Senility

Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

FIG. 21-47c Business data and report svstem using ont]->nt ol Ha -ssen Yamato Data -eigJr senile as input to eompnters. 

In recent years increasing attention has been paid to the possibility of delaying or even reversing the memory loss that accompanies old age or the more tragic loss of human capabilities associated with premature senility - Alzheimer s disease. Progress is hampered by the difficulty of identifying suitable animal tests, and there is presently no reliable therapy. 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

They are useful against hypertension but also for cases of angina, heart failure, heart attack, arythmia, silent ischemia, stroke and senility. 

CV-2619) Use senile dementia therapeutic, coenzyme QIO derivative, nootropic... 

Late 30S-40S Early senile lentigines Dyschromia Early actinic keratoses Parallel smile lines Early wrinkling Some foundation worn Mild acne scarring... 

Azelaic acid is a naturally occurring dicarboxyl-ic acid (1,7-heptanedicarboxylic acid) that has demonstrated beneficial therapeutic effects in the treatment of acne and several disorders of hyperpigmentation [48]. There are minimal effects on normally pigmented human skin, freckles, senile lentigines, and nevi. The cytotoxic and antiproliferative effects of azelaic acid may be mediated via inhibition of mitochondrial ox-idoreductase activity and DNA synthesis. Disturbance of tyrosinase synthesis by azelaic acid may also influence its therapeutic effects. Azelaic acid can be used as a hypopigmenting agent in patients sensitive to hydroquinone. 

Solar lentigo are a macular area of brown pigmentation appearing after either acute or chronic sun exposure. The term solar lentigo is In younger patients solar lentigo are seen on preferred to senile lentigo, which is sometimes sim-exposed areas (Fig. i8.i). There is usually a... 

In addition to such direct advantages, pervasive computing has a big social contribution to make. It can be used, for example, to enable patients and their relatives to keep in touch, and to help people with cognitive disabilities function on a daily basis. One illness that lends itself to such treatment is senile dementia, which is likely to be a growing trend in the graying populations of the Western World. 

Homogenates of MetruUum senile, possibly the world s most common large sea anemone, yield extracts that are powerfully hemolytic for washed mammalian erythrocytes (22). The active substance, metridiolysin, is a protein of molecular weight approximately 80,000. In contrast to the sphingomyelin-inhibitable toxins, metridiolysin is an acidic protein having a pi of about 5. It is thermolabile and is inactivat by proteolytic enzymes. The optimal pH for hemolysis is between 5 and 6, and at pH 8 the lysin is inactive. It can be dissociated into two subunits of unequal size. Besides being cytolytic in vitro, metridiolysin is lethal when injected intravenously into mice. As shown in Table IV erythrocytes from the horse or dog are about a hundred times as sensitive to lysis as those from the mouse, and erythrocytes from other animals tested are intermediate in sensitivity. 

Despite its characteristic symptoms and even after the exclusion of other established causes, AzD can only be reliably diagnosed by neuropathology and microscopic examination of the brain. Indeed that is how it came by its name. In 1907, a German physician, Alois Alzheimer, described two distinct post-mortem changes in the brain of a woman patient who had died with an unusual mental illness. These were the now characteristically accepted markers of the disease, namely senile plaques and neurofibrillary tangles (Fig. 18.1). 

Most cases of AzD show cerebrovascular amyloid deposits and the amyloid protein of senile plaques is the same as that found in blood vessels. It is referred to as )S-amyloid protein and is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP, which is a transmembrane protein and although its precise function is not clear, it is widely distributed and APP knock-out mice show reduced motor function. Normally so-called short 40 amino-acid-soluble derivatives of APP are produced by proteolytic cleavage of APP within the j] (A4) amino-acid sequence but APP can also be cleaved... 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

Bowen, DM, Smith, CB, White, P and Davison, AN (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99 454 66. 

Perry, EK, Tomlinson, BE, Blessed, G, Bergmann, K, Gibson, PH and Perry, RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Brit. Med. J. 2 1457-1459. 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Garner, M.H. and Spector, A. (1980). Selective oxidation of cysteine and methionine residues in normal and senile cataractous lenses. Proc. Natl Acad. Sci. USA 77, 1274-1277. 

The identification, using analytical microprobe and solid-state magic-angle nuclear magnetic resonance (NM techniques, of aluminosilicate deposits in the cores of the pathognomic senile plaques in the brains of Alzheimer subjects (Candy et al., 1986) has prompted widespread scientific and public concern, and controversy with regard to the possible aetiological role of environmental aluminium and aluminosilicates in senile dementia (Walton, 1991). 

Evidence for a neuroimmunological involvement in Alzheimer s disease is accumulating. Activation of the complement cascade by beta amyloid (Rogers et al., 1992), the recruitment, proliferation and activation of microglia in intimate juxtaposition to the senile plaques (Davis et al., 1992), and the increased synthesis of microglia-derived pro-inflammatory cytokine interleukin-1 (Griffin et al., 1989) is indicative of a chronic inflam-... 

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