Neuroimaging safety during pregnancy and lactation: a review.

PURPOSE: Imaging studies are crucial adjuncts when studying acute and chronic diseases, so pregnant and lactating women are as likely to be evaluated with one of the available imaging modalities. Due to the specific condition of the mother and child in this time period it is crucial to make an appropriate selection of imaging studies. METHODS: We review the existing literature and analyse the latest evidence and guidelines regarding neuroimaging safety during pregnancy and lactation, proposing an algorithm of action based on risk/benefits assessment. RESULTS: Choosing the most appropriate neuroimaging modality implicates assessing the pretest pertinence of the study-the possibility of a serious treatable neurologic disease, pondering what is the most useful imaging modality for the diagnosis and evaluating the associated risks. Among physicians (and patients), however, the risk component is perhaps the least well understood, with misperceptions regarding safety and potential hazards. Computed tomography (CT) risks are principally related to ionizing radiation and intravenous (IV) administration of iodinated contrast. However, as very low risks for the mother and foetus have been reported and CT remains the most available tool for initial rapid diagnosis of acute neurological conditions, it should not be withheld in urgent situations. Magnetic resonance imaging (MRI), unlike CT, does not use ionizing radiation or iodinated contrast mediums, having the best anatomical detail possible. However, there are some usage safety concerns regarding the magnetic field strength and gadolinium-based contrast use. CONCLUSION: There are lacking longitudinal and prospective studies to sustain evidence based choices of imaging studies during pregnancy and lactation. Ultimately the decision should be based on the risk/benefit, taking into account the patient's safety, care and outcomes. However, using a specific algorithm can guide decisions in daily clinical practice.

Assessment of the acid phosphatase CP01850 from Corynebacterium pseudotuberculosis in DNA and subunit vaccine formulations against caseous lymphadenitis / Avaliação da fosfatase ácida recombinante CP01850 de Corynebacterium pseudotuberculosis em formulações vacinais de subunidade e de DNA contra a linfadenite caseosa

The target cp1002_RS01850 from Corynebacterium pseudotuberculosis was used to construct a DNA and recombinant subunit vaccine against caseous lymphadenitis. Recombinant protein rCP01850 was expressed in Escherichia coli using pAE vector, and DNA vaccine was engineered with pTARGET vector. BALB/c mice were divided in five groups containing eight animals each, inoculated with: pTARGET/cp01850 as DNA vaccine (G1); rCP01850 plus Al (OH)3 as recombinant subunit vaccine (G2); pTARGET/cp01850 and a boost with rCP01850 plus Al (OH)3 (G3); pTARGET (G4); or Al (OH)3 (G5). Mice were inoculated and blood samples were collected on days 0, 21, and 42 for the analysis of total IgG, IgG1 and IgG2a by ELISA. In each group, five animals were challenged with Mic-6 C. pseudotuberculosis strain, and three were used for cytokine quantification by qPCR. Although no group has been protected by vaccines against lethal challenge, G2 showed an increase in the survival rate after challenge. Significantly higher levels of IL-4, IL-12, IFN-γ, total IgG, IgG1 and IgG2a were also detected for G2, evidencing a mixed Th1/Th2 immunological profile. In conclusion, despite no protection level provided by different vaccinal strategies using cp1002_RS01850 from C. pseudotuberculosis, G2 developed a Th1/Th2 immune response with an increase in survival rate.(AU)

