use of kaurane diterpenes as substrates in fungal biotransformation to achieve bioactive compounds has been widely reported. In this work, the natural product kaurenoic acid, a diterpene widely distributed in the plant Kingdom, was chemically converted into ent-15α-hydroxy-kaur-16-en-19-oic acid (1). Substrate 1 was subjected to biotransformation by the fungus Fusarium proliferatum, furnishing a new derivative, ent-2α,15α-dihydroxy-kaur-16-en-19-oic acid (2). The structure of metabolite 2 was deduced on the basis of spectroscopy and MS data. Derivative 2 showed allelopathic activity on germination and growth of root and stem of lettuce (Lactuca sativa), inhibiting 100% of germination and growth of roots and stem, at higher concentration assayed (10-4 mol/L).

Constituents from stem barks of Luehea ochrophylla Mart and evaluation of their antiparasitic, antimicrobial, and antioxidant activities.

Luehea species are found in almost all Central and South American countries. The present work describes the phytochemical study, isolation, and structural characterisation of friedelin, ß-friedelinol, lupeol, pseudotaraxasterol, ß-sitosterol, betulinic acid, taraxasterol, (-)-epicatechin, ß-sitosterol-3-O-ß-d-glucopyranoside, and (+)-epicatechin-(4ß→8)-epicatechin from stem barks of Luehea ochrophylla Mart. The structural identification of the isolated compounds was mainly performed by NMR analyses and comparison with the data from literature. These compounds were isolated for the first time in the genus Luehea, except ß-sitosterol glucopyranoside, (-)-epicatechin, and lupeol. Hexane extract (HE) and dichloromethane (DF) and ethyl acetate (AF) fractions exhibited antiparasitic activity against amastigote (intracellular) and trypomastigote culture forms of Trypanosoma cruzi. The ethanol extract (EE), DF, and ethanol fraction (EF) exhibited considerable antifungal activity against Candida albicans. Moreover, extracts and fractions exhibited significant percentage of capture free radicals of 2,2-diphenyl-picrylhydrazyl (DPPH) when compared to the standard of ascorbic acid.

New jacaranone glucoside from Jacaranda oxyphylla leaves.

Jacaranda oxyphylla Cham. is popularly known as 'caroba-de-São-Paulo' and it is used in traditional medicine for microbial infections. A new phytoquinoid (α/ß-glucoside-4-phenylacetate-6-(1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate) (1) was isolated from J. oxyphylla leaves, together with three known compounds: quercetin-3-O-ß-d-galactoside (2), verbascoside (3) and polystyrene (4). Their chemical structures were elucidated using spectroscopic techniques and by comparison with the related known compounds. In addition, it was found a pronounced acetylcholinesterase inhibitory activity for the quinoid 1 (100.0 ± 0.8%) and phenolic compounds 2 and 3 (99.9 ± 0.7 and 99.3 ± 0.5%, respectively), if compared to the standard eserine (92.7 ± 0.4%), that was analysed by a microplate spectrophotometer.

Antioedematogenic activity, acetylcholinesterase inhibition and antimicrobial properties of Jacaranda oxyphylla.

Jacaranda oxyphylla Cham. (Bignoniaceae) is a shrub found in the Brazilian cerrado and used in folk medicine to treat microbial infections. The aim of this study was to carry out a phytochemical screening and evaluate antioedematogenic, antimicrobial and antiacetylcholinesterase properties of J. oxyphylla crude extracts. All extracts analysed showed presence of terpenoids, which are potentially active chemical substances. A high AChE inhibitory activity for hexane extract from leaves and for the extracts from twigs was found. Ethanol extract from leaves of J. oxyphylla showed activity against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria. This extract was also effective in inhibiting the stages of inflammation evaluated. Biological investigation and phytochemical screening of J. oxyphylla extracts provided additional evidence of its traditional medicinal value.

Yarrowia lipolytica and its multiple applications in the biotechnological industry.

