Behçet's disease

Behçet's disease is characterized by recurrent aphthous stomatitis, uveitis, genital ulcers, and skin lesions. The role of the HLA-B*51 gene has been confirmed in recent years, although its contribution to the overall genetic susceptibility to Behçet's disease was estimated to be only 19%. The production of a variety of cytokines by T cells activated with multiple antigens has been shown to play a pivotal role in the activation of neutrophils. As regards the treatment, anti-tumor necrosis factor alpha therapy has been shown to be effective for mucocutaneous symptoms as well as for sight-threatening panuveitis, although a randomized, controlled trial is required.     

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.     

Parkin-associated Parkinson’s disease

Mutations in the PARK2 gene coding for parkin cause autosomal recessive juvenile parkinsonism (AR-JP), a familial form of Parkinsons disease (PD). Parkin functions as an E3 ubiquitin ligase, and loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of AR-JP. Recently, the spectrum of genetic, clinical, and pathological findings on AR-JP has been significantly expanded. Moreover, a considerable number of parkin interactors and/or substrates have been identified and characterized, and animal models of parkin deficiency have been generated. In this review, we provide an overview of the most relevant findings and discuss their implications for the pathogenesis of AR-JP and sporadic PD.     

Network dysfunction in Alzheimer's disease: does synaptic scaling drive disease progression?

Accumulation of beta-amyloid protein (Abeta) in the brain is a key feature of Alzheimer's disease (AD). The build-up of aggregated forms of Abeta leads to synaptic loss and to cognitive dysfunction. Although the pathways controlling production and aggregation of Abeta are well studied, the mechanisms that drive the spread of neurodegeneration in the brain are unclear. Here, the idea is presented that AD progresses as a consequence of synaptic scaling, a type of neuronal plasticity that helps maintain synaptic signal strength. Recent studies indicate that brain-derived neurotrophic factor, tumour necrosis factor-alpha and alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) regulate synaptic scaling in the AD brain. It is suggested that further studies on synaptic scaling in AD could reveal new targets for therapeutic drug development.     

Penile Mondor’s disease

Mondor’s disease is a rare, self-limiting, benign process with acute presentation characterized by subcutaneous bands in several parts of the body. Penile Mondor’s disease (PMD) is thrombophlebitis of the superficial dorsal vein of the penis. It is usually considered as thrombophlebitis or phlebitis of subcutaneous vessels. Some findings suggest that it might be of lymphatic origin. The chest, abdominal wall, penis, upper arm, and other parts of the body may also be involved by the disease. Although its physiopathology is not exactly known, transection of the vessel during surgery or any type of trauma such as external compression may trigger its possible development. This disease almost always limits itself. It may be associated with psychological distress and sexual incompatibility. The patients usually feel the superficial vein of the penis like a hard rope and present with complaint of pain around this hardness. Diagnosis is usually easy with physical examination but color Doppler ultrasound examination is important for differential diagnosis. Thus, a close collaboration is required between radiologist and urologist in order to determine the correct diagnosis and appropriate therapies.     

Does antiperspirant use increase the risk of aluminium-related disease,including Alzheimer's disease?

Aluminium salts are the major constituent of many widely used antiperspirant products. The use of such antiperspirants has been linked with the systemic accumulation of aluminium and an increased risk of Alzheimer's disease. But can the frequent use of aluminium-based antiperspirants lead to the accumulation of toxic levels of aluminium? And are there measures that we can take to reduce such accumulation without reducing the effectiveness of antiperspirants?     

Glutamate and Parkinson’s disease

Altered glutamatergic neurotransmission and neuronal metabolic dysfunction appear to be central to the pathophysiology of Parkinson’s disease (PD). The substantia nigra pars compacta—the area where the primary pathological lesion is located—is particularly exposed to oxidative stress and toxic and metabolic insults. A reduced capacity to cope with metabolic demands, possibly related to impaired mitochondrial function, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. In this way, glutamate may participate in the pathogenesis of PD. Degeneration of dopamine nigral neurons is followed by striatal dopaminergic denervation, which causes a cascade of functional modifications in the activity of basal ganglia nuclei. As an excitatory neurotransmitter, glutamate plays a pivotal role in normal basal ganglia circuitry. With nigrostriatal dopaminergic depletion, the glutamatergic projections from subthalamic nucleus to the basal ganglia output nuclei become overactive and there are regulatory changes in glutamate receptors in these regions. There is also evidence of increased glutamatergic activity in the striatum. In animal models, blockade of glutamate receptors ameliorates the motor manifestations of PD. Therefore, it appears that abnormal patterns of glutamatergic neurotransmission are important in the symptoms of PD. The involvement of the glutamatergic system in the pathogenesis and symptomatology of PD provides potential new targets for therapeutic intervention in this neuro-degenerative disorder.     

Α-synuclein misfolding and Parkinson's disease

Substantial evidence links α-synuclein, a small highly conserved presynaptic protein with unknown function, to both familial and sporadic Parkinson's disease (PD). α-Synuclein has been identified as the major component of Lewy bodies and Lewy neurites, the characteristic proteinaceous deposits that are the hallmarks of PD. α-Synuclein is a typical intrinsically disordered protein, but can adopt a number of different conformational states depending on conditions and cofactors. These include the helical membrane-bound form, a partially-folded state that is a key intermediate in aggregation and fibrillation, various oligomeric species, and fibrillar and amorphous aggregates. The molecular basis of PD appears to be tightly coupled to the aggregation of α-synuclein and the factors that affect its conformation. This review examines the different aggregation states of α-synuclein, the molecular mechanism of its aggregation, and the influence of environmental and genetic factors on this process.     

Is bacterial vaginosis a disease?

Bacterial vaginosis (BV) has been described as a disease, a disorder, a vaginal inflammation, an infection, a microbial dysbiosis, a condition, and in some women, a normal situation. In order to fit the definition of a disease, BV would have to be a disorder of function that produces specific signs or symptoms or affects the vagina in an aberrant way. Yet, there is little consistency in patients reporting signs and symptoms when BV is diagnosed, nor the appearance of aberrations to the vagina. If BV is not a disease, there are implications for its management and coverage of treatment costs, and for the conclusions drawn in a multitude of previous studies. It is time for BV to be redefined and for the various subsets to be given a separate terminology with specific methods of diagnosis and appropriate treatment and preventive strategies.