Estudo metanalítico da resposta de gramíneas perenes de verão à adubação nitrogenada / Meta-analytic study of response of nitrogen fertilization on perennial summer grasses

O presente trabalho visou empregar um estudo metanalítico para sumarizar e analisar dados sobre adubação nitrogenada em pastagens formadas por gramíneas dos gêneros Brachiaria, Cynodon e Panicum. Foram selecionados 36 trabalhos de pesquisa realizados no Brasil nos últimos 10 anos, incluindo artigos científicos, teses e dissertações. Com base nos dados contidos nesses trabalhos, foi calculado o incremento relativo de matéria seca e de proteína bruta em relação ao tratamento controle (ausência de adubação nitrogenada) e a eficiência da utilização do nitrogênio na produção de matéria seca e proteína bruta. Os dados obtidos foram submetidos à análise de variância para efeito linear e quadrático em cada uma das variáveis dentro de cada gênero e, no caso de significância, foi realizada análise de regressão. A produção de matéria seca e de proteína bruta de forrageiras tropicais responde de forma expressiva à adubação nitrogenada, principalmente a segunda, porém o acréscimo nas doses de nitrogênio reduz a eficiência da adubação. Verificou-se uma frequente omissão de informações relevantes em trabalhos com adubação nitrogenada em pastagens.(AU)

The study aimed to employ a meta-analytic study to summarize and analyze data on nitrogen fertilization in grasslands formed by grasses of the genera Brachiaria, Cynodon and Panicum. A sample of 36 research projects carried out in Brazil in the last ten years, including scientific papers, theses and dissertations were selected. From the data contained in these works, relative dry matter and crude protein increment compared to the control treatment (absence of nitrogen fertilization) and the efficiency of nitrogen use in the production of dry matter and crude protein were calculated. Data were subjected to analysis of variance for linear and quadratic effect on each variable within each genus and, in case of significance, regression analysis was performed. The production of dry matter and crude protein of tropical forages responds greatly to nitrogen fertilization, especially the second, but the increase in nitrogen rates reduces the efficiency of fertilization. There was a frequent omission of relevant information in scientific works on nitrogen fertilization in grasslands.(AU)

Diversidade e estrutura genética de populações de Varronia curassavica Jacq. em restingas da Ilha de Santa Catarina / Genetic diversity and structure of Varronia curassavica Jacq. populations in the restinga of Santa Catarina Island

RESUMO Varronia curassavica Jacq. (Boraginaceae) está presente na vegetação de restinga e apresenta relevantes propriedades medicinais. A espécie é explorada especialmente por comunidades locais e pela indústria farmacêutica, porém, carece de informações ecológicas e genéticas a seu respeito. Nesse contexto, o estudo foi conduzido com o objetivo de caracterizar a diversidade genética de três populações de V. curassavica em áreas de restinga na Ilha de Santa Catarina. Foram coletadas folhas de 50 indivíduos adultos em cada uma das três áreas de estudo e as frequências alélicas das populações foram obtidas a partir de 14 locos alozímicos. Foram encontrados 25 alelos distintos nas três populações, sendo dois alelos exclusivos. As populações apresentaram diversidade genética média de 0,111 e índice de fixação médio de -0,060 (-0,273 até 0,222). Os níveis de diversidade são intermediários, semelhantes aos exibidos por espécies da mesma família ou de características ecológicas semelhantes. Os índices de fixação foram todos significativos e discrepantes entre as populações, sendo que duas delas apresentaram excesso de heterozigotos. A divergência genética interpopulacional foi significativa e igual a 0,079, considerada moderada e sugerindo efeitos de subdivisão populacional. Os níveis de diversidade genética encontrados e a redução populacional causada pela redução e fragmentação dos habitats em que a espécie ocorre sugerem medidas de conservação ex situ e demandam maior rigor na proteção legal de áreas de proteção permanente.

