Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.     

Extended pericranial flap and bone graft reconstruction in anterior skull base surgery.

OBJECTIVES: The objectives of this study was to establish a rationale for repairing large anterior skull base defects with an extended pericranial flap and split calvarial bone graft; to define large anterior skull base defects as those spanning the anterior cranial measuring at least 3.0 x 4.0 cm; and to describe the surgical technique and compare it with alternative strategies.Study design Thirty-four patients underwent anterior craniofacial resection of anterior skull-based tumors of varying histology with reconstruction using an extended pericranial flap and split calvarial bone graft. RESULTS: The survival of the pericranial flap and bone graft was maintained in 33 of 34 patients. There was 1 episode of postoperative cerebrospinal fluid leak, 1 episode of osteomyelitis of the bone graft and an epidural abscess, and 1 episode of asymptomatic pneumocephalus. CONCLUSION: Split calvarial bone graft with an extended pericranial flap is an effective technique for reconstructing large anterior skull base defects.     

Reproducibility of the Structural Connectome Reconstruction across Diffusion Methods

Analysis of the structural connectomes can lead to powerful insights about the brain's organization and damage. However, the accuracy and reproducibility of constructing the structural connectome done with different acquisition and reconstruction techniques is not well defined. In this work, we evaluated the reproducibility of the structural connectome techniques by performing test‐retest (same day) and longitudinal studies (after 1 month) as well as analyzing graph‐based measures on the data acquired from 22 healthy volunteers (6 subjects were used for the longitudinal study). We compared connectivity matrices and tract reconstructions obtained with the most typical acquisition schemes used in clinical application: diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI), and diffusion spectrum imaging (DSI). We observed that all techniques showed high reproducibility in the test‐retest analysis (correlation >.9). However, HARDI was the only technique with low variability (2%) in the longitudinal assessment (1‐month interval). The intraclass coefficient analysis showed the highest reproducibility for the DTI connectome, however, with more sparse connections than HARDI and DSI. Qualitative (neuroanatomical) assessment of selected tracts confirmed the quantitative results showing that HARDI managed to detect most of the analyzed fiber groups and fanning fibers. In conclusion, we found that HARDI acquisition showed the most balanced trade‐off between high reproducibility of the connectome, higher rate of path detection and of fanning fibers, and intermediate acquisition times (10‐15 minutes), although at the cost of higher appearance of aberrant fibers.     

Can the self-selection of aerobic exercise be used in individuals with different cardiorespiratory fitness levels?

Sport Sciences for Health - To compare the intensity and duration self-selected by participants with higher and lower cardiorespiratory fitness to that recommended by the American College of Sports...     

Nitric oxide in the exhaled breath condensate of healthy volunteers collected with a reusable device

BackgroundThe analysis of exhaled breath condensate (EBC) is a non-invasive technique that enables the determination of several volatile and nonvolatile substances produced in the respiratory tract, whose measurement may be useful for the diagnosis and monitoring of several respiratory diseases.ObjectiveThe aim of this study was to produce a low-cost reusable device in order to sample exhaled breath condensate in healthy adult volunteers, and to determine the concentration of nitric oxide in the sample collected.Material and methodsThe apparatus was made with a U-shaped tube of borosilicate glass. The tube was placed in a container with ice, and unidirectional respiratory valves were fitted to the distal end. Afterwards, nitric oxide was measured in the exhaled breath condensate (EBC) by chemiluminescence.ResultsThe total cost of the device was $120.20. EBC samples were obtained from 116 volunteers of both sexes, aged between 20 and 70. The mean volume of exhaled breath condensate collected during 10 minutes was 1.0±0.6 mL, and the mean level of nitric oxide was 12.99±14.38 μM (median 8.72 μM). There was no correlation between the nitric oxide levels in the exhaled breath condensate and age or gender.ConclusionWe demonstrate that it is possible to fabricate a low-cost, efficient, reusable device in order to collect and determine nitric oxide levels in EBC. We have identified no correlation between the nitric oxide levels present in the EBC obtained with this method with either age or sex.     

Effects of polyunsaturated fatty acids (PUFAs) in the treatment of experimental chronic renal failure

Purpose

A diet with polyunsaturated fatty acid (PUFA) supplementation has been reported to reduce renal and cardiac diseases. This study sought to elucidate whether PUFAs derived from plant or marine oils could have beneficial effects on the progression of experimental chronic renal failure (CRF).

Methods

Experimental CRF was achieved by a 5/6 nephrectomy model. Male Wistar rats were divided into groups and given daily supplements of fish oil (group FO), flaxseed oil (group FXO), or soybean oil (control?Cgroup SO) for 30?days. Serum creatinine (sCr), 24-h proteinuria, total cholesterol, triglycerides, and creatinine clearance (CLcr) were measured at day 0 and 30?days after surgery when the rats were euthanized for histological analysis of the remnant kidney.

Results

After 30?days, we observed lower levels of sCr in the groups supplemented with PUFA when compared with the control group (FO: 0.92?±?0.13; FXO: 1.06?±?0.28; SO: 1.32?±?0.47?mg/dL) and significantly slower variations of sCr (??sCr) in the groups treated with PUFAs (FO?=?0.35?±?0.16; FXO?=?0.47?±?0.31; OS?=?0.72?±?0.43; mg/dL, P?=?0.041). Similarly, the CLcr of both of the groups that received PUFAs was significantly slower than the rats in the control group (FO: 0.45?±?0.15; FXO: 0.60?±?0.09; SO: 0.28?±?0.06?mL/min/day; P?=?0.01). The rats that received PUFA supplements also presented significantly less histological lesions compared with the control group.

Conclusions

These results suggest a beneficial effect of dietary supplementation with flaxseed or fish oil in rats with CRF.     

Oral administration of antioxidants improves skin wound healing in diabetic mice

Oxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b⁺ and Ly6G⁺ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG⁺/CD206^? macrophages whereas CD206⁺/MIG^? macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.