Prevention of DNA damage and anticarcinogenic activity of Activia® in a preclinical model.

Colorectal cancer is a global public health issue. Studies have pointed to the protective effect of probiotics on colorectal carcinogenesis. Activia® is a lacto probiotic product that is widely consumed all over the world and its beneficial properties are related, mainly, to the lineage of traditional yoghurt bacteria combined with a specific bacillus, DanRegularis, which gives the product a proven capacity to intestinal regulation in humans. The aim of this study was to evaluate the antigenotoxic, antimutagenic, and anticarcinogenic proprieties of the Activia product, in response to damage caused by 1,2-dimethylhydrazine (DMH) in Swiss mice. Activia does not have shown antigenotoxic activity. However, the percent of DNA damage reduction, evaluated by the antimutagenicity assay, ranged from 69.23 to 96.15% indicating effective chemopreventive action. Activia reduced up to 79.82% the induction of aberrant crypt foci by DMH. Facing the results, it is inferred that Activia facilitates the weight loss, prevents DNA damage and pre-cancerous lesions in the intestinal mucosa.

Antimutagenic and anticarcinogenic effects of wheat bran in vivo.

Previous studies in rodents treated with the pro-carcinogen 1,2-dimethylhydrazine suggested that the consumption of wheat bran protected against DNA damage in the colon and rectum. Based on this information, we evaluated wheat bran as a functional food in the prevention and treatment of colon cancer. We used the aberrant crypt focus assay to evaluate the anticarcinogenic potential of wheat bran (Triticum aestivum variety CD-104), the comet assay to evaluate its antigenotoxicity potential, and the micronucleus assay to evaluate its antimutagenic potential. The wheat bran gave good antimutagenic and anticarcinogenic responses; the DNA damage decreased from 90.30 to 26.37% and from 63.35 to 28.73%, respectively. However, the wheat bran did not significantly reduce genotoxicity. Further tests will be necessary, including tests in human beings, before this functional food can be recommended as an adjunct in the prevention and treatment of colon cancer.

Evaluation of the antimutagenic and anticarcinogenic effects of inulin in vivo.

The incidence of colorectal cancer is growing worldwide. The characterization of compounds present in the human diet that can prevent the occurrence of colorectal tumors is vital. The oligosaccharide inulin is such a compound. The aim of this study was to evaluate the antigenotoxic, antimutagenic and anticarcinogenic effects of inulin in vivo. Our study is based on 3 assays that are widely used to evaluate chemoprevention (comet assay, micronucleus assay, and aberrant crypt focus assay) and tests 4 protocols of treatment with inulin (pre-treatment, simultaneous, post-treatment, and pre + continuous). Experiments were carried out in Swiss male mice of reproductive age. In order to induce DNA damage, we used the pro-carcinogenic agent 1,2-dimethylhydrazine. Inulin was administered orally at a concentration of 50 mg/kg body weight following the protocols mentioned above. Inulin was not administered to the control groups. Our data from the micronucleus assay reveal antimutagenic effects of inulin in all protocols. The percentage of inulin-induced damage reduction ranged from 47.25 to 141.75% across protocols. These data suggest that inulin could act through desmutagenic and bio-antimutagenic mechanisms. The anticarcinogenic activity (aberrant crypt focus assay) of inulin was observed in all protocols and the percentages of damage reduction ranged from 55.78 to 87.56% across protocols. Further tests, including human trials, will be necessary before this functional food can be proven to be effective in the prevention and treatment of colon cancer.

Anaesthetic management of intracranial hypertension and pregnancy. A case report. / Manejo anestésico de hipertensión intracraneal y embarazo. Informe de un caso.

