Bixin and norbixin protect against DNA‐damage and alterations of redox status induced by methylmercury exposure in vivo

Populations in the Amazon are exposed to organic mercury via consumption of contaminated foods. These ethnic groups consume a specific plant seed “annatto” which contains certain carotenoids. The aim of this study was to find out if these compounds (bixin, BIX and norbixin, NOR), protect against DNA‐damage caused by the metal. Therefore, rats were treated orally with methylmercury (MeHg) and with the carotenoids under conditions that are relevant to humans. The animals were treated either with MeHg (30 μg/kg/bw/day), BIX (0.1–10 mg/kg/bw/day), NOR (0.01–1.0 mg/kg/bw/day) or combinations of the metal compound and the carotenoids consecutively for 45 days. Subsequently, the glutathione levels (GSH) and the activity of catalase were determined, and DNA‐damage was measured in hepatocytes and leukocytes using single cell gel electrophoresis assays. Treatment with the metal alone caused a decrease in the GSH levels (35%) and induced DNA damage, which resulted in increased DNA migration after electrophoresis in liver and blood cells, whereas no effects were seen with the carotenoids alone. When BIX or NOR were given in combination with organic mercury, the intermediate and the highest concentrations of the carotenoids (1.0 and 10.0 mg/kg/bw/day BIX and 0.1 and 1.0 mg/kg/bw/day NOR) protected against DNA‐damage. Furthermore, we found with both carotenoids, a moderate increase in the GSH levels in both metal‐treated and untreated animals, while the activities of catalase remained unchanged. Our results indicate that consumption of BIX and NOR may protect humans against the adverse health effects caused by exposure to organic mercury. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

Evaluation of the clastogenicity and anticlastogenicity of vitamin B6 in human lymphocyte cultures.

Insufficient intakes of many micronutrients found in fruits and vegetables, such as folic acid, vitamins C and B6 may lead to DNA damage, cancer, and degenerative disease. The investigation of dietary antioxidants is a field of great interest for elucidating mechanisms of mutagenesis/carcinogenesis. The present study was undertaken to investigate the effects of vitamin B6 on the induction of chromosomal aberrations in cultured human lymphocytes and to examine the possible anticlastogenic effect of this vitamin on chromosomal damage induced by the antitumor drug doxorubicin. The results showed that when the cultures treated with vitamin B6 were compared with the untreated control in terms of total chromosomal damage and abnormal metaphases, pre- and simultaneous treatment with this vitamin showed no significant differences. In the post-treatment, average and above average concentrations of vitamin B6 alone showed a clastogenic effect. In the simultaneous protocol, this vitamin (15, 90 and 120 microg/mL) was effective in inhibiting chromosomal aberrations induced by doxorubicin (p<0.05), with a reduction of 33.1% with the highest concentration tested. However, in the post-treatment, the associations of vitamin B6 and doxorubicin exerted a more evident clastogenic effect than that observed in the cultures exposed only to the antitumor drug. In the present investigation, the inability of vitamin B6 to decrease chromosomal damage induced by doxorubicin in the pre- and post-treatments could be justified by the instability of this vitamin as a free radical scavenger. In conclusion, the results from this study confirmed that vitamin B6 is protective against chromosomal damage induced by doxorubicin in cultured human lymphocytes, but that the effects depend on concentration and form of treatment.     

Does surgery for Scheuermann kyphosis influence sagittal spinopelvic parameters?

Purpose

To analyze changes in sagittal spinopelvic parameters (SSPs) after surgical treatment of Scheuermann’s Kyphosis (SK).

Methods

We analyzed 20 patients affected by SK and subjected to posterior correction of the kyphosis by facetectomy, Ponte osteotomy, fusion and multilevel instrumentation with pedicle screw system. Four spinal and three pelvic parameters were measured: sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS) and pelvic tilt (PT). Analysis of changes in postprocedural SSPs compared to preoperative values was performed.

Results

TK passed from 78.6° preoperatively to 45.8° (p = 0.003). LL passed from 74.5° preoperatively to 53.5° (p = 0.01). No significant changes occurred in SVA, SS, PT and PI compared to preoperative values.

Conclusion

We confirm the positive effect of surgery by Ponte osteotomy and posterior spinal fusion on TK and LL in patients with SK. In our experience, pelvic parameters did not change after surgery.