ABSTRACT The Varronia curassavica Jacq. (Boraginaceae) is present in restinga vegetation and shows relevant medicinal properties. The species is exploited by local communities and by the pharmaceutical industry; however, it lacks ecological and genetic information. Thus, this study aimed to characterize the genetic diversity of three V. curassavica populations in restinga areas of Santa Catarina Island. Leaves of 50 adult individuals were sampled in each of the three study areas and the allelic frequencies were obtained from 14 allozyme loci. Twenty-five different alleles were found in the three populations, two of them being exclusive. The populations showed, on average, a genetic diversity of 0,111 and a fixation index of -0,060 (-0,273 to 0,222). The diversity levels are intermediary, similar to those ones owned by species of the same family or with similar ecological traits. The fixation indexes were all significant and discrepant among the populations, with two of them showing excess of heterozygotes. The genetic divergence among populations was significant and equal to 0,079, which is considered moderate and suggests effects of population subdivision. The levels of genetic diversity found and the population decrease caused by reduction and fragmentation of habitats in which the species are present implies in ex situ conservation measures and a higher enforcement of the legal preservation of permanent protected areas.

Secondary repair of flexor tendon injuries.

Tendon adhesions or even secondary ruptures causing severe hand functional impairment still represent a frequent complication after repair of flexor tendon injuries. Secondary treatment of these problems includes tenolysis, one or two stages flexor tendons reconstruction by grafts or even the use of tendon prosthesis. The mechanism and severity of injury, the status of the surrounding tissues and injured finger, the presence of associated lesions, the age of the patient, post-operative management, patient motivation and the surgeon's skill, may all have implications in the final outcome of the tendon reconstruction. A correct evaluation of the problem by means of classifications such as the one described by Boyes, may help the surgeon in choosing the appropriate technique.

Staining tumor cells with biotinylated ACL-I, a lectin isolated from the marine sponge, Axinella corrugata.

Axinella corrugata lectin 1 (ACL-1) was purified from aqueous extracts of the marine sponge, Axinella corrugata. ACL-1 strongly agglutinates native rabbit erythrocytes. The hemagglutination is inhibited by N-acetyl derivatives, particularly N, N', N"-triacetylchitotriose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine and N-acetyl-D-galactosamine. We investigated the capacity of biotinylated ACL-1 to stain several transformed cell lines including breast (T-47D, MCF7), colon (HT-29), lung (H460), ovary (OVCAR-3) and bladder (T24). ACL-I may bind to both monosaccharides and oligosaccharides of tumor cells, N-acetyl-D-galactosamine, and N-acetyl-D- glucosamine glycan types. The lectins are useful, not only as markers and diagnostic parameters, but also for tissue mapping in suspicious neoplasms. In addition, they provide a better understanding of neoplasms at the cytological and molecular levels. Furthermore, the use of potential metastatic markers such as lectins is crucial for developing successful tools for therapy against cancer. We observed that biotinylated ACL-I stains tumor cells and may hold potential as a probe for identifying transformed cells and for studying glycan structures synthesized by such cells.

Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species.

The coumarins 5-methoxy-6,7-methylenedioxycoumarin 1 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin 2 and 5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin 3 isolated from Pterocaulon species showed significant cytotoxicity against two glioma cells lines. Compound 1 presented IC(50) values of 34.6 µM and 31.6 µM against human (U138-MG) and rat (C6) glioma cells, respectively, and this compound was at least two times more potent than compounds 2 and 3. This result could be explained by the planar conformation adopted by 1 through a non-classical hydrogen bond between a hydrogen of the methoxy and the oxygen of the methylenedioxy groups. Another important finding was that the cytotoxic effect induced by 1 in glioma cells was not observed in organotypic cultures, indicating a selective cytotoxicity for tumor cells.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats.

BACKGROUND AND PURPOSE: The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. EXPERIMENTAL APPROACH: The following models of inflammation were employed: carrageenan-induced acute oedema (measured between 30 min and 4 h), sub-chronic oedema induced by complete Freund's adjuvant (CFA) (determined between 2 h and 72 h), and CFA-induced arthritis (oedema measured between 14 and 21 days). KEY RESULTS: IndOH or IndOH-NC produced equal inhibition of carrageenan-elicited oedema. However, IndOH-NC was more effective in both the sub-chronic (33 +/- 4% inhibition) and the arthritis (35 +/- 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 +/- 2% and 14 +/- 3% inhibition respectively) (P < 0.01). In the CFA arthritis model, treatment with IndOH-NC markedly inhibited the serum levels of the pro-inflammatory cytokines tumour necrosis factor alpha and IL-6 (by 83 +/- 8% and 84 +/- 11% respectively), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased (196 +/- 55%). The indices of gastrointestinal damage in IndOH-NC-treated animals were significantly less that those after IndOH treatment (58 +/- 16%, 72 +/- 6% and 69 +/- 2%, for duodenum, jejunum and ileum respectively). CONCLUSIONS AND IMPLICATIONS: IndOH-NC produced an increased anti-inflammatory efficacy in long-term models of inflammation, allied to an improved gastrointestinal safety. This formulation might represent a promising alternative for treating chronic inflammatory diseases, with reduced undesirable effects.

Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases.

Procollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the prototype of a small group of proteases that have key roles in extracellular matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related proteases TLL-1 and TLL-2 are considered as promising drug targets for the treatment of excessive fibrosis and muscle wasting. We report here the crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation of a cysteine-rich loop within the active site, and suggest that a flap movement is required in order to allow substrate binding. On the basis of these substantial differences between the BMP-1 and astacin active sites, a structural basis for their differing substrate specificities is proposed.

The ethics of off-label use of drugs: oncology pharmacy in Italy.

The off-label use of drugs is very common in cancer treatment for many reasons. This practice is challenging for pharmacists who practice in oncology, for bureaucratic and medico-legal reasons and for reasons concerning ethics. Several Italian legislative Acts and Laws allow pharmacists to have a voice in the management of off-label use of drugs in oncology and offer instruments to allow reasoning from an ethical perspective. The main aim of this paper was to identify the role of pharmacists within the ethical context in the off-label use of drugs in oncology, taking into account the legislative framework and clinical oncology setting. We consider the existing norms to develop an ethical perspective, through the values underlying the Laws and Acts. From a hermeneutical perspective, we focus on the actual oncology setting to identify the ethical space. The off-label use of drugs in Italy is currently regulated by Law 648/96, Law 94/98 and Decree Law on the therapeutic use of drugs under clinical investigation. From the oncology pharmacist's perspective, the application of the Laws mentioned is often problematic. The disease itself brings forth many ethical issues. In particular, human experience is extremely important in oncology and cannot be separated from other considerations. When faced with the common choice of oncologists to use drugs off-label the late stages of the disease or after many chemotherapy attempts, pharmacists have to take responsibility for the sick person. This usually involves collaboration with the physician, within a process oriented by the 'circumstances of compromise in ethics'. The pharmacist practising in oncology should promote real collaboration especially with the physician for the benefit of the sick person. The pharmacist has to maintain his/her professional integrity, and orient it towards accurate evaluation of the so-called 'circumstances of compromise in ethics'.

C-reactive protein and coronary composition in patients with percutaneous revascularization.

BACKGROUND: C-Reactive Protein (CRP) is considered a predictive factor for cardiovascular events and its serum levels have been shown to correlate with thin cap coronary plaques in sudden coronary death. Whether serum CRP levels are associated with in vivo atherothrombotic features is unclear. We thus analysed samples from coronary atherectomy specimens obtained during percutaneous coronary intervention. MATERIALS AND METHODS: Patients with coronary artery disease undergoing directional atherectomy, distinguished by unstable versus stable coronary syndrome diagnosis, provided coronary specimens from culprit lesions. Assessment was conducted by means of conventional histology, morphometry and immunohistochemistry. Specific antibodies against erythrocyte-specific protein glycophorin A, endothelial and macrophage antigens were also used. RESULTS: There were 51 patients with unstable coronary disease and 47 patients with stable angina. Serum CRP levels >/= 1 mg L(-1) were detected in 24/98 patients, and were significantly associated with hypercellularity, macrophage infiltrates, neoangiogenesis and intraplaque haemorrhage (all P < 0.05). Furthermore, coronary plaques from patients with unstable angina contained larger atheromas, more hypercellular plaques, with abundant macrophages, neoangiogenesis and intraplaque haemorrhages and lesser fibrous tissue (all P < 0.05). CONCLUSIONS: We observed a positive correlation between increased serum CRP levels and typical pathological features of complex atherothrombotic coronary disease, confirming in vivo the mechanistic role of CRP in coronary atherothrombosis.

