IDH1 Mutation in Brain Stem Glioma: Case Report and Review of Literature.

The role of isocitrate dehydrogenase 1 (IDH1) mutation in brain stem glioma is not clear. To the best of our knowledge, six cases of brain stem gliomas carrying IDH1/2 mutations are currently reported in the literature. One case of diffuse brain stem glioma with IDH1 mutation, which was followed for 2 years, is presented and compared with IDH1 negative tumors. A 22-year-old lady was referred with diplopia and left arm palsy. Neuroimaging detected a nonenhancing, nonhomogeneous diffuse infiltrating brain stem tumor extending from pons to medulla. Microsurgical debulking was performed. Microscopic evaluation of the tissue specimen and immunohistochemistry revealed an astrocytoma WHO Grade II with proliferation rate of 3% and glial fibrillary acidic protein (GFAP)-positive tumor cells. Interestingly, the tumor cells expressed mutated IDH1 R132H protein. The patient underwent adjuvant radiation and chemotherapy. The primary and 2 years' clinical/radiological characteristics did not indicate any significant difference from other cases without IDH1 mutation. the prognostic value of IDH1/2 mutation in brain stem glioma is unclear. Brain stem biopsies may allow determination of a tissue-based tumor diagnosis for further investigations.

Chronic arsenic intoxication diagnostic score (CAsIDS).

Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions.

Pairomics, the omics way to mate choice.

The core aspects of the biology and evolution of sexual reproduction are reviewed with a focus on the diploid, sexually reproducing, outbreeding, polymorphic, unspecialized, altricial and cultural human species. Human mate choice and pair bonding are viewed as central to individuals' lives and to the evolution of the species, and genetic assistance in reproduction is viewed as a universal human right. Pairomics is defined as an emerging branch of the omics science devoted to the study of mate choice at the genomic level and its consequences for present and future generations. In pairomics, comprehensive genetic information of individual genomes is stored in a database. Computational tools are employed to analyze the mating schemes and rules that govern mating among the members of the database. Mating models and algorithms simulate the outcomes of mating any given genome with each of a number of genomes represented in the database. The analyses and simulations may help to understand mating schemes and their outcomes, and also contribute a new cue to the multicued schemes of mate choice. The scientific, medical, evolutionary, ethical, legal and social implications of pairomics are far reaching. The use of genetic information as a search tool in mate choice may influence our health, lifestyle, behavior and culture. As knowledge on genomics, population genetics and gene-environment interactions, as well as the size of genomic databases expand, so does the ability of pairomics to investigate and predict the consequences of mate choice for the present and future generations.

Distribution of substance-P nerves inside the infrapatellar fat pad and the adjacent synovial tissue: a neurohistological approach to anterior knee pain syndrome.

INTRODUCTION: The purpose of the study was to determine the distribution and number of nerves inside the infrapatellar fat pad and the adjacent synovium, in particular with regards to nociceptive substance-P nerves. MATERIALS AND METHODS: The infrapatellar fat pad of the knee was resected from 21 patients (4 male, 17 female, mean age 69 years) during the course of standard total knee arthroplasty operations performed in our clinic. The fat pad was dissected into five standardized segments, fixed in formalin and embedded in paraffin. Immunohistochemical techniques using antibodies against S-100 protein and substance-P (SP) were employed to determine and specify the nerves. RESULTS: Studying all the detectable nerves present in 50 observation fields (200-fold magnification), we found an average of 106 S-100 versus 25 SP nerves (24%) in the synovium and 27 S-100- versus 7 SP nerves (26%) in the interior of the fat pad. The total nerve count was significantly (P < 0.001) higher in the synovium than in the fat pad for both marker types. The number of S-100 nerves was significantly (P < 0.05) higher in the central and lateral segments of the fat pad, while SP nerves were equally distributed throughout all segments of the fat-pad. SP nerves were significantly more frequently associated with blood vessels inside the fat pad (43%, P < 0.05) than in the synovial tissue (28%). CONCLUSION: The occurrence and distribution of SP nerves inside the infrapatellar fat pad suggest a nociceptive function and a neurohistological role in anterior knee pain syndrome. The data support the hypothesis that a neurogenous infection of the infrapatellar fat pad could contribute to anterior knee pain syndrome.

Cerebral hypoperfusion and delayed hippocampal response after induction of adult kaolin hydrocephalus.

BACKGROUND AND PURPOSE: In chronic hydrocephalus, a role for tissue hypoxia resulting from cerebrovascular compression is suggested. The purpose of this study was to evaluate whether changes in cerebral blood flow (CBF) in the time course of adult kaolin-induced hydrocephalus correlated with immunohistochemical neuronal responses. METHODS: In 46 adult Sprague-Dawley rats, kaolin hydrocephalus was induced and immunostaining of neurofilament protein (NF68), synaptophysin (SYN38), and neuronal nitric oxide synthase (NOS) was performed at 2 (short term), 4 (intermediate term), and 6 and 8 (long term) weeks. Local CBF was measured quantitatively by [14C]iodoantipyrine ([14C]IAP) autoradiography in the short-term stage and in both long-term stages. RESULTS: At 2 weeks, neuronal NOS immunoreactivity was globally increased in cortical areas and within the hippocampus. Four weeks after hydrocephalus induction, a reactive increase of SYN38 and NF68 immunoreactivity in the periventricular cortex was seen. At 6 and 8 weeks, when the ventricular size was decreasing, immunohistochemical changes in the hippocampus became most evident. A maintained toxic NOS reactivity in the CA1 subfield was accompanied by a loss of NF68 staining. In the CA3 subfield, however, focal increases in NF68 and SYN38 immunoreactivity were found. Cortical and hippocampal blood flow showed prolonged decreases of 25% to 55% compared with control animals. At 8 weeks, control levels were reached. CONCLUSIONS: The observed temporary CBF decrease appears to correlate with an early global neuronal ischemic response. In addition, it may also account for the delayed selective response of ischemia-vulnerable structures, eg, hippocampus, in chronic adult kaolin-induced hydrocephalus.

Effects of IL6 and IL1beta on aFGF expression and excitotoxicity in NT2N cells.

The interleukin-1beta (IL1beta) and interleukin-6 (IL6) have pro-inflammatory and neuroprotective functions and are elevated in many diseases of the brain. Here, mechanisms and effects of IL1beta and IL6 on neuronal survival after excitatory stimulation were investigated in vitro. IL6 upregulated the expression of the neuroprotective acidic fibroblast growth factor (aFGF) and reduced the glutamate-induced cytotoxicity. IL1beta treatment amplified the excitotoxic effects after 24 h, but longer treatment with IL1beta stimulated the neuronal release of IL6 resulting in increased levels of aFGF and a decreased excitotoxicity. These data suggest that (1) IL6 exerts protective functions by upregulating the expression of aFGF and (2) the IL6/IL1beta balance in the brain may regulate neuronal survival during neuropathological processes.