Implants composed of digoxin and poly(ε-caprolactone): development, characterization, anti-proliferative and anti-angiogenic activities.

Drug delivery systems could be applied to locally treat cervical cancer, thus preventing the drawbacks of conventional therapy. In this study, anti-proliferative and anti-angiogenic effects of digoxin incorporated into poly(ε-caprolactone) implants were evaluated, aiming at the local treatment of cervical cancer. Implants were characterized, and the in vitro release profile of digoxin was demonstrated. Anti-proliferative and anti-angiogenic activities of digoxin were investigated by using chorioallantoic membrane and human cervix carcinoma (HeLa) cells, respectively. The chemical structure of digoxin and the semi-crystalline nature of poly(ε-caprolactone) were preserved after designing implants. The hydrophobicity of drug and polymer as well as the semi-crystalline structure provided a controlled diffusion of digoxin from implants. Digoxin released from implantable devices exhibited anti-proliferative activity against HeLa cells. The anti-angiogenic effect was also shown. Finally, implants composed of digoxin and poly(ε-caprolactone) could be applied as a therapeutic alternative to treat the early stage of cervical cancer, once they were able to locally control the release of this anti-angiogenic and anti-proliferative drug, minimizing its systemic side effects and toxicity.

Antimicrobial effect of Lippia sidoides and thymol on Enterococcus faecalis biofilm of the bacterium isolated from root canals.

The species Lippia sidoides Cham. (Verbenaceae) is utilized in popular medicine as a local antiseptic on the skin and mucosal tissues. Enterococcus faecalis is the bacterium isolated from root canals of teeth with persistent periapical lesions and has the ability to form biofilm, where it is responsible for the failure of endodontic treatments. Essential oil of L. sidoides (EOLS) and its major component, thymol, were evaluated for reducing the CFU in biofilms of E. faecalis in vitro. The essential oil was obtained by hydrodistillation and examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC-MS). The GC-MS analysis has led to the identification of thymol (84.9%) and p-cymene (5.33%). EOLS and thymol reduced CFU in biofilms of E. faecalis in vitro (time of maturation, 72 h), with an exposure time of 30 and 60 min at concentrations of 2.5 and 10%. There was no statistical difference in effect between EOLS and thymol, demontrating that this phenolic monoterpene was the possible compound responsible for the antimicrobial activity of EOLS. This study provides a basis for the possible utilization of EOLS as an adjuvant in the treatment of root canals that show colonization by E. faecalis.

GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer.

The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the post-therapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wild-type or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.

Investigation of the cytocidal potential of Rhinella jimi skin methanol extracts.

CONTEXT: Amphibian skins have wide variety of biologically active compounds associated with the natural defenses of these animals. OBJECTIVES: To study the in vitro anticancer activity of methanol extracts of the skin of Rhinella jimi Stevaux (Anura: Bufonidae). MATERIAL AND METHODS: The extract was obtained by cold methanol extraction for 96 h using dried skins (295 mg). The methanol skin extract was dried under reduced pressure, giving a 5.5% yield. In order to test for growth-inhibitory activity, in vitro tests were performed with the following cancer cell lines using concentrations ranging between 0.25-250 µg/mL of the extract by 48 h: K562 (leukemia), MCF-7 (breast), NCI-ADR (breast with MDR phenotype), UACC-62 (melanoma), NCI460 (lung), PCO3 (prostate), HT-29 (colon), OVCAR (ovary), and 786-0 (kidney). RESULTS: The methanol extract of R. jimi produced a growth inhibition in a dose-dependent manner against the most of the assayed cell lines. In addition to the growth inhibition, the extract induced the cell death in the ovary and colon lines (EC50 0.125 and 0.2 µg/mL, respectively), demonstrating 100% of inhibition with 2.5 µg/mL. However, prostate and leukemia cell lines demonstrated less sensitivity, with EC50 of 24 and 235 µg/mL, respectively. This is the first report about the anticancer activity by natural products from the skin of R. jimi. CONCLUSIONS: The methanol extracts of R. jimi significantly affected the growth of several cell lines, demonstrating that these compounds are a potential source of substances that could be utilized in cancer treatments.

