Kurup Ravi Kumar, Kurup Parameswara Achutha
Medical College Hospital, Trivandrum, Kerala, India.
Med Hypotheses. 2003 Feb;60(2):243-57. doi: 10.1016/s0306-9877(02)00382-1.
A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na(+)-K(+) ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na(+)-K(+) ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na(+)-K(+) ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na(+)-K(+) ATPase inhibition can result in increased intracellular Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.
已描述了一个帕金森病、精神分裂症、肿瘤、X综合征、类风湿性关节炎和癫痫患病率较高的家族。该家族的心理行为模式如下：创造力和高智商、性行为亢进、食欲减退和进食行为异常、失眠和睡眠模式改变、精神性倾向增加、成瘾倾向增加、情感联系和亲昵行为减少以及左利手。研究发现，下丘脑分泌的内源性钠钾ATP酶抑制剂地高辛水平升高，并且在所有这些疾病以及所研究的索引家族中，红细胞膜钠钾ATP酶活性降低。下丘脑地高辛可调节意识感知，其功能障碍可能导致精神分裂症。地高辛还可优先上调色氨酸转运而非酪氨酸转运，导致去极化色氨酸分解代谢产物——血清素、喹啉酸、士的宁和尼古丁水平升高，而超极化酪氨酸分解代谢产物多巴胺、去甲肾上腺素和吗啡水平降低，这导致上述所有疾病以及索引家族中膜钠钾ATP酶受到抑制。地高辛诱导的膜钠钾ATP酶抑制可导致细胞内钙增加和镁水平降低，从而导致谷氨酸兴奋性毒性、癌基因激活和免疫激活。地高辛诱导的钙/镁比例改变、泛醌减少和多萜醇增加可影响糖缀合物代谢、膜形成和结构以及线粒体功能，从而导致上述多种疾病，包括索引家族中的疾病。对右利手/左半球优势和左利手/右半球优势个体的类异戊二烯途径和神经递质模式进行了比较。索引家族和所研究的多种疾病中的生化模式与右半球优势个体中获得的模式相关。高血地高辛状态表明右半球优势。因此，下丘脑地高辛可作为神经免疫内分泌乐团的总指挥，并协调各种细胞器的功能。
