Infrared Spectroscopy of Matrix-Isolated Neutral and Ionized Anthracoronene in Argon.

The matrix-isolated mid-IR (MIR) spectrum of neutral and ionized anthracoronene (C36H18, AnthCor) in argon has been measured experimentally, compared to the spectrum of its parent molecules, coronene and anthracene, and analyzed by comparison to a theoretical spectrum computed using density functional theory (DFT). The experimental and theoretical band positions generally agree within 0-10 cm-1. Anthracoronene exhibits extremely intense cation and anion bands around 1330 and 1318 cm-1. The intensity of these two bands approaches what is traditionally observed over the entire 1000-1600 cm-1 range for a typical PAH cation or anion. The matrix-isolated near-IR (NIR) through overlap region (OVR) spectrum of ionized AnthCor in argon has been reported for the first time and compared to the spectrum of its parent molecules, coronene and anthracene. The spectrum of AnthCor contains a very strong electronic transition around 6175 cm-1, placing it outside the range of the electronic transitions typically observed for PAHs. Anthracoronene is one of the few PAHs studied to date which has exhibited the formation of anions upon UV photolysis.

Photochemistry of coronene in cosmic water ice analogs at different concentrations.

This work presents the photochemistry of ultraviolet (UV) irradiated coronene in water ices at 15 K, studied using mid-infrared Fourier transform (FTIR) spectroscopy for C24H12:H2O at concentrations of (1:50), (1:150), (1:200), (1:300) and (1:400). Previous UV irradiation studies of anthracene:H2O, pyrene:H2O and benzo[ghi]perylene:H2O ices at 15 K have shown that aromatic alcohols and ketones, as well as CO2 and H2CO are formed at very low temperatures. Like-wise, here, in addition to the coronene cation, hydroxy-, keto-, and protonated coronene (coronene-H+) are formed. The rate constants for the decay of neutral coronene and for the formation of photoproducts have been derived. It is shown that PAHs and their UV-induced PAH:H2O photoproducts have mid-infrared spectroscopic signatures in the 5-8 µm region that can contribute to the interstellar ice components described by Boogert et al. (2008) as C1-C5. Our results suggest that oxygenated and hydrogenated PAHs could be in UV-irradiated regions of the ISM where water-rich ices are important.

Infrared spectroscopy of matrix-isolated neutral polycyclic aromatic nitrogen heterocycles: The acridine series.

The matrix-isolated, mid-infrared spectra of seven acridine-based polycyclic aromatic nitrogen heterocycles (PANHs) have been measured and compared to their non-nitrogen containing parent molecule. The acridine species investigated include acridine, benz[a]acridine, benz[c]acridine, dibenz[a,j]acridine, dibenz[c,h]acridine, dibenz[a,h]acridine and dibenz[a,c]acridine. The previously reported results for 1 and 2-azabenz[a]anthracenes are included for comparison. The experimentally determined band frequencies and intensities are compared with their B3LYP/6-31G(d) values. The overall agreement between experimental and theoretical values is good and in line with our previous investigations. Shifts, typically to the blue, are noted for the C-H out-of-plane (CHoop) motions upon insertion of a nitrogen atom. The formation of a bay region upon addition of additional benzene rings to the anthracene/acridine structure splits the solo hydrogen motions into a bay region solo and an external solo hydrogen, with the bay region solo hydrogen coupling to the quartet hydrogen motions and the external solo hydrogen coupling with the duo hydrogen motions resulting in an extreme decrease in intensity for the CHoop solo hydrogen band when the external hydrogen is replaced by a nitrogen atom. The C-C and C-H in-plane region of this acridine series exhibits the characteristic two fold increase in intensity, noted previously for PANHs. The strong ≈1400cm-1 band, which was identified in the previous PANH study, is noted in several molecular species as well as another strong PANH feature between 1480 and 1515cm-1 for several molecules. The presence of these strong bands appear to be primarily responsible for the two-fold increase in the C-H in-plane region's (1100-1600cm-1) intensity. The C-H stretching region can be characterized by contributions from the solo (bay or external), duo and quartet hydrogens, similar to what was observed in the dibenzopolyacene compounds.

Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model.

Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29 °C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFPe dose response as a neuroprotectant at 7 and 24 h post-embolization without lysis of arterial obstructions and investigated blood pharmacokinetics. New Zealand White rabbits (N = 56) received cerebral angiography and embolic spheres (diameter = 700-900 µm) occluded middle and/or anterior cerebral arteries. Intravenous DDFPe dosing (2 % w/v emulsion) began at 60 min and repeated every 90 min until sacrifice at 7 or 24 h post-embolization. Seven-hour groups: (1) control (embolized without treatment, N = 6), and DDFPe treatment: (2) 0.1 ml/kg (N = 7), (3) 0.3 ml/kg (N = 9), (4) 0.6 ml/kg (N = 8). Twenty-four-hour groups: (5) control (N = 16), and DDFPe treatment: (6) 0.1 ml/kg (N = 10). Infarcts as percent of total brain volume were determined using vital stains on brain sections. Other alert normal rabbits (N = 8) received IV doses followed by rapid arterial blood sampling and GC-MS analysis. Percent infarct volume means significantly decreased for all DDFPe-treated groups compared with controls, p = <0.004 to <0.03. Blood DDFP (gas) half-life was 1.45 ± 0.17 min with R = 0.958. Mean blood clearance was 78.5 ± 24.9 ml/min/kg (mean ± SE). Intravenous DDFPe decreases ischemic stroke infarct volumes. Blood half-life values are very short. The much longer therapeutic effect, >90 min, suggests multiple compartments. Lowest effective dose and maximum effective therapy duration are not yet defined. Rapid development is warranted.

relA over-expression reduces tumorigenicity and activates apoptosis in human cancer cells.

We previously demonstrated that bcl-2 over-expression increases the malignant behaviour of the MCF7 ADR human breast cancer cell line and enhances nuclear factor-kappa B (NF-kappa B) transcriptional activity. Here, we investigated the direct effect of increased NF-kB activity on the tumorigenicity of MCF7 ADR cells by over-expressing the NF-kappa B subunit relA/p65. Surprisingly, our results demonstrated that over-expression of relA determines a considerable reduction of the tumorigenic ability in nude mice as indicated by the tumour take and the median time of tumour appearance. In vitro studies also evidenced a reduced cell proliferation and the activation of the apoptotic programme after relA over-expression. Apoptosis was associated with the production of reactive oxygen species, and the cleavage of the specific substrate Poly-ADP-ribose-polymerase. Our data indicate that there is no general role for NF-kappa B in the regulation of apoptosis and tumorigenicity. In fact, even though inhibiting NF-kappa B activity has been reported to be lethal to tumour cells, our findings clearly suggest that an over-induction of nuclear NF-kappa B activity may produce the same effect.

bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells.

bcl-2 expression is often associated with poor prognosis in several types of tumors; however, the role of this molecule in breast cancer is still controversial. We found earlier that over-expression of bcl-2 in a human breast-cancer cell line (MCF7(ADR)) enhances its tumorigenicity and metastatic potential by inducing metastasis-associated properties such as increased secretion of the matrix metalloproteinase-9 (mmp-9). In the present study, we investigated the effect of bcl-2 over-expression on the activity of the transcription factor NF-kappaB, an important regulator of genes involved in tumor progression and invasion. Transient transfection experiments indicate that over-expression of bcl-2 in the MCF7(ADR) cell line, enhances NF-kappaB-dependent transcriptional activity. Mobility-shift analysis revealed an increase of NF-kappaB DNA-binding in bcl-2-over-expressing clones that correlated with lower levels of the NF-kappaB cytoplasmic inhibitor IkappaBalpha. Moreover, point mutations of 2 highly conserved residues within the BH1 and BH2 domains that abrogate the interaction of bcl-2 with bax, or deletion of the N-terminal BH4 domain, completely eliminate the ability of this molecule to up-regulate NF-kappaB-dependent transactivation. Since mmp-9 is a NF-kappaB-regulated gene, we also investigated whether bcl-2 over-expression up-regulated mmp-9 transcription. We found that induction of mmp-9 mRNA correlates with the activation of an mmp-9-promoter-reporter-gene construct in transient transfection assay, and a mutation of the (-600)mmp-9-NF-kappaB binding element abolishes this effect. The overall data indicate that bcl-2-mediated regulation of NF-kappaB-transcription-factor activity may represent an important mechanism for the promotion of malignant behavior in MCF-7(ADR) cells.

Primary splenic lymphoma in patient with hepatitis C virus infection: case report and review of the literature.