Detecção da produção de slime por estafilococos coagulase-negativa isolados de cateter venoso central / Detection of slime production by coagulase-negative staphylococci isolated from central venous catheter

A produção de slime é um importante fator de virulência dos estafilococos coagulase-negativa, permitindo-lhes aderir sobre as superfícies lisas de biomateriais, e por isso, é associada aos processos de infecção de implantes. No presente estudo a produção de slime em 27 cepas de estafilococos coagulase-negativa foi investigada por cultura em ágar vermelho Congo (77,7% de positividade), método espectrofotométrico ou damicroplaca (81,4% de positividade) e microscopia eletrônica de varredura (88,9% de positividade). Foi também avaliada a resistência de estafilococos coagula-se negativa a vários antimicrobianos usando a técnica do disco difusão. A porcentagem de resistência à penicilina G, oxacilina, eritromicina, clindamicina e gentamicinaem estafilococos produtores de slime foi respectivamente de 88,9%; 70,4%; 81,5%; 66,7% e 59,2%; todos os estafilococos coagulase-negativa foram vancomicina sensíveis. As cepas isoladas de cateter venoso central foram identificadas por método convencional e sistema API Staph. Os 27 estafilococos coagulase-negativa foram identificados como: S. saprophyticus (3,7%), S. xylosus(7,4%), S. haemolyticus (14,8%), S. epidermidis (37,0%), S. warneri (14,8%), S. lugdunensis (7,4%), S. hominis (7,4%), S. schleiferi (3,7%) e S. chromogenes (3,7%). Pode-se concluir que entre a maioria das espécies Staphylococcus coagulase-negativa houve associação entre a produção de slime, origem nosocomial das cepase reduzida sensibilidade aos antimicrobianos, sugerindo potencial patogênico no ambiente hospitalar.

Slime production is an important virulence factor of coagulase-negative Staphylococcus spp., allowing them to attach to smooth surfaces of biomaterials, and it has been associated with infections of implanted medical devices. In the present study the production of slime capsules in 27 strains of coagulase-negative Staphylococcus was investigated by culture in Congo Red agar (77.7% positivity), spectrophotometric or microplate method (81.4% positivity) and scanning electron microscopy (88.9% positivity). The resistance of coagulase-negative strains of Staphylococcus to various antimicrobial agents was also determined by agar disk diffusion. The proportion of strains resistant to penicillin G, oxacillin, erythromycin, clindamycin and gentamicin among the slime-producing staphylococci was 88.9%, 70.4%, 81.5%, 66.7% and 59.2%, respectively; all of the coagulase-negative staphylococci were susceptible to vancomycin. The strains isolated from central venous catheters were identified by a conventional method and the API Staph system. The 27 coagulase-negative taphylococcus strains were identified as: S. saprophyticus (3.7%), S. xylosus (7.4%), S. haemolyticus (14.8%), S. epidermidis (37.0%), S. warneri (14.8%), S. lugdunensis (7.4%), S. hominis (7.4%), S. schleiferi (3.7%) and S. chromogenes (3.7%). It can be concluded that in the most of the coagulase-negative Staphylococcus species there was an association between slime production, the nosocomial origin of the strains and reduced sensitivity to the antibiotics, suggesting a pathogenic potential in the hospital environment.

Gastric metaplasia and small bowel ulcerogenesis in a case of ulcerative jejunitis not related to celiac disease.

The possible relationship between gastric metaplasia and ulcerative lesions in an unusual case of ulcerative jejunitis not related to celiac disease and with extensive gastric metaplasia is discussed. Previous studies have described gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some authors maintain that acid secretion in metaplastic mucosa could represent a pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the absence of functional evidence, we could provide data, in a case of ulcerative jejunitis, about morphologic signs of acid secretion in gastric metaplastic epithelium using an antibody against HMFG-1, a good marker of acid-secreting fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and these finding are suggestive of local acid secretion.

Prevalence of intestinal metaplasia in the distal oesophagus, oesophagogastric junction and gastric cardia in symptomatic patients in north-east Italy: a prospective, descriptive survey. The Italian Ulcer Study Group "GISU".

