Brain and heart specific alteration of methamphetamine (MAP) distribution in MAP-sensitized rat

The repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the high accumulation of MAP was observed in the MAP-sensitized animal brain, which suggested that this phenomenon is an important factor in the development or expression of behavioral sensitization. The purpose of the present study is to elucidate the MAP distribution in the MAP-sensitized rat using gas chromatography/mass spectrometry (GC/MS). As a result, the MAP distribution in the heart at 10 min when showing a high accumulation of MAP in the MAP-sensitized rat brain was significantly higher than that of the control rat, whereas no significant differences in the liver, kidney, abdominal muscle, femoral muscle and blood were observed. In the brain and heart, there was no different distribution at 1 min, reflecting only the influx process from blood to brain and heart. On the contrary, there was the significant difference at 10 min, reflecting both the influx and efflux process, suggesting that the efflux process of MAP from brain or heart to blood may be slow due to MAP sensitization. In conclusion, it was clear that the brain and heart specific alteration of the MAP distribution occurred in the MAP sensitization. It was considered that the high accumulation of MAP in the MAP-sensitized rat brain may be related to the expression of behavioral sensitization and that the delayed efflux of MAP in the MAP-sensitized rat heart may be connected with the cardiac toxicity.     

Fluid and electrolyte balance in extremely preterm infants <24 weeks of gestation in the first week of life

Background: Extremely preterm infants, especially those <24 weeks of gestation, displayed extremes in changes of fluid/electrolyte balance. The purpose of the present study was to retrospectively investigate abnormalities in fluid/electrolyte balance during the first postnatal week.
Methods: Of 32 subjects admitted during 20 years, 17 infants with no severe complications were examined, and 72 appropriate-for-dates infants at 24–28 weeks of gestation were taken as controls. The subjects were managed in closed incubators in a highly humidified environment and fluid/electrolyte balances were monitored in retrospect.
Results: The subjects had higher urine contents, while the insensible water loss was higher than in controls. As for weight loss, no remarkable changes were noted between the two groups. On day 4 and thereafter, serum Na⁺ levels were high, indicating a high complication rate of hypernatremia without differences in hyperkalemia. The decrease in blood base excess was rapid, requiring supplementation of sodium bicarbonate up to postnatal day 5 in all preterm infants.
Conclusion: Due to the relatively higher urine output and insensible water loss in extremely preterm infants during postnatal week 1, higher water intake was required. As such, metabolic acidosis was bound to have occurred.     

Clinical evaluation of transrectal power Doppler imaging in the detection of prostate cancer

To evaluate the clinical usefulness of power Doppler imaging (PDI), we compared this method to gray-scale transrectal ultrasound (TRUS) in the detection of prostate cancer. A total of 101 men with abnormally high serum prostate specific antigen (PSA) levels and/or abnormal digital rectal examination (DRE) findings were assessed using TRUS and PDI. Random systematic sextant and bilateral far lateral prostate biopsies were performed in all cases. In addition, when TRUS revealed a hypoechoic lesion or PDI revealed a hypervascular lesion (HVL), these lesions were directly biopsied. Of the 101 patients, 48 (47.5%), 42 (41.5%) and 42 (41.5%) were suspicious of having prostate cancer by DRE, TRUS and PDI, respectively. Prostate needle biopsy revealed prostate cancer in 39 patients (38.6%) and benign prostatic diseases in 62 patients (61.4%). If prostate needle biopsy was avoided when PDI was negative, then PDI eliminated the need for biopsy in 59 of the 101 patients (rate of biopsy procedures saved: 58.4%) and missed only 8 (13.6%) prostate cancers. Moreover, in 63 patients with intermediate PSA (3-10 ng/ml), the rate of biopsy procedures saved by DRE, TRUS, and PDI was 60.3%, 65.1%, and 68.3%, respectively, and the rate of cancers missed was 26.3%, 19.5%, and 14.0%, respectively. In a total of 826 specimens of TRUS-guided prostate biopsy, 126 (15.3%) specimens had adenocarcinoma. Site by site based analysis of the present series revealed 34.1% of prostate cancer sites were isoechoic and hypervascular. On a site by site basis, PDI had better sensitivity, specificity, positive predictive value and negative predictive value than TRUS. In 48 patients without abnormal DRE findings, on a site by site basis, the sensitivities of TRUS and PDI were 22.9% and 34.4%, respectively. Gleason score was associated with a positive rate of PDI on both a patient basis and site by site basis. From these results, on a patient basis, we conclude that PDI was helpful in the indication for prostate biopsy for all patients or patients with intermediate PSA level. On a site by site basis, PDI may be able to select prostate cancer sites at biopsy, in particular in patients without abnormal DRE findings.     

A guide to initial management of minor head injury

We reviewed the records of 1,335 minor head injury patients with initial Glasgow Coma Scale (GCS) scores of 15 treated by our neurosurgery service between January 1998 and December 2000. Skull X-ray was performed in 945 patients (71%), and Computed tomography (CT) was performed in 590 patients (44%). Skull fracture was shown radiographically in 24 patients (2.5%), and abnormalities on the initial CT were seen in 29 patients (4.9%). The most frequent intracranial lesion on CT was acute epidural hematoma with skull fracture. Significantly more intracranial lesions were found in those with a fracture than in those without by chi2 analysis. Post-traumatic vomiting was significantly associated with radiographical abnormalities, but headache and nausea did not increase the risk of skull fracture and intracranial lesions on the CT. Patients required neurosurgical intervention in 4 cases, and all of those were acute epidural hematoma with skull fracture. In this study, the first thing we should do for asymptomatic minor head injury patients with a GCS score of 15 is to investigate the presence of a skull fracture by skull X-ray. Head trauma patients with a skull fracture and post-traumatic vomiting should undergo CT to facilitate detection of intracranial lesions, even when there are no abnormal neurological signs.     

