A Gain-of-Function Mutation on Gene and Its Possible Pathogenic Role in Branched-Chain Amino Acid Metabolism.

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the gene in a neonate, picked up by newborn screening, with a biochemical phenotype of a mild form of maple syrup urine disease (MSUD).

Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.

Objective: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study.

Background: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans.

Central cholinergic challenging of migraine by testing second-generation anticholinesterase drugs.

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg(-1) i.p.

Preanesthetic clinical problems of morbidly obese patients submitted to bariatric surgery: comparison with non-obese patiens.

Background And Objectives: Morbid obesity is associated to clinical problems responsible for decreased life expectancy. Morbidly obese patients are candidates to gastric bypass and pose new challenges to the anesthesiologist. This study compared the prevalence of clinical problems among morbidly obese patients submitted to bariatric surgery to non-obese patients submitted to other elective surgical procedures.

Triptans. A support to the central link between serotonin and acetylcholine in migraine.

Recently synthesized triptans, sumatriptan derivatives, display aborting migraine activity at doses and with plasmatic maximum peak dramatically lower (20-40 times) than sumatriptan, the 5-HT like agonist, which is the original molecule. That triptans easily cross blood-brain barrier strongly supports the central theory of migraine. We recently discovered the anti-migraine prophylactic action of centrally acting anti-cholinesterase agents, that seems a further support to the central theory of migraine.

L-5-hydroxytryptophan can prevent nociceptive disorders in man.

Prevention of primary pain is a new topic, endowed with social and economic interest. We observed that L-5-HTP can induce a significant decrease of the cropping out of migraine, the commonest primary pain. This finding seems interesting, since it represents the first data in the field and was obtained in a prospective, long-term, placebo controlled study.

Wine and migraine: compatibility or incompatibility?

According to popular belief, alcoholic beverages are to be avoided in the case of headache, a term which includes migraine, the most common type of headache. An imbalance between pain transmission and inhibition has been suggested and partly proved to be the mechanism of migraine. This means that peripherally acting substances following wine intake are unlikely to trigger migraine attacks.

Negative modultors of excitatory amino acids in episodic and chronic migraine: preventing and reverting chronic migraine. Special lecture 7th INWIN Congress.

The mechanism capable of transforming episodic migraine into chronic migraine is attributed by the authors to hyperalgesia and related neuroplastic changes, chiefly long-term potentiation, due to the action of excitatory amino acids, chiefly the ones acting at N-methyl D-aspartate (NMDA) receptor. A preeminent role has been attributed to 'third hyperalgesia', a newly observed type of hyperalgesia which is inheritable and can act as a ground for the above-mentioned mechanism of 'chronicization' of migraine. The role of primary and secondary hyperalgesia in giving redundance to neuraxial abnormalities is also discussed.

Painful and non-painful effects of low doses of morphine in migraine sufferers partly depend on excitatory amino acids and gamma-aminobutyric acid.

Having a differential sensitivity to morphine can distinguish migraine suffers from healthy people who are headache-exempt. The aim of the present study was to investigate whether such an abnormal response to morphine challenge is entirely dependent on opioid receptor activation. A role for excitatory amino acids and gamma-aminobutyric acid has been proposed on the basis of the effect of diazepam.

Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D-aspartate-mediated neuronal plasticity: their common clues.

A defect in serotonergic analgesia and a hyperalgesic state are proposed as features common to headache and fibromyalgia. The benefit to both migraine and fibromyalgia from inhibiting ionotropic N-methyl-D-aspartate receptor activity implies that redundant hyperalgesia-related neuroplastic changes are crucial for severe or chronic migraine and primary fibromyalgia. The fact that migraine and primary fibromyalgia share some pivotal set-up of serotonergic and excitatory amino acid systems led us to analyse epidemiological data supporting the hypothesis that analgesic disruption and a consequent hyperalgesic state are mechanisms of both migraine and fibromyalgia.

Phantom eye: features and prevalence. The predisposing role of headache.

We prospectively evaluated the frequency, time-course and predisposing factors of phantom eye syndrome in 53 patients who underwent surgical eye amputation to cure ocular cancer. Before surgery, patients were classified as Group I (n = 25) if they had no history of headache or Group II (n = 28) if they were headache sufferers. Three clinical patterns were distinguished: phantom pain, non-painful phantom phenomena and photopsias.