Association of MBL2 gene exon 1 variants with autoimmune thyroid disease in Brazilian patients.

We investigated the association between MBL2 gene exon 1 functional polymorphisms and autoimmune thyroid disease (AITD) in 163 Brazilian patients (87 with Hashimoto thyroiditis, HT; 76 with Graves' disease) and 214 healthy controls. Individuals carrying MBL2 O allele are at higher risk of developing AITD (OR = 1.58, 95% CI: 1.11-2.26; P-value = 0.009) and HT (OR = 1.67, 95% CI: 1.09-2.55; P-value = 0.013) as suggesting a possible role for mannose-binding lectin in influencing disease susceptibility.

GSTT1, GSTM1, and GSTP1 polymorphisms and chemotherapy response in locally advanced breast cancer.

The glutathione S-transferase (GST) family consists of phase II detoxification enzymes that catalyze the conjugation of toxic substances, such as chemotherapeutic agents, to glutathione. We examined whether GSTT1/GSTT1"null", GSTM1/GSTM1"null" and GSTP1Ile105Ile/GSTP1Ile105Val polymorphisms are associated with different response rates to neoadjuvant chemotherapy in the treatment of stage II and III breast cancer. Forty Brazilian women with invasive ductal adenocarcinoma of the breast submitted to neoadjuvant chemotherapy, using 5-fluorouracil, epirubicin and cyclophosphamide, were genotyped for the GSTT1, GSTM1 and GSTP1 genes. Clinical response was assessed by RECIST criteria. Comparisons were made for the three genes alone and in pairs, as polymorphic and as wild-type combinations and polymorphic/wild-type combinations. We analyzed all possible combinations and their response rate. Patients with the GSTT1/GSTP1105Ile combination were found to have a significantly better response than GSTT1"null"/GSTP1105Val (P = 0.0209) and GSTT1/GSTM1 (P = 0.0376) combinations. Analysis of all possible combinations showed the GSTM1"null" polymorphic genotype to be present in four, and the wild-type GSTP1105Ile in six of the combinations associated with the largest number of responding patients. We found that patients with the GSTT1/GSTP1105Ile wild-type combination had a significantly higher response rate to chemotherapy than patients with the respective polymorphic GSTT1"null"/GSTP1105Val combination or patients with the wild-type GSTT1/GSTM1. The six gene combinations associated with the largest number of responding patients were found to contain the wild-type GSTP1105Ile and the polymorphic-type GSTM1"null". These specific combinations were virtually absent in the combinations with few responding patients.

Avaliação da atividade antibacteriana e prospecção fitoquímica de Solanum paniculatum Lam. e Operculina hamiltonii (G. Don) D. F. Austin & Staples, do semi-árido paraibano / Evaluation of antibacterial activity and phytochemical prospection of Solanum paniculatum Lam. and Operculina hamiltonii (G. Don) D. F. Austin & Staples from the semi-arid region of Paraíba State, Brazil

Devido ao aparecimento de populações de parasitos resistentes, as drogas farmacêuticas, alternativas de controle, estão sendo pesquisadas utilizando plantas medicinais. O objetivo deste estudo foi avaliar a atividade antibacteriana e realizar a análise fitoquímica do extrato etanólico de duas espécies do semi-árido paraibano, Solanum paniculatum Lam. e Operculina hamiltonii (G. Don) D. F. Austin & Staples. As referidas espécies são muito utilizadas pela população rural contra verminoses gastrintestinais de ovinos. A prospecção fitoquímica foi obtida a partir dos extratos etanólicos para análise dos constituintes químicos existentes nas duas espécies. As análises dos extratos indicaram a presença de taninos flobabênicos, flavononóis, flavononas e alcalóides em ambas as espécies. A atividade antibacteriana foi determinada inicialmente pelo método de difusão em cavidade. A espécie S. paniculatum apresentou atividade contra Staphylococcus aureus (ATCC 12692), Escherichia coli (ATCC 25922) e Pseudomonas aeruginosa (ATCC 15442), no entanto O. hamintonii não demonstrou atividade contra as linhagens bacterianas testadas.

