Mg Of Pyridoxine Research Articles

The fasting B6 vitamer profile and response to a pyridoxine load in normal and cirrhotic subjects.

This study established the fasting plasma and urine profiles of vitamin B6 in cirrhotics and assessed the response to an oral dose of pyridoxine. High-performance liquid chromatography was used to measure all vitameric coenzymatic and degradatory forms. In 31 patients with cirrhosis and 15 healthy controls, fasting plasma and 24-hr urine collection showed: plasma pyridoxal-5'-phosphate, the biologically active form, was significantly (p less than 0.001) reduced in cirrhotics (mean +/- S.D.: 5.7 +/- 3.2 ng per ml) compared to normals (14.2 +/- 7.5 ng per ml); plasma pyridoxal was detected in more cirrhotics (48%) than normals (28%); pyridoxic acid, the end catabolite, was significantly (p less than 0.05) lower in plasma of cirrhotics compared to normals, but 24-hr urine excretion was not different. Administration of 25 mg of pyridoxine to 7 cirrhotics and 5 normals showed the following plasma changes: pyridoxine rapidly peaked at 30 min and was totally cleared from plasma by 3 hr; plasma pyridoxal and pyridoxic acid increased in parallel up to 40-fold over baseline by 1 to 2 hr and rapidly fell toward baseline by 8 hr, and plasma pyridoxal-5'-phosphate, in contrast, increased significantly (p less than 0.05) from baseline by 60 min and was maintained above normal for 24 hr. The area under the plasma concentration vs. time curve (AUC) for pyridoxal-5'-phosphate was significantly (p less than 0.05) less for the cirrhotics than normals and showed a significant negative correlation to hepatocyte function and blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary observations on short-course chemotherapy in tuberculous serositis.

Short-course chemotherapy has not been previously assessed in tuberculous serositis. In this study, 18 patients with tuberculous serositis were studied. 600 mg of rifampicin, 300 mg of isoniazid and 25 mg of pyridoxine were given daily for 6 months. 14 patients completed the therapeutic regimen and were evaluated. 11 of these showed excellent results on the long-term follow-up (18-24 months) and 3 of shorter-term follow-up (9-12 months). Short-course chemotherapy appears to be efficacious in the treatment of tuberculous serositis. However, further and larger trials are recommended.

The Effects of Pyridoxine on Pituitary Hormone Secretion in Amenorrhea-Galactorrhea Syndromes

