Comparison of the development of the fatty acid content and composition of the brain of a precocial species (guinea pig) and a non-precocial species (rat)

The fatty acid compositions of the brains of a precocial (guinea pig) and a non-precocial (rat) species have been studied as a function of development. In the rat brain the total fatty acid content expressed as mg g wet wt.-1 increased more than fourfold during the period from 5 days after birth to adulthood. However, the percentage composition of this total fatty acid content when expressed per individual fatty acid remained fairly constant, with the exception of nervonic acid (C24:1) which also increased fourfold on a percentage basis. In the guinea pig brain, however, at birth the total fatty acid content, expressed as mg g wet wt-1, is the same as that of the adult, the concentration doubling during the period from 25 days before birth until birth. Again, if the fatty acid content is analysed and expressed on a percentage basis, the relative concentrations of the individual fatty acids remain fairly constant over the period from 25 days before birth until adulthood, with the exception of nervonic (C24:1) acid which increases about fivefold from 25 days before birth to birth and only marginally (20%) from birth to adulthood. These results are discussed in relationship to the onset of neurological competence in the two species. It is concluded that the increase in fatty acid content (both total and individually) of the brains of these species as a function of the foetal and neonatal development follows a pattern which is similar to the pattern of development of certain key enzymes of energy metabolism and of neurological competence.     

Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.     

Caudal morphine in paediatric patients: a comparison of two different doses in children after major urogenital surgery

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.     

Effects of feeding Lunaria oil rich in nervonic and erucic acids on the fatty acid compositions of sphingomyelins from erythrocytes, liver, and brain of the quaking mouse mutant

Feeding an oil from Lunaria biennis rich in 22:1n-9 and 24:1n-9 to homozygous quaking (qk.qk) mice caused a large increase in the percentage of 24:1n-9 and corresponding decreases in the percentage of 24:0 and 22:0 in sphingomyelins from liver, erythrocytes, and milk. Brain sphingomyelin from 2-wk-old qk.qk pups born to qk.qk mothers maintained on the Lunaria oil had essentially normal percentage of 24:1n-9 and 18:0, in contrast to pups born to mothers maintained on a control oil rich in 18:1n-9 whose brain sphingomyelin had a markedly reduced percentage of 24:1n-9 and an increased percentage of 18:0. After 2 wk and up to and beyond weaning, the qk.qk pups from Lunaria-fed mothers weaned on to the Lunaria diet had a markedly decreased percentage of 24:1n-9 in their brain sphingomyelin, accompanied by an increased percentage of 18:0, as compared to heterozygous quaking mice. However, the percentage of 24:1n-9 in brain sphingomyelin in qk.qk pups weaned on to the Lunaria diet continued throughout this period (2-8 wk postbirth) to be significantly higher than in qk.qk pups weaned on to the control diet. We conclude that dietary 24:1n-9 influences the fatty acid composition of brain sphingomyelin in qk.qk mice, but only via the mother in pre- or early postnatal animals. We further consider that the dietary effects may be elicited mainly in the sphingomyelin of nonmyelinated brain cells, and that the nervonic acid in myelin sphingomyelin may be formed mainly by chain elongation in oligodendrocytes from shorter chain fatty acid precursors.     

Localization of nervonic acid beta-oxidation in human and rodent peroxisomes: impaired oxidation in Zellweger syndrome and X-linked adrenoleukodystrophy

Studies with purified subcellular organelles from rat liver indicate that nervonic acid (C24:1) is beta-oxidized preferentially in peroxisomes. Lack of effect by etomoxir, inhibitor of mitochondrial beta-oxidation, on beta-oxidation of lignoceric acid (C24:0), a peroxisomal function, and that of nervonic acid (24:1) compared to the inhibition of palmitic acid (16:0) oxidation, a mitochondrial function, supports the conclusion that nervonic acid is oxidized in peroxisomes. Moreover, the oxidation of nervonic and lignoceric acids was deficient in fibroblasts from patients with defects in peroxisomal beta-oxidation [Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD)]. Similar to lignoceric acid, the activation and beta-oxidation of nervonic acid was deficient in peroxisomes isolated from X-ALD fibroblasts. Transfection of X-ALD fibroblasts with human cDNA encoding for ALDP (X-ALD gene product) restored the oxidation of both nervonic and lignoceric acids, demonstrating that the same molecular defect may be responsible for the abnormality in the oxidation of nervonic as well as lignoceric acid. Moreover, immunoprecipitation of activities for acyl-CoA ligase for both lignoceric acid and nervonic acid indicate that saturated and monoenoic very long chain (VLC) fatty acids may be activated by the same enzyme. These results clearly demonstrate that similar to saturated VLC fatty acids (e.g., lignoceric acid), VLC monounsaturated fatty acids (e.g., nervonic acid) are oxidized preferentially in peroxisomes and that this activity is impaired in X-ALD. In view of the fact that the oxidation of unsaturated VLC fatty acids is defective in X-ALD patients, the efficacy of dietary monoene therapy, "Lorenzo's oil," in X-ALD needs to be evaluated.     