Primary splenic lymphoma is uncommon, constituting only 1-2% of all patients with malignant lymphoma. Despite the rarity of this malignancy, the number of primary splenic lymphoma being reported has increased due to its ambiguous definition used in the literature. We describe a case of a 41-year-old man with chronic hepatitis C virus infection presenting abdominal discomfort in the upper left quadrant, weakness, nausea and vomiting. Abdominal computed tomography revealed nodules in the congested splenic parenchyma. Splenectomy was performed and an analysis of the spleen diagnosed B-cell non-Hodgkin's lymphoma. Biopsy of the liver showed evidence of hepatitis C virus. Bone marrow biopsy revealed no tumor infiltration. The patient has been followed to date, has progressed quite well and remains essentially asymptomatic. Recently, an etiologically important role has been suggested for hepatitis C virus infection in the development of B-cell non Hodgkin's lymphoma. Lymphotropism of hepatitis C virus may play a pathological role in the development of non Hodgkin's lymphoma. It is important to add lymphoma to the list of differential diagnosis of extrahepatic disorders in patients with chronic hepatitis C virus infection.

Spontaneous hematoma of the rectus abdominis sheath: a review of 177 cases with report of 7 personal cases.

Hematoma of the rectus abdominis muscle sheath is a little known and rarely diagnosed condition, in spite of its definite clinical setting and treatment. It is very important to the surgeon, as it may be mistaken frequently for acute inflammatory abdominal conditions and should be considered in the differential diagnosis of intra-abdominal tumors. The literature on 177 cases of non-traumatic hematomas of the rectus abdominis muscle sheath is reviewed, including seven personal cases reported by the authors. Its epidemiology, pathogenesis, clinical features, diagnostic examinations and treatment are discussed.

Specifically designed polymeric nanospheres increase cellular uptake of unmodified antisense ODNs.

The cellular uptake and the inhibitory effect of c-myb unmodified antisense oligonucleotides reversibly bound to new polymeric nanoparticles in HL-60 cellular system have been found to increase by 50 folds if compared with the free ODN. An initial single dose (320 nM) of the nanoparticle bound unmodified antimyb ODN has been able to specifically inhibit HL-60 leukemia cell proliferation for at least 8 days.

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule.

In this article, we investigated the effect induced by the reintroduction of wild-type p53 (wt-p53) protein on BCNU sensitivity in the ADF glioblastoma line. Using a wt-p53 recombinant adenovirus (Ad-p53), we demonstrated that exogenous wt-p53 expression was able to increase the sensitivity to BCNU in ADF cells. Interestingly, this effect was more evident when Ad-p53 infection was performed after BCNU treatment compared with the opposite sequence. To understand the biological basis of these different behaviors, we analyzed the cell cycle of the differently treated cells. We found that Ad-p53 infection induced a persistent accumulation of cells in the G0/G1 phase while, as expected, BCNU induced a block in the G2-M phase. Ad-p53-->BCNU sequence did not significantly modify the cell cycle profile in respect of Ad-p53 infected cells. In contrast, BCNU-->Ad-p53 sequence provoked G2-M arrest similar to that observed after treatment with BCNU alone, but prevented the later recovery of the cells through the cell cycle, by driving the cells to apoptotic death. These results demonstrate that the administration sequence is important to increase drug sensitivity. To generalize the phenomenon observed on ADF line, the antiproliferative effect of the two different schedules was analyzed on other glioblastoma lines (A172, CRS-A2, U373MG) with different BCNU sensitivity and p53 status. The data obtained confirm that the wt-p53 gene transfer enhances BCNU sensitivity in glioblastoma cells depending on the administration sequence.

Highly efficient cellular uptake of c-myb antisense oligonucleotides through specifically designed polymeric nanospheres.

c-myb antisense oligonucleotides (AS ODNs) were reversibly immobilized to a novel polymeric core shell nanosphere and their cellular uptake and inhibitory effect on HL60 leukemia cell proliferation studied. The nanosphere surface was so designed as to directly bind ODNs via ionic interactions and reversibly release them inside the cells. Compared with the cellular uptake of free oligonucleotide, the use of AS ODN (immobilized to the nanospheres) produced a 50-fold increase in the intracellular concentration. Specifically, a single dose of 320 nM of AS ODN immobilized to the nanospheres was capable of inhibiting HL60 cell proliferation with the same degree of efficiency obtained using a 50-fold higher dose of free AS ODN. Flow cytometric experiments with fluoresceinated ODNs showed a temperature-dependent uptake, which was detectable as early as 2 h after the beginning of treatment. The inhibitory effect on cell proliferation was maintained for up to 8 days of culture. Moreover, the level of c-Myb protein decreased by 24% after 2 days and by 60% after 4 days of treatment, thus indicating a continuous and sustained release of non-degraded AS ODN from the nanospheres inside the cells.

