Progress in brain research
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Levodopa therapy represents a major breakthrough in the treatment of Parkinson's disease (PD). As time and disease severity progresses, however, the shortcomings and adverse effects of this neurotransmitter replacement strategy become apparent and patients develop disabilities despite best medical therapy. The heightened awareness of these difficulties has given birth to a re-examination of functional neurosurgery for advanced PD. ⋯ Other problems are less or non-responsive. Further, despite the widespread use of this technology, the mechanism through which DBS alleviates symptoms is not fully understood. This review will discuss the patient population most likely to benefit from surgery, what aspects of the disease are most responsive, the current limitations of DBS, and new therapeutic targets that are being examined to address these limitations.
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Review
Sexual differentiation of the human brain in relation to gender identity and sexual orientation.
It is believed that during the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. According to this concept, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation should be programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. ⋯ To what extent fetal programming may determine sexual orientation is also a matter of discussion. A number of studies show patterns of sex atypical cerebral dimorphism in homosexual subjects. Although the crucial question, namely how such complex functions as sexual orientation and identity are processed in the brain remains unanswered, emerging data point at a key role of specific neuronal circuits involving the hypothalamus.
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Over the last years, a plethora of genetic findings have completely changed our views on the aetiology of Parkinson's disease (PD). Linkage studies and positional cloning strategies have identified mutations in a growing number of genes which cause monogenic autosomal-dominant or autosomal-recessive forms of the disorder. ⋯ Thus, an increasingly complex network of genes contributing in different ways to disease risk and progression is emerging. These findings provide the 'genetic entry points' to identify molecular targets and readouts necessary to design rational disease-modifying treatments.
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Somatostatin (SS) and SS receptors (ssts) are broadly expressed in the human body where they exert many physiological actions. Moreover, they can be expressed in many pathological tissues. Particularly, a high density of ssts has been described in human neuroendocrine tumors (NETs). ⋯ Indeed, SS-analogues coupled with (111)In are used to perform sst-scintigraphy, which is a very useful first-line imaging technique in the diagnosis and follow-up of GEP-NETs. Moreover, SS-analogues conjugated to (111)In or to other radioisotopes, such as (177)Lu or (90)Y, have promising effects in the treatment of advanced NETs. ssts are expressed in some non-neuroendocrine tumors as well and in some non-tumoral diseases, suggesting that SS-analogues might have a role in the diagnosis and treatment of these pathological conditions as well. The development of novel SS-analogues with new pharmacokinetic and pharmacodynamic characteristics may further improve the clinical applications of such compounds.