The emergence of resistant parasite populations has led to the study of pharmaceutical drugs, which represent an alternative control. This study aimed to evaluate the antibacterial activity and to perform the phytochemical analysis of the ethanol extract from two species belonging to the semi-arid region of Paraíba State, Brazil: Solanum paniculatum Lam. and Operculina hamiltonii (G. Don) D. F. Austin & Staples. Such species have been largely used by the rural population against ovine gastrointestinal helminthes. Phytochemical prospection was obtained from ethanol extracts for analysis of chemical compounds present in both species. Extract analyses indicated the presence of condensed tannins, flavonols, flavanones, and alkaloids in both species. The antibacterial activity was initially determined by the cavity method. The species S. paniculatum had activity against Staphylococcus aureus (ATCC 12692), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 15442); however, O. hamintonii did not present activity against the tested bacterial strains.

Effects of 5'-adenosine triphosphate on intestinal ischemia-reperfusion in rabbits.

To study whether treatment with 5'-adenosine triphosphate (ATP), an agonist of P2 purine receptors, attenuated intestinal dysfunction caused by ischemia (I) and/or reperfusion (R), rabbits were treated with ATP (15 mgxkg(-1), intravenously) or saline solution (SS) 60 minutes before I by occlusion of the superior mesenteric artery and/or R (120 minutes). After I or I/R isolated 2-cm jejunal segments were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for optical microscopy. Compared to a sham group, the jejunal contractions were similar to sham hosts among I + ATP, but reduced in I + SS, I/R + SS, and I/R + ATP groups. The jejunal-enteric nerves were damaged in I + SS, I/R + SS, and I/R + ATP, but not the I + ATP group. These results suggested that ATP attenuated intestinal dysfunction produced by I, but not that caused by R.

Correlation of polymorphism C3435T of the MDR-1 gene and the response of primary chemotherapy in women with locally advanced breast cancer.

Primary chemotherapy is a useful strategy for the treatment of locally advanced breast cancer and therefore allows in vivo evaluation of the action of cytotoxic drugs and the possibility of accomplishing conservative breast surgeries, as well as the early treatment of metastasis. Mechanisms of resistance to the drugs include the action of protein associated with the efflux of drugs from the intracellular environment hindering their activity; one of the most studied proteins is P-glycoprotein codified by the MDR-1 gene. The presence of polymorphisms can determine different physiological actions of these proteins, intervening with the response of the drug's action. We evaluated the presence of single nucleotide polymorphism (SNP) C3435T of the MDR-1 gene and its correlation with the response to primary chemotherapy using the RECIST criteria. Forty-one Brazilian women with stages II and III breast cancer using the PCR-RFLP analysis were evaluated. Thirty-three patients with the SNP genotype (TT and CT) and eight patients with the wild genotype (CC) were found; there was no statistically significant correlation between the diverse genotypes and the clinical and pathological responses according to the Cramer correlation coefficient (V = 0.14). The parameters: nuclear and histological degree, and estrogens, progesterone and c-erb B2 receptors did not demonstrate a statistical correlation with the SNP C3435T. Patients with complete pathological response (12.5%) showed only the polymorphic genotype and not the wild genotype. The characteristics of miscegenation in our population could explain the absence of the characterization of a sub-group of individuals where the presence of the polymorphic genotype influenced the response to the primary chemotherapy.

Correlation of polymorphism C3435T of the MDR-1 gene and the response of primary chemotherapy in women with locally advanced breast cancer

Primary chemotherapy is a useful strategy for the treatment of locally advanced breast cancer and therefore allows in vivo evaluation of the action of cytotoxic drugs and the possibility of accomplishing conservative breast surgeries, as well as the early treatment of metastasis. Mechanisms of resistance to the drugs include the action of protein associated with the efflux of drugs from the intracellular environment hindering their activity; one of the most studied proteins is P-glycoprotein codified by the MDR-1 gene. The presence of polymorphisms can determine different physiological actions of these proteins, intervening with the response of the drug’s action. We evaluated the presence of single nucleotide polymorphism (SNP) C3435T of the MDR-1 gene and its correlation with the response to primary chemotherapy using the RECIST criteria. Forty-one Brazilian women with stages II and III breast cancer using the PCR-RFLP analysis were evaluated. Thirty-three patients with the SNP genotype (TT and CT) and eight patients with the wild genotype (CC) were found; there was no statistically significant correlation between the diverse genotypes and the clinical and pathological responses according to the Cramer correlation coefficient (V = 0.14). The parameters: nuclear and histological degree, and estrogens, progesterone and c-erb B2 receptors did not demonstrate a statistical correlation with the SNP C3435T. Patients with complete pathological response (12.5%) showed only the polymorphic genotype and not the wild genotype. The characteristics of miscegenation in our population could explain the absence of the characterization of a sub-group of individuals where the presence of the polymorphic genotype influenced the response to the primary chemotherapy.

