Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats.

Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin deficiency is relatively rare but can cause dermatitis, alopecia, and perosis. Low biotin levels occur in individuals with type-2 diabetes, and supplementation with biotin plus chromium may improve blood sugar control.

Antihypertensive and neuroprotective actions of pyridoxine and its derivatives.

Vitamin B6 plays a crucial role in the nervous system as the amino acid decarboxylases involved in the synthesis of all putative neurotransmitters requires the coenzyme pyridoxal phosphate. Vitamin B6 in its various forms has antioxidant properties. Pyridoxal phosphate has a role in regulating cellular calcium transport through both the voltage-mediated and ATP-mediated purinergic mechanisms of cellular calcium influx and, hence, has a role in the control of hypertension.

Vitamins and their derivatives in the prevention and treatment of metabolic syndrome diseases (diabetes).

A cluster of inter-related conditions such as central obesity, dyslipidemia, impaired glucose metabolism, and hypertension is referred to as Metabolic Syndrome, which is a risk factor for the development of type-2 diabetes. The micro- and macro-vascular complications of diabetes contribute to its morbidity and mortality. In addition to its calcitropic effect, vitamin D is a regulator of gene expression as well as cell proliferation and differentiation.

Biotin--a regulator of gene expression.

The role of biotin as the prosthetic group of the four biotin-dependent carboxylases in higher organisms is well recognized. Based on the roles of these carboxylases in metabolism, the requirement of biotin for cell viability, growth and differentiation was established. Biotin seems to have a role in cell functions other than as the prosthetic group of biotin enzymes.

Neuroprotective actions of pyridoxine.

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background.

Blood pressure regulation and micronutrients.

This review attempts to delineate the underlying mechanisms leading to the development of hypertension as well as the function of vitamins and minerals in the regulation of blood pressure. Physiological processes that regulate cardiac output and systemic vascular resistance impact on the control of blood pressure. Metabolic abnormalities associated with the tetrad of hypertension, dyslipidaemia, glucose intolerance and obesity share insulin resistance, which might be organ or cell specific, as an underlying feature representing different tissue manifestation of a common cellular ionic defect.

Atherosclerosis risk factors: the possible role of homocysteine.

Atherosclerosis is the leading cause of death in North America. It is characterized by thickening of the coronary artery wall by the formation of plaques, resulting in reduced blood flow. Plaque rupture and the consequent thrombosis may lead to sudden blockage of arteries and causing stroke and heart attack.

Pyridoxal 5'-phosphate is an ATP-receptor antagonist in freshly isolated rat cardiomyocytes.

Although extracellular ATP is considered to exert a positive inotropic action on the myocardium through purinoceptors, very little information is available regarding interventions which may modify the actions of ATP on the heart. We report here that pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, shows antagonism towards ATP-induced positive inotropic effect in isolated perfused rat hearts, ATP-induced increase in [Ca2+] in freshly isolated adult cardiomyocytes and ATP-binding in cardiac sarcolemma; ED50 for PLP in each of these cases varied from 10-15 microM. PLP (5-50 microM) was observed to antagonize the positive inotropic effect of ATP but did not modify the action of isoproterenol in the isolated perfused heart.

Alterations of KCl- and ATP-induced increase in [Ca2+]i in cardiomyocytes from vitamin B6 deficient rats.

Although vitamin B6 deficiency is related to coronary heart disease, no information regarding changes in myocardium due to vitamin B6 deficiency is available in the literature. In view of the critical role played by Ca2+ in cellular function, we investigated alterations in [Ca2+]i induced by KCI or ATP in vitamin B6 deficient and age-matched control rats. [Ca2+]i was measured in isolated cardiomyocytes by using the Fura-2 fluorescence technique.

Hypertension, calcium channel and pyridoxine (vitamin B6).

The moderately pyridoxine (vitamin B6)-deficient male rat was introduced by us as an animal model (B6DHT) for the study of hypertension. Hypertension in this rat is associated with increased sympathetic stimulation. Arterial segments from B6DHT rats maintained a higher resting tone.

Cardiac sarcolemmal Na(+)-Ca2+ exchange and Na(+)-K+ ATPase activities and gene expression in alloxan-induced diabetes in rats.

To determine the sequence of alterations in cardiac sarcolemmal (SL) Na(+)-Ca2+ exchange, Na(+)-K+ ATPase and Ca(2+)-transport activities during the development of diabetes, rats were made diabetic by an intravenous injection of 65 mg/kg alloxan. SL membranes were prepared from control and experimental hearts 1-12 weeks after induction of diabetes. A separate group of 4 week diabetic animals were injected with insulin (3 U/day) for an additional 4 weeks.

Biophysical characterization of rat cardiac Ca2+/Mg2+ ecto-ATPase (myoglein).

Sarcolemmal Ca2+/Mg2+ ecto-ATPase (Myoglein; MW 180 kD) is a membrane bound enzyme which requires a millimolar concentration of either Ca2+ or Mg2+ for maximal hydrolysis of ATP. The isoelectric point (pI) of the cardiac ecto-ATPase was 5.7.

The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension.

Objective: To investigate whether a dietary supplement of vitamin B6 could attenuate the elevation of systolic blood pressure (SBP) in Zucker obese or spontaneously hypertensive rats, or rats ingesting sucrose.