O alvo cp1002_RS01850 de Corynebacterium pseudotuberculosis foi utilizado para construir uma vacina recombinante de subunidade e de DNA contra a linfadenite caseosa. A proteína recombinante rCP01850 foi expressa em Escherichia coli usando o vetor pAE, e a vacina de DNA foi construída com o vetor pTARGET. Camundongos BALB/c foram divididos em grupos de oito animais, inoculados com: pTARGET/cp01850 como vacina de DNA (G1); rCP01850 e Al (OH)3 como vacina recombinante de subunidade (G2); pTARGET/cp01850 e um boost com rCP01850 e Al (OH)3 (G3); pTARGET (G4); ou Al (OH)3 (G5). Os animais foram inoculados e amostras de sangue foram coletadas nos dias 0, 21, e 42 do experimento para a análise de IgG total, IgG1 e IgG2a por ELISA. De cada grupo, cinco animais foram desafiados com a cepa Mic-6 de C. pseudotuberculosis, e três foram usados para a quantificação de citocinas por qPCR. Apesar de nenhum grupo ter sido protegido pelas vacinas testadas contra o desafio letal, G2 apresentou taxa de sobrevida e níveis de IL-4, IL-12, IFN-γ, IgG total, IgG1 e IgG2a significativamente mais altos, evidenciando um perfil imunológico misto Th1/Th2. Conclui-se que apesar das diferentes estratégias vacinais utilizando cp1002_RS01850 de C. pseudotuberculosis não terem sido capazes de gerar proteção, G2 desenvolveu uma resposta Th1/Th2 e elevou a taxa de sobrevida.(AU)

KGF Enhances Oral Epithelial Adhesion and Rete Peg Elongation via Integrins.

Oral epithelial adhesion to the lamina propria underlies the physiologic function of the oral mucosa and contributes to resisting bacterial invasion, preventing body fluid loss, and maintaining routine chewing; thus, understanding the factors that positively influence oral epithelial adhesion is a research topic of great interest. Rete pegs contribute to oral epithelial adhesion by enlarging the contact areas, whereas integrins are the major molecules that mediate epithelial cell adhesion to the basement membrane. Keratinocyte growth factor (KGF) can promote both rete peg elongation in the skin and the expression of integrins in various cell types. Herein, we tested the effects of submucosal injection of KGF in the ventral surfaces of rat tongues on oral epithelial adhesion. The data confirmed that topical injection of KGF elevated the adhesive forces, elongated the rete pegs, and increased the abundance of integrins, KGF, and KGF receptor on the rat tongue ventral surface. However, HYD-1 (Lys-Ile-Lys-Met-Val-Ile-Ser-Trp-Lys-Gly), an integrin antagonist, inhibited the KGF-enhanced epithelial adhesion and rete peg elongation. Moreover, KGF promoted the expression of integrin subunits α6, ß4, α3, and ß1 in human immortalized oral epithelial cells in 2- and 3-dimensional culture systems. In vitro cell attachment assays demonstrated that HYD-1 inhibited the adhesion of human immortalized oral epithelial cells on Matrigel. Strikingly, the expression of integrins, KGF, and KGFR in human masticatory mucosae with longer rete pegs was more abundant than that in the lining mucosae with shorter rete pegs. In addition, rete peg lengths were positively correlated with the expression levels of integrins, KGF, and KGF receptor. These findings indicate that KGF strengthens oral epithelial adhesion and rete peg elongation via integrins.

Homofobia internalizada e religiosidade entre casais homoafetivos / Internalized homophobia and religiosity among homosexual couples / La homofobia internalizada y religiosidad entre las parejas homosexuales

O objetivo deste estudo foi investigar a relação entre a religiosidade e o constructo “homofobia internalizada”. Parte-se da hipótese de que a religiosidade é uma das variáveis de forte argumento moral negativo sobre as minorias sexuais, sendo então parte da construção pessoal que rejeita a própria homossexualidade. Participaram do estudo 94 pessoas, 49 homens e 45 mulheres, vivendo em um relacionamento estável com parceiro do mesmo sexo. O instrumento investigou quatro dimensões: dados sociodemográficos (idade, sexo, renda, escolaridade, religião, tempo de relacionamento, tempo que mora junto, ocupação e filhos), religiosidade, satisfação conjugal e homofobia internalizada. Os dados foram coletados de forma presencial com instrumento autoaplicável e analisados a partir de teste t, correlação de Pearson e regressão linear com a homofobia internalizada. Os resultados apontaram maiores níveis de homofobia internalizada entre os grupos de maior religiosidade, confirmando a hipótese inicial. O modelo de regressão linear final mostrou como variáveis associadas à homofobia internalizada: religiosidade, tempo de relacionamento, ter fi lhos e satisfação conjugal. Os dados alertam para a importância da influência de comportamentos como a religiosidade na vivência da sexualidade. Discute-se que o preconceito contra as minorias sexuais pode ser introjetado por parte dos indivíduos que pertencem ao grupo minoritário, provocando sofrimento.(AU)

