Brain calcification

Further work on ADH may identify the molecular mechanisms underlying the brain calcification and tonic-clonic seizures associated with the CASR-activating mutations. This information may refine therapy for ADH patients as well as hypoparathyroidism patients who harbor CASR mutations. Further details about ADH can be found in the CASR locus-specific database at http //www.casrdb. mcgill.ca/f4/). 

Null Occludin Growth retardation, male sterility, chronic inflammation, hyperplasia of gastric epithelium, brain calcification... 

A CT scan or MRI of the brain following a strokelike episode reveals a lucency (an area of luminosity) that is consistent with infarction. Later, cerebral atrophy and calcifications may be observed on brain imaging studies. The vascular territories of focal brain lesions and the prior medical history of these patients differ substantially from those of typical patients with stroke. Serial MRI studies often demonstrate lesion resolution, differentiating these lesions from typical ischemic strokes. An electroencephalogram is often performed when seizures are a concern. This is especially necessary in MELAS since patients occasionally have intractable status epilepticus as a terminal condition. Mental deterioration usually progresses after repeated episodic attacks. Psychiatric abnormalities (e.g., altered mental status, schizophrenia) may accompany the strokelike episodes. The encephalopathy may progress to... 

Fig. 6.10. A CT brain scan of a 40-year-old man with mitochondrial cytopathy, showing calcification of the basal ganglia and hypodensity in the left temporal...

Infection with T. gondii is an important cause of diseases of the central nervous system and the eye in immunocompromised as well as immunocompetent individuals. When first acquired by the mother, this infection can be transmitted to the fetus. Infants with the most severe clinical signs in the brain and eye are those infected early in pregnancy when fetal immunity is low (Jamieson et ah, 2009). At birth, infants infected in utero may have intracranial calcification, hydrocephalus, convulsions, and ocular diseases such as retinochoroiditis or inflammation of the retina and choroid, with associated vitritis. The severity of disease is influenced by the trimester in which the infection is acquired by the mother (Dunn et al, 1999 Remington et ah, 2006). A positive correlation exists between the rate of transmission and infection during the second or third trimesters of pregnancy (Desmonts and Couvreur, 1984 Dunn et ah, 1999). 

Ectopic calcifications in the blood vessels, brain, subcutaneous tissue, muscles, and cartilage (calcium phosphate is an insoluble salt) (see Figure 75). 

Some causes of intracranial calcifications can be speculated, such as latent hypoxic damage, vasculitis and direct brain injury due to energy insufficiency because of hypothyroidism. In previous studies, the correlation between basal ganglia calcifications and spasticity or other neurological symptoms in EC was controversial (Halpern et ai, 1991 DeLong et ai, 1985) although they are found in asymptomatic or nonspecific symptoms, such as dementia, in adult-onset myxedema (Burke et ai, 1988). However, the frequency of hypothyroidism-associated intracranial calcification is 30% in patients with EC (Halpern et al, 1991). 

Shear stress induces larger amounts of elastin in cells and inhibits tissue calcification. Occludin, a transmembrane protein that forms tight junctions between cells, and is the main contributor to the blood-brain barrier (an obstacle to free passage of complex molecules into the central nervous system), is present in lesser amounts at high shear stress values (about 10% less at 20-30 dynes/cm ). 

Ide-Ektessabi et al. (2005) used X-ray fluorescence spectrosopy to measnre the concentrations of lead and several trace elements in the brains of three gronps of patients. The groups included patients with (1) diffnse neurofibrillary tangles with calcification (DNTC), (2) Alzheimer s disease (AD) with calcification, and (3) AD without calcification. They found high concentrations of lead, zinc, and calcium in the brain tissues of DNTC and AD patients with calcification, but no lead in the tissues of AD patients without calcification. There was a strong correlation between degree of calcification and lead concentration in the calcified areas of the brain in these patients. 

Although no cause and effect relationship can be determined from this study, the results support the hypothesis that lead may be involved in the development of some progressive neurodegenerative diseases, particularly those associated with calcification in brain tissues. 

At postmortem examination there were no gross abnormalities, except for mild atrophy of the brainstem, and microscopy showed only mild gliosis in the medial reticular formation of the medulla oblongata. There was slight myelin pallor in the cerebral hemispheres and brainstem. There was bilateral focal necrosis and calcification in the brain stem nuclei. The distribution of the lesions extended into the tegmentum of the pons and medulla oblongata, with involvement of the nuclei of cranial nerves VI, VII, X, and XII, where there was moderate to severe neuronal loss and free... 

The CT appearance of a cavernoma depends on the amount of internal thrombosis, hemorrhage, and calcification. Examples are shown in Figures 2.2, 2.4a, 2.7a, 2.8a, 2.10a, 2.12a, and 2.13a,b. The lesions appear hyperdense compared to adjacent brain parenchyma, but can have variable attenuation values. Because the density of blood on CT depends on clot formation, the attenuation of a thrombosed cavernoma changes with time. Calcifications do not change that much however, cavernomas tend to calcify only partially (see Figs. 2.12 and 2.13). In patients with a recent hemorrhage, the cavernoma may be suspected on CT mainly by taking into account... 

Fig. 2.4a-c. CT (a) and sagittal Tl-weighted magnetic resonance (MR) (b) scan of another brain-stem cavernoma. Due to its calcification, it is easy to see even on the CT scan. The MR nicely reveals the typical cavernoma pattern with the dark rim of hemosiderin. Note that the acute hemorrhage occurred at the dorsal aspect of the cavernoma and now facilitates easy surgical removal. A view through the microscope while removing the cavernoma (c). Note the typical mulberry aspect of the malformation... 

The term biocompatibility is defined as the ability of a material to perform with an appropriate host response in a specific situation" (Williams 2008). A biocompatible material can be inert, where it would not induce a host immune response and have little or no toxic properties. A biocompatible material can also be bioactive, initiating a controlled physiological response. For porous silicon, bioactive properties were initially suggested based on the observation that hydroxyapatite (HA) crystals grow on microporous silicon films. HA has implications for bone tissue implants and bone tissue engineering (Canham 1995). An extension of this work showed that an applied cathodic current was able to further promote calcification on the surface (Canham et al. 1996). More recently, Moxon et al. showed another example of bioactive porous silicon where the material promoted neuron viability when inserted into rat brains as a potential neuronal biosensor, whereas planar silicon showed significantly fewer viable neurons surrounding the implant site (Moxon et al. 2007). 

Placental transport of lead may be associated with placental transport of calcium. Barltrop (1969) observed that femur lead increased rapidly in the third trimester, corresponding to onset of ossification and deposition of calcium. There is a question whether the increased deposition of lead in the femur along with calcium is because of some commonality between lead and calcium metabolism. Figure 2 shows the close correlation between size of fetal brain and increase in lead content as the brain matures. Whether the movement of lead into the brain is a matter of simple diffusion or whether there is some relationship to brain calcium is not known. Calcium deficiency does enhance lead absorption and the pathological effects of lead (Mahaffey et al. 1973). The placenta also contains a calcium-binding protein identical to that present in the intestine (Van Dijk 1981). A comparison of placental transfer of toxic metals by Nakano and Kurosa from the Minamata Institute in Japan (unpublished observation) found that lead levels in the placenta were strongly correlated with calcium, suggesting that lead deposition is associated with calcium deposition or with areas of dystrophic calcification that are present in the mature placenta. 

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