Modifying the n-3 fatty acid content of the maternal diet to determine the requirements of the fetal and suckling rat

During perinatal development, docosahexaenoic acid (22:6n-3) accumulates extensively in membrane phospholipids of the nervous system. To evaluate the n-3 fatty acid requirements of fetal and suckling rats, we investigated the accumulation of 22:6n-3 in the brain and liver of pup rats from birth to day 14 postpartum when their dams received increasing amounts of dietary 18:3n-3 (from 5 to 800 mg/100 g diet) during the pregnancy-lactation period. The fatty acid composition of brain and liver phospholipids of pups, as well as that of dam's milk, was determined. At birth, 22:6n-3 increased regularly to reach the highest level when the maternal diet contained 800 mg 18:3n-3/100 g. On days 7 and 14 postpartum, brain 22:6n-3 plateaued at a maternal dietary supply of 200 mg/100 g. Docosapentaenoic acid (22:5n-6) had the opposite temporal pattern. The unusually high concentration of eicosapentaenoic acid (20:5n-3) in liver and dam's milk observed at the highest 18:3n-3 intake suggests an excessive dietary supply of this fatty acid. All these data suggest that the n-3 fatty acid requirements of the pregnant rat are around 400 mg 18:3n-3 and those of the lactating rat at 200 mg (i.e., 0.9 and 0.45% of dietary energy, respectively). The values of 18:3n-3 and 22:6n-3 milk content which allowed brain 22:6n-3 to reach a plateau value in suckling pups were 1% of total fatty acids and 0.9% (colostrum) to 0.2% (mature milk), respectively. These levels are similar to those recommended for infant formulas.     

More recent aspects of treatment for hypothyroidism and goitre in children and adolescents (author's transl)

According to more recent knowledge L-thyroxine alone is recommended for thyroid hormone replacement therapy, no longer the combination of L-thyroxine and triiodothyronin, since L-thyroxine is converted to triiodothyronine in the periphery of the body. Additional application of triiodothyronine causes unphysiological elevations of blood levels of triiodothyronine. When changing from the combined thyroid hormone therapy to treatment with L-thyroxine alone it is enough in most cases to replace the previous amount of L-thyroxine only; previous recommendations for the dosage of thyroid hormone were rather high. Average requirements of adults for L-thyroxine are around 170 mug per day. Children need about 90--100 mug per m2 body surface per day. -- When hypothyroidism is suspected in newborns or infants no protracted diagnostic procedures are justified with respect to brain development and its requirement of thyroid hormone during this period of life. Replacement therapy should be started within 1--2 days. The exact diagnosis can be established later, for instance during the third day of life when a temporary interuption of treatment for diagnostic purposes has no longer such negative effect on normal brain development. As long as physiological doses of L-thyroxine are used no side effects are to be expected for patients who later turn out to be euthyroid. -- Following exclusion of hyperthyroidism goitres in children and adolescents equally need thyroid hormone replacement therapy to reduce the size or prevent further enlargement or even the development of nodules within the gland. The dosage for this is about half to three quarters of the full replacement dose. The nature of thyroid nodules should be investigated, even surgically, since malignancies can develop in children and juveniles as well as in adults.     

Elongation of (omega-14C)oleic acid and (omega-14C)nervonic acid

During feeding experiments with [omega-14C]oleic acid and [omega-14c]nervonic acid to adult rats, 14C-labelled C26, C28 and C30 fatty acids were recovered from the intestinal mucosa, liver, plasma, kidney and stools. The structures of these fatty acids were determined by g.l.c., radio-g.l.c. and mass spectrometry. The Schmidt and Ginger degradation methods indicated that most of the 14C found in these extra-long fatty acids remained in the omega position. These radioactive extra-long fatty acids were found mainly in the polar lipids of rats killed 3 or 15 h after being fed on labelled oleic acid or nervonic acid. Rats killed 63 h later yielded only traces of these extra-long fatty acids. When the rats were given antibiotics or received the same radioactive fatty acids by intravenous injection, the labelled extra-long fatty acids could not be detected in any of the tissues. We conclude that they were probably synthesized by elongation of oleic acid and nervonic acid by intestinal micro-organisms (probably yeasts) and then absorbed by the intestinal mucosa.     

Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as hypoxia-selective cytotoxins

A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.     

Incidence of febrile convulsions in children with congenital hypothyroidism

Brain excitability has been inconsistently reported to be increased both in hypo- and hyperthyroidism, but there have been few studies on the effects of thyroid hormones on brain excitability in children. With this in mind, we investigated the incidence of febrile convulsions (FCs) among patients with congenital hypothyroidism, who have been taking L-thyroxine since the age of 1 month. The incidence of FCs among congenital hypothyroid patients was 1.6% (1/63) which was significantly low (p < 0.05) compared with that of normal control children who visited our hospitals as outpatients (28/341, 8.2%) and that of others (322/3301, 9.8%) investigated 33 years ago in the same area. The incidence of FC among siblings of the 63 patients (7/74, 9.5%) was not statistically different from the controls. At least 8 of the 126 parents (6.4%) had experienced FC, however, only one child was affected in the 8 families. In conclusion, it seems likely that patients with congenital hypothyroidism on regular L-T4 replacement are less prone to experience FC. More studies on the incidence of convulsive disorders in children with thyroid diseases are needed to clarify the effects of thyroid hormones on brain excitability.     

Developmental characteristics of histamine methyltransferase and phenylethanolamine-N-methyl-transferase of rat brain

The specific activity of histamine methyltransferase of rat brain increases rapidly from the 16th until the 25th day of gestation (7 days after birth). The specific activity of phenylethanolamine-N-methyl-transferase shows a rapid increase during the 1st and the 2nd week after birth, the adult values being obtained by the end of the 2nd week.     

The role of maternal thyroid hormones on the development of the brushtail possum, Trichosurus vulpecula

Thyroxine (T4) is a vital hormone for the development of mammals. To determine the role of maternal thyroid hormones on organ development, methimazole, an inhibitor of T4, was first administered via a minipump to 13 mothers with pouch young between days 10 and 80 post partum for 28 days. Three young survived and 10 of the young died at 104.0 +/- 10.8 days post partum (mean, SEM). Methimazole was then administered for 28 days to 6 lactating adult possums with pouch young at day 20 post partum. The effects of this treatment on the maternal plasma concentrations of T4 were monitored and the development of the lung, kidney and brain of the young were examined at day 90 post partum. There was no difference in the morphology of the lung, kidney and brain of pouch young at day 90 post partum whose mothers were treated with methimazole or saline. Thus methimazole administered to lactating possums for a short period early in lactation can cause the demise of the young about day 100 post partum although the cause of death is unknown. It is possible that the development of the central nervous system or some other vital organ has been inhibited, this altered state not being apparent morphologically. Nevertheless the marsupial appears to be similar to the eutherian in its requirement for thyroxine for normal development. However whereas this requirement is apparent during fetal development and around the time of birth in eutherians thyroxine is of importance during pouch development in marsupials.     

Influence of gynecologic surgery on the blood concentration of adenosine phosphate

After operations of benign gynaecological diseases we recorded changes of the lipid metabolism which were manifested by the following deviations of serum cholesterol and non-esterified and esterified fatty acid concentrations: 1. Total serum cholesterol levels declined markedly after operation either throughout the six-day period after operation, or they began to rise starting on the third day. 2. The esterified fatty acid concentrations rose after a brief drop, usually already from the first day. 3. The non-esterified fatty acid concentrations rose after operation. The peak was as a rule reached on the third day after operation. Subsequently they had a declining trend. 4. The preoperative values of the above lipids were slightly altered (we observed higher cholesterol and esterified fatty acid concentrations). This change was at least partly explained as the consequence of the preoperative stress. In our opinion is it important to attempt to restrict sudden changes of the lipid metabolism, as these changes may become the basis of various postoperative complications.     

Evolutive study of the vectorcardiogram from the 14th day to the 6th month of life on the normal infant

With the purpose of a better evaluation of the changes of cardiac potentials during the early hemodynamic arrangement of the normal heart, the authors analyze the VCG of 10 normal children periodically recorded from the 14th day to the 6th month from birth. Rotation of QRS, T and P loops in the three planes, direction and voltage of principal planar and spatial vectors were analyzed. The QRS loop showed a balanced distribution between right and left ventricular forces in the second week and developed a leftward orientation from the 4th week to the 3rd month, as demonstrated both by the loss of clockwise rotation of horizontal QRS loop and by the progressive leftward and backward direction of intermediate vectors. The initial vectors were sketched or absent in the 14th day and increased successively until the typical Q loop. The voltage of terminal vectors did not change in the course of time, but the S loop in the horizontal plane lost its original clockwise rotation and shifted to middle posterior line. The T loop progressively shifted backward so that it was always posterior after the 30th day. The P loop in the frontal plane was similar to the adult's one while in the horizontal plane it often presented a figure-of-eight. The semeiological aspects and the electrogenic considerations of these changes were discussed.     