Hydrocephalus is an active distension of the ventricular system of the brain. The improved survival rates of patients with neurosurgical pathology is accompanied by a greater number of non-neurosurgical procedures in patients who have therapeutic neurosurgical devices. The real incidence of pregnancy in patients with obstructive hydrocephalus controlled with ventriculoperitoneal shunt (VPS) is unclear. We present a case of a pregnant 34-year-old female with a VPS for obstructive hydrocephalus. Due to VPS obstruction secondary to uterus volume, she presented several episodes of neurological impairment during pregnancy. An elective caesarean section (C-section) and VPS review were planned for the same operative time. This rare case reflects the challenge that the anaesthesiologist has to face in order to provide the best and simultaneous management of the wellbeing of the mother, the mother's brain and the foetus.

SAFIIRA: A heavy-ion multi-purpose irradiation facility in Brazil.

This work describes the new facility for applied nuclear physics at the University of Sao Paulo, mainly for irradiation of electronic devices. It is a setup composed of a quadrupole doublet for beam focusing/defocusing plus multiple scattering through gold foils to produce low intensity, large-area, and high-uniformity heavy-ion beams from 1H to 107Ag. Beam intensities can be easily adjusted from 102 particles cm2/s to hundreds of nA for an area as large as 2.0 cm2 and uniformity better than 90%. Its irradiation chamber has a high-precision motorized stage, and the system is controlled by a LabViewTM environment, allowing measurement automation. Design considerations and examples of use are presented.

LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.

Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system.

Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A.

Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241 fibrosarcoma and VEGF-A-/- embryonic stem cells) grown in murine dorsal skinfold chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression elevated vascular permeability in T241 tumors, but not in VEGF-A-/- tumors. Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing antibody DC101 reduced vascular density and permeability of both VC+ and mock-transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels.

TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16(INK4a) protein expression.

Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis.

Long-term contraception with a single implant of the progestin ST-1435.

Silastic capsules containing the synthetic progestin ST-1435 was inserted in 282 women of reproductive age who desired long-term contraception. Each woman received a single implant for 6 months' use. After evaluating the experience of the first 45 subjects, replacement capsules were offered to women desirous of continuing the method after the initial 6 months of use. In the first 6-month segment one pregnancy and 1720 woman-months of use were recorded. The total experience, through as many as six segments of use was 3373 woman-months of use and one pregnancy. The Pearl Index is 0.36 per 100 woman-years. The single pregnancy, recorded in the 1st month of the first segment, may represent a conception prior to implant placement. Amenorrhea was the most common side effect reported, with 83% of the women having at least one nonbleeding interval longer than 60 days during the first segment of use.

Conception control by vaginal administration of pills containing ethinyl estradiol and dl-norgestrel.

One hundred twenty-four women of reproductive age have used vaginal pills containing 50 micrograms dl-norgestrel and 35 micrograms ethinyl estradiol to prevent conception for periods ranging from 6 to 20 months. One thousand four hundred thirty-eight woman-months were recorded. No pregnancies occurred. Cycle control was good. Bleeding usually lasted 3 to 5 days, and the interval between withdrawal bleeding events was 26 to 30 days in 86% of the cycles. Amenorrhea, breakthrough bleeding, and spotting occurred rarely. The continuation rate at 1 year was 64%.

PIP: This paper reports the results of a clinical trial of124 women of reproductive age who relied on daily administration of a vaginal pill containing 50 mg dl-norgestrel in combination with 35 mcg ethinyl estradiol fro contraceptive purposes for 6-20 months. No pregnancies occurred in 1438 woman-months of abservation. Bleeding generally developed 3-5 days after insertion of the last pill and lasted an average of 3-5 days. The interval between withdrawal bleeding events was 26-30 days in 86% of cycles. Incidence of intermenstrual bleeding, spotting, and amenorrhea was minimal. No siginificant alterations in blood pressure or blood cell counts and hematocrit were noted. Vaginal discharge requiring treatment developed in 20.9% od subjects; however, this incidence is comparable to that found in oral contraceptive (OC) and IUD users and may thus be unrelated to the vaginal pill. After 1 year of use, 64% of the subjects opted to continue the vaginal pill. This contrasts favorably with continuation rates recorded at the same clinic for vaginal ring users (48%) and OC users (47%). Only 7 of the 44 vaginal pill discontinuers cited medical reasons; the majority gave trivial reasons, and several reapplied for inclusion in the vaginal pill trial a few months after discontinuation. These findings suggest that the vaginal pill avoids the undesirable side affects of the vaginal ring (e.g., expulsion, interference with coitus, odor) as well as those associated with the gastric absorption os steroids, demonstrates a low incidence of complications, and is highly effective in preventing pregnancy.