Yarrowia lipolytica is a nonpathogenic dimorphic aerobic yeast that stands out due to its ability to grow in hydrophobic environments. This property allowed this yeast to develop an ability to metabolize triglycerides and fatty acids as carbon sources. This feature enables using this species in the bioremediation of environments contaminated with oil spill. In addition, Y. lipolytica has been calling the interest of researchers due to its huge biotechnological potential, associated with the production of several types of metabolites, such as bio-surfactants, γ-decalactone, citric acid, and intracellular lipids and lipase. The production of a metabolite rather than another is influenced by the growing conditions to which Y. lipolytica is subjected. The choice of carbon and nitrogen sources to be used, as well as their concentrations in the growth medium, and the careful determination of fermentation parameters, pH, temperature, and agitation (oxygenation), are essential for efficient metabolites production. This review discusses the biotechnological potential of Y. lipolytica and the best growing conditions for production of some metabolites of biotechnological interest.

The phytochemistry and biological aspects of Caryocaraceae family / Aspectos fitoquímicos e biológicos da família Caryocaraceae

The Caryocaraceae family is constituted of 25 species distributed in two genera (Caryocar and Anthodiscus). Plants of this family have been used in several phytochemical studies for isolation and characterization of chemical compounds. Some of these studies evaluated in vitro and in vivo biological activities of extracts and pure substances isolated from plants of this family. Nine species of Anthodiscus genus have been described, while no phytochemical study related to them has been reported. On the other hand, Caryocar genus presents 16 species with several medicinal uses like for the treatment of colds and bronchitis, in the prevention of tumours, as a regulating agent of the menstrual flow, to treat ophthalmological problems and for the cure of hematomas and bruises. Some species of this genus were targeted by phytochemical studies and presented, in their composition, the following classes of secondary metabolites: triterpenes, fatty acids, tannins, carotenoids, triterpenic saponins, phenolic coumarins, phenolic glycosides, and others. The fruits of Caryocar species are very nutritive, containing in their composition fibers, proteins, carbohydrates and minerals. Seeds have been widely used as oil source with nutritional and cosmetic value. The biological evaluation of some species was carried out by using relevant biological assays such as: antioxidant, allelopathic and antifungal activities against Biomphalaria glabrata and toxicity on Artemia salina.

A família Caryocaraceae é constituída por 25 espécies distribuídas em dois gêneros (Caryocar e Anthodiscus). Plantas desta família têm sido utilizadas em diversos estudos fitoquímicos para isolamento e caracterização de constituintes químicos. Alguns destes estudos avaliaram atividades biológicas in vitro e in vivo de extratos e substâncias puras isoladas a partir de plantas desta família. São descritas nove espécies dentro do gênero Anthodiscus e nenhum estudo fitoquímico relacionado a elas foi relatado. Por outro lado, o gênero Caryocar apresenta 16 espécies com diversos usos medicinais, tais como: para o tratamento de resfriados, bronquites, na prevenção de tumores, como reguladores do fluxo menstrual, em problemas oftalmológicos, e na cura de hematomas e contusões. Algumas espécies deste gênero foram submetidas a estudos fitoquímicos e apresentaram, em sua composição, as seguintes classes de metabólitos secundários: triterpenos, ácidos graxos, taninos, carotenoides, saponinas triterpênicas, cumarinas, glicosídeos fenólicos, entre outros. Os frutos de espécies Caryocar são muito nutritivos contendo em sua composição, fibras, proteínas, carboidratos e minerais. As sementes têm sido amplamente usadas como fonte de óleo com valor nutricional e cosmético. A avaliação biológica de algumas espécies foi realizada utilizando-se testes biológicos relevantes, entre eles: a atividade antioxidante, alelopática, antifúngica, contra Biomphalaria glabrata, e toxicidade sobre Artemia salina.

Screening filamentous tropical fungi for their nutritional potential as sources of crude proteins, lipids and minerals.