The goal of this study was to investigate the relationship between religiosity and the “internalized homophobia” construct. The mean hypothesis is that religiosity is one of the strongest negative variables associated with moral arguments about sexual minorities, being part of the personal construction who rejects its own homosexuality. The study included 94 people, 49 men and 45 women living in a stable relationship with a same sex partner. The instrument investigated four dimensions: sociodemographic data (age, sex, income, education, religion, relationship time extension, time living together, occupation and children), religiosity, marital satisfaction and internalized homophobia. Data was collected in person with a self-administered questionnaire and analyzed with t test, Pearson correlation and linear regression with internalized homophobia. The results showed higher levels of internalized homophobia among the most religious groups, confi rming the initial hypothesis. The fi nal linear regression model showed how variables such as the effect of religiosity, relationship time, the fact of having children and marital satisfaction associate with internalized homophobia. The data indicated the importance of religious behaviors in infl uencing the experience of sexuality. It is argued that prejudice against sexual minorities can be introjected by individuals belonging to the minority group, which causes suffering.(AU)

El objetivo de este estudio fue investigar la relación entre religisidade y el constructo “homofobia internalizada”. Se inicia con la hipótesis de que la religiosidad es uno de los fuertes variables de argumentos morales negativos sobre la minoría sexual, por lo que ser parte de la costrucción personal que rechaza su propia homosexualidad. Participó en la población de estudio 94 que se declararon homosexuales que viven en una relación estable. Se utilizaron, una escala de homofobia internalizada, escala de religiosidad, los datos acerca de la sexualidad y la escala de satisfacción marital. Los datos fueron recogidos en persona con el instrumento autoadministrado. Los datos mostraron mayores niveles de homofobia internalizada entre los grupos más religiosos, lo que confi rma la hipótesis inicial. Un modelo fi nal para las variables asociadas con la homofobia internalizada destacó la religiosidad, el tiempo de relacion, el hecho de tener hijos y la satisfacción marital. Los datos llaman la atención sobre la importancia de la comprensión de cómo la religiosidad infl uencia en la experiencia de la sexualidad. Se argumenta que los prejuicios contra las minorías sexuales puede ser internalizado por los mismos individuos que forman parte del grupo minoritario y causa sufrimiento. (AU)

Homofobia internalizada e religiosidade entre casais homoafetivos / Internalized homophobia and religiosity among homosexual couples / La homofobia internalizada y religiosidad entre las parejas homosexuales

O objetivo deste estudo foi investigar a relação entre a religiosidade e o constructo "homofobia internalizada". Parte-se da hipótese de que a religiosidade é uma das variáveis de forte argumento moral negativo sobre as minorias sexuais, sendo então parte da construção pessoal que rejeita a própria homossexualidade. Participaram do estudo 94 pessoas, 49 homens e 45 mulheres, vivendo em um relacionamento estável com parceiro do mesmo sexo. O instrumento investigou quatro dimensões: dados sociodemográficos (idade, sexo, renda, escolaridade, religião, tempo de relacionamento, tempo que mora junto, ocupação e filhos), religiosidade, satisfação conjugal e homofobia internalizada. Os dados foram coletados de forma presencial com instrumento auto-aplicável e analisados a partir de teste t, correlação de Pearson e regressão linear com a homofobia internalizada. Os resultados apontaram maiores níveis de homofobia internalizada entre os grupos de maior religiosidade, confirmando a hipótese inicial. O modelo de regressão linear final mostrou como variáveis associadas à homofobia internalizada: religiosidade, tempo de relacionamento, ter filhos e satisfação conjugal. Os dados alertam para a importância da influência de comportamentos como a religiosidade na vivência da sexualidade. Discute-se que o preconceito contra as minorias sexuais pode ser introjetado por parte dos indivíduos que pertencem ao grupo minoritário, provocando sofrimento.