Ovulation inhibition following vaginal administration of pills containing norethindrone and mestranol.

Plasma levels of estradiol and progesterone were investigated in women using daily vaginal pills containing 1 mg norethindrone and 50 mcg mestranol. Of 13 treatment cycles in ten women using one vaginal pill daily, six were ovulatory and seven anovulatory. All 12 cycles in ten women using two vaginal pills daily were anovulatory.

PIP: Plasma levels of estradiol and progesterone were investigated in 20 healthy women, 21-28 years of age, using daily vaginal pills containing 1 mg norethindrone and 50 mcg mestranol. All patients were using a copper T IUD for 1 year or longer. Blood samples were provided 2-3 times a week during a control pretreatment cycle and during 1 or more treatment cycles. Plasma estradiol and progesterone were measured by radioimmunoassay. Each of 2 groups of 10 women was instructed to insert either 1 or 2 pills daily for 21 days in the vagina, always at the same time of day. A total of 25 treatment cycles was available for analysis. Of the 10 women inserting 1 pill daily, 13 treatment cycles were available. In 6 of these cycles, both progesterone and estradiol levels remained within the normal ovulatory pattern, indicating that ovulation occurred. In the remaining 7 cycles, no preovulatory estrogen peak nor postovulatory progesterone rise occurred, indicating that no ovulation occurred. Of the 10 women inserting 2 pills daily, 12 cycles were available for analysis. In all 12 cycles, no rise in progesterone levels occurred, indicating that ovulation was suppressed. In some cycles estradiol levels rose above 300 pg/ml but progesterone levels remained below 2 ng/ml. Except for 1 patient who complained of vaginal irritation with pruritus, no side effects associated with vaginal pill insertion occurred. In a previous study it was shown that a combination pill containing dl-norgestrel and ethynylestradiol could inhibit ovulation. This studies shows that another combined pill containing norethindrone and mestranol may be as effective as the norgestrel ethynylestradiol combination. To obtain contraceptive efficacy, 2 mg of norethindrone and 100 mcg of mestranol have to be administered daily. The requirement for higher dose by the vaginal route as compared to the oral route stems from the fact that much lower blood levels of the steroids are obtained through vaginal absorption. This dose could be contained in a single tablet if the compounds tested in this study are to be used as a vaginal pill contraceptive.

Contraceptive effectiveness of Silastic implants containing the progestin R-2323.

PIP: The long-term contraceptive effectiveness of subdermal silastic implants containing 30-40 mg of the progestin R-2323 (13-ethyl-17 alpha ethinyl-17 hydroxy-gona-4, 9,11-trien-3-one), was studied in 531 women. 98 women received 2 capsules (Group A), 180 received 3 capsules (Group B), 181 received 4 capsules (Group C) and 68 received 5 capsules (Group D). There were 5 pregnancies reported for Group A over 610 months of use, 3 pregnancies for 2124 months of use in Group B, 4 pregnancies for 2128 months of use in Group C, and Group D had 3 pregnancies over 732 months of use. All of the pregnancies in Group A occurred in the first 4 months while pregnancies in the other 3 groups generally occurred between Months 6-12 of use. Amenorrhea was most frequent during Months 2-6. The frequency of spotting and breakthrough bleeding was minimal.^ieng

Heart rate and avoidance conditioned activity in rats.

