Mutagenic activity in waste from an aluminum products factory in Salmonella/microsome assay

The mutagenic activity of waste material originating from an aluminum products factory was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory floor at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the mutagenic activity at varying concentrations. All the extracts from the factory had mutagenic activity, especially in the YG1024 strain, suggesting the presence of aromatic amines, later confirmed by chemical analysis. The TA98 strain also showed mutagenic activity, though it did not exhibit the highest mutagenicity index observed with the YG1024 strain. In TA100, mutagenic activity was not observed. This study should serve as an alert to management and those who are occupationally exposed, and as a warning that this type of waste should not be discarded in the environment without any control.     

Evidence of zinc deficiency in competitive swimmers

ObjectiveThe aim of this study was to assess the nutritional zinc (Zn) status of elite swimmers during different training periods.MethodsA longitudinal paired study was performed at the University of Sao Paulo in eight male swimmers 18 to 25 y old who had been swimming competitively at the state and national levels for at least 5 y. The swimmers were evaluated over a total period of 14 wk: before the basic and specific preparatory period (BSPP-baseline), at the end of the basic and specific preparatory period (post-BSPP), and at the end of the polishing period (PP). Levels of Zn were determined in the plasma, erythrocyte, urine, and saliva by atomic absorption spectrophotometry. Anthropometric measurements and a 3-d food record were also evaluated.ResultsThe median plasma Zn concentration was below the reference value in all training periods (BSPP-baseline 59 μg/dL, post-BSPP 55.9 μg/dL, after PP 58.8 μg/dL, P > 0.05), as were threshold values for erythrocytes (BSPP-baseline 36.5 μg of Zn/g of hemoglobin, post-BSPP 42 μg of Zn/g of hemoglobin, after PP 40.7 μg of Zn/g of hemoglobin, P > 0.05), urinary Zn (BSPP-baseline 280 μg/24 h, post-BSPP 337 μg/24 h, after PP 284 μg/24 h, P > 0.05), and salivary Zn (BSPP-baseline 66.1 μg/L, post-BSPP 54.1 μg/L, after PP 79.7 μg/L, P > 0.05). Salivary Zn did not correlate with plasma and erythrocyte Zn levels.ConclusionThe results suggest that the elite swimmers studied presented a possible Zn deficiency and that salivary Zn was not adequate to evaluate the Zn nutritional status.     

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy (¹H‐MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD⁺) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild‐type (WT) and PARP1 knock‐out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. ¹H‐MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD⁺ levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD⁺ levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD⁺ levels in the temozolomide‐treated group. The combination of rucaparib and temozolomide did not prevent the NAD⁺ depletion caused by temozolomide treatment. The ¹H‐MRS results show that NAD⁺ levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD⁺ would be valuable.     

Long-Term Outcome and Prognostic Factors After Spontaneous Cerebellar Hemorrhage

Cerebellar hemorrhage is the least common type of intracranial hemorrhage (ICH) encountered in clinical practice, and clinical data concerning the long-term outcomes are limited. This study aimed to investigate the long-term outcomes following spontaneous cerebellar hemorrhage in a cohort of Chinese patients. This single-center observational study was carried out between 1996 and 2010 and included 72 consecutive Chinese patients with a first spontaneous cerebellar hemorrhage. Of 440 patients with primary ICH, 72 (16.4%) had primary cerebellar hemorrhage. The mean age was 67.5?±?12.3?years and patients were predominantly male (54%). The 30-day mortality was 16.7% with Glasgow coma scale ??8 as the only predictor. At 6?months, 56.7% of patients who survived the first 30?days had a persistently poor functional status with modified Rankin scale score >2. After a mean follow-up of 4.7?years, 3.3% of patients had recurrent ICH, a recurrence rate of 7.3 per 1,000 patient-years. Ischemic stroke occurred in 12% of patients, an incidence of 25.5 per 1,000 patient-years. This study provided data on the long-term outcome of post-cerebellar hemorrhage in Chinese patients.     

Semi-mechanistic Modeling of the Interaction Between the Central and Peripheral Effects in the Antinociceptive Response to Lumiracoxib in Rats

The model-based approach was undertaken to characterize the interaction between the peripheral and central antinociceptive effects exerted by lumiracoxib. The effects of intraplantar and intrathecal administrations and of fixed ratio combinations of lumiracoxib simultaneously administered by these two routes were evaluated using the formalin test in rats. Pain-related behavior data, quantified as the number of flinches of the injected paw, were analyzed using a population approach with NONMEM 7. The pain response during the first phase of the formalin test, which was insensitive to lumiracoxib, was modeled using a monoexponential decay. The second phase, which was sensitive to lumiracoxib, was described incorporating synthesis and degradation processes of pain mediators that were recruited locally after tissue injury. Upregulation at the local level and in the central nervous system (CNS) was set to be proportional to the predicted levels of pain mediators in the local (injured) compartment. Results suggest a greater role of upregulated COX-2_Local in generating the pain response compared to COX-2_CNS. Drug effects were described as inhibition of upregulated COX-2. The model adequately described the time course of nociception after formalin injection in the absence or presence of lumiracoxib administered locally and/or spinally. Data suggest that the overall response is the additive outcome of drug effects at the peripheral and central compartments, with predominance of peripheral mechanisms. Application of modeling opens new perspectives for understanding the overall mechanism of action of analgesic drugs.     

Can progesterone be a better alternative to dexamethasone for use in routine brain surgery?

<正>Can progesterone be a better alternative to dexamethasone for use in routine brain surgery?Surgical brain injury(SBI)is a form of brain trauma caused by various forms of neurosurgical interventions including brain tumor excision,evacuation of intracerebral hemorrhage and brain lobectomy(e.g.,in epilepsy surgery).Cerebral edema and brain swelling typically occurs soon after SBI and commonly peaks on post-operative days 3 to 7.SBI may cause