Genotoxicity and cytotoxicity of antineoplastic drugs at environmentally relevant concentrations after long-term exposure.

Introduction: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations. Aims: Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model. Methods: Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL-1; 5-FU received 5-fluorouracil at 10ngL-1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL-1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained. Results: Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression. Conclusion: These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.

Nutrient-dense protein as a primary dietary strategy in healthy ageing: please sir, may we have more?

A progressive decrement in muscle mass and muscle function, sarcopoenia, accompanies ageing. The loss of skeletal muscle mass and function is the main feature of sarcopoenia. Preventing the loss of muscle mass is relevant since sarcopoenia can have a significant impact on mobility and the quality of life of older people. Dietary protein and physical activity have an essential role in slowing muscle mass loss and helping to maintain muscle function. However, the current recommendations for daily protein ingestion for older persons appear to be too low and are in need of adjustment. In this review, we discuss the skeletal muscle response to protein ingestion, and review the data examining current dietary protein recommendations in the older subjects. Furthermore, we review the concept of protein quality and the important role that nutrient-dense protein (NDP) sources play in meeting overall nutrient requirements and improving dietary quality. Overall, the current evidence endorses an increase in the daily ingestion of protein with emphasis on the ingestion of NDP choices by older adults.

Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 µA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 µA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation.

In vivo genotoxicity of treated water containing the cylindrospermopsin-producer Cylindrospermopsis raciborskii.

Cylindrospermopsin (CYN) is an alkaloid commonly produced by some cyanobacteria that has been implicated in outbreaks of human illness. The aim of this study was to investigate the genotoxicity of Cylindrospermopsis raciborskii cellular content (including CYN) and its byproducts resulting from chlorination during water treatment. DNA damage in blood and liver cells was analysed by the comet assay and micronucleus test (MN). Mice were injected intraperitoneally with the following treatments: (a) physiological saline, (b) treated water, (c) treated water plus C. raciborskii extract (CYN producer strain, CYPO-011 K), (d) C. raciborskii extract (CYN producer strain, CYPO-011 K), (e) C. raciborskii extract (CYN non producer strain), and (f) treated water plus C. raciborskii extract (CYN non producer strain) extract. After 48 h, samples were taken to perform tests (blood and liver cells to the comet assay and bone marrow to MN test). The CYPO-011 K had a genotoxic and mutagenic effects on liver and bone marrow cells. The group that received chlorine-treated water plus CYPO-011 K also exhibited genotoxic effects in the liver, as well as in the blood, and a mutagenic effect in blood marrow cells. The results emphasise the need of improving CYN monitoring in waters bodies in order to reduce the risk of human exposure.

Electromyographic analysis of masseter and temporal muscles, bite force, masticatory efficiency in medicated individuals with schizophrenia and mood disorders compared with healthy controls.

This study aimed to comparatively analyse the electromyographic activity of the masseter and temporal muscles at rest and during mandible postural clinical conditions (right and left laterality, protrusion and maximum voluntary contraction), right and left maximum molar bite forces and the masticatory efficiency of individuals with schizophrenia or mood disorders - all medicated (medicated groups) compared with control group (healthy volunteers) via electromyography. Individuals were distributed into three groups: Group I (Schizophrenia - 20 individuals), Group II (mood disorders - 20 individuals) and Group III (Control - 40 individuals). Basically, the results were only statistically significant for the clinical mandible conditions and bite force. The most unsatisfactory results were observed in the medicated groups in relation to the control group. The group with mood disorders obtained the most unsatisfactory results compared with the group with schizophrenia. It was suggested by these observations that the association of mood disorders and schizophrenia with medication has negatively affected the stomatognathic system in relation to controls when the electromyography and bite force were used for the analysis.

Glucose homoeostasis in rats exposed to acute intermittent hypoxia.

AIM: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. METHODS: Male adult rats were submitted to 10 episodes of hypoxia (6% O2 , for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. RESULTS: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the ß-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. CONCLUSIONS: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased ß-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization.

The effect of dietary supplementation with 9-cis:12-trans and 10-trans:12-cis conjugated linoleic acid (CLA) for nine months on serum cholesterol, lymphocyte proliferation and polymorphonuclear cells function in Beagle dogs.

Conjugated linoleic acids (CLA), 9-cis:11-trans and 10-trans:12-cis, have been shown to be able to modify some immune cells parameters and plasma lipids in a variety of experiment models. Since lymphocytes and polymorphonuclear cells (PMNC) have a large spectrum functions in the immune response, the knowledge in this field has to be expanded. Beagle dogs were fed a control diet or a CLA supplemented diet for nine months. Blood was collected for biochemical analysis and lymphocyte and PMNC isolation. PMNC were assayed for lysosome content, phagocytic activity and superoxide anion production. A lymphocyte proliferation capacity assay was done. The CLA fed dogs had a 34% reduction in total cholesterol (P < 0.05), 28% in LDL (P < 0.05) and 28% non-HDL-cholesterol (P < 0.05). Neither of the PMNC parameters evaluated demonstrated significant alteration. Lymphocytes from CLA group increased by 45% their mitotic capacity (P < 0.05). Our study demonstrates that CLA can successfully modify the lipid profile of dogs (monogastrics) when fed at reasonable levels, but did not significantly alter inflammatory function as would generally predicted. Further, we had some indication that CLA modulated T cell responsiveness.

Patterns of anti-tuberculosis drug resistance among HIV-infected patients in Maputo, Mozambique, 2002-2003.

SETTING: Two tuberculosis (TB) reference hospitals in Maputo, Mozambique. OBJECTIVES: To assess the pattern of TB drug resistance and its risk factors in human immunodeficiency virus (HIV) patients. DESIGN: Adult HIV-positive patients with TB diagnosed by culture of sputum or bronchial washing were enrolled during 2002-2003. Cultures of 111 patients were tested for rifampicin, isoniazid, streptomycin and ethambutol sensitivity. Chest X-ray, haemoglobin (Hb), total lymphocyte and CD4 counts were also performed. RESULTS: Overall resistance to any drugs was found in 18% and multidrug-resistant TB (MDR-TB) in 9%. New cases of TB accounted for 62% of the studied group. Drug resistance in this subgroup was 13% compared with 26.3% in the previously treated subgroup, and MDR-TB was 5.8% vs. 15.8%. All patients presented Hb levels < 9 g/dl and total lymphocyte counts < 1200/microl. CD4 counts were significantly low in the drug resistance subgroup, with levels mostly < 100/microl. Cavities on X-ray were seen only in drug-sensitive patients. No risk factors for drug resistance were detected. CONCLUSIONS: Overall observed drug resistance was 18%, and MDR-TB 9%. Previously treated patients had high drug resistance (26.3%) and MDR-TB (15.8%).