Tokio Shimomura

Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese.

AbstractWe determined polymorphism in the serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the polymerase chain reaction of Lesch et al., with minor modifications. The distribution of allele frequencies was determined and found to differ from that in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR to anxiety traits, by having 189 of the 501 subjects complete a self-rating questionnaire for anxiety and depression. Subjects with the short/short (s/s) genotype had significantly higher anxiety scores than those with the long/long (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the l allele.

A Polymorphism in the Serotonin Transporter Gene Regulatory Region and Frequency of Migraine Attacks

Background.—The serotonergic system has been thought to play an important part in the pathophysiology of migraine.

Platelet superoxide dismutase in migraine and tension‐type headache

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.

Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in migraine and tension-type headache.

Substance P, 5‐hydroxytryptamine, and γ‐aminobutyric acid levels in saliva were measured in 55 patients with migraine during headache attacks (15 men and 40 women, average age 37.6 years), 36 patients with migraine in interictal periods (8 men and 28 women, average age 43.9 years), 48 patients with tension‐type headache during headache attacks (18 men and 30 women, average age 47.3 years), and 25 patients with tension‐type headache in interictal periods (10 men and 15 women, average age 48.6 years). Forty‐three normal healthy volunteers composed the control group (17 men and 26 women, average age 32.7 years). Substance P levels in saliva were determined using competitive enzyme‐linked immunosorbent assay, and were 26.9 ±± 45.1 pmol/mL in the patients with migraine during headache attacks, 30.0 ±± 59.7 pmol/mL in the patients with migraine in interictal periods, 243.5 ±± 1137 pmol/mL in the patients with tension‐type headache during headache attacks, 101.3 ±± 364 pmol/mL in the patients with tension‐type headache in interictal periods, and 21.2 ±± 17.4 pmol/mL in the healthy controls. 5‐hydroxytryptamine levels in saliva were determined using reversed‐phase high‐performance liquid chromatography with electrochemical detection, and were 895 ±± 1075 ng/mL in the patients with migraine during headache attacks, 758 ±± 1375 ng/mL in the patients with migraine in interictal periods, 1646 ±±1945 ng/mL in the patients with tension‐type headache during active headache periods, 1167 ±± 1495 ng/mL in the patients with tension‐type in headache‐free periods, and 450 ±± 405 ng/mL in the healthy controls. Gamma‐aminobutyric acid levels in saliva were determined using high‐performance liquid chromatography with precolumn ortho‐phthalaldehyde fluorescence detection. Gamma‐aminobutyric acid levels in saliva were 36.8 ±± 49.8 pmol/mL in the patients with migraine during headache attacks, 17.9 ±± 25.2 pmol/mL in the patient, with migraine in interictal periods, 16.0 ±± 18.3 pmol/mL in the patients with tension‐type headache during active headache periods, 14.1 ±± 6.8 pmol/mL in the patients with tension‐type headache in headache‐free periods, and 21.6 ±± 22.7 pmol/mL in the healthy controls. The salivary substance P and 5‐hydroxytryptamine levels in the patients with tension‐type headache during active headache periods were significantIy higher than those in healthy controls. In contrast, we found no significant differences between the salivary γ‐aminobutyric acid levels in the patients with tension‐type headache and healthy controls. The high levels of salivary substance P and 5‐hydroxytryptamine in tension‐type headache patients during headache periods might reflect release of substance P from the pain sensory system. Saliva could represent a fluid particularly suitable to the study of neuropeptide release under specific conditions such as migraine and tension‐type headache.

Platelet Activation in Muscle Contraction Headache and Migraine

In migraine, the role of platelets is regarded as an important factor. We investigated plasma beta-thromboglobulin (BTG), platelet factor 4 (PF4), and 5-hydroxytryptamine (5-HT) in migraine patients and muscle contraction headache (MCH) patients during headache-free periods. The mean values of the plasma BTG, PF4, and 5-HT concentrations in the migraine group and the MCH group were significantly higher than those in healthy controls. The mean value of the plasma BTG concentration was significantly higher in the migraine group than in the MCH group, but the differences in the mean plasma PF4 and 5-HT concentrations between the two groups were not significant. Continuous platelet activation exists in both MCH patients and migraine patients. From the biochemical point of view, we have provided evidence for a similarity between migraine and MCH.