The goal of this study was to investigate the relationship between religiosity and the "internalized homophobia" construct. The mean hypothesis is that religiosity is one of the strongest negative variables associated with moral arguments about sexual minorities, being part of the personal construction who rejects its own homosexuality. The study included 94 people, 49 men and 45 women living in a stable relationship with a same sex partner. The instrument investigated four dimensions: sociodemographic data (age, sex, income, education, religion, relationship time extension, time living together, occupation and children), religiosity, marital satisfaction and internalized homophobia. Data was collected in person with a self-administered questionnaire and analyzed with t test, Pearson correlation and linear regression with internalized homophobia. The results showed higher levels of internalized homophobia among the most religious groups, confirming the initial hypothesis. The final linear regression model showed how variables such as the effect of religiosity, relationship time, the fact of having children and marital satisfaction associate with internalized homophobia. The data indicated the importance of religious behaviors in influencing the experience of sexuality. It is argued that prejudice against sexual minorities can be introjected by individuals belonging to the minority group, which causes suffering.

El objetivo de este estudio fue investigar la relación entre religisidade y el constructo "homofobia internalizada". Se inicia con la hipótesis de que la religiosidad es uno de los fuertes variables de argumentos morales negativos sobre la minoría sexual, por lo que ser parte de la costrucción personal que rechaza su propia homosexualidad. Participó en la población de estudio 94 que se declararon homosexuales que viven en una relación estable. Se utilizaron, una escala de homofobia internalizada, escala de religiosidad, los datos acerca de la sexualidad y la escala de satisfacción marital. Los datos fueron recogidos en persona con el instrumento autoadministrado. Los datos mostraron mayores niveles de homofobia internalizada entre los grupos más religiosos, lo que confirma la hipótesis inicial. Un modelo final para las variables asociadas con la homofobia internalizada destacó la religiosidad, el tiempo de relacion, el hecho de tener hijos y la satisfacción marital. Los datos llaman la atención sobre la importancia de la comprensión de cómo la religiosidad influencia en la experiencia de la sexualidad. Se argumenta que los prejuicios contra las minorías sexuales puede ser internalizado por los mismos individuos que forman parte del grupo minoritario y causa sufrimiento.

Neuro-ophthalmologic manifestations in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect different ocular structures, such as cornea, conjunctiva, episclera, sclera, uveal tract, retina, optic nerve and vessels. Neuro-ophthalmologic manifestations in SLE include different degrees of involvement of retina, choroid and optic nerve. Retinal changes are one of the most common ocular involvements and are frequently used as clinical criteria for activity, even if isolated. Studies show that up to 29% of patients with active SLE manifest retinal disease. The exact prevalence of choroidal disease is unknown, but is thought to be less common than retinopathy, due to under-diagnosis. Optic nerve disease, represented by optic neuritis and anterior/posterior ischaemic optic neuropathy, affects approximately 1% of SLE patients. These ocular manifestations have been associated with neurologic flares, antiphospholipid antibodies, nephropathy, and increased mortality. The aim of this paper is to review the different aspects of neuro-ophthalmologic involvement in SLE. Since these manifestations are frequent and potentially severe, a multi-professional team approach is needed to investigate properly and provide early aggressive treatment in order to avoid visual sequelae.

Use of luminescent gunshot residues markers in forensic context.