Lipossarcomas abdominais / Abdominal liposarcomas

Lipossarcomas àbdominais constituem um grupo de tumores pouco freqüentes e, por isso, os princípios de tratamento desses tumores baseiam-se em experiências acumuladas no passado em séries retrospectivas. OBJETIVO. Apresentar sete casos de lipossarcomas abdominais de grandes proporçöes e discutir os principais aspectos diagnósticos e terapêuticos desses tumores na atualidade.MÉTODOS. Foram estudados sete doentes operados com lipossarcoma abdominal em um período de dois anos e meio na Disciplina de Gastroenterologia Cirúrgica da Escola Paulista de Medicina. Foram coletados os principais aspectos clínicos, ultrasonográficos e tomográficos, bem como os achados cirúrgicos e histopatológicos decada caso. RESULTADOS. Os autores chamam a atençäo para a raridade desses tumoree para sua tendência, quando primários, a crescer localmente, sem invadir os tecidos ao seu redor ou metastizar a distância, e, quando recidivantes, a exibir maior multicentricidade e malignidade mais agressiva. Consideram a tomografia computadorizada e mais útil procedimento diagnóstico e descartam a necessidade de biópsia percutânea, dirigida ou näo, no pré-operatório. Ressaltam o papel fundamental da cirurgia excisional radical no tratamento desses tumores e chamam a atençäo para a importância da ressecçäo com margens de segurança adequadas, mesmo quepara tal haja necessidade de ressecçäo associada de vísceras. Consideram a radioterapia e a quimioterapia como métodos pouco eficazes, no momento, para o tratamento adjuvante desses tumores. CONCLUSÄO. É importante um seguimento acurado dospacientes operados, com a indicaçäo, quando necessário, de repetidas cirurgias de ressecçäo, mesmo paliativas (cirurgias citorredutoras), no sentido de melhoriana expectativa de sobrevida.

[Abdominal liposarcomas]. / Lipossarcomas abdominais.

Abdominal liposarcomas are a rare group of tumors and their principles of treatment are based in accumulated experiences of retrospective series. PURPOSE--To report seven cases of abdominal liposarcomas and to discuss the main diagnostic and therapeutic aspects of these tumors nowadays. METHODS--Seven patients operated for abdominal liposarcomas were in the Surgical Gastroenterology Discipline of Escola Paulista de Medicina (UFESP) during 30 months. The major clinic, ultrasonographic, tomographic, surgical and histopathological features were collected in each case. RESULTS--Authors call attention to the unusualness of these tumors, their propensity (while primary) to grow in their own place, without invading the tissues around or metastasizing, and when they are recurrent to their more aggressive malignity. They consider that computerized tomography is the most useful diagnostic procedure and they discard the need of percutaneous biopsy (guided or not) in the preoperative period. They emphasize the fundamental role of radical excision surgery in these tumors treatment and also emphasize the importance of the resection with proper margins, even if an associated resection of visceral organs is necessary. They consider that now radiotherapy and chemotherapy are not very effective methods to the adjuvant treatment of these tumors. CONCLUSION--It is important an accurate follow-up of the operated patients in order to indicate, when necessary, repetitive resection surgeries, even if they are palliative (citoredution surgeries), with the purpose of improving the expectation of life.

Escleroterapia endoscópica de varizes esofagogástricas sangrantes e estado funcional do fígado / Endoscopic sclerotherapy of bleeding esophagogastric varices and functional liver status

Os autores analisam os resultados da esclerose endoscópica aplicada em 52 doentes com hemorragia digestiva por varizes de esôfago e estômago. A avaliaçäo funcional do fígado, de acordo com critérios de Child, permitiu a classificaçäo de 34,6// Child A, 23,1// Child B e 42,1// Child C. Os doentes foram submetidos a endoscopia digestiva alta após anestesia tópica do orofaringe com xilocaina 10// e sedaçäo com benzodiazepínico 10 mg endovenoso. Foi empregada soluçäo de oleato de etnolamina a 4// em volume médio total de 28mL injetada preferencialmente intravasal. Foi observado, durante exame endoscópico, sangramento ativo das varizes do esôfago em 46,1//, sangramento recente em 53,9//, neste último o local tendo sido identificado em mamilo varicoso. A hemostasia do sangramento foi obtida em 72,2// nos doentes Child A, 58,3// nos Child B e 45,4// Child C após primeira sessäo de esclerose. A recidiva hemorrágica ocorreu em 28,6// Child A, 41,7// Child B e 54,6// Child C. A hemostasia após segunda sessäo de esclerose foi de 94,4// Child A, 75// child B e 54,5// Child C. As complicaçöes ocorreram em 30,7// dos doentes por escara no nível do mamilo varicoso esofágico, em 19,2// por dor retro-esternal e em 11,5// por febre. A mortalidade foi de 68,1// para doentes Child C, dos quais 45,4 por hemorragia persistente das varizes esofagianas e 22,7// por coma hepático. Neste grupo ocorreram três casos nos quais o sangramento foi por varizes de fundo gástrico e que a esclerose endoscópica näo foi eficaz para coibi-lo e todos evoluíram para óbito. Nos doentes Child B o óbito esteve representado por coma hepático em 16,6//. Entre os doentes Child A näo ocorreram óbitos. A esclerose de varizes esofágicas sangrantes constituiu método hemostático eficaz; entretanto, essa eficácia esteve diretamente relacionada com o estado funcional do fígado. A esclerose de varizes sangrantes do fundo gástrico näo constituiu método hemostático eficaz e este fato näo esteve relacionado com a funçäo hepática