Intensity of X-ray reflections from skeletal muscle thin filaments partially occupied with myosin heads: effect of cooperative binding

For quantitative analysis of contractile proteins of muscle by means of X-ray diffraction, it is important to know how the intensities of individual reflections are related to the number of diffracting objects, i.e., the amount of constituent contractile protein in the muscle cell. Here we diffused various amounts of exogenous myosin subfragment-1 (S1) into overstretched skinned skeletal muscle fibers, either in the presence or absence of Ca²⁺ , and derived the relationship between the S1 content and the intensities of reflections arising from the S1. In theory, the intensities should be proportional to the square of the S1 content (square law). However, the intensity--content relation deviated systematically from the square law as the S1 content was lowered, and it was better described as a linear function at the lower end of the S1 contents (<20% of saturation level). Model calculations show that the way of deviation is explained by the cooperative manner of S1 binding to the regulated thin filament. This revised version was published online in July 2006 with corrections to the Cover Date.     

Alleviation of ischemic neuronal damage by postischemic loading with histidine in the rat striatum

Inflammatory reactions play an important role in ischemia-reperfusion injury in the brain. Since histamine H(2) action suppresses inflammatory reactions, effects of postischemic loading with histidine, a precursor of histamine, were examined. Focal cerebral ischemia for 15 min was provoked by transient occlusion of the right middle cerebral artery in rats, and delayed neuronal death were evaluated in striatal neurons after 7 days. Histidine was administered four times, immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p., each time). To examine the role of histaminergic action on changes in histologic outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine-treated rats. Transient ischemia for 15 min provoked severe neuronal damage in the saline-injected control group, and the number of striatal neurons decreased to 21% of that on the contralateral side. Administration of histidine alleviated ischemic neuronal damage, and the number of preserved neurons was 76% of that on the contralateral side. Simultaneous administration of mepyramine with histidine did not affect the histologic outcome. However, administration of ranitidine abolished the alleviation by histidine. These findings indicate that the elevation of histamine H(2) receptor stimulation by massive administration of histidine suppresses reperfusion injury in the brain.     

Effect of cyclohexenonic long-chain fatty alcohol on rat overactive bladder induced by bladder neck obstruction

We attempted to clarify the preventive effects of cyclohexenonic long-chain fatty alcohol on detrusor overactivity induced by mild bladder neck obstruction. Bladder neck obstruction was created by partial ligation of the urethra. Female Sprague-Dawley rats were divided into three groups: those with bladder neck obstruction treated without long-chain fatty alcohol, those with bladder neck obstruction with long-chain fatty alcohol (8 mg/kg, i.p., every day) and the sham-operated control group (A, B, and C groups, respectively). Six weeks after the induction of bladder neck obstruction, voiding behavior was observed in the metabolic cage, and a cystometrogram was performed in the experimental animals. Furthermore, Hematoxylin and Eosin, Azan-Mallory, and Bodian stainings were performed in these bladders. Bladder weight, voiding behaviors and a cystometry indicated that rats in the A group showed detrusor overactivity, which was improved by treatment with long-chain fatty alcohol. The proportion of connective tissue and the density of bundles of neurofibers in the bladder of the A group was significantly less than that in the other bladders. Mild bladder neck obstruction induces detrusor overactivity, which is improved by treatment with long-chain fatty alcohol.     

Suppressed permeation of linoleic acid in a liposomal formulation through reconstructed skin tissue

Since the liposomal formulation of linoleic acid (LA) exhibited an enhanced skin-whitening effect, the influence of liposomalization on the cutaneous absorption of LA was examined using a three-dimensional (3D) reconstructed skin model. Liposome entrapped [(14)C]-LA was applied on the skin model, and the permeation of LA through the skin was monitored. The permeation rate of LA in the liposomal formulation was found to be lower than that in the conventional formulation without liposomes, suggesting the increased retention time of LA in the skin by the liposomal formulation. Next, to investigate the dependence of the LA permeation on melanocyte conditions and intactness of the reconstructed skin model, the effect of UV irradiation on LA permeation was examined. Low-dose UVB irradiation (0.03 J/cm(2) for 3 times), which activated melanocytes in the skin, did not influence the extent of LA permeation, while high-dose irradiation (0.30 J/cm(2) for 3 times) enhanced the permeation of LA in both the conventional and liposomal formulation. The present results suggest the importance of skin intactness for LA permeation and that the 3D reconstructed skin model would be useful for evaluating the characteristics of skin-oriented cosmetics and drugs.     

Urinary acidification in extremely low birth weight infants

Premature infants often present metabolic acidosis without protein load in the early neonatal period, around days 4–6. In order to elucidate the cause of acidosis, we investigated urinary acidification of infants in the early neonatal period.

Urine pH, fractional excretion of HCO₃⁻ (FEHCO₃), excretion of HCO₃