Chemical evaluation of gunshot residues (GSR) produced by non-toxic lead-free ammunition (NTA) has been a challenge to forensic analyses. Our group developed some luminescent markers specific to the detection of GSR. Here, we evaluated the performance of selected markers in experiments that mimic forensic context and/or routines in which luminescent characteristics would be very useful. We evaluated the influence of markers' addition on the bullet's speed, the rate of shot failure (i.e., when the cartridge case is not fully ejected and/or a new ammunition is not automatically replaced in the gun chamber) as a function of marker percentage, the possibility of collecting luminescent gunshot residue (LGSR) in unconventional locations (e.g. the shooters' nostrils), the LGSR lifetime after hand washing, the transfer of LGSR to objects handled by the shooter, and the dispersion of LGSR at the crime scene and on simulated victims. It was observed that high amounts of marker (10 wt%) cause high rates of failure on pistols, as well as a substantial decrease in bullet speed. However, the use of 2 wt% of marker minimizes these effects and allows LGSR detection, collection and analysis. Moreover, in all conditions tested, markers showed high performance and provided important information for forensic analyses. For instance, the LGSR particles were found on the floor, ranging from 0 to 9.4 m away from the shooter, on the door panel and seats after a car shooting experiment, and were found easily on a pig leg used to simulate a victim. When a selective tagging was done, it was possible to obtain positive or negative correlation between the victim and shooter. Additionally LGSR possesses a fairly long lifetime (9 h) and good resistance to hand washing (up to 16 washes).

ROS-PIASγ cross talk channelizes ATM signaling from resistance to apoptosis during chemosensitization of resistant tumors.

With the existing knowledge of ATM's role in therapeutic resistance, the present study aimed at identifying the molecular mechanisms that influence ATM to oscillate between chemoresistance and chemosensitivity. We observed that the redox status of tumors functions as a major determinant of ATM-dependent 'resistance-to-apoptosis' molecular switch. At a low reactive oxygen species (ROS) condition during genotoxic insult, the ATM/sumoylated-IKKγ interaction induced NFκB activation that resisted JNK-mediated apoptosis, whereas increasing cellular ROS restored ATM/JNK apoptotic signaling. A search for the upstream missing link revealed that high ROS induces oxidation and ubiquitin-mediated degradation of PIASγ, thereby disrupting PIASγ-IKKγ cross talk, a pre-requisite for IKKγ sumoylation and subsequent NFκB activation. Interruption in the PIASγ-mediated resistance pathway channels ATM signaling toward ATM/JNK pro-death circuitry. These in vitro results also translated to sensitive and resistant tumor allograft mouse models in which low ROS-induced resistance was over-ruled in PIASγ knockout tumors, while its overexpression inhibited high ROS-dependent apoptotic cues. Cumulatively, our findings identified an unappreciated yet critical combinatorial function of cellular ROS and PIASγ in regulating ATM-mediated chemosensitization of resistant tumors. Thus, therapeutic strategies employing ROS upregulation to inhibit PIASγ during genotoxic therapy may, in future, help to eliminate the problems of NFκB-mediated tumor drug resistance.

Evidence of the participation of electronic excited states in the mechanism of positronium formation in substitutional Tb(1-x)Eu(x)(dpm)3 solid solutions studied by optical and positron annihilation spectroscopies.

Positronium formation in the bimary molecular solid solutions Tb(1-x)Eu(x) (dpm)(3) (dpm = dipivaloylmethanate) has been investigated. A strong linear correlation between the (5)D(4) Tb(iii) energy level excited state lifetime and the positronium formation probability has been observed. This correlation indicates that the ligand-to-metal charge transfer LMCT states act in both luminescence quenching and positronium formation inhibition, as previously proposed. A kinetic mechanism is proposed to explain this correlation and shows that excited electronic states have a very important role in the positronium formation mechanism.

Restoration of tumor suppressor p53 by differentially regulating pro- and anti-p53 networks in HPV-18-infected cervical cancer cells.

