Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease.

The kynurenine pathway (KP) of L-tryptophan metabolism produces several neuroactive metabolites with an amino acid structure. These metabolites may play an important role in the pathophysiology of irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, AIDS-dementia complex, depression, epilepsy and the aging process. Modulation of the KP through inhibition or stimulation of enzyme synthesis and activity can be an alternative approach to traditional therapy. Furthermore, it may be responsible for the altered functioning of the enteric nervous system and the central nervous system. There is evidence that the KP is sensitive to changes in the concentration of many vitamins and minerals that play a crucial role as coenzymes and cofactors in the de novo synthesis of nicotinamide adenine dinucleotide coenzyme. A reduction in the availability of the active form of vitamin B6 (pyridoxal 5'-phosphate, PLP) is known to affect tryptophan hydroxylase, kynurenine aminotransferase and kynureninase (KYNU). Vitamin B2 deficiencies result in a reduction in the activity of the flavin adenine dinucleotide dependent enzyme, kynurenine 3-monooxygenase. Minerals are also responsible for the proper functioning of enzymes engaged in L-tryptophan metabolism. Mn(2+), Zn(2+), Co(2+) and Cu(2+) influence KYNU activity, and Mg(2+) regulates quinolinate phosphoribosyl transferase. Fe(2+) is responsible for the proper functioning of both indoleamine 2,3-dioxygenase and 3-hydroxy-anthranilic acid dioxygenase. Changes in the concentration of KP metabolites and in enzymatic activity have been found in many pathological states. Therefore, it is justifiable to regulate the concentration of certain kynurenines or enzymes in the KP which may provide a potential therapeutic target for the treatment of various health impairments. This review demonstrates the role of vitamin and mineral activity on the KP, which may have an effect on the proper functioning of the human organism. Surplus administration of vitamins did not elicit any beneficial effects on L-tryptophan metabolism. Whether a mineral surplus influences L-tryptophan metabolism is still not established. It seems that cofactor deficiencies influence the KP far more than surpluses.

The influence of steroids on noradrenaline-mediated contractile reactivity of the superficial nasal and facial veins in cycling gilts.

The nasal venous blood may be directed through the facial vein into the systemic circulation or through the frontal vein into the venous cavernous sinus of the perihypophyseal vascular complex, where hormones and pheromones permeate from the venous blood into the arterial blood supplying the brain and hypophysis. The present study was designed to determine the effect of noradrenaline (NA) on the tension of the nasal, frontal and facial veins of cycling gilts, and influence of ovarian steroid hormones on NA-mediated contractile reactivity. Additionally, the enzyme dopamine-beta-hydroxylase catalysing the conversion of dopamine to noradrenaline (DbetaH) was immunolocalized in these vessels. Among three studied veins, the frontal proximal vein, that fulfill a key role in the supply of the nasal venous blood into the venous cavernous sinus, reacted to NA most strongly (P < 0.001) and this reaction was weaker in the periestrous period than in luteal phase (P < 0.001). Inversely, the reaction to NA of the facial proximal vein, that carry blood to the peripheral circulation, was stronger in the periestrous period than in luteal phase (P < 0.05). P4, E2 and T significantly lowered NA-mediated tension of the frontal proximal vein during the periestrous period (P < 0.001), while in the luteal phase P4 might antagonize relaxing effect of E2 to this vessel. The result suggests that supply of the nasal venous blood into the venous cavernous sinus is greater during the periestrous period than during the luteal phase. DbetaH was clearly expressed in the muscular layer of the isolated superficial nasal and facial veins of gilts in both studied stages of the estrous cycle. We suggest that the reactivity of the superficial veins of the nose and face to NA combined with the previously demonstrated reactivity of these veins to steroid ovarian hormones and male steroid pheromones may regulate the access of priming pheromone androstenol (resorebed in the nasal cavity) to the brain of gilts during periestrous period via humoral local destination transfer.

The influence of steroids on the vascular tension of isolated superficial nasal and facial veins in gilts during sexual maturation.

The arrangement of the superficial facial veins enables blood flow from the nasal cavity into the peripheral circulation by two pathways: through the facial vein into the external jugular vein and through the frontal vein into the cavernous sinus. The venous cavernous sinus is the site where hormones and pheromones permeate from venous blood into the arterial blood supplying the brain and hypophysis. The present study was designed to: (1) determine whether estradiol (E2) and progesterone (P4) affect the vascular tone of the superficial veins of the nose and face in maturating prepubertal gilts (PP) and in prepubertal gilts deprived of ovarian hormones (PPov), and (2) to analyze the immunolocalization of progesterone receptors (PR), and estradiol receptors alpha (ER alpha) and beta (ER beta) in these veins. The influence of hormones on the vascular tension differed depending on the type of vessel, the hormonal status and dose of hormone used. Estradiol decreased the vascular tension in the nasal and facial veins of PP gilts (P < 0.01). In PPov gilts, the effect of E2 was opposing, however it caused strong tension in the proximal and distal parts of the facial vein (P < 0.01 and P < 0.001, respectively). Progesterone increased the vascular tension in the proximal segment of the nasal vein and in the distal segment of the frontal and facial veins, and decreased the tension in the distal segment of the nasal and facial veins (P < 0.05) of PP gilts. In PPov gilts, P4 produced strong increase in the tension of distal and proximal segments of the nasal vein (P < 0.001 and P < 0.01, respectively) and of distal segment of the facial vein (P < 0.01), strong decrease in the tension of the distal part of the nasal vein (P < 0.01) and had limited effect on other veins. Expression of ER beta, but not of PR, was observed in the superficial nasal and facial veins. In conclusion, the ovarian steroid hormones that modulate the vascular tension of the nasal and facial veins in prepubertal gilts may influence the transfer of boar pheromones from the nasal mucosa to the brain via local humoral pathway during sexual maturation.

