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The responsibility of the folate deficiency in some neuropsychiatric disorders is recent knowledge. The role of the folate on the nervous system is not yet well definite, but the action on the metabolism of the amino-acids, on the purine and the pyrimidine synthesis and on the metabolism of the catecholamins are certainly essential. The neuropsychiatric diseases secondary to the folate deficiency are numerous: dementia, schizophrenia like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, pueperal psychosis, peripheral neuropathy, myelopathy (spinal cord syndrome and/or pyramidal tract damage), restless legs syndrome. Clinically the diagnosis may be difficult with sub acute combined degenration secondary to the pernicious anaemia, and the dosage of the folate (in serum, in red-cells and in cerebrospinal fluid) is necessary. The congenital defects in the uptake or utilization of the folate are associated with neuropsychiatric disturbances. The treatment is easy and safe if the vitamin B12 deficiency is eliminated and if employed with caution in epileptic patients because folate can induced seizures.
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PMID:[Folate and the nervous system (author's transl)]. 22 16

Recently there have been reports that long-term use of estrogen- containing oral contraceptives (OCs) can induce folic acid and vitamin B deficiency which can lead to hematopoiesis. The symptoms are paleness, forgetfulness, sleeplessness, and euphoric and depressive states. This deficiency occurs when serum folic content falls below 8 nmol/1 or 3 ng/ml. According to a nutrition group blood folic acid level declined up to 40% in patients taking OCs. In a Sri Lanka study of healthy women aged 20-45 taking Ovulen 50 (.05 mg of ethinyl estradiol and 1 mg of ethynodiol diacetate) folic acid level dropped in the 1st 6 months stabilizing at 2.2 ng/ml in those from the lowest social classes and at 2.9 ng/ml in those from privileged classes. Prophylactic substitution of folic acid in the diet was recommended by WHO, but it is less effective since it appears in the diet as polyglutamate that has to be broken down to absorbable monoglutamate. A US study found that taking OCs for 60 months resulted in a 40% reduction of the vitamin B12 serum level, while vitamin B12 concentrations in erythrocytes and peripheral blood stayed normal. Vitamin B12 helps recover tetrahydrofolic acid from N-methyltetrahydrofolic acid. Possibly this is another manifestation of OC-induced folic acid hypovitaminosis. OCs can also influence tryptophan metabolism reducing its blood concentration whereby less 5-hydroxytryptamine (serotonin) is produced. This results in headache, concentration decreases irritability, and sleep disturbances. In addition, lower riboflavin (vitamin B2) and thiamin concentration in erythrocytes was reported after using OCs. Counseling on the possible effect on vitamin stores and on proper nutrition including folic acid as monoglutamate is necessary for women who use OCs or estrogen substitution therapy for postmenopause or for osteoporosis prophylaxis.
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PMID:[Folic acid and vitamin deficiency caused by oral contraceptives]. 192 42

American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million persons in Latin America. Two drugs are currently being used for treatment of the acute phase of Chagas' disease: 4-[(5-nitrofurfurylidene)amino-3-methylthiomorpholine-1,1-di oxide] (Nifurtimox; Nfx) and (N-benzl-2-nitro-1-imidazole acetamide) (Benznidazole; Bz). Nfx and Bz have serious undesirable effects, which have been reported during their clinical use, including anorexia and weight loss, nausea and vomiting, nervous excitation, insomnia, psyche depressions, convulsions, vertigo, headache, sleepiness, myalgias, arthralgias, loss of balance, disorientation, forgetfulness, paresthesias, adynamia, acoustic phenomena, peripheral neuropathies, gastralgia, mucosal edema, hepatic intolerance, skin manifestations, and intolerance to drinking alcohol. Effects in the central and peripheral nervous system of Nfx were also reproduced in animals. Signs of testicular and ovarian injury were reported for both Nfx and Bz, the effects of Bz being in general less intense than those of Nfx. Both drugs evidenced mutagenicity. In light of the present knowledge about the toxicity of Nfx and Bz, further studies on the mutagenic, teratogenic, carcinogenic, and reproductive effects of both drugs are recommended. Lack of information is particularly serious for Bz. Studies on Nfx and Bz biotransformation, activation to reactive metabolites, and potential mechanisms for their toxic effects were analyzed. Risk-benefit considerations of the use of Nfx and Bz were made and an analysis of the need for research on Chagas' disease chemotherapy was also performed.
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PMID:Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease). 315 55