Pyridoxine (vitamin B6) is metabolized in vivo to pyri-doxal-5′-phosphate, which serves as a cofactor for dopa decarboxylase. This enzyme converts dopa to dopamine, for which reason it has been thought that pyridoxine might function as a dopaminergic agent. The data concerning the effects of pyridoxine on pituitary hormones in normal subjects and in patients with hyperprolactine-mia have been conflicting. The present study was undertaken because of the lack of information concerning the effects of pyridoxine on gonadotropins and because of unexplained reports of the amelioration of galactorrhea by pyridoxine. The study was designed in an attempt to determine if acute or chronic pyridoxine administration could be shown to have any dopamine-like effect on the pituitary function in patients with amenorrhea and galactorrhea. The major emphasis, however, was to evaluate the effect of pyridoxine on prolactin and gonadotropins. Six patients (ages 22 to 37 years) with amenorrhea were studied, five of whom also had galactorrhea and elevated serum prolactin levels. Four provocative or suppressive tests were performed on alternate days after an overnight fast: TRH (500 mg) was injected as an intravenous bolus; L-dopa (500 mg) was given orally; chlorpromazine (25 mg) was injected intramuscularly (four patients); and a 300-mg intravenous bolus of pyridoxine was given. Blood samples were taken at intervals after each test. They were assayed for LH, FSH, and prolactin after L-dopa and chlorpromazine, and for these plus hGH and TSH after pyridoxine and TRH. The patients were then placed on 600 mg of pyridoxine per day orally (in three divided doses) and were readmitted 21 days later for a repeat of the above protocol on pyridoxine. They remained on 600 mg of pyridoxine per day orally for 3 to 4 months, with monthly clinical evaluations and basal serum prolactin, LH, and FSH measurements. The patients were similarly followed for 3 months after discontinuing pyridoxine. There were no significant responses of prolactin, LH, FSH, hGH, or TSH to pyridoxine under either basal or treatment conditions. TRH induced similar responses in plasma TSH before and during administration of pyridoxine. Before therapy, prolactin rose after TRH in four of the six patients. On pyridoxine, prolactin increased after TRH in two patients who had not responded initially. One of these women resumed menses while on pyridoxine. There was, however, no significant difference in mean prolactin reponse to TRH before or during pyridoxine therapy, whether comparison is made of maximum levels or increments of prolactin. The administration of 25 mg of chlorpromazine did not change the basal prolactin, LH, or FSH concentrations in any patient significantly. L-dopa caused a decrease in the basal prolactin concentration in all patients before pyridoxine treatment. The degree of suppression was unchanged after 3 weeks of pyridoxine therapy. Gonad-otropin levels did not change after L-dopa in either the pre- or post-therapy test. The L-dopa-induced rise in GH was unchanged before and after pyridoxine. Within individual tests, both before and after pyridoxine, prolactin increased after TRH and decreased after L-dopa, and hGH increased after L-dopa similarly. The means for each sampling time within tests were, however, significantly different (P < 0.05) for the TSH response to TRH. The mean basal prolactin, LH, and FSH (97.1 ± 14.8 ng/ml, 23.6 mlU/ml, and 18.8 ± 1.9 mlU/ml, respectively) during chronic pyridoxine treatment were not significantly different from pretreatment levels or from those 3 months after cessation of therapy. In addition, the mean basal prolactin of all tests after 21 days of pyridoxine (96.1 ± 10.3 ng/ml) was unchanged. Nevertheless, two of the six patients resumed regular menses during the chronic pyridoxine therapy. These patients had the lowest basal prolactin levels but could not be distinguished from the group on the basis of responses to the provocative tests nor on the basis of hormone levels after chronic therapy. One of these patients continued to have monthly menstrual periods during the 3 months after discontinuing pyridoxine, whereas the other had only two periods with light bleeding. Pretreatment levels of pyridoxal-5′-phosphate and hemolysate pyridoxal kinase were similar among the four patients in whom they were measured. After 3 to 4 months of pyridoxine treatment, the pyridoxal-5′-phosphate concentrations were also similar in the two patients who began menses (3 and 427 ng/1010 red blood cells; 89 and 156 ng/ml of plasma) and two of the patients whose menses did not begin (437 and 153 ng/1010 red blood cells; 126 and 67 ng/ml of plasma). The hemolysate pyridoxal kinase activity was likewise similar in the two pairs. No adverse effects were noted during pyridoxine therapy.

Methionine Transamination and Catabolism in Vitamin B-6 Deficient Rats

G. BELI VEAU EVERETT,2 A. D. MITCHELL 3ANDN. J. BENEVENGADepartments of Nutritional Sciences and Meat andAnimal Science, University of Wisconsin,Madison, Wisconsin 53706ABSTRACT Methionine (Met) transamination and oxidation of theMet or a-keto-y-methiolbutyrate (aKyMB) carboxyl and methyl carbonswere studied in weanling rats fed control or vitamin B8 deficient diets containing 18 or 60% casein for a period of 21 days. In homogenates preparedfrom the livers of Be deficient rats, transamination of Met was reduced to8 to 16% of controls. Transamination was partially restored by addition ofpyridoxal phosphate (PALP) to the homogenates. Vitamin B6 deficiencyresulted in a 61 to 76% reduction in oxidation of the Met carboxyl carbonwhich was also partially restored by the addition or PALP. The high proteindiet stimulated transamination of Met and oxidation of the carboxyl carbonsof both Met and aKyMB. Oxidation of the methyl carbon was relativelyunaffected by either B6 deficiency or high protein diet. In vivo, the oxidation of the Met carboxyl carbon was not influenced by either B8 deficiencyor high protein diet, however, oxidation of the methyl carbon increased 32to 53% in rats fed the B6 deficient diets. It appears that transamination wasnot rate limiting in vivo, even with a B6 deficiency, however, in vitro withgreater substrate loading transamination may become rate limiting foroxidation of the carboxyl carbon of Met. In vivo the B8 deficiency may haveresulted in a shift of Met metabolism from the transsulfuration pathway,which conserves the methyl carbon and partially conserves the carboxylcarbon depending on the fraction of homocysteine remethylated, to thetransaminatA¬vepathway which results in extensive oxidation of both carbons. J. Nutr. 109: 597-605, 1979.INDEXING KEY WORDS methionine •transamination •pyri-doxine •o-keto-y-methiolbutyrate •ratPyridoxal-5'-phosphate (PALP) functions in rats fed an 18% casein diet deficient inas a coenzyme for a number of enzymes in- pyridoxine. This was overcome by additionvolved in L-methionine (Met) and L-cys- of 0.6 mg of pyridoxine •HC1 per kg of diet.teine metabolism. These include cystathio- Much attention has centered on the trans-nine /3-synthase (EC 4.2.1.22), cystathionase sulfuration pathway (fig. 1) of methionine(EC 4.4.1.1), cysteine sulfinic acid trans-