Estudo químico-biológico dos óleos essenciais de Hyptis martiusii, Lippia sidoides e Syzigium aromaticum frente às larvas do Aedes aegypti / Chemical-biological study of the essential oils of Hyptis martiusii, Lippia sidóides and Syzigium aromaticum against larvae of Aedes aegypti and Culex quinquefasciatus

O interesse pelos bioensaios frente à larvas de Aedes aegypti e Culex quinquefasciatus deve-se ao fato de que estas espécies estão distribuídas por todo o território nacional, sendo portanto uma atividade realizada por inúmeros pesquisadores do Brasil. Os óleos essenciais de Syzigium aromaticum (L.) Merr. & Perry, Lippia sidoides Cham.,e Hyptis martiusii Benth.,foram testados no combate ao transmissor da dengue e da filariose. As larvas de terceiro estádio foram expostas em triplicatas a diferentes concentrações (1000, 500, 250, 100, 50, 25 e 10 ppm). As análises foram observadas após dez minutos do início do tratamento, e mostraram resultados bastante significativos, com potencialidade de mortalidade de até 100 por cento das larvas testadas, indicando acentuados efeitos tóxicos de alguns constituintes voláteis presentes nos óleos. Para os óleos de S. aromaticum, L. sidoides e H. martiusii foram constatadas, frente à Aedes aegypti, valores respectivos de CL50 de 21,4; 19,5 e 18,5 ppm e frente ao Culex quinquefasciatus, 14,5; 16,6 e 27,5 ppm, respectivamente.

The interest for a biological assay against larvae of Aedes aegypti and Culex quinquefasciatus is due to the fact that these species are distributed by the whole national territory, being therefore an activity carried out by countless researchers of Brazil. The essential oils of Syzigium aromaticum, Hyptis martiusii and Lippia sidoides were tested in the combat of the transmitter of the dengue and of the filariosis, using larvae of third stadium were exposed in triplicate to different concentrations (1000, 500, 250, 100, 50, 25 and 10 ppm). The larvicidal activity was observed after ten minutes of the beginning of the treatment, in the end showed very significant results, with mortality potentials of up to 100 percent of the tested larvae, indicating accentuated toxical effects in some representatives of the volatile compounds present in the oils. For the oils of S. aromaticum, L. sidoides and H. martiusii DL50 of 1,0; 1,0 and 8,0 ppm, respectively, were observed.

Xantoastrocitoma Pleomórfico: relato de um caso. (Aspectos histopatológicos e terapêuticos) / Pleomorphic Xantoastrocytoma: case report. (Hystophatological and therapeutic aspects)

Os autores apresentam um caso de xantoastrocitoma pleomórfico e discutem a incidência, a apresentação clínica, os aspectos histopatológicos e a conduta terapêutica deste raro tipo de glioma. O controle das crises convulsivas foi obtido pela ressecção do tumor

[Segmental dystonia as manifestation of cavernous angioma: case report]. / Distonia segmentar como manifestação de angioma cavernoso: relato de caso.

Dystonia is a neurologic syndrome whose etiology is not well recognized. We report a sixteen year old patient with difficulty in playing piano, with disability of the left hand, forearm and arm. Short after, she underwent "absence" crises and headache. Neuroradiological exams showed a deep temporal lobe cavernous angioma. It is a rare association between both diseases and there are no reports about segmental dystonia associated to pseudoabsence epilepsy and sporadic migraine secondary to cavernous angioma. Twenty five per cent of dystonias have a secondary cause and we suggest a neuroradiologic investigation.

[Rathke's pouch cysts: diagnosis and treatment]. / Cistos de bolsa de Rathke: diagnóstico e tratamento.