Abrogation of functional p53 is responsible for malignant cell transformation and maintenance of human papilloma virus (HPV)-infected cancer cells. Restoration of p53 has, therefore, been regarded as an important strategy for molecular intervention of HPV-associated malignancies. Here we report that differential regulation of pro- and anti-p53 setups not only upregulates p53 transcription but also stabilizes and activates p53 protein to ensure p53-induced apoptosis in HPV-18-infected cervical cancer. Functional restoration of p53 can be achieved by non-steroidal anti-inflammatory drug celecoxib via multiple molecular mechanisms: (i) inhibition of p53 degradation by suppressing viral oncoprotein E6 expression, (ii) promoting p53 transcription by downmodulating cycloxygenase-2 (Cox-2) and simultaneously retrieving p53 from Cox-2 association and (iii) activation of p53 via ataxia telangiectasia mutated-/p38 mitogen-activated protein kinase-mediated phosphorylations at serine-15/-46 residues. That restored p53 is functional has been confirmed by its ability of transactivating Bax and p53-upregulated modulator of apoptosis, which in turn switch on the apoptotic machinery in these cells. Studies undertaken in biopsy samples of cervical carcinoma further validated celecoxib effect. Our approaches involving gene manipulation and pharmacological interference finally highlight that celecoxib alters pro- and anti-p53 networks, not in isolation but in concert, to rejuvenate p53-dependent apoptotic program in HPV-infected cervical cancer cells.

Follow-up study of unknowingly pregnant women vaccinated against rubella in Brazil, 2001-2002.

BACKGROUND: Brazil conducted mass immunization of women of childbearing age in 2001 and 2002. Surveillance was initiated for vaccination of women during pregnancy to monitor the effects of rubella vaccination on fetal outcomes. METHODS: Women vaccinated while pregnant or prior to conception were reported to the surveillance system. Susceptibility to rubella infection was determined by anti-rubella immunoglobulin (Ig) M and IgG immunoassays. Susceptible women were observed through delivery. Live-born infants were tested for anti-rubella IgM antibody; IgM-seropositive newborns were tested for viral shedding and observed for 12 months for signs of congenital rubella syndrome. Incidence of congenital rubella infection was calculated using data from 7 states. RESULTS: A total of 22 708 cases of rubella vaccination during pregnancy or prior to conception were reported nationwide, 20,536 (90%) of which were from 7 of 27 states in Brazil. Of these, 2332 women were susceptible to rubella infection at vaccination. Sixty-seven (4.1%) of 1647 newborns had rubella IgM antibody (incidence rate, 4.1 congenital infections per 100 susceptible women vaccinated during pregnancy [95% confidence interval, 3.2-5.1]). None of the infants infected with rubella vaccine virus was born with congenital rubella syndrome. CONCLUSIONS: As rubella elimination goals are adopted worldwide, evidence of rubella vaccine safety aids in planning and implementation of mass adult immunization.

Aspectos neuroimaginológicos en las mucopolisacaridosis: correlación con el retraso mental / Neuroimaging features in mucopolysaccharidosis: their correlation with mental retardation

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Giant solitary fibrous tumour of the meninges: MR-pathological correlation.

The authors present the clinical, MR imaging and pathological features of the largest intracranial solitary fibrous tumour of the meninges ever reported in the literature. This well-circumscribed dural-based tumour strikingly demonstrated two different solid components. The first one demonstrated a suggestive T2 hypointensity that strongly enhanced after gadolinium administration while the other showed more classic homogeneous T2 hyperintensity and mild enhancement. These two components were also identifiable on the pathological examination, allowing an interesting imaging-histological correlation. Differential diagnoses of this rare extra-axial lesion are discussed.

Intramolecular energy transfer through charge transfer state in lanthanide compounds: a theoretical approach.

A theoretical approach for the intramolecular energy transfer process involving the ligand-to-metal charge transfer (LMCT) state in lanthanide compounds is developed. Considering a two-electron interaction, both the direct Coulomb and exchange interactions are taken into account, leading to expressions from which selection rules may be derived and transfer rates may be calculated. These selection rules show that the direct Coulomb and exchange mechanisms are complementary, in the same way as obtained in previous works for the case of ligand-lanthanide ion energy transfer processes. An important result from numerical estimates is that the channel ligand-LMCT state is by far the dominant case, leading to transfer rates higher than for the channel lanthanide ion-LMCT state by several orders of magnitude. The analysis of the emission quantum yield as a function of the relative energy position of the LMCT state in a typical Eu(3+) compound allows the identification of two quenching regions, the most pronounced one occurring close to the lower ligand triplet level.