The use of fungal and yeast biomass in foodstuff, either as supplements or as major ingredients in formulations is an area of growing interest for the modern food industry. The aim of this study was to evaluate the nutritional potential of biomasses obtained from filamentous fungi Penicillium sclerotiorum, Penicillium janthinellum, Rhizopus stolonifer and Syncephalastrum racemosum. Biomasses presented 26-37% of total proteins, 1.7-3.5% of lipids and 4.6-9.1% of ashes. The humidity level reached 75-83%. Ashes were screened for minerals contents with a special outcome for S. racemosum biomass that presented 3438 mg/100 g (dw) of magnesium. Fatty acids present in the biomasses were screened and the palmitic (C16:0), estearic (C18:0), elaidic (18:1n9-t), oleic (18:1n9-c), linolelaidic (C18:2n6-t), linoleic (C18:2n6-c) and γ-linolenic (C18:3n6) acids were found to be the most abundant, from a total of 88-90% of identified fatty acids. Overall data indicate that the filamentous fungi studied have good nutritional properties, possessing a combination of good level of proteins, low level of fat, and presence of essential fatty acids, including omega-3 derivatives, along with the presence of Ca, Mg, Zn and Fe.

Novel agents for enzymatic and fungal hydrolysis of stevioside / Novos agentes para a hidrólise enzimática e fúngica do esteviosídeo

A comparative study on the potential of some biological agents to perform the hydrolysis of stevioside was carried out, aiming at establishing an alternative methodology to achieve the aglycon steviol or its rearranged derivative isosteviol, in high yields to be used in the preparation of novel bioactive compounds. Hydrolysis reactions were performed by using filamentous fungi (Aspergillus niger, Rhizopus stolonifer and Rhizopus arrhizus), a yeast (Saccharomyces cerevisiae) and enzymes (pancreatin and lipases PL250 and VFL 8000). Pancreatin showed the best hydrolytic activity, furnishing isosteviol at 93.9% of yield, at pH 4.0, using toluene as a co-solvent. Steviol was produced using both pancreatin at pH 7.0 (20.2% yield) and A. niger atpH 7 (20.8% yield).

Um estudo comparativo do potencial de alguns agentes biológicos capazes de hidrolisar o esteviosídeo foi realizado,objetivando-se estabelecer uma metodologia alternativa para a obtenção da aglicona esteviol ou seu produto de rearranjo, isoesteviol, em rendimentos elevados que permitam o uso destas agliconas para o preparo de novos compostos bioativos. As reações de hidrólise foram realizadas usando fungosfilamentosos (Aspergillus niger, Rhizopus stolonifer e Rhizopus arrhizus), uma levedura (Saccharomyces cerevisiae) e enzimas(pancreatina, lipase PL250 e lipase VFL 8000). A pancreatina mostrou a melhor atividade hidrolítica dentre os sistemastestados, fornecendo isoesteviol com rendimento de 93,9% em pH 4,0, usando tolueno como co-solvente. Esteviol foi produzido tanto usando pancreatina em pH 7,0 (20,2% derendimento) quanto usando A. niger em pH 7,0 (20,8% de rendimento).

Novel agents for enzymatic and fungal hydrolysis of stevioside.

A comparative study on the potential of some biological agents to perform the hydrolysis of stevioside was carried out, aiming at establishing an alternative methodology to achieve the aglycon steviol or its rearranged derivative isosteviol, in high yields to be used in the preparation of novel bioactive compounds. Hydrolysis reactions were performed by using filamentous fungi (Aspergillus niger, Rhizopus stolonifer and Rhizopus arrhizus), a yeast (Saccharomyces cerevisiae) and enzymes (pancreatin and lipases PL250 and VFL 8000). Pancreatin showed the best hydrolytic activity, furnishing isosteviol at 93.9% of yield, at pH 4.0, using toluene as a co-solvent. Steviol was produced using both pancreatin at pH 7.0 (20.2% yield) and A. niger at pH 7 (20.8% yield).

Frameless stereotactic radiosurgery with a bite-plate: our experience with brain metastases.

