Apolipoprotein E epsilon3 allele is not a risk factor of schizophrenia: a study of 314 Japanese patients

The association between apolipoprotein E (ApoE) alleles and schizophrenia has remained controversial. A recent report claiming that ApoE epsilon3 Taiwan Chinese carriers have an increased risk of schizophrenia prompted us to investigate the allele frequency in a large group of Japanese schizophrenic patients. Serum samples were obtained from 314 schizophrenic patients and 188 controls in Japan and examined using isoelectric focusing/immunoblotting. There were no significant differences in ApoE allele frequencies between schizophrenic patients and controls and in the odds ratios for schizophrenia among the epsilon2, epsilon3 and epsilon4 carriers. In contrast to the report from Taiwan, our findings and results of the majority of previous studies suggest no effects of ApoE alleles on the development of schizophrenia.     

Dynamic changes in the middle cerebral artery perfusion in normal full-term human fetuses in relation to the timing of behavioral state

Our aim is to evaluate serial changes in normal full-term fetal cerebral circulation according to the behavioral states. Flow velocity waveforms in the middle cerebral artery and fetal heart rate (FHR) were well recorded in ten of 19 cases by pulsed Doppler ultrasonography and actocardiography over 45 min, respectively. Behavioral states were classified as resting or active phase by FHR patterns. Resistance indices (RIs) were calculated every 5 s as an average of two consecutive waveforms, and median RI was chosen in each 2-min segment. In order to evaluate changes in median RI from active-to-resting transition to resting-to-active one statistically, differences in RI between two 2-min segments were examined using Mann-Whitney U-test. As a result, median RI was decreased to the minimum one in the active-to-resting transition for 12 min in all cases: significant decrease to the 2-min segment with the minimum one (P<0.01). Various types of increase to the maximum median RI during resting phase followed the minimum one: significant increase from the 2-min segment with the minimum one to that with the maximum one in all cases (P<0.001 in eight cases, P<0.01 in two cases). Thereafter, median RI was decreased from the end of resting phase in the resting-to-active transition for 12 min in all cases: significant decrease from the last 2-min segment of resting phase in all cases (P<0.01). We reveal that fetal cerebral circulation changes dynamically in relation to the timing in each behavioral state.     

Comparison of testicular volumes between patients with undescended testes and inguinal hernias

During the past 29 years from 1962 to 1990, 222 cases of undescended testes were operated upon in our department. The ratio of right to left undescended testes was 1.15:1, and 18% were bilateral. Associated diseases were found in 22% of the patients, more than half of which were inguinal hernias. The volumes of the undescended testes were compared to those on the unaffected side of patients with unilateral inguinal hernias. The undescended testes were found to be significantly smaller than those of the controls in all age groups. Furthermore, the volumes of the scrotal testes also became significantly smaller than the controls in patients older than 5 years. These results suggest poor postnatal development of undescended and scrotal testes. Correspondence to: M. Kubota     

Anti-hyperalgesic effects of intrathecally administered neuropeptide W-23, and neuropeptide B, in tests of inflammatory pain in rats

Neuropeptide W-23 (NPW23) is an endogenous ligand of both GPR7 and GPR8, and neuropeptide B (NPB) is an endogenous ligand of GPR7. GPR7 mRNA has been detected in regions of the cortex, the hippocampus, the hypothalamus, and the spinal cord in the rat, but GPR8 has not been found in rodents. GPR7 and GPR8 receptors have structural features in common with both opioid and somatostatin receptors. The effects of intrathecal (i.t.) application of NPW23 and NPB were tested in two inflammatory pain models (plantar injection of formalin or carrageenan) and two thermal nociceptive tests (52.5 degrees C and 50.5 degrees C hot plates) and one mechanical nociceptive test in the rat. I.t. injection of either NPW23 or NPB decreased the number of agitation behaviors induced by paw formalin injection and attenuated the level of mechanical allodynia, but not the level of thermal hyperalgesia, induced by paw carrageenan injection in a dose-dependent manner at a dose between 0.1 and 10 microg, significantly. The effects of either 10 microg of NPW23 or 10 microg of NPB were not antagonized by 10 microg of naloxone. I.t. injection of either NPW23 or NPB had no effect in both the 52.5 degrees C hot plate test or in the 50.5 degrees C hot plate tests at a dose between 1 and 100 microg. I.t. injection of either 10 microg of NPW23 or 10 microg of NPB had no effect in the mechanical nociceptive test. I.t. injection of either 10 microg of NPW23 or 10 microg of NPB significantly suppressed the expression of Fos-like immunoreactivity of the L4-5 spinal dorsal horn induced by paw formalin injection. These data suggest that both spinally-applied NPW23 and NPB suppressed the input of nociceptive information to the spinal dorsal horn, produced an analgesic effect in the formalin test, and attenuated the level of mechanical allodynia in the carrageenan test, and that either spinally applied NPW23 or spinally applied NPB had no effect in the physiological condition.     