Imunoterapia em carcinoma de células escamosas em cão

O artigo não apresenta resumo.

A brincadeira simbólica nas situações lúdicas de crianças com necessidades especiais e crianças normais / Symbolic playing in children with special needs and normal children

Este artigo apresenta um estudo comparativo de situações lúdicas com três grupos de crianças: 1)normais, 2)com disfunções físicas e 3)crianças com retardo mental de 4 a 6 anos de idade de desenvolvimento. Cada um dos três grupos foi composto por cinco crianças que foram convidadas a participar de sessões em que eram oferecidos brinquedos e materiais lúdicos. As vivências dessas situações de brincadeira foram registradas por meio de filmagens em vídeo e analisadas posteriormente. Os principais resultados mostram o potencial dos brinquedos para o desenvolvimento de representações simbólicas; as diferenças entre os tipos de interações estabelecidas entre as crianças e o brinquedo, as funções dadas a ele pela crianças, e também os diferentes papéis que o adulto exerce na interação com os grupos de crianpças (AU)

Protein A-activated macrophages induce apoptosis in Ehrlich's ascites carcinoma through a nitric oxide-dependent pathway.

Protein A (PA) of Staphylococcus aureus has been demonstrated to possess anti-tumor activity against a wide variety of tumors. In the current study we endeavored to obtain a mechanistic insight into PA-mediated Ehrlich's ascites carcinoma (EAC) killing. Our results indicate that PA stimulates generation of nitric oxide (NO) from murine peritoneal macrophages. Nitric oxide in turn induces cytotoxic damage to the tumor cells. Analysis of the morphological features and cell cycle phase distribution pattern of nuclear DNA revealed an induction of apoptosis (appearance of sub-G0/G1 population) in EAC after PA treatment. We have further elaborated the alterations in the expressions of the proto-oncoproteins p53 and Bax, together with a change in the ratio of Bcl-2/Bax in the treated tumor cells, which favor apoptosis. PA-induced apoptosis and changes in the expression of oncoproteins in the tumor cells was prevented by the suppression of NO release by the addition of L-NAME, the competitive NOS inhibitor, suggesting a possible mechanism by which PA exerts its anti-tumor activities involving nitric oxide through the alteration in the expressions of pro-apoptotic proteins.

Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells.

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is a potent antioxidant and anti-inflammatory agent. It has been recently demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin still remain unrealized, although it has been postulated that induction of apoptosis in cancer cells might be a probable explanation. In the current study, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the induction of apoptosis in the tumor cells as evident from flow-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation. Probing further into the molecular signals leading to apoptosis of EAC cells, we observed that curcumin is causing tumor cell death by the up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the mitochondria, and activation of caspase-3. The status of Bcl-2 remains unchanged in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apoptosis.

Elective neck dissection versus observation in stage I squamous cell carcinomas of the tongue and floor of the mouth.

A retrospective study was undertaken of patients with T1N0M0 squamous cell carcinoma of the oral tongue and floor of the mouth who underwent surgical treatment between 1985 and 1995. Evaluation of two groups of patients (neck dissection versus observation) was made according to the management of the neck. Results were obtained regarding the presence of occult metastases, recurrence in the neck, treatment failure, results of salvage treatment, and disease-free survival. Forty-nine patients underwent surgical treatment: 25 resection of primary and 24 resection plus neck dissection. Overall incidence of regional metastases was 24.5%. Eight patients (16%) developed recurrence of the disease. Seven (14%) had regional recurrences (including 1 with distant metastases) and 1(2%) had local recurrence. Twenty-four percent of patients from the resection of primary group developed neck recurrences in comparison with 4% of the resection plus neck dissection group (P = 0.05). Overall salvage rate was 37.5%. Second primary tumors developed in 16% of patients. Patients who underwent elective neck dissection had a 23% higher disease-free survival rate compared with those who underwent resection of the tumor alone (P = 0.03). The findings of this study stress the importance of control of the neck in early oral cancer. Elective neck dissection significantly improved regional control of the disease.