     

A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group

Anthracyclines and platinum derivates are active drugs for advanced endometrial carcinoma (AEC), but new schedules with higher efficacy and better tolerability are needed. A phase II study was conducted to describe activity and tolerability of carboplatin (C)+pegylated liposomal doxorubicin (PLD) in patients with AEC. Patients with chemonaive AEC, PS < or = 2, aged < 75 years, with at least one measurable lesion were eligible. Treatment was C (area under curve 5)+PLD (40 mg m(-2)) on day 1 every 4 weeks, up to six cycles. Forty-two patients were needed in a single-stage design, with at least 13 objective responses to define the treatment active. Forty-two patients were enrolled. Median age was 64 years (31-74). A total of 64% of patients were recurrent while 36% were advanced. Three complete (7%) and 22 partial responses (52%) were observed, for an overall response rate of 59.5% (95% exact CI: 43.3-74.3). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of patients) were grade 3/4 neutropaenia 33%/14%, febrile neutropaenia 5%, grade 3/4 thrombocytopaenia 17%/5%, grade 3/4 anaemia 31%/2%. Skin toxicity was mild: grade 1 14%, grade 2 10%, grade 3 5%. Hair loss: complete 5%, partial 12%. The combination of carboplatin and PLD shows good activity and favourable toxicity as first-line chemotherapy of patients with AEC, deserving further studies in this setting.     

Pathological dislocation of the hip in neurofibromatosis: a case report

The Authors report the case of a 28-year-old patient with type 1 neurofibromatosis, who presented a pathological dislocation of the hip. This event was preceded by the development of a neurological pattern of spastic paraparesis and decreased pain sensation in both lower limbs, secondary to the progression of a dystrophic kyphoscoliosis. Pathological dislocation of the hip in neurofibromatosis has been reported in the literature as a consequence of intra-articular growth of neurofibromas. Conversely, in the case described here, clinical and radiographic features and the absence of neurofibromas in the joint, verified by means of radiographic and histological examinations, suggested the diagnosis of neuropathic arthropathy. The treatment of hip dislocation should be differentiated according to the aetiology, given the underlying articular instability in cases of neuropathic arthropathy.     

Activity of chemotherapy in mucinous epithelial ovarian cancer: a retrospective study

OBJECTIVE: Mucinous ovarian carcinoma has a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of first-line and second-line chemotherapy in patients with mucinous ovarian cancer in a mono-institutional series. PATIENTS AND METHODS: In the period under survey (1996-2003), 225 new patients with ovarian cancer were treated. Twenty-one out of these patients (9.3%) received a diagnosis of mucinous ovarian cancer. The median age, performance status, stage at diagnosis and residual disease after surgery were similar in the mucinous compared to the other histological groups (P=NS). RESULTS: In mucinous ovarian cancer the grading of the tumors was 2 in 76% of the cases, while grade 3 was more frequent in the other subtypes (p<0.002). Eighty-five % of the patients had received carboplatin/paclitaxel, while the remaining cases had been treated with a cisplatin-based chemotherapy not containing paclitaxel. Two patients with early stage were treated with adjuvant chemotherapy and were not evaluable for response while 19 patients had measurable disease (12 pts) or were assessed at second-look (7 pts). Forty-seven % of the 19 patients experienced disease progression during first-line, while 31.5% and 10.5% complete and partial responses were recorded, respectively. Fifteen out of the 21 patients had progressed at the time of the analyses. Sixty % of the progressed patients were platinum-refractory, 3 cases were platinum-sensitive and 3 platinum-resistant. The 3 platinum-sensitive patients were treated with single agent carboplatin without any response. No response was recorded with topotecan or liposomal doxorubicin when given as second- or third-line treatment in platinum-refractory/resistant patients. CONCLUSION: Mucinous ovarian cancer has a poor response to chemotherapy both in the first-line and in the recurrence settings. Studies with alternative chemotherapy combinations are mandatory in this histological subgroup.     

Biomaterials in spinal fixation. An experimental animal study to improve the performance

Different pedicle screws were biomechanically and morphologically studied and compared through the use of an animal model to determine their efficacy and resistance in spinal fixation. The principal objective was to compare biomechanical and histomorphological aspects of HA-coated screws to uncoated ones. Fourty-eight cylindrical transpedicular self-tapping screws divided into three groups of sixteen each were employed; Group A: stainless steel screws; Group B: titanium screws; Group C: HA-coated titanium screws. The screws were implanted bilaterally and randomly into the L3, L4, and L5 pedicles of eight adult mongrel sheep. The final insertion torque was measured in all the implants. After one and four months, upon euthanization, four samples per group were extracted from the surrounding bone and the screw extraction torque was measured. The remaining samples were examined and processed for histological and histomorphological evaluations. No differences were observed at one month among the extraction torque of the three groups. After four months the only significance between insertion and extraction values was for the HA group, i.e. p=0.001. Comparing the extraction torque values of the three groups after four months of healing, the HA-coated group showed a greater than twofold increase (p<0.0005). No differences were observed at one month among the percentages of bone-implant contact in the three groups. After four months the percentage was significant only for the C group (p<0.0005). At four months a correlation was found between the morphological and the biomechanical data of group C (p<0.0005). The use of hydroxyapatite-coated screws could act as an effective method to improve the bone-implant interface, thus obtaining a strong fixation of the implant independently of the arthrodesis achieved with bone graft.     

Macronutrients, fatty acids and cholesterol intake and endometrial cancer.

BACKGROUND: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear. PATIENTS AND METHODS: We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids. CONCLUSION: Energy and cholesterol intake were associated with endometrial cancer.