Reversal of neuromuscular effects of adenosine by specific adenosine A1-receptor antagonist in live rats

Intravenous adenosine in-vivo was shown to potentiate the effects of non-depolarizing neuromuscular blocking agents. This study aimed to determine whether adenosine A1-receptors mediated this potentiation. The authors investigated the effects of intravenous adenosine, N6-cyclopentyladenosine, specific A1-receptor agonist, and 8-cyclopentyl-1,3-dipropylxanthine, specific A1-receptor antagonist, on neuromuscular block by vecuronium, in in-vivo rat sciatic nerve-tibialis anterior preparations. In the presence of 50% steady state block by vecuronium, adenosine, and N6-cyclopentyladenosine caused similar degree of depressions of twitch tension. Twitch tension returned to its pre-injection value more rapidly when 8-cyclopentyl-1,3-dipropylxanthine was given at the maximal block than when it was allowed to recover spontaneously. It was concluded that in in-vivo adenosine potentiated the neuromuscular effects of vecuronium through adenosine A1-receptors in rats.     

The effect of a prenatal androgen disruptor, vinclozolin, on gubernacular migration and testicular descent in rats

Background/purpose

Androgen has been shown to regulate inguinoscrotal testicular descent. This study aims to clarify the effect of one of the major endocrine disrupters, vinclozolin (V), on both gubernacular migration and inguinoscrotal testicular descent in rats.

Methods

Time-pregnant rats were segregated into 2 groups. In group I, the rats were administered 200 mg/kg/d of V by gavage on days 15 to 18 of gestation. In group II, the rats were administered the same volume of solvent and were used as controls. At birth, the anogenital distance was measured in pups, and gubernacular migration was examined at 10 days of age in some of male offspring. Next, the incidence of testicular descent and the growth of external genitalia were investigated in the remaining male offspring at 60 days of age. The χ² test was used for statistical analysis of the results.

Results

At birth, the anogenital distance (AGD) index decreased significantly more in group I than in group II in male offspring. However, there was no significant difference in the AGD index between the 2 groups in the female offspring. At 10 days of age, an aberrant migration of the gubernaculum was found in the 51.5% of V-treated rats in group I. At 60 days of age, the incidence of cryptorchidism was 57.7% in group I and 0% in group II (P < .05). In addition, hypospadias with cleft phallus and pseudo vagina with a blind pouch also were observed in some of the V-treated rats.

Conclusions

Prenatal administration with V thus caused intrauterine defects, which resulted in testicular maldescent caused by the induction of an aberrant migration of the gubernaculum associated with an abnormal extension of the processus vaginalis, and this may have been caused by the antiandrogenic effect of V in utero.     

Optimum pain relief with continuous epidural infusion of local anesthetics shortens the duration of zoster-associated pain

OBJECTIVE: To investigate effects of continuous epidural infusion (CEI) of 0.5% bupivacaine added to intermittent epidural boluses (IEB) on the duration of zoster-associated pain (ZAP), as compared with continuous infusion of normal saline placebo added to IEB. DESIGN: A prospective, double-blind, randomized, placebo-controlled study. SETTING: A university hospital and an affiliated clinic in Japan from 1996 through 1999. PATIENTS: 56 immunocompetent herpes zoster (HZ) patients, 50 years or older, within 10 days of rash onset and with severe pain and eruption. INTERVENTIONS: Patients were hospitalized and randomly allocated into 2 groups. CEI group given CEI of 0.5% bupivacaine (0.5-1.0 mL/h) plus IEB of 0.5% bupivacaine 4 times daily (n = 29). IEB group given normal saline infusion plus IEB of 0.5% bupivacaine 4 times daily (n = 27). All patients received oral acyclovir 800 mg, 5 times daily, for 7 days. OUTCOME MEASURES: The number of days required for complete cessation of ZAP and the proportion of subjects with allodynia beyond 30 days. RESULTS: The median time to cessation of ZAP was significantly shorter in the CEI group than in the IEB group (29 days vs. 40 days, P = 0.002). The number of patients whose allodynia persisted beyond 30 days of treatment was significantly lower in the CEI group than in the IEB group (10% vs. 37%, P = 0.027). CONCLUSIONS: CEI of 0.5% bupivacaine plus IEB was associated with a shorter duration of ZAP and fewer patients with allodynia beyond 30 days, compared with IEB plus normal saline infusion. Patients at high risk for developing postherpetic neuralgia (PHN) can be managed with intensive therapies at the early stage of disease, such as CEI, which maintains effective analgesia and may reduce the burden of PHN.