Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre- BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.     

Multiple brain metastases from malignant thymoma.

A rare case of thymic carcinoma with multiple brain metastasis is reported. In our extensive review of the literature only six of 30 reports of intracranial thymoma metastasis describe multiple metastases. A 38-year-old man presented with signs of raised intracranial pressure that had began 15 days previously. Cranial MRI revealed over 70 cystic lesions in the supra and infratentorial regions. Stereotactic biopsy was planned. On the second day of his admission he deteriorated and died the following day. The autopsy revealed a mass in the mediastinum. In the brain parenchyma were multiple cystic lesions between 0.5 and 3 cm in diameter. Histopathologically they were diagnosed as metastases from the thymic carcinoma. The mean survival with a single brain metastasis is approximately 256 days, whereas with multiple brain metastases it is only 64 days, thus treatment of this tumor demands prompt surgery whenever possible and optimal adjuvant therapy.     

Relationship of knee joint proprioception to pain and disability in individuals with knee osteoarthritis.

Proprioception plays an integral role in neuromotor control of the knee joint and deficits in knee joint proprioception are well documented in individuals with knee osteoarthritis (OA). However, the functional relevance of these deficits is not clear. This cross-sectional study evaluated the relationship between knee joint proprioception and pain and disability in a large cohort of individuals with knee OA. Two hundred and twenty participants (145 F, 75 M) with symptomatic knee OA were recruited from the community. Five non-weight bearing active tests with ipsilateral limb matching responses were performed at 20 degrees and 40 degrees flexion to measure knee joint position sense. Pain and disability were assessed by self-reported questionnaires and objective measures of balance and gait. Results showed little association between knee joint position sense variables and measures of pain and disability (r values <0.24, most p>0.05). When comparing participants with the worst and best joint position sense, no significant differences in pain and disability could be found (p>0.05). While our study design does not allow causality to be established, these results suggest that deficits in joint position sense may be due to factors other than pain and that deficits are not large enough to impact upon disability.     

Sexual dysfunction in patients with schizophrenia on antipsychotic medication.

OBJECTIVE: The objective of this study was to determine the prevalence of sexual dysfunction in patients with schizophrenia under antipsychotic therapy and to investigate the effect of various parameters on sexual dysfunction. METHOD: A total of 827 stabilized outpatients who met DSM-IV criteria for schizophrenia, were recruited in the study. Arizona Sexual Experience Scale (ASEX) and the subscale on sexual function of the UKU Side Effects Rating Scale were applied at a single interview. RESULTS: In total, 52.6% of the patients had sexual dysfunction, 54.2% reported a low sexual desire and 41.7% reported problems in having an orgasm. Erectile dysfunction and ejaculation problems were seen in 48.1% and 64.2% of the men, respectively; amenorrhea was seen in 24.9% of the women. ASEX score and severity of disease were found to be correlated (p=0.02). Higher ASEX scores were observed in patients who smoked (p=0.01). Men receiving atypical monotherapy had lower ASEX scores than those receiving a combination of atypical and conventional antipsychotics (p=0.017). Patients on combination therapy had more ejaculation problems than the atypical group (p=0.001). Low sexual desire was more prevalent among women using conventional drugs than those on atypical drugs (p=0.004). In linear regression analyses, ASEX was affected significantly and independently by the severity of the disease only in men (p=0.005). CONCLUSION: Our results show that sexual dysfunction is widespread among patients with schizophrenia on antipsychotic medications.     

The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the efficacy of methylphenidate in treating adults with attention-deficit hyperactivity disorder (ADHD), using subjective (self-report) and objective (computerized test) measures. METHOD: This double-blind crossover trial of placebo vs methylphenidate included subjects with childhood and current ADHD symptoms, IQs above 80, no other psychiatric condition explaining their difficulties or requiring other treatment, and no substance abuse in the previous 6 months. We administered 10 mg 3 times daily of medication (that is, placebo or methylphenidate) for 2 weeks. On the final day, subjects completed self-report measures and were tested on computerized tests. We then increased dosage to 15 mg 3 times daily for 2 weeks and administered a complete reassessment on the final day. Following a 1-week washout, we repeated this process on the second medication (that is, placebo or methylphenidate). RESULTS: Thirty adults with ADHD participated. Self-report measures and computerized tests showed significant improvements in ADHD symptoms on methylphenidate, compared with placebo. Other psychiatric symptoms (notably, anxiety and depression) were alleviated with methylphenidate. There was no significant difference between the 2 dosages of methylphenidate. CONCLUSION: Methylphenidate is effective in improving ADHD symptoms in adults with ADHD, is well tolerated, and has minimal side effects.     

Innervation of rat molar teeth: II. A quantitative analysis of primary sensory neurons innervating a mandibular molar tooth

This study was conducted to determine the source and number of primary sensory neurons (PSNs) innervating a mandibular molar tooth of a population of 15-18-week-old Sprague-Dawley rats. The pulpal tissue was exposed to horseradish peroxidase (HRP) pellets for 24 hours. Subsequently the animals were perfusion fixed and the following PSN structures were examined for the presence of HRP-labelled cells: trigeminal (TGs) and cervical dorsal root ganglia (DRGs) and mesencephalic nucleus (MN). Only the TGs contained labelled cells and they thus were the sole source of PSN pulpal innervation. The number of TG cells was highly variable, 49-407, but most of this variability was attributable to insufficient HRP filling of the pulp chamber or leakage of HRP into periapical tissue. Selection of TGs whose respective experimental teeth demonstrated that HRP filled and was restricted to the pulp chamber revealed a narrower range of TG cells providing pulpal innervation to the first molars, 142-288, with an average of 213. A detailed mapping of these cells indicated a somatotopic distribution within the mandibular territory of the TGs. It was concluded that these findings represent TG's contribution to the pulpal innervation of this specific population of rat first molar teeth. This suggests that from animal to animal the density of innervation may be quite variable and it is hypothesized that the sensitivity of the pulp would likewise vary. In addition, these findings may contribute to the explanation of why there is variability in the stimulus strength needed to elicit a pain response in the human dentition.     

Prevention of work‐related airway allergies; summary of the advice from the Health Council of the Netherlands

The Health Council of the Netherlands published a report in which the best procedure and method for recommending health‐based occupational exposure limits (OELs) for inhaled allergens were identified by evaluating the scientific state of the art. Many respiratory disorders in the workplace arise from inhalation of substances which can cause allergy. To protect workers against respiratory allergy, various preventive measures are taken, one of them being reduction of exposure by setting legally binding standards. These are based on health‐based OELs that specify a level of exposure to an airborne substance, a threshold level, below which it may reasonably be expected that there is no risk of adverse health effects. The Council is of the opinion that an OEL should prevent against allergic sensitization, as sensitization plays a crucial biological role and is a prerequisite for the development of allergy. Furthermore, the Council considers it most likely that the exposure level below which no allergic sensitization develops for most allergens is so low, that OELs are difficult to set with the current knowledge and technical feasibilities. An alternative approach is to accept exposure, which carries a small predefined risk in developing allergic sensitization. In addition, it is worth considering periodic screening of exposed workers on allergic sensitization, because timely intervention can prevent worse. The feasibility of periodic screening and what else is needed to comply with the most important criteria, should however be judged case‐by‐case.