Treatment of tension-type headache with tizanidine hydrochloride : its efficacy and relationship to the plasma MHPG concentration

SYNOPSIS

Decreased serum interleukin-2 level in patients with chronic headache

SYNOPSISSome cellular immune functions are impaired in cluster headache patients. Interleukin‐2 (IL‐2) is a polypeptide secreted by antigen or mitogen‐actuated T lymphocytes that functions as a growth factor for T cells. To investigate cellular immune functions in patients with chronic headache, we measured the IL‐2 concentration of sera in patients with migraine and in patients with tension‐type headache. Thirteen subjects suffering from migraine without aura (5 males and 8 females, mean age: 32.8 years) and 46 subjects (20 males and 26 females, mean age: 39.7 years) with tension‐type headache (TH) were selected for this study. Forty‐three normal healthy volunteers composed the control group (15 males and 28 females, average age 41.6 years}. The IL‐2 levels of sera were determined using enzyme‐linked immunosorbent assay (ELISA) techniques. The IL‐2 levels of sera were 3.18±1.8 U/ml (mean±SD) in the healthy controls, 2.29±2.6 U/ml in the patients with migraine and 1.59±1.0 U/ml in the patients with TH. The serum level of IL‐2 in the patients with migraine was significantly lower than in the controls. The serum level of IL‐2 in the patients with TH was significantly lower than in the controls. The central nervous system (CNS) has been considered to be involved in the development of the immune phenomena. In the patients with TH or migraine, reduction in platelet 5‐hydroxytryptamine (5‐HT) levels and sympathetic hypofunction have been observed. These phenomena might reflect decrease in 5‐HT levels in CNS in the patients with TH or migraine. The decreased serum IL‐2 level, observed in this study, might reflect a reduction in 5‐HT or catecholamine levels in CNS in the patients with migraine or TH.

The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and alpha1-blockers.

Objective Hyperuricemia is associated with the vascular injury of hypertension, and purine oxidation may play a pivotal role in this association, but the pathophysiology is not fully understood. We tested the hypothesis that in hypertensive patients, the excess amount of the purine metabolite, hypoxanthine, derived from skeletal muscles, would be oxidized by xanthine oxidase, leading to myogenic hyperuricemia as well as to impaired vascular resistance caused by oxygen radicals. Methods We investigated the production of hypoxanthione, the precursor of uric acid and substrate for xanthine oxidase, in hypertensive patients and found that skeletal muscles produced hypoxanthine in excess. We used the semi-ischemic forearm test to examine the release of hypoxanthine (ΔHX), ammonium (ΔAmm) and lactate (ΔLAC) from skeletal muscles in essential hypertensive patients before (UHT:n = 88) and after treatment with antihypertensive agents (THT:n = 37) in comparison to normotensive subjects (NT:n = 14). Results ΔHX, as well as ΔAmm and ΔLAC, were significantly higher in UHT and THT (P < 0.01) than in NT. This release of ΔHX from exercising skeletal muscles correlated significantly with the elevation of lactate in NT, UHT and THT (y = 0.209 + 0.031 x;R2 = 0.222, n = 139:P < 0.01). Administration of doxazosin (n = 4), bevantolol (n = 5) and alacepil (n = 8) for 1 month significantly suppressed the ratio of percentage changes in ΔHX by − 38.4 ± 55.3%, − 51.3 ± 47.3% and − 76.3 ± 52.2%, respectively (P < 0.05) but losartan (n = 3), atenolol (n = 7) and manidipine (n = 10) did not reduce the ratio of changes; on the contrary, they increased it in ΔHX by +188.2 ± 331%, +96.2 ± 192.2% and +42.6 ± 137.3%, respectively. The elevation of ΔHX after exercise correlated significantly with the serum concentration of uric acid at rest in untreated hypertensive patients (y = 0.194 − 0.255x;R2 = 0.185, n = 30:P < 0.05). The prevalence of reduction of both ΔHX and serum uric acid was significantly higher in the patients treated with alacepril, bevantolol and doxazosin (67%:P < 0.02) than in the patients treated with losartan, atenolol and manidipine (12%). Conclusions It is concluded that the skeletal muscles of hypertensive patients released ΔHX in excess by activation of muscle-type adenosine monophosphate (AMP) deaminase, depending on the degree of hypoxia. The modification of ΔHX by angiotensin-converting enzyme inhibitors and α1-blockers influenced the level of serum uric acid, suggesting that the skeletal muscles may be an important source of uric acid as well as of the substrate of xanthine oxidase in hypertension.

Platelet Ionized Magnesium, Cyclic AMP, and Cyclic GMP Levels in Migraine and Tension-Type Headache

Decreased serum and intracellular levels of magnesium have been reported in patients with migraine. It has been suggested that magnesium may play an important role in the attacks and pathogenesis of headaches. We measured ionized magnesium cyclic AMP (adenosine monophosphate), and cyclic GMP (guanosine monophosphate) in platelets of patients with migraine in patients with tension‐type headache, and in healthy controls. The platelet level of ionized magnesium from patients with tension‐type headache was significantly lower than the levels from the other two groups. The platelet level of cyclic AMP from patients with migraine was higher than those from the other groups. We found no significant differences in the platelet cyclic GMP levels among the three groups. It is suggested that reduced platelet ionized magnesium in patients with tension‐type headache is related to abnormal platelet function, and that increased platelet cyclic AMP in patients with migraine is related to alteration of neurotransmitters in the platelet.

Platelet gamma-aminobutyric acid levels in migraine and tension-type headache.

SYNOPSIS