In accordance with the determination of base-line heart rate and running in an activity wheel, 14 Long-Evans male rats were given ten 30 minute sessions of Immobile-Avoid conditioning followed by 30 minute sessions of Active-Avoid conditioning. Control Ss were yoked to the experimental Ss. Experimental Ss made significantly fewer responses in the immobile-avoid period and significantly more responses in the active-avoid period than did the yoked control Ss. Heart rate was correlated with skeletal activity both for experimental and control Ss. For experimental Ss, low heart rate was concomitant with a low amount of activity in the immobile-avoid peroid and high heart rate was concomitant with greater skeletal activity in the active-avoid period. These results support the position that heart rate is secondary to responses of the somatic-motor system and that heart rate during immobile-avoid or active avoid conditioning is more closely related to the level of somatic-motor activity than to the emotional stress which purportedly motivates instrumental avoidance behavior.

[Mobile liver and colonic volvulus. A case report]. / Hígado móvil y vólvulo de colon. Presentación de un caso.

A <> liver is an exceptional situation in which the laxness or absence of the ligaments supporting liver allow it to move in the transversal plane so that it is always located on the dependent side. This condition is usually associated to a long and lax mesocolon, which is usually responsible for the symptoms. Very few cases have been described in the literature. To our knowledge, this is the first report of the computed tomography (CT) findings of a mobile liver with acute abdomen caused by associated colonic volvulus.

[Diagnosis and treatment of benign breast lesions during pregnancy]. / Diagnóstico y tratamiento de las lesiones benignas de la mama en el embarazo.

OBJECTIVES: To retrospectively study the diagnosis and treatment of benign breast disease during pregnancy and breastfeeding at our department. To review the relevant literature. MATERIALS AND METHODS: From January 2001 to March 2005, a total of 91 pregnant or breastfeeding women (age range: 23-36 years) were diagnosed with benign breast pathology. All patients presented with palpable nodules or inflammatory symptoms. Ultrasound-guided fine-needle cytology was performed in all cases and percutaneous core biopsy was considered necessary in three cases. Abscesses were drained when present. Patients provided their informed consent before all procedures. RESULTS: Tumors were detected in 28 cases (30%): fibroadenomas (n = 12), lactating adenomas (n = 9), galactoceles (n = 5), and papillomas (n = 2). Conservative treatment with ultrasound follow-up was employed in all cases except one, which required surgical treatment in the third trimester. On 63 occasions (70%), the pathology was inflammatory, including abscesses in 24 cases (38%); abscesses were drained using fine-needle aspiration (n = 16) or pig-tail catheter (n = 3), according to protocol, depending on the size of the abscess (less than or greater than 3 cm). In 5 cases the abscesses were drained surgically. CONCLUSIONS: The most common benign breast pathology during pregnancy is inflammatory and is satisfactorily managed with antibiotics and percutaneous drainage with good esthetic results. Ultrasound is the diagnostic technique of choice, together with cytology; percutaneous biopsy is only performed in uncertain cases to minimize the risk of fistulas. Management of tumors after histological confirmation should be conservative with close follow-up. These tumors cause no problems for the child, the mother, or breastfeeding.

Mammary tuberculosis: percutaneous treatment of a mammary tuberculous abscess.

It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis.

Synaptotagmin-1 is required for fibroblast growth factor-1 release.

By using p65 synaptotagmin-1 and fibroblast growth factor (FGF)-1:beta-galactosidase (beta-gal) NIH 3T3 cell co-transfectants, we demonstrate that a proteolytic fragment consisting of the extravesicular domain of synaptotagmin-1 is released into the extracellular compartment in response to temperature stress with similar kinetics and pharmacological properties as FGF-1:beta-gal. Using a deletion mutant that lacks 95 amino acids from the extravesicular domain of synaptotagmin-1, neither synaptotagmin-1 nor FGF-1:beta-gal are able to access the stress-induced release pathway. Furthermore, the p40 extravesicular fragment of synaptotagmin-1 is constitutively released in p40 synaptotagmin-1 NIH 3T3 cell transfectants, and this release is potentiated when the cells are subjected to temperature stress. These data demonstrate that the p40 fragment derived from synaptotagmin-1 is able to utilize the FGF-1 non-classical exocytotic pathway and that the release of FGF-1 is dependent on synaptotagmin-1.