Hyperactive

Mode of Action. DDT and its analogues specifically affect the peripheral sense organs of insects and produce violent trains of afferent impulses that result in hyperactivity, convulsions, and paralysis. Death results from metaboHc exhaustion and the production of an endogenous neurotoxin. The very high lipophilic nature of these compounds faciUtates absorption through the insect cuticle and penetration to the nerve tissue. The specific site of action is thought to be the sodium channels of the axon, through inhibition of Ca " ATPase. 

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Health and Safety Factors. Clinical side effects and LD q values of most commercially available analeptics have been summarized (2). Overdoses produce symptoms of extreme CNS excitation, including resdessness, hyperexcitabiUty, skeletal muscle hyperactivity, and ia some cases convulsions. 

For many years, there has been concern by medical professionals and nutritionists over the effects of dietary sugar on human health. Sucrose has been imphcated as a cause of juvenile hyperactivity, tooth decay, diabetes meUitus, obesity, atherosclerosis, hypoglycemia, and nutrient deficiencies. 

Other studies indicate that sucrose does not cause hyperactivity. Carbohydrate ingestion increases levels of serotonin (5-hydroxytryptamine), a brain neurotransmitter that promotes relaxation and sleep. Dietary sucrose should theoretically have a calming effect and reduce activity, manifestations which have been observed in case studies (63). To date, clinical investigations have failed to show a significant connection between sucrose consumption and aggressive or dismptive behavior (66). 

Fig. 11.5. Microstructures during the slow cooling of a hypereutectoid steel. is the standard labelling for the temperature at which FejC first appears. Hypereutectoid means that the carbon content is above that of a eutectoid steel (in the sense that a hyperactive child has an above-normal activity ).

Here, one mutated subunit is sufficient to strongly reduce ATP sensitivity thereby inducing additional symptoms in extrapancreatic tissues. To date two mutants within SlIRl are known (11424V and HI 023Y), resulting in hyperactive channels and PNDM. 

The rationale behind CDK inhibition during anticancer treatment is to stop hyperactive cell cycles and to inhibit the activity of cyclins that are frequently overexpressed in human cancer. 

Cessation of prolonged heavy alcohol abuse may be followed by alcohol withdrawal or life-threatening alcohol withdrawal delirium. Typical withdrawal symptoms are autonomic hyperactivity, increased hand tremor, insomnia and anxiety, and are treated with benzodizepines and thiamine. Alcoholism is the most common cause of thiamine deficiency and can lead in its extreme form to the Wernicke s syndrome that can be effectively treated by high doses of thiamine. 

Inflammatory disorders are due to hyperactivity of leukocytes and overexpression of their associated integrins, cytokines, and chemokines, which leads to various disorders including arthritis, bowel diseases and other chronic inflammations. 

Liddle s syndrome is an autosomal dominant disorder that is caused by persistent hyperactivity of the epithelial Na channel. Its symptoms mimic aldosterone excess, but plasma aldosterone levels are actually reduced (pseudoaldosteronism). The disease is characterized by early onset arterial hypertension, hypokalemia, and metabolic alkalosis. 

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

Treatment of attention deficit hyperactivity disorder (ADHD) in children with psychostimulants... 

On the pathophysiological side, hyperactive nNOS has been implicated in A/-methyl-D-aspartate (NMDA)-receptor-mediated neuronal death in cerebrovascular-stroke. Some disturbances of smooth muscle tone within the gastrointestinal tract (e.g., gastroesophageal reflux disease) may also be related to an overproduction of NO by nNOS in peripheral nitrergic nerves. 

Hyperactivity of the orexin system, e.g. triggered by energy depletion, metabolic failure, hypoglycemia or hypoxia, in the context of starvation, sleep derivation, and stress, may predispose to addiction and... 

SUR2B/Kir6.2 Efforts have also focused on the development of selective KAXP channel openers for vascular and nonvascular indications including angina, airway hyperactivity, bladder overactivity, and erectile... 

Psychostimulants are drugs that substantially influence cognitive and affective functioning and behaviors. Effects are increased motivational desire, agitation, heightened vigilance, euphoria, hyperactivity, and... 

The main indication for certain psychostimulants is ADHD in children and adults [4]. Recent research shows that the clinical effect and benefit are dramatic even in adults. About 60% of adult patients receiving stimulant medication showed moderate-to-marked improvement, as compared with 10% of those receiving placebo. The core symptoms of hyperactivity,... 

Psychostimulants. Figure 3 Effect of methylphenidate depending on baseline tonic (T) and phasic (P) dopamine levels. In a normal state only minimal changes are noted (which points to a rather low abuse potential). From a hypoactive state, methylphenidate increases both Tand P levels. However, this is much more true for the strongly lowered P tone. In contrast, in moderately hyperactive states and ADHD, T levels are increased and P levels are decreased, respectively, correlating with the baseline levels (adapted from [2]). 

Gibson AP, Bettinger TL, Patel NC, Crismon ML (2006) Atomoxetine versus stimulants for treatment of attention deficit/hyperactivity disorder. Ann Pharmacother 40 1134-1142... 

Ras Mutations yielding hyperactive Ras protein are frequent in human cancers... 

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