The influence of steroids on vascular tension of isolated superficial veins of the nose and face during the estrous cycle of gilts.

The arrangement of the superficial facial veins enables blood flow from the nasal cavity into the peripheral circulation by two pathways: through the frontal vein into the cavernous sinus and through the facial vein into the external jugular vein. The current study was designed to determine whether estradiol and progesterone affect the vascular tone of the superficial veins of the nose and face in cycling gilts (Sus scrofa f. domestica) and to analyze the immunolocalization of progesterone receptors and estradiol receptors in these veins. The influence of hormones on vascular tension differed depending on the type of vessel and the phase of the estrous cycle. Estradiol decreased vascular tension in the nasal vein during the follicular phase (P<0.05) and increased tension in the frontal vein during the luteal phase (P<0.05). Progesterone increased the vascular tension of the frontal vein (P<0.05) and decreased the tension of the other veins (P<0.05) in both phases of the cycle. Expression of estradiol receptor beta but not of progesterone receptor was observed in the superficial veins of the nose and face. In conclusion, the effect of ovarian steroid hormones on the vascular tension of the superficial veins of the nose and face in female pigs as well as the reactivity of these veins to steroid boar pheromones can affect the blood supply from the nasal cavity to the venous cavernous sinus. We propose that the ovarian steroid hormones that modulate the vascular tension of the nasal and facial veins may also influence the action of boar pheromones absorbed into the nasal mucosa in gilts and may reach the brain via local destination transfer.

The influence of boar pheromones on the contractile reactivity of the isolated superficial veins of the nose and face in ovariectomized prepubertal gilts and in gilts during sexual maturation.

This study was designed to establish: a) whether boar pheromones, 5alpha-androstenone and 5alpha-androstenol, may affect the contractile reactivity of superficial veins of the face in prepubertal gilts deprived of ovarian hormones, and b) what is the influence of ovarian hormones secreted during sexual maturation on the contractility of these veins. The isolated rings of frontal, facial and dorsal nasal veins were treated with androstenone (5alpha-androst-16-en-3-one), androstenol (5alpha-androst-16-en-3-ol) and testosterone (17beta-hydroxy-4-androsten-3-one) in concentrations of either 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded on HSE-ACAD W software. Sex boar pheromones androstenol and androstenone affected the contractility of the superficial veins of the face and nose in both of the prepubertal ovariectomized gilts and prepubertal intact animals. The way these veins reacted to pheromones differed between animal groups, particular vessels and even their parts and was also dose - dependent. In prepubertal ovariectomized gilts, androstenol had stronger action and caused the constriction of the facial vein, dorsal nasal vein and the distal part of the frontal vein. Androstenone produced constriction of the nasal vein, distal part of the frontal vein and proximal part of facial vein, but relaxation of the proximal part of the frontal vein and the distal part of the facial vein. In prepubertal untreated gilts, androstenone was more effective and strongly influence on the constricted of the frontal vein and facial vein and produced the relaxation of the nasal vein. Androstenol influence on the constriction the frontal vein and the distal parts of the facial vein and nasal vein, and influence o the relaxtion their proximal parts. Testosterone used as a control androgen affected both superficial veins of the face veins in a dose-dependent manner, and, at a higher dose, increased the contractility more effectively. Only the nasal vein did not react to this hormone. The present results suggest the existence in prepubertal gilts of frontal and facial veins' specific reactivity which may participate in the regulation of blood flow from the nasal cavity to the perihypophyseal vascular complex and play a role in the humoral pathway for the male pheromone priming functions in the central nervous system. This reactivity was displayed by the vessels in prepubertal gilts without ovarian hormones. The presence of active ovaries in maturing gilts changed the reactivity of these veins to pheromones and testosterone.

The influence of boar pheromones on the vasoreactivity of the facial superficial veins in ovariectomized and estradiol-treated pubertal gilts.