BACKGROUND: Incidence of adenocarcinoma of distal oesophagus and gastric cardia, probably arising from areas of intestinal metaplasia, has been increasing rapidly. AIMS: To define prevalence of intestinal metaplasia of distal oesophagus, oesophagogastric junction and gastric cardia and to evaluate potential associated factors, by means of a prospective multicentre study including University and teaching hospitals, and primary and tertiary care centres. PATIENTS: Each of 24 institutions involved in study enrolled 10 consecutive patients undergoing first-time routine endoscopy for dyspeptic symptoms. METHODS: Patients answered symptom questionnaires and underwent gastroscopy Three biopsies were taken from distal oesophagus, oesophago-gastric junction and gastric cardia, and were stained with haematoxylin and eosin. Specimens were also evaluated for Helicobacter pylori infection. RESULTS: A total of 240 patients (124 male, 116 female; median age 56 years, range 20-90) were enrolled in study. Intestinal metaplasia affected distal oesophagus in 5, oesophago-gastric junction in 19 and gastric cardia in 10 patients. Low-grade dysplasia was found at distal oesophagus and/or oesophago-gastric junction of 3/24 patients with intestinal metaplasia vs 2/216 without intestinal metaplasia (p<0.05). A significant association was found between symptoms and presence of intestinal metaplasia, regardless of location, and between Helicobacter pylori infection and intestinal metaplasia at oesophago-gastric junction. CONCLUSIONS: Intestinal metaplasia of distal oesophagus, oesophagogastric-junction and gastric cardia is found in a significant proportion of symptomatic patients undergoing gastroscopy and is associated with dysplasia in many cases. Although prevalence of dysplasia seems to decrease when specialized columnar epithelium is found in short segment, or even focally in oesophago-gastric junction, these small foci of intestinal metaplastic cells may represent source of most adenocarcinomas of cardia.

Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides.

[structure: see text]. A small library of cyclic RGD pseudopentapeptides incorporating stereoisomeric 6,5- and 7,5-fused bicyclic lactams was synthesized with the aim of developing active and selective integrin antagonists. The solid-phase synthesis and activity of these RGD derivatives is described. The approach led to two of the most active known inhibitors of alpha(V)beta3 receptor.

NF2 gene in neurofibromatosis type 2 patients.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that predisposes to nervous system tumors. The schwannomin (also termed merlin) protein encoded by the NF2 gene shows a close relationship to the family of cytoskeleton-to-membrane proteins linkers ERM (ezrin-radixin-moesin proteins). Even though penetrance of the disease is >95% and no genetic heterogeneity has been described, point mutations in the NF2 gene have been observed in only 34-66% of the screened NF2 patients, depending on the series. In order to generate tools that would enable an exhaustive alteration screening for the NF2 gene, we have deduced its entire genomic sequence. This knowledge has provided the delineation of a mutation screening strategy which, when applied to a series of 19 NF2 patients, has revealed a high recurrence of large deletions in the gene and has raised the efficiency of mutation detection in NF2 patients to 84% of the cases in this series. The remaining three patients who express two functional NF2 alleles are all sporadic cases, an observation compatible with the presence of mosaicism for NF2 mutation.

A new function of p120-GTPase-activating protein. Prevention of the guanine nucleotide exchange factor-stimulated nucleotide exchange on the active form of Ha-ras p21.

This work studies the coordination of the action of GTPase-activating protein (GAP) and guanine nucleotide exchange factor (GEF) on activated human c-Ha-Ras p21. Purified human p120-GAP was obtained with a new efficient procedure. To distinguish the GTPase-activating effect of p120-GAP from other effects dependent on the interaction with activated Ha-Ras, the nonhydrolyzable GTP analogue guanosine 5'-O-(thiotriphosphate) (GTPgammaS) was used. The results showed that the GTPgammaS/GTPgammaS exchange enhanced by the C-terminal catalytic domain of the yeast GEF Sdc25p (C-Sdc25p) is prevented by p120-GAP. This effect is strictly specific for the activated form of Ha-Ras, the target of GAP; no effect on Ha-Ras.GDP was detectable. The GAP catalytic domain also inhibited C-Sdc25p but to a lower extent. The interfering effect by p120-GAP was also evident in a homologous mammalian system, using full-length mouse RasGEF, its C-terminal half-molecule, or C-terminal catalytic domain. As a consequence of this inhibition, presence of p120-GAP enhanced the regeneration of Ha-Ras.GTPgammaS by GEF at a GDP:GTPgammaS ratio mimicking the in vivo GDP:GTP ratio. Our work describes a novel function of p120-GAP and suggests a mechanism by which GAP protects Ha-Ras.GTP in vivo against unproductive exchanges. This constrain is likely involved in the regulation of the physiological GDP/GTP cycle of Ras and in the action of p120-GAP as downstream effector of Ras. Helix alpha3 is proposed as a Ras element playing a key-role in the interference between GAP and GEF on Ras.