Ineffectiveness of pyridoxine in evalution and treatment of the hyperprolactinemic amenorrhea-galactorrhea syndrome

Pyridoxine hydrochloride (vitamin B6) has been proposed as a diagnostic and therapeutic agent for patients with amenorrhea and galactorrhea associated with elevated serum prolactin levels. Therefore five normal premenopausal women and nine consecutive patients with amenorrhea, but with no other evidence of pituitary tumor, were given 200 to 300 mg of pyridoxine IV. Mean serum prolactin and growth hormone concentrations did not change significantly from baseline following the infusion in either group. Eight of the nine amenorrhea patients had elevated serum prolactin levels and were treated with oral PDX for 91.0 ± 10.1 (S.E.) days, including 42.0 ± 8.2 days at a maximum dosage of 600 mg. per day in divided doses. Mean serum prolactin concentrations of the eight patients at completion of therapy (82.6 ± 19.1 ng. per milliliter) did not differ significantly from the pretreatment value (69.1 ± 18.4 ng. per milliliter). No subject acquired normal prolactin levels, and in two patients the serum prolactin levels increased during treatment. Galactorrhea diminished very slightly in three of the seven lactating patients but was unchanged in the remainder. Amenorrhea persisted throughout pyridoxine treatment in all eight patients. While receiving 600 mg. per day, three patients complained of headaches, lethargy, and lightheadedness which subsequently resolved when the PDX was discontinued. Thus, pryidoxine does not appear to be a useful agent for evaluation or treatment of the galactorrhea-amenorrhea syndrome.

Long term treatment of Huntington disease with L‐glutamate and pyridoxine

Decreased levels of gamma aminobutyric acid (GABA) and its synthetic enzyme, glutamic acid decarboxylase, have been found in the brains of patients with Huntington disease. In an attempt to augment GABA-mediated neurotransmission, daily doses of 25 gm of L-glutamate (the substrate for glutamic acid decarboxylase) and 500 mg of pyridoxine, its cofactor, were given to five patients with Huntington disease. This regimen was continued for 2 years. Assessment of motor and behavioral function indicated no improvement on this regimen.

Subacute toxicity of pyridoxine hydrochloride in the beagle dog

Supplemental doses of 0, 50, or 200 mg of pyridoxine HCl/kg/day were administered po to three groups of dogs for an average of 107 days. Ataxia, muscle weakness, and loss of balance developed between 40 and 75 days of treatment in the group that received 200 mg/kg/day. Clinical signs of toxicity were not observed in the 50-mg/kg/day dose group. Histologic examination of the tissues in the animals receiving the highest dose revealed bilateral loss of myelin and axons in the dorsal funiculi (f. cuneatus and f. gracilis) and loss of myelin in individual fibers of the dorsal nerve roots. In the group receiving 50 mg/kg/day pathological damage was limited to a bilateral loss of myelin in the dorsal nerve roots. Serum glutamic oxaloacetic transaminase and creatine phosphokinase activities were greater and cholesterol concentrations were decreased in the serum of animals receiving 200 mg/kg/day at the termination of the study. Analyses of tissues for pyridoxine concentrations revealed elevated values in the blood, cerebral cortex, spinal cord, spleen, kidney, and muscle in the group receiving 200 mg/kg/day. The group receiving 50 mg/kg/day had elevated pyridoxine values only in blood and cerebral cortex.