Non-invasive frameless stereotactic radiosurgical systems have recently been developed. We report our experience of frameless stereotactic radiosurgery (SRS) with a bite-plate for brain metastases. Between February 2002 and December 2005, 147 patients with brain metastases were treated with C-arm linear accelerator-based SRS and 122 patients were followed up by our institute. An optic tracking system with infrared light-emitting diodes was used for real-time monitoring. A bite-plate with fiducial markers was applied as a first-line method for frameless SRS. Head-ring fixation was used in patients lacking teeth. Lung carcinomas (63%) were the most common primary tumors, followed by breast carcinomas (13%). Ninety patients underwent radiosurgery with a bite-plate and 32 patients underwent fixation of a head ring. Males were significantly more predominant in the head-ring group (26 men and 6 women), compared with the bite-plate group (47 men and 43 women, p < 0.01). The average age (62 years) in the bite-plate group was significantly younger than that (68 years) in the head-ring group (p < 0.01). The median survival time was 12.0 months in the bite-plate group and 8.0 months in the head-ring group (p = 0.0621). Nine patients who had brain metastases in or close to the brain stem were treated with fractionated stereotactic radiotherapy. The frameless stereotactic radiosurgical system with a bite-plate is safe and effective for the treatment of brain metastasis. Elderly male patients sometimes are edentulous and require placement of a head ring for radiosurgery.

Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus.

We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 x MIC) in combination with ampicillin (0.5 x MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.

Pomegranate extract inhibits Staphylococcus aureus growth and subsequent enterotoxin production.

In Brazil, pomegranate (Punica granatum L. (Punicaceae)) is widely used as a phytotherapeutic agent. This study evaluates the effect of pomegranate extract on Staphylococcus aureus FRI 722 growth and subsequent enterotoxin production. Bacterial susceptibility was determined by tube dilution method and production of enterotoxin was assessed using membrane-over-agar (MOA) plates. At a low extract concentration (0.01% v/v) bacterial growth was delayed, while a higher concentration (1% v/v) eliminated bacterial growth. Most interestingly, a 0.05% (v/v) concentration of extract was found to inhibit Staphylococcal enterotoxin (SE) A production. These data further implicate pomegranate extracts as potential antibacterial therapeutics with the added ability to inhibit enterotoxin production.

Radical resection for intrinsic midbrain pilocytic astrocytoma: report of two cases.

BACKGROUND: Intrinsic midbrain glioma has been one of the most challenging therapeutic tasks in neurosurgery due to its prognosis and risks associated with surgical procedures. It is known that the prognosis of pilocytic astrocytoma is relatively good if radical resection can be achieved without severe complications. In order to remove pilocytic astrocytoma within the midbrain radically, we used microsurgical techniques. METHOD: Two patients with intrinsic pilocytic astrocytomas located at the midbrain were operated on. The subtemporal approach was used with a point of entry on the lateral surface of the midbrain just behind the cerebral peduncle. Major vessels were preserved, followed by resection of the intrinsic tumor making the cleavage between tumour and midbrain. FINDINGS: In both patients, intrinsic pilocytic astrocytoma was grossly totally removed with minimal permanent morbidity. They have been able to maintain independent activities in their daily lives without tumor recurrance. CONCLUSIONS: Surgical cure can be accomplished in some cases of midbrain pilocytic astrocytoma, even if the lesions are intrinsic to the midbrain. To remove the tumor totally without further neurological deficits, it is necessary to select a safe access or entrance point to the tumor, and to demarcate the gliotic plane between tumour and midbrain. A long-term follow up with a larger number of patients is needed to establish the significance of radical resection for intrinsic midbrain pilocytic astrocytoma.

Intradural en-bloc removal of the anterior clinoid process.

BACKGROUND: Anterior clinoidectomy is useful in the surgical treatment of paraclinoid and parasellar lesions. Previously reported procedures require expertise in drilling, the alternative method reported here reduces the drilling procedure. METHODS AND RESULTS: En-bloc clinoidectomy is performed intradurally via the standard pterional approach. A 1 to 2 mm-wide narrow drill line is placed with a 1 mm-wide diamond burr through the lesser sphenoid wing. It encircles the medial border of the optic canal and the lateral border of the lesser sphenoid wing over the superior orbital fissure, and is located about 1 cm anterior to the posterior margin of the optic canal. After drilling, one bony piece that includes the anterior clinoid process (ACP) and the optic canal roof remains connected to the basisphenoid bone by the optic strut alone. The optic strut is then fractured easily by applying leverage near its junction with the basisphenoid bone and the piece is removed en bloc with the major part of the optic strut, requiring little or no additional drilling of the residual bony fragments. Of 37 patients who underwent our en-bloc clinoidectomy, only one suffered complications consisting of cerebrospinal fluid (CSF) leakage through the sphenoid sinus. Our procedure requires an average of 20 min. CONCLUSIONS: Intradural en-bloc removal of the ACP with fracture of the optic strut requires minimal drilling, resulting in decreased risk of injury to the optic nerve and a shortened time for clinoidectomy.