Methods: Zucker obese rats (fa/fa), Sprague-Dawley rats with sucrose-induced elevation of SBP, spontaneously hypertensive rats (SHRs) and their corresponding controls were tested for the effects of vitamin B ingestion in different ways: (1) vitamin B6 was included as a supplement (five times the normal intake) from the start of the experiment until the development of hypertension; (2) vitamin B6 supplement was removed from the diet of Zucker obese and Zucker lean control groups after 16 weeks on the dietary treatments; and (3) a diet deficient in vitamin B6 was instituted in SHRs and control Wistar-Kyoto (WKY) rats. The SBP of rats in all groups was monitored in the conscious animal by tail-cuff plethysmography.

Biotin influences palatal development of mouse embryos in organ culture.

Maternal biotin deficiency is strongly teratogenic in CD-1 mice. The most common malformations are craniofacial and limb defects such as cleft palate, micrognathia and micromelia. The effect of biotin deficiency on palatal development in mouse embryos on d 12 of gestation was studied by culturing mouse embryonic palates in serum-free medium using a suspension culture system.

The relationship between low-calcium-induced increase in systolic blood pressure and vitamin B6.

Objective: To investigate the relationship between the increase in systolic blood pressure caused by a low-calcium (0.1%) diet and the vitamin B6 status in the rat.

Methods: Male Sprague-Dawley rats fed a vitamin B6-deficient diet did not show any change in systolic blood pressure (SBP) for the first 4 weeks (prehypertensive phase), but from week 5 there was an increase in SBP lasting until week 10 (hypertensive phase).

Effects of serotonergic agents on plasma prolactin levels in pyridoxine-deficient adult male rats.

Plasma concentration of prolactin was significantly reduced in pyridoxine-deficient as compared to control (pyridoxine-supplemented) adult male rats. Administration of pyridoxine to deficient rats resulted in a significant increase in plasma prolactin. The reduction in plasma prolactin in pyridoxine-deficient rats corresponded with the significantly reduced hypothalamic contents of pyridoxal phosphate and serotonin in pyridoxine-deficient rats.

Transcriptional regulation of liver phosphoenolpyruvate carboxykinase by biotin in diabetic rats.

Rat liver phosphoenolpyruvate carboxykinase (PEPCK) activity was followed over a time period of 5 h following administration of biotin to streptozotocin-induced diabetic rats. In parallel with the decrease in enzyme activity liver PEPCK mRNA decreased by 85% at 3 h after injection of biotin to diabetic rats. There was no significant change in the accumulation of kidney PEPCK mRNA.

Picrotoxin and pentylene tetrazole induced seizure activity in pyridoxine-deficient rats.

Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local (VPL) application of either picrotoxin or pentylene tetrazole. Frequency and amplitude of thalamic VPL unit activity were significantly reduced in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls.

Calcium channels in vitamin B6 deficiency-induced hypertension.

Objective: To compare the acute hypotensive effects of various calcium channel modulators in vitamin B6-deficient hypertensive (B6DHT) rats.

Methods: Adult male Sprague-Dawley rats were fed a vitamin B6-deficient diet for 7-10 weeks, during which systolic blood pressure (SBP) was measured in the B6DHT and control rats, using tail-cuff plethysmography. The effects of the calcium antagonists nifedipine, verapamil, diltiazem and (-)-202-791 on SBP were determined in conscious B6DHT rats.

Hippocampal changes in developing postnatal mice following intrauterine exposure to domoic acid.

Domoic acid (0.6 mg/kg) was injected intravenously through the caudal vein in pregnant female mice on the 13th day of gestation and EEG was monitored in the developing progeny during postnatal days 10-30. No clinical seizure activity was observed during this period.

Regulation of calcium influx into vascular smooth muscle by vitamin B6.

In the vitamin B6 deficiency-induced hypertensive (B6DHT) rat there is an increased influx of calcium into the vascular smooth muscle. Vitamers which possess vitamin B6 activity blocked the in vitro calcium influx into the caudal artery of B6DHT rats and the BAY K 8644-induced influx into artery segments from vitamin B6-supplemented (control) rats. BAY K 8644 did not increase further the calcium influx into caudal artery segments from B6DHT rats.

Hypotensive action of 5-HT receptor agonists in the vitamin B6-deficient hypertensive rat.

Feeding a vitamin B6-deficient diet to rats causes a moderate hypertension. The blood pressure responses to 5-HT1A receptor agonists were studied in conscious vitamin B6-deficient hypertensive rats. They were all effective in lowering blood pressure with the following rank order of potency: 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) > flesinoxan > 5-methylurapidil > urapidil.

Suppression of domoic acid induced seizures by 8-(OH)-DPAT.

Microinjections of the neuroexcitotoxin, domoic acid (DOM), in the ipsilateral rat hippocampal CA-3 region, induced generalized electrical seizure discharge activity, characterized by spikes and waves, followed by intermittent burst discharges. Computerized EEG analysis exhibited relative dominance of delta and theta and reductions in alpha and beta activities during domoic acid epileptogenesis. Seizure discharge activity was attenuated by the microinjection of the 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin(8-(OH)-DPAT) and augmented by the specific 5-HT1A antagonist, spiroxatrine in the contralateral hippocampal CA-3 region.

Determination of vitamin B6 vitamers and pyridoxic acid in biological samples.

For the determination of vitamin B6 vitamers (pyridoxal phosphate, pyridoxamine phosphate, pyridoxal, pyridoxine, pyridoxamine) and 4-pyridoxic acid in biological samples such as plasma, cerebrospinal fluid and rat brain regions, a sensitive micromethod using high-performance liquid chromatography (HPLC) with fluorescence detection in combination with post-column derivatization is described. Metaphosphoric acid tissue extracts with deoxypyridoxine as an internal standard were injected into the HPLC system with a binary gradient elution at a flow-rate of 1.2 ml/min.