Vitamin B-6 requirement for irreversible inactivation of rat liver tyrosine aminotransferase

In vitro inactivation of tyrosine aminotransferase at pH 7.0 did not occur in liver homogenates prepared from vitamin B-6-deficient rats, although it was previously demonstrated that the enzyme was inactivated in liver homogenates from vitamin B-6-adequate rats (R. D. Reynolds and S. D. Thompson, 1974, Arch. Biochem. Biophys. 164, 43–51) . Addition of 2 m m pyridoxine or pyridoxal- P to the incubated homogenate did not restore the inactivation, but injection of 1 mg of pyridoxine to deficient rats restored full inactivating activity by 12 h. All forms of vitamin B-6 injected restored inactivating activity in vitro. This effect appears to be specific for vitamin B-6, since no restoration of in vitro inactivation of tyrosine aminotransferase was observed following injection of riboflavin, thiamin, niacin, or folic acid. The restoration of inactivating activity in vitro following injection of pyridoxine was not inhibited by repeated injections of puromycin or cycloheximide. Apparently, in vivo protein synthesis is not required for the restoration of the in vitro inactivating activity. However, in vivo inactivation was similar in the vitamin B-6-adequate and -deficient rats. Inactivating activity is present in homogenates of liver and kidney, but not of abdominal muscle, small intestine, heart, testes, whole blood, or erythrocyte ghosts, and is found only in the plasma membrane fraction of liver. Similar to liver, the activity in the kidney homogenate requires the presence of l-cysteine and depends upon the vitamin B-6 status of the animal. Rapid inactivation in the liver occurs between pH 6.75 and 7.75 (final pH), with minimal inactivation above or below this range. No inhibition of inactivation was observed with homogenates incubated in the presence of several protease inhibitors.

TREATMENT OF PREGNANCY SICKNESS

A double-blind comparison was undertaken between Debendox with 10mg of extra pyridoxine and placebo with 10mg of pyridoxine, in 56 women suffering from nausea and/or vomiting during the first 10 weeks of pregnancy. The results of treatment were assessed on the patient's own dialy records of:the time of nausea, the frequency of nausea, and the severity of nausea, retching and vomiting. There were statistically significant differences in favour of Debendox with extra pyridoxine in respect of the days of nausea all day (P les than 0-02), the severity of nausea (P less than 0-05) and the severity of retching (P less than 0.05).

Adequacy of vitamin B6 supplementation during pregnancy: a prospective study

This prospective study assesses the effect of 2.5, 4, and 10 mg of pyridoxine supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal 5'-phosphate (PLP) and on the degree of coenzyme saturation (activation factor) of aspartate aminotransferase and alanine aminotransferase (alphaEGOT and alphaEGPT) in maternal erythrocytes. More than 4 mg of pyridoxine supplementation daily was required for most pregnancies to maintain maternal plasma PLP levels within the range observed during the first trimester and in the nonpregnant state. The plasma PLP concentrations in maternal and cord blood were highly correlated and indicated a dependence of fetal vitamin B6 nutrition on maternal circulating PLP. Measurements of alphaEGOT and alphaEGPT were not as reproducible as plasma PLP assays and were less sensitive and quantitative indicators. In the majority of subjects, the changes in alphaEGOT and alphaEGPT with time correlated poorly with the changes in plasma PLP. However, when the data were analyzed without regard for their dependence on time, they demonstrated a negative, linear correlation between alphaEGOT and log plasma PLP and between alphaEGPT and log plasma PLP for the group on 2.5 mg of pyridoxine and for all the subjects combined. Finally, the dietary records showed that most of the subjects consumed less than 2 mg of vitamin B6 daily from their food. The results indicate that the current Recommended Dietary Allowance for vitamin B6 during pregnancy (2.5 mg) is too low and that supplementation of this vitamin in an amount more than 4 mg daily is recommended.

Abnormal Regulation of Plasma Pyridoxal 5'-Phosphate in Patients with Liver Disease

Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B6, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P less than 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P greater than 0.05). (1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.

Vitamin supplements to women using oral contraceptives (studies of vitamins B 1, B 2, B 6 and A)

Additional requirement of pyridoxine, thiamin and riboflavin necessary to prevent a decline in the nutritional status of these vitamins in women using an oral contraceptive — Ovral (ethinyl estradiol 0.05 mg and dl-norgestrel 0.5 mg) was examined. Ten mg of pyridoxine daily could mitigate the defect in tryptophan metabolism to a large extent. This amount could prevent the defect in erythrocyte aspartate amino transferase activity. Daily supplements of 3 mg thiamin and 2 mg riboflavin could prevent the decline in the nutritional status of these vitamins. Higher amounts of riboflavin would, however, be required to correct the initial deficiency of the vitamin.