Involvement of central cholinergic system in antinociception induced by sumatriptan in mouse.

The antinociceptive effect of the antimigraine drug sumatriptan was assessed in mice (hot-plate and abdominal constriction tests). Antinociception induced by sumatriptan (10-30 mg kg-1 i.p.

Modulation of excitatory amino acids pathway: a possible therapeutic approach to chronic daily headache associated with analgesic drugs abuse.

The use of antagonists of N-methyl-D-aspartate (NMDA) receptors, or the administration of inhibitors of the synthesis or of the release of excitatory amino acids, enables the analgesic drug-dependence associated with chronic daily migraine to be overcome without any physical abstinence sign. Follow-up period indicates that negative modulators of excitatory amino-acid function can induce a stable benefit. The persistent benefit is seemingly due to an inhibitory effect on the process underlying the hyperalgesia state which is a crucial feature of migraine.

Bradykinin and cerebral circulation: selective non-receptor interaction with histamine and serotonin through the system of nitric oxide.

Bradykinin, histamine and serotonin were the most active physiological agonists in increasing jugular levels of nitric oxide when administered into the left common carotid artery of anaesthetized rabbits. Bradykinin potentiated selectively the effects of histamine and serotonin (but not vice versa) on both nitric oxide and carotid blood flow, without involving activation of specific receptors. Since these effects were demonstrated using doses of the three agonists in the order of their physiological plasma concentrations, it was concluded that cerebral circulation in regulated, also within its autoregulatory limits, by bradykinin through selective autocoidal interactions converging on nitric oxide.

Inheritable and acquired hyperalgesia associated to abnormal opioid receptor set-up seem to act as opiate addiction preventors.

Hyperalgesia is known to depend on neuroplastic changes chiefly represented by long-term potentiation. These phenomena are proved to depend on excitatory amino acids (EAAs) action at the level of NMDA receptors. This action is known to be related to nitric oxide (NO) release.

The way to serotonergic use and abuse in migraine.

5-HT is currently indicated to play a role in migraine (M). Previously evidenced 5-HT supersensitivity which characterizes M is insufficient to compensate for a possible deficit in 5-HT bioavailability. Inducing a further up-regulation of 5-HT receptor can yield improvement of M syndrome.

Decentralization monoamine super-sensitivity of migraine and opiate abstinence: common features and different target mechanisms?

The similarity between opiate withdrawal and migraine (M) has been confirmed regarding increased monoamine sensitivity at the neuromuscular junction of the hand's dorsal vein as well as at the neuraxis where dopamine (DA) supersensitivity was observed. Similarities also included an increase in cAMP levels as a precocious sign in both M and opiate withdrawal. Particular attention has been devoted to the time-course of monoamine supersensitivity in M and in abstinence.

The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan.

The antinociceptive effect of the antimigraine drug sumatriptan was assessed in mice and rats (hot-plate, abdominal constriction and paw-pressure tests) and in guinea pigs (paw-pressure test). The ACh extracellular concentration also was detected in the hippocampus of freely moving rats by microdialysis experiments. Antinociception was induced by sumatriptan administered both parenterally (5-10 mg.

Differential sensitivity to morphine challenge in migraine sufferers and headache-exempt subjects.

The effectiveness of a therapeutic dose of morphine in relieving migraine attacks was compared with placebo. Morphine was no more effective than placebo and provoked severe side effects. When low-dose morphine was administered to normal non-headache controls and migraineurs when headache-free, physical and psychologic reactions were induced only in migraineurs.

Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy.

In this study fibromyalgia sufferers were randomly administered a combination of monoamine-oxidase inhibitors (MAOIs)-A/B with 5-HTP, 5-HTP alone, MAOIs-A/B alone, or the tricyclic drug amitriptyline in order to compare the efficacy of these treatments. The benefits on the painful syndrome were assessed by using Visual Analogic Scale score rating from 0 to 4. The combination of MAOIs with 5-HTP significantly improved fibromyalgia syndrome as determined by Visual Analogic Scale whereas the other treatments yielded poorer benefits.