Even in the presence of normal blood pressure (B.P.) in both arms in some individuals, abnormal B.P. and circulatory disturbances can be found in the brain and lower extremities. The author discovered the following five types of abnormal B.P. in the brain in the presence or absence of normal B.P. in the arms: unilateral cephalic hypertension; bilateral cephalic hypertension; unilateral cephalic hypotension; bilateral cephalic hypotension; mixed cephalic hypertension and hypotension. When the B.P. of the head exceeds about 160 mm Hg, patients experience sensation of increased pressure buildup in the head to moderate headache. When it exceeds over 220 mm Hg, most of them experience severe headache in that side of the head. When the B.P. is very low (less than 30 mm Hg in both sides), majority of the subjects experience sleep disturbance pattern, mainly insomnia and some develop excessive sleepiness; difficulty in concentration and easy forgetfulness of recent events; various degrees of irritability. They are often associated with injury of neck-shoulder area with the presence of spastic muscles in the area. Relaxation of the spastic muscles by acupuncture, TES or soft laser beam from He-Ne (7 approximately 15m Watts) often change the abnormal cephalic B.P. toward normal. Among individuals with cephalic hypotension some of them develop eye problems. Blind patients with macular degeneration and retinitis pigmentosa often have severe cephalic hypotension and reduced blood flow. Improvement of B.P. and blood flow induced by safe and effective electrical stimulation resulted in significant improvement in vision. In some patients, abnormal B.P. and blood flow of the brain are dependent on the position of the head and neck which can be classified as "Cephalo-cervical Position Dependent Dysfunction Syndrome" which interferes with the function of some of the internal organs. In many psychiatric patients with schizophrenia or severe depression, cephalic B.P. and blood flow are often reduced significantly with additional abnormal function of pancreas, thyroid gland or liver. These abnormalities can explain some of the abnormal behavior, particularly when hypoglycemia, decrease in serotonin level and decreased circulation in the brain coexist.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Non-invasive circulatory evaluation and electro-acupuncture & TES treatment of diseases difficult to treat in Western medicine. 614

The premenstrual symptom complex many women experience in a moderate to severe form can be divided into four subgroups. Because there is more than one syndrome and nervous tension is one of the most common symptoms, the term premenstrual tension syndromes (PMTS) is used. The most common subgroup, PMT-A, consists of premenstrual anxiety, irritability and nervous tension, sometimes expressed in behavior patterns detrimental to self, family and society. Elevated blood estrogen and low progesterone have been observed in this subgroup. Administration of vitamin B6 at doses of 200-800 mg/day reduces blood estrogen, increases progesterone and results in improved symptoms under double-blind conditions. Women in this subgroup consume an excessive amount of dairy products and refined sugar, and progesterone may be of value in them. The second-most-common subgroup, PMT-H, is associated with symptoms of water and salt retention, abdominal bloating, mastalgia and weight gain. The severe form of PMT-H is associated with elevated serum aldosterone. Vitamin B6 at high dosage suppresses aldosterone and results in diuresis and clinical improvement. Vitamin E helps the breast symptoms. Methylxanthines and nicotine should be curtailed and sodium limited to 3 gm/day. PMT-C is characterized by premenstrual craving for sweets, increased appetite and indulgence in eating refined sugar followed by palpitation, fatigue, fainting spells, headache and sometimes the shakes. PMT-C patients have increased carbohydrate tolerance and low red-cell magnesium. Adequate magnesium replacement results in improved glucose tolerance tests and decreased PMT-C symptoms. Deficiency of the prostaglandin PGE1 may also be involved in PMT-C. PMT-D is the least common but most dangerous because suicide is most frequent in this subgroup. The symptoms are depression, withdrawal, insomnia, forgetfulness and confusion. In ten PMT-D patients the mean blood estrogen was lower and the mean blood progesterone higher than normal during the midluteal phase. Elevated adrenal androgens are observed in some hirsute PMT-D patients. Two PMT-D patients with normal blood progesterone and estrogens had high lead levels in hair tissue and chronic lead intoxication. This subgroups needs careful medical attention when the symptoms are severe. Therapy should be individualized according to the results of the evaluation.
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PMID:Nutritional factors in the etiology of the premenstrual tension syndromes. 668 67