The effect of vitamin B6 supplements on development of seizures in the gerbil, [formula omitted

To see if a Vitamin B6 deficiency is responsible for seizure-proneness in the gerbil, Meriones unguiculatus , a diet supplemented with 0.5mg of pyridoxine per gram of Purina Lab Chow was fed to 8 experimental (E) mated pairs and their litters while 8 control (C) pairs and their litters were fed Purina Lab Chow which contains .004mg per gram of pyridoxine. All litters were tested for seizures every 2 weeks from 2 through 7 mos. of age once a month in a standard (SS) test cage and 2 weeks later in a clean home cage (CC) — and again at 1 yr in the SS cage. There were no differences on any of the measures between E and C litters. Significantly more seizures were elicited in the SS than in the CC tests, and the SS test became increasingly more effective with age. It was concluded that gerbil seizures were not due to a Vitamin B6 deficiency and that some age-related process might be a productive area for future investigation.

Decreased taurine excretion in relation to childbirth, lactation and progestin-estrogen therapy

Values in the literature for the mean daily excretion of taurine for normal adults range from 156–196 mg/24 h. The mean daily taurine excretion of seven women 4 weeks after childbirth was 7.4 mg; this was increased to 121 mg 6 months after delivery. Lactation did not have any effect on taurine excretion. The mean daily taurine excretion of four women on a progestin-estrogen regimen was 12.0 mg; administration of 40 mg of pyridoxine daily for 5 days did not affect the amount of taurine they excreted.

Biochemical assessment of the nutritional status of vitamin B6 in the human

It has been found that the human body stores only a small amount of Vitamin-B6 and can quickly be depleted of this vitamin. Pyridoxal phosphate is the active form of Vitamin-B6. Normal adults have blood plasma levels of Vitamin-B6 in excess of 50 ng/ml whereas in those with a deficiency the levels fall below 25 ng/ml. In a study of 172 alcoholic patients 25% of those with liver cirrhosis had low serum Vitamin-B6 levels. In a group of New York City schoolchildren a serum level of 36 ng/ml of B6 was determined. The vitamin appears in the urine mainly as pyridoxal but also as pyridoxamine and pyridoxine. A rapid decrease in excretion has been noted when patients received only .16 mg of Vitamin-B 6 daily. A daily supplement of 1.5 mg of pyridoxine corrected this. Age differences in excretion have been shown with children excreting more than adults. The ingestion of oral contraceptives did not alter the excretion of Vitamin-B6. Normal subjects excrete .5-1.3 mg of 4-pyridoxic acid a day. This represents 40% of daily ingested Vitamin-B6. Thus a 2 mg daily intake of Vitamin-B6 would result in a daily excretion of .8 mg of 4-pyridoxic acid. Tryptophan metabolism has been shown to be influenced by Vitamin-B6 dietary restriction. Following a loading dose of tryptophan excretion of xanthurenic acid and other tryptophan metabolites have been increased. This test has been used for detecting Vitamin-B6 deficiency. Prolonged fasting modifies interpretation of this test and oral contraceptives containing estrogen and progsterone increase the amounts of tryptophan metabolites in the urine. Large doses of pyridoxine supplements correct this increase in urinary metabolites. Transaminase activities in erythrocytes leukocytes and plasma have been used as measurements of Vitamin-B6 nutritional status. Other tests have been suggested but have not been shown to be better.

Effect of Daily MgO and Vitamin B6 Administration to Patients with Recurring Calcium Oxalate Kidney Stones

Patients with histories of recurring calcium oxalate renal stone formation have been given daily oral supplements of 200 mg of MgO and 10 mg of pyridoxine for extended periods of time. Thirty of 36 patients maintained on this program for 5 years or more have shown no recurrence or decreased recurrence of stone formation. After 1 year on this regimen, urines obtained from 51 patients showed a marked increase in their capacity to maintain calcium oxalate in solution, significantly raised calcium and citric acid levels, and decreased xanthurenic acid levels. No significant changes were observed in urinary magnesium, oxalic acid, phosphate-P or pyrophosphate-P values. Decreases in serum β-lipoproteins were also observed in a group of 25 of these subjects.