This study was designed to establish: a) whether boar pheromones, androstenone and androstenol, may affect the vasocontractility of the facial superficial veins in ovariectomized pubertal gilts and b) what is the effect of estradiol on this contractility. The gilts ovariectomized after two controlled estrous cycles, and the ovariectomized gilts treated with estradiol benzoate were used in the experiment. The isolated rings of dorsal nasal, frontal and facial veins were incubated with androstenone (5alpha-androst-16-en-3-one) and androstenol (5alpha-androst-16-en-3-ol) in concentrations of either 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded with HSE-ACAD W software. In ovariectomized gilts both the androstenone and androstenol caused a relaxing effect on the nasal vein, flow of the blood from the nasal cavity, and on the frontal vein, by which the blood may by directed into the perihypophyseal vascular complex. An opposing reaction to these pheromones was found in the distal part of the facial vein by which the blood is directed to the systemic circulation. Treating ovariectomized gilts with estradiol benzoate changed mainly the reactivity of the frontal vein to androstenone, which produces constriction, but this treatment did not affect the reactivity of the facial superficial veins to androstenol. The present results demonstrated that both boar sex pheromones, androstenone and androstenol, may contribute to the regulation of their humoral pathway from the nasal cavity to the brain and hypophysis in the ovariectomized pubertal gilts and suggest the effect of estradiol to this pathway.

The influence of male pheromones on the contractile reactivity of the isolated superficial veins of the nose and face during the estrous cycle in gilts.

This study was designed to determine whether steroid sex pheromones of the boar may affect the contractile activity of the superficial venous vessels of the nose and face in gilts, and in this way contribute to recently discovered humoral transfer of pheromones to the brain and hypophysis. The dependence between the reactivity of nasal and facial veins to male pheromones and the phase of the estrous cycle in gilts was also studied. The gilts were used in the luteal phase of the cycle and in the follicular phase of the cycle. The dorsal nasal, frontal and facial veins were isolated on an appropriate day of the estrous cycle. The isolated rings of veins were treated with androstenone (5alpha-androst-16-en-3-one), androstenol (5alpha-androst-16-en-3-ol) and testosterone (17beta-hydroxy-4-androsten-3-one) in concentrations of 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded on HSE-ACAD software for Windows. Androstenone--main signaling boar pheromone--induced much stronger reactions of the vessels than androstenol. Androstenone caused significant relaxation of the dorsal nasal and frontal veins, and significant increased tension of the facial vein in the follicular phase of the estrous cycle. The results obtained suggest a direct effect of male pheromones on the contractile reactivity of the superficial veins of the nose and face in the female, and in this way contribute to a humoral pathway for transfer of pheromones to the brain and hypophysis. Moreover, the present study revealed changes in the reactivity during the estrous cycle of the veins, transporting blood from the region of the nasal cavity, to male pheromones participating in the regulation of female reproductive processes.

Countercurrent transfer of 125I-LHRH in the perihypophyseal cavernous sinus-carotid rete vascular complex, demonstrated on isolated pig heads perfused with autologous blood.

The objective of the study was to determine whether the local permeability of luteinizing hormone-releasing hormone (LHRH) from the venous blood of the perihypophyseal cavernous sinus into the arterial blood of the carotid rete, supplying the brain and hypophysis in gilts, depends on the day of the estrous cycle, as well as to determine whether this transfer exists when LH concentration in the blood is reduced (the experimental short-loop negative feedback for LH secretion after estradiol injection in ovariectomized gilts). Experiments were conducted on isolated gilt heads with necks, on chosen days of the estrous cycle (n = 40), and on previously ovariectomized gilts treated with estradiol benzoate (EB) (n = 5) or corn oil (n = 3). After exsanguination, the gilt heads with necks were disarticulated and about 30-45 min later were supplied with autologous, oxygenated, and heated blood at a stable blood flow and pressure through the left carotid artery for 30 min. 125I-LHRH was infused into both cavernous sinuses through the cannulated angularis oculi veins for 5 min. After 125I-LHRH infusion, radiolabeled LHRH was found (P < 0.001) in arterial blood taken from the carotid rete through the open right carotid artery in all animals used in the experiment: on Days 1-2 (six gilts), on Days 12-14 (seven gilts) of the estrous cycle, and in five ovariectomized gilts during negative feedback for LH surge (40 hr after EB). No significant radioactivity of 125I-LHRH was found in the arterial blood on Days 3-5 (n = 6), 9-11 (n = 4), and 15-21 (n = 17) of the estrous cycle. A very low level of radioactivity was found in the ovariectomized control group after the injection of corn oil (n = 3). These results provide evidence for the permeability of LHRH from the venous to the arterial blood and its retrograde transport with the arterial blood to the hypophysis and brain, after the ovulation period (Days 1-2) and on Days 12-14 of the estrous cycle. This suggests that a close relationship exists between the day of the estrous cycle and LHRH permeability from the venous to the arterial blood in the perihypophyseal cavernous sinus-the carotid rete complex in gilts-and that this mechanism may be included in a short-loop feedback for LHRH secretion.