Lipid metabolism and membrane composition are altered in the brains of type II diabetic mice

CBL/57 strain db/db mice exhibit type II (noninsulin-dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane-bound synaptosomal acetylcholinesterase, Na+,K(+)-ATPase, and Mg(2+)-ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic enzyme--lactate dehydrogenase--are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1-14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.     

Thyrotropic action of human chorionic gonadotropin

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.     

Thyroid hormone is required for dietary fish oil to induce hypersecretion of biliary cholesterol in the rat

In the rat, both fish oil diet and thyroid hormone replacement are reported to augment bile cholesterol secretion out of proportion to bile flow or secretion of other bile lipids. We sought common mechanisms for these effects and evaluated the role of phospholipid fatty acid composition in the process. Methimazole-treated hypothyroid rats were fed low-fat chow or chow supplemented with 10% corn oil or fish oil, and were studied before and after thyroid hormone treatment. Serum, hepatic, and bile lipids were measured, phospholipid fatty acid composition determined, and hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity assayed. Fish oil diet stimulated cholesterol secretion into bile only after thyroid hormone was given, and this action was synergistic with that of thyroid hormone. Reduced serum cholesterol in fish oil-treated rats was associated with increased biliary cholesterol secretion and diminished hepatic cholesterol content. This suggests that augmented biliary cholesterol secretion may contribute to the fish oil-induced reduction of serum cholesterol. No definite relationship between hepatic or biliary phospholipid fatty acid composition and biliary secretion was apparent, although high bile cholesterol secretion was associated with a low percentage of hepatic and bile phospholipid linoleic acid.     

Poyps and cancer of the large bowel

A total of 85 cows were used to study the clinical course of the involution processes in the genital tract following calving. According to the season of calving the animals were divided into two groups: 1st group consisting of 29 cows whose calving and puerperium had taken place during the spring/summer period; IInd group of 56 cows with which these processes were observed in the autumn/winter period. Seven cows of each group were subjected to endocrinologic studies for the evaluation of the pituitary gonadotropic hormones (FSH, and LH) in the blood plasma, applying Brown's method and Parlow's method, respectively. The following conclusions were drawn: 1. The intensity of the involution processes in the sexual apparatus of cows depends on the season. In the spring/summer period they usually last 34.3 days, and in the autumn and winter -- 37.5 days. 2. Fast involution of the uterus has been observed during the first two weeks after calving. This process is considerably delayed during the third week. 3. The yellow body regresses in the course of 14 days following calving. Up to the 35th day this has been established only im 3.5 per cent of the cows. Clinically, follicles in the ovaries are established as early as the 15th day after calving. 4. The FSH and LH level in the blood plasma during the first days after calving has been low -- 73.7 mg/% for FSH, and 7.04 mg/% for LH, both showing a rising trend. The peak values have been established between the 15th and 40th, and the 22nd and 28th day, respectively.     

Interleukin 1alpha and interleukin 6 promote the in vitro growth of both normal and neoplastic human cervical epithelial cells

We report here on a patient who was diagnosed with follicular carcinoma in 1985, and who was treated with total thyroidectomy. Two years later, when metastasis was found in his neck lesion, lung, pelvis and right femur, the patient received 131I treatment. Six years after receiving 131I treatment, the patient presented with hyperthyroidism. Whole-body scan with 131I revealed functioning metastasis in his right femur and pelvis. There was no hot spot in the neck region, confirming that no thyroid tissue remained. Blood panels revealed an increase in both TSH binding inhibitory immunoglobulin (TBII. 36.2%; normal. -10 approximately 10%) and thyroid stimulating antibody (TSAb, 176%; normal, less than 145%). Treatment with antithyroid drugs, dexamethasone and radioisotope therapy rapidly resolved his hyperthyroidism. Thyrotoxicosis and positive TRAb occurred in the absence of thyroid tissue, and many years after the completion of R1 therapy. The overproduction of thyroid hormone can therefore only be attributed to some mechanism of activity in the metastatic tumor tissue.