Biological screening of Annonaceous Brazilian Medicinal Plants using Artemia salina (brine shrimp test).

Eighteen different extracts from five Annona species collected in Minas Gerais state, Brazil, were submitted to the brine shrimp lethality test in order to detect potential sources of novel cytotoxic, antitumor, pesticidal and anti-Trypanosoma cruzi compounds. All of the Annonaceous species tested showed good larvicidal activity as compared to a reference compounds and literature data.

Constituents from aerial parts of Wedelia paludosa.

Tetrachyrin (1), 3alpha-tigloyloxykaur-16-en-19-oic acid (2) and 3alpha-cinnamoyloxykaur-16-en-19-oic acid (3) have been isolated from the ethanol extract of Wedelia paludosa aerial parts.

Central neurogenic hyperventilation with primary cerebral lymphoma: a case report.

We report a case of a bright, alert patient with central neurogenic hyperventilation (CNH) associated with cerebral malignant lymphoma. CNH is a syndrome comprising normal or elevated arterial oxygen tension, decreased arterial carbon dioxide tension, and respiratory alkalosis in the absence of cardiac or pulmonary disease that stimulates a compensatory hyperpnea. A-72-year-old man with recurrent central nervous system lymphoma presented with hyperpnea. showing a respiratory rate over 30 per minute. He was fully awake and conscious. Routine laboratory studies and chest X-ray were normal, but arterial blood gas examination on room air showed respiratory alkalosis, regardless of wakefulness or sleep. Pulmonary infarction was denied by pulmonary flow scintigram. Rebreathing from a paper bag, intravenous administration of diazepam, and oxygen inhalation failed to alter the respiratory pattern. Brain MRI demonstrated two mildly enhanced lesions within the left side of the medulla oblongata and right side of the pons. CNH is rare in patients with normal consciousness. It seems to be caused by brainstem injury that includes the respiratory center.

Induction of apoptosis in glioma cells: an approach to control tumor growth by blocking basic fibroblast growth factor autocrine loop.

Glioma is a group of neoplasms derived from neuroepithelial tissue. High grade glioma is characterized by the presence of mitotic figures and the occurrence of vascular endothelial hyperplasia. This article reviews the effects of growth factors which are secreted by glioma cells on the proliferative activity of both glioma cells and vascular endothelial cells. Among various glioma-derived growth factors, we have found that basic fibroblast growth factor (bFGF) plays an important role in determining malignant trait of human glioma via its autocrine loop. Furthermore, we discuss candidate molecular targets for the therapy of high-grade glioma by blocking the autocrine loop of bFGF.

Efficacy of conventional radiotherapy for recurrent meningioma.

Results of radiation therapy for 20 patients with recurrent meningioma were analyzed. The patients included 8 men and 12 women, with a median age of 55 years. All of the patients had undergone at least one operation prior to the reoperation preceding radiotherapy. Ten patients had benign meningiomas, while 4 and 6 patients had atypical and malignant meningiomas, respectively, at the time of radiotherapy. The median radiation dose was 59.4 Gy (range: 50-61.2 Gy). The local control rate at 5 years was 36% for all 20 patients (41% for benign meningiomas and 30% for atypical or malignant meningiomas). The 5-year survival rate was 47%. Excluding 2 patients whose follow-up period was shorter than the preradiotherapy interval from the previous operation, the postradiation recurrence-free period was longer than the preradiotherapy interval in 50% (9/18) of the patients. No serious complications of radiotherapy were observed. Radiotherapy seemed to be effective in controlling the tumor or delaying recurrence in at least half of the patients. However, higher doses of radiation, using sophisticated radiation techniques, may be necessary to obtain higher control rates.

Long-term results of radiation therapy for pituitary adenoma.

PURPOSE: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. CONCLUSION: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.