We studied retrospectively a series of four patients with Rathke pouch cysts and pointed out to their clinical presentation and treatment. They all occurred with female patients. Predominant symptoms were amenorrhea, headache and visual disorders. We present a revision of the literature concerning various series of Rathke's pouch cysts. We conclude that surgery is the best therapeutical procedure and transsphenoidal approach is the best surgical technique.

[Complications of pituitary surgery. Analysis of 120 operations at HUCFF-UFRJ]. / Complicações das cirurgias hipofisárias. Análise de 120 cirurgias no HUCFF-UFRJ.

We evaluated 120 pituitary operations performed at Hospital Universitario Clementino Fraga Filho of the Universidade Federal do Rio de Janeiro from 1979 to July 1998 with the aim of analysing the immediate post operative morbidity and mortality. The ages ranged from 15 to 70 years and the clinical diagnoses were: nonsecreting adenomas, 46 (38.34%); acromegaly, 30 (25%); prolactinomas, 29 (24.16%) and Cushing's disease 15 (12.5%). The main endocrine complications were: panhypopituitarism, 16 (13.34%); diabetes insipidus, 15 (12.5%) and adrenocortical insufficiency, 4 (3.34%). Neurological complications: infection, 13 (10.84%); and cerebrospinal fluid leakage, 6 (5%). Two patients died. Our results agree with those of the international literature. We identified a progressive decrease of morbidity and mortality due to surgeon's skill increase and to the uniformity of the clinical team which managed those patients.

[Acromegaly. Diagnostic and therapeutic aspects. Analysis of 18 cases]. / Acromegalia. Aspectos diagnósticos e terapêuticos. Análise de 18 casos.

The authors present a retrospective study of a series of eighteen patients with acromegaly diagnosed, treated and followed by the Endocrinology and Neurosurgery Services of the Hospital Universitário Clementino Fraga Filho of the Federal University of Rio de Janeiro. The average age of the patients was 43.2% years (varying between 15 and 63). Initial complaints were mainly due to somatic alterations in 83.33%; half the cases had manifestations secondary to tumor compression and 53.33% had neuro-ophtalmological alterations. Hypersecretion of growth hormone was demonstrated by basal hormone determinations and dynamic tests. Neuroradiological assessment showed supraselar expansion in 61.11% of cases. Surgical approach was transsphenoidal in all cases. The main objective of this study was to establish diagnostic criteria, discuss the therapeutic conduct and evaluate the results obtained, comparing them with other series of literature.

[Intra-adenomatous pituitary apoplexy]. / Apoplexia hipofisária intradenomatosa.

The authors review the literature on intra-adenomatous pituitary apoplexy with special emphasis on pathophysiology, diagnosis and therapeutic approach. They present five cases, from a series of 86 patients with pituitary tumors, that developed this syndrome. The patients were diagnosed and followed by the Neurosurgery and Endocrinology Services of Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro. Diagnosis was confirmed by CT-Scan and MRI in all cases, and the treatment of choice was surgical. Conclusions point to the diagnostic difficulties and the urgency of treatment in this clinical setting.

Sarcoidosis-tuberculosis association: a case report.

The association of sarcoidosis and tuberculosis is rare and, its differentiation is sometimes very difficult. We report the case of a young man who presented with type III sarcoidosis complicated by pulmonary tuberculosis within 17 months of the diagnosis, leading to a fatal outcome. A change in antimycobacterial antigen complex A60 immunoglobulin G (IgG) titres, as seen in our case, may be helpful in differentiating between the two diseases.

Cranio-orbital approach for the paraclinoidal and anterior communicating aneurysms.

Aneurysms arising at the proximal intracranial carotid artery (between cavernous sinus and posterior communicating artery) and at the anterior communicating complex may present with technical difficulties regarding appropriate access without excessive brain retraction. In a series of 15 patients the authors show the use of the cranio-orbital approach, formerly designed in the access of skull base tumors, for these subgroups of aneurysms. They discuss the advantages of a basal avenue in minimizing brain retraction, better anatomical orientation, obviation of tissue ressection and easier extra-dural bone removal. It was not identified any complication due to the described approach.