A menstrual symptom questionnaire was used to assess the incidence of premenstrual tension (PMT) in 1,395 regularly menstruating women not on hormonal contraceptives or any other hormonal therapy during routine visits to a gynecologic clinic. Nineteen symptoms were divided into four PMT subgroups: PMT-A (anxiety, irritability, mood swings, nervous tension), PMT-H (weight gain, swelling of extremities, breast tenderness, abdominal bloating), PMT-C (headache, craving for sweets, increased appetite, heart pounding, fatigue and dizziness or fainting) and PMT-D (depression, forgetfulness, crying, confusion, insomnia). The ages of the patients ranged from 13 to 54 years, with a mean +/- S.D. of 32 +/- 8.5 years. Using strict criteria for PMT, 702 patients scored positive for at least one subgroup of PMT, giving an incidence of 50%. When the patients were divided into five-year age groups, a peak incidence of 60% was observed in the third decade of life. The most common PMT subgroups were PMT-A and PMT-H, occurring either alone or in combination. The least common subgroup was PMT-D, occurring in only 12 patients and by itself. The mean cycle length in pure PMT-D patients was significantly shorter (p less than 0.05) than in patients without PMT.
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PMID:The incidence of premenstrual tension in a gynecologic clinic. 689 20

Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect. Therapeutically, folic acid can reduce homocysteine levels and the occurrence of neural tube defects, might play a role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis, appears to be a rational aspect of a nutritional protocol to treat vitiligo, and can increase the resistance of the gingiva to local irritants, leading to a reduction in inflammation. Reports also indicate that neuropsychiatric diseases secondary to folate deficiency might include dementia, schizophrenia-like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, peripheral neuropathy, myelopathy, and restless legs syndrome.
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PMID:Folates: supplemental forms and therapeutic applications. 963 Jul 38

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun
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PMID:[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning]. 1050 96

In the menopause transition, around 35% of women will seek medical help for menopausal symptoms. At the climacteric, various symptoms such as forgetfulness, anxiety, depressive neurosis, abnormal sensation, hot flush and sleeplessness are often observed due to hypofunction of the ovaries. There is some indication that women become more anxious during times of relatively low level of estrogen and progesterone such as premenstrual syndrome, premenstrual dysphoric disorder, maternity blues and menopausal state. The exact mechanism behind it is still unclear but is probably related to the decrease of ovarian hormones, which may be triggering psychiatric mood disorders. It is known that ovarian hormones act on specific areas of the brain and appear to act as anxiolytics. Certain progesterone metabolites are anesthetic and have antiepileptic and anxiolytic properties. These steroids modulate the type A gamma-aminobutyric acid (GABAA)/benzodiazepine receptor. This may help explain the increased frequency of anxiety disorders and mood disorders in the early postmenopausal period. In addition, estrogen also improves memory and performance in patients with mild Alzheimer's dementia. These effects can be related to amplifying effects of estrogen on excitatory amino acids in the brain. This is suggested that gonadal steroidal hormones seemed to be one of the essential substances for the maintenance of the limbic system and forebrain function which regulated anxiety, mood, memory and cognitive functions in menopausal women.
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PMID:[Menopause and anxiety: focus on steroidal hormones and GABAA receptor]. 1087 12

Changes in neuroendocrine function may predispose menopausal women to psychological disturbances characterized by depressed mood, anxiety, irritability, fatigue, insomnia, forgetfulness and decline in libido. The acute tryptophan depletion paradigm was employed to examine the serotonergic contribution to mood and cognitive function in menopausal women who were within 4 weeks of recovery from an episode of major depression. Menopausal women whose depression was responsive to treatment with oestradiol, the selective serotonin reuptake inhibitor fluoxetine, or a combination of both treatments underwent assessment of mood and verbal memory on active tryptophan depLetion and sham depletion test days. Although performance on the delayed paragraph recall subtest of the Wechsler Memory Scale was impaired by tryptophan depletion, no subjects experienced a relapse of depression or a significant worsening of mood. Results from this pilot study indicate that menopausal women who have recently recovered from a major depressive episode do not experience a worsening of mood with acute tryptophan depletion, despite the existence in this sample of some known risk factors for depressive relapse as a result of these procedures. While preliminary, the results suggest that serotonin may be less critical to the pathogenesis of depression during the menopause.
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PMID:The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings. 1689 41


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