The mutagenicity and carcinogenicity of inorganic manganese compounds: a synthesis of the evidence

Manganese (Mn), a naturally occurring element present in many foodstuffs, is an essential trace element with many biological functions. In industry, inorganic Mn compounds have a range of different applications, although the majority of Mn is used to make alloys and steel. For the general population, the major source of exposure to Mn is dietary, although drinking water may constitute an additional source in some regions. However, in occupationally exposed humans, inhalation of Mn is likely to be an important additional route. In general, Mn and its inorganic compounds are considered to possess low mutagenic or carcinogenic potential compared with some heavy metals. In this review, an up-to-date analysis of the available published studies on the carcinogenic and genotoxic potential of inorganic Mn is provided (organic Mn compounds are not considered). The current literature indicates that Mn may be weakly mutagenic in vitro and possibly clastogenic in vivo, with unknown genotoxic effects in humans; the possible mechanisms underlying these effects are discussed. The experimental evidence on carcinogenicity (quantitative increase in incidence of thyroid tumors in mice but not rats) does not provide any clear evidence, while the available occupational and environmental epidemiological evidence is equivocal as to whether exposure to inorganic Mn is associated with a significant cancer risk. Hence, it is concluded that there is insufficient evidence to indicate that inorganic Mn exposure produces cancer in animals or humans.     

The association of the PTPN22 620W polymorphism with Behcet's disease

Objectives

A single nucleotide polymorphism (SNP) of the gene encoding protein tyrosine phosphatase type 22 (PTPN22 620W) has recently been described as a strong common genetic risk factor for human autoimmune disease. We have analysed the association of PTPN22 620W in patients with Behçet''s disease (BD).

Methods

Genomic DNA was obtained from 270 patients with BD from the UK and the Middle East. Normal controls (n  =  203) were collected from the same populations. Patients with idiopathic retinal vasculitis from the UK (n  =  136) were used as disease controls. PTPN22 620W was detected by SSP–PCR analysis and agarose gel electrophoresis.

Results

The results showed an inverse correlation between the presence of PTPN22 620W and Behçet''s disease in either patient group tested. There was a greatly reduced prevalence in Middle Eastern compared to UK patients and controls. Finally, there was no association with either UK patients with retinal vasculitis compared with UK controls.

Conclusions

The presence of PTPN22 620W was inversely associated with BD and the distribution of the SNP in the Middle East supports previous findings in the global prevalence.     

Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80 cases

The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.     

Schooling of young people with cancer

The schooling of young people with cancer poses various problems, similar to those experienced by disabled or chronically ill children. Published data on this subject in the medical literature comes mainly from studies carried out in the USA and the UK. Cancer and its treatment can cause both direct (learning difficulties or other disabilities...) and indirect (discrimination...) problems. Academic failure, and other problems linked to school absenteeism, can affect the future of adolescents with cancer. Sustaining schooling during the illness enables such patients to avoid falling behind academically, and to maintain his or her social status as a student. Due to the organisation of treatment regimes, education is provided in three environments : in hospital (during in-patient stays), at home (generally whilst the patient is convalescing), or at school. Paediatric oncologists have underlined the importance of establishing links between hospital and educational personnel (with parental approval), and suggest that a teachers'illness information manual should be produced. School re-entry is recommended as soon as possible. During the illness, the patient's presence in class is dependent on his or her general health, the progress of the cancer, and the treatment regime being followed. School absenteeism, inevitable during treatment periods and the year following diagnosis, is often associated with academic problems or failure. While many cancer patients worry about their school work and future educational progress, such problems remain rare. In the long term, the educational level of childhood or adolescent cancer survivors remains similar to that of the general population. In order to understand the issues surrounding the schooling of young cancer patients in France, long-term multi-centre studies, focusing on adolescents, must be initiated.     

Protein-losing enteropathy in gastrointestinal sarcoidosis associated with malignant lymphoma.

A patient with disseminated gastrointestinal sarcoidosis and non-Hodgkin's malignant lymphoma developed diarrhea and polyadenopathy. Laboratory analysis revealed the presence of protein-losing enteropathy without biological signs of malabsorption. Gastrointestinal biopsy specimens showed numerous sarcoidosis nodules without neoplastic proliferation in the stomach, small intestine, and rectum. The patient's course was favorable after treatment with prednisone and chlorambucil. Disseminated gastrointestinal sarcoidosis may be a previously unidentified cause of protein-losing enteropathy.     

Estrogen–BDNF interactions: Implications for neurodegenerative diseases

Since its’ discovery over 20 years ago, BDNF has been shown to play a key role in neuronal survival, in promoting neuronal regeneration following injury, regulating transmitter systems and attenuating neural-immune responses. Estrogen’s actions in the young and mature brain, and its role in neurodegenerative diseases in many cases overlaps with those observed for BDNF. Reduced estrogen and BDNF are observed in patients with Parkinson’s disease and Alzheimer’s disease, while high estrogen levels are a risk factor for development of multiple sclerosis. Estrogen receptors, which transduce the actions of estrogen, colocalize to cells that express BDNF and its receptor trkB, and estrogen further regulates the expression of this neurotrophin system. This review describes the distribution of BDNF and trkB expressing cells in the forebrain, and the roles of estrogen and the BDNF–trkB neurotrophin system in Parkinson’s disease, Alzheimer’s disease and multiple sclerosis.