[Endoscopic sclerotherapy of bleeding esophagogastric varices and functional liver status]. / Escleroterapia endoscópica de varizes esofagogástricas sangrantes e estado funcional do fígado.

Endoscopic sclerotherapy of bleeding gastroesophageal varices was carried out in 52 patients within a sclerosis program for acute hemorrhage. According to Child's classification, 18 (34.6%) were A, 12 (23.1%) B and 22 (42.3%) C. The hemorrhagic focus was endoscopically proven in oesophageal varices in 45 (86.5%) and in 7 (13.5%) in gastric varices. The sclerotherapy was performed by both intra and extravascular injections of 3% ethanolamine according to treatment for emergency bleeding. The procedure was repeated on the 7th day or when necessary for recurrent hemorrhage. Hemostasis was achieved in 94.4% Child's class A, 75.0% Child's class B and 54.5% Child's class C, all of them with bleeding oesophageal varices. All patients with severe gastric hemorrhage (2 Child's class A, 2 Child's class B and 3 Child's class C) needed surgical treatment for uncontrolled bleeding. Liver failure and bleeding were the leading causes of death in 15 (68.1%) Child's class C and 2 (16.6%) Child's class B. There was no death in Child's class A. The conclusion was drawn that the results of endoscopic sclerotherapy of bleeding oesophageal varices was effective and clearly related to liver function. The endoscopic sclerotherapy, however, was not able to control severe hemorrhage from gastric varices and this was not related to liver function.

Structure-activity relationship between the 3D distribution of the electrophilicity of sugar derivatives and their cytotoxic and antiviral properties.

The cytotoxic activities of a series of sugar derivatives bearing electrophilic groups (1-cyanovinyl, 4-cyanochromen-2-yl and 3-nitrochromen-2-yl) have been correlated with their electrophilic properties. To this end, an electrophilic index was defined as an isovalue surface where the interaction energy with an incoming model nucleophile (H-) was equal to a predefined value. This index, calculated from extended Hückel wave functions, allows one to quantify the electrophilic character of the substrates and to describe its spatial localization within the molecular volume (at Michael acceptor sites or on other parts of the molecules). Only sugars for which Michael acceptor reactivity was predicted were retained, and they were subdivided into two groups: those showing antiviral activity against a retrovirus and those devoid of such activity. Under these conditions, good correlations between cytotoxic activity and electrophilic reactivity--positive for the first group, negative for the second--were found. In addition, the ratio electrophilicity/sum of the absolute value of the dipole plus its projection along the principal axis of inertia, Z, of the molecule allows one to predict to which of these groups a sugar derivative belongs.

Aspectos endoscópicos das varizes do esôfago e do estomago em doentes esquistossomóticos no pós-operatório imediato e tardio (dez anos) de anastomose espleno-renal distal / Endoscopic aspects of esophageal and gastric varices in schistosomiatic patients in the early and late (ten years) post-operative of distal spleno-renal anastomosis

Os autores apresentam observaçöes endoscópicas de varizes do esôfago e do estômago no pós-operatório imediato e tardio (dez anos) de 18 doentes esquistossomáticos submetidos a anastomose espleno-renal distal.

Spin-labelled sulfur containing neoglycolipids.

A neoglycolipid of structure beta-D-Glcp-S-(CH2)3N(OH)(CH2)4-O-cholest-5-en-3 beta-yl has been prepared in fair overall yield by reduction of the nitrone obtained by condensation of beta-D-Glcp-S-(CH2)3NHOH and OCH-(CH2)3-O-cholest-5-en-3 beta-yl. This synthetic procedure is very flexible, allowing a large range of lengths for the spacer arm, different positions for the NOH group along the spacer arm chain and the replacement of the sulfur by other bio-isosteric groups. The new neoglycolipid spontaneously oxidized to the corresponding nitroxide free radical whose EPR spectrum gave information on its conformational equilibrium which was further studied by molecular mechanics.