Vitamin B6 Depletion in Man: Urinary Excretion of Quinolinic Acid and Niacin Metabolites

The effect of vitamin B6 depletion on the conversion of tryptophan to niacin by 6 male subjects was studied during a 55-day experiment. The urinary excretion of quinolinic acid, nicotinic acid, N1-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide was measured (a) during a 5-day pre-depletion period when the subjects ate self-selected diets; (b) during depletion while they consumed a diet containing only 0.16 mg of vitamin B6 daily, (c) when they were fed diets supplemented with 0.6 or 0.9 mg of pyridoxine/day; and (d) when they received 50 mg of pyridoxine daily. The urinary levels of the 4 metabolites were determined before and after loading with 2 g of L-tryptophan during each of these periods. Post-tryptophan quinolinic acid excretion levels and yields (post-tryptophan values minus basal values) were significantly elevated during vitamin B6 depletion and these returned to pre-depletion levels upon repletion and saturation with pyridoxine. During the height of depletion, N1-methylnicotinamide values were not significantly different from values during repletion or saturation but differed from pre-depletion values probably because the subjects were eating self-selected diets during the pre-depletion period. The excretion levels of the 4 metabolites in other periods were not statistically different. The results of this experiment suggest a possible requirement for vitamin B6 coenzymes in the metabolism of quinolinic acid.

EFFECTS OF PYRIDOXINE DEFICIENCY ON AUDIOGENIC SEIZURE SUSCEPTIBILITY IN INBRED MICE.

SummaryMice of inbred strains DBA/2J, P/J, BDP/J, C57BL/6J, and F1 hybrid B6D2F1 (C57BL/6J × DBA/2J) mice were maintained on diets containing either 0, 10, or 30 mg of pyridoxine (vitamin B6) per kg of diet. Animals were placed on these diets when 3 to 4 weeks old and maintained on the diets for 7 weeks. Susceptibility to audiogenic seizures was determined 3, 5, and 7 weeks after the mice had been put on these respective dietary regimens. Mice of the dilute strain (homozygous d/d), i.e., strains DBA/2J, BDP/J, and P/J were found to be more susceptible to audiogenic seizures in the pyridoxine deficient state. Body weights were also recorded every 3 to 4 days. Dilute strains (DBA/2J, BDP/J and P/J) and the hybrid B6D2F1 showed smaller increments in body weights on the pyridoxine deficient diets than did C57BL/6J mice.

Vitamin B6 Depletion in Man: Urinary Excretion of Tryptophan Metabolites

The effects of vitamin B6 depletion on the metabolism of tryptophan by 6 male subjects were studied during a 55-day experiment. The excretion of several urinary metabolites of the amino acid was measured quantitatively during a 5-day predepletion period when the subjects ate self-selected diets and at intervals throughout the study while they consumed a diet containing only 0.16 mg of vitamin B6 daily. In response to the ingestion of a 2-g supplement of L-tryptophan, the levels of hydroxykynurenine, kynurenine, xanthurenic acid, acetylkynurenine and kynurenic acid were significantly increased in the urine of the subjects as the deficiency was induced. Two subjects showed evidence of abnormal tryptophan metabolism after only 5 days of depletion. The rate and extent to which the individuals exhibited abnormal tryptophan metabolism varied among the 6 males and determined the order in which supplementation with pyridoxine was begun. The excretion of metabolites following tryptophan loading decreased to the normal range when the subjects were given supplemental pyridoxine at a level of 0.6 or 0.9 mg/day. In three of the men, however, tryptophan metabolism did not return to pre-depletion status until the end of the experiment when 50 mg of pyridoxine were administered on 3 consecutive days. The pattern of abnormal tryptophan metabolism observed in this situation was strikingly similar to that found in tuberculosis patients receiving deoxypyridoxine and thus appears to indicate that the pyridoxine antagonist and a dietary deficiency of the vitamin prevent normal functioning of the vitamin B6-dependent enzymes involved in tryptophan metabolism in an analogous manner.

Tuberculous Meningitis Occurring During Isoniazid Therapy

The authors describe a patient who developed tuberculous meningitis while receiving isoniazid in a dosage of 9 mg/kg/day. The child when first seen had miliary tuberculosis. She was treated at this time with isoniazid and streptomycin. The streptomycin was discontinued after 13 weeks, when the patient was discharged to receive isoniazid in a dosage of 9 mg/kg/day. Four months later, the child developed signs and symptoms of tuberculous meningitis. It was well-documented that the patient had been receiving the medication regularly. The child was then treated with isoniazid in a dosage of 14 mg/kg/day which was increased to 22 mg/kg/day, and in addition, streptomycin and p-aminosalicylic acid were given. Reversal of the tuberculous process occurred after this therapy, and the patient was well 1 year later. From a review of the literature, and their experience with this patient, the authors conclude that isoniazid should be given in dosages of 15 to 30 mg/kg/day in treatment of children with active disseminated tuberculosis. They also recommend that 50 mg of pyridoxine be given each day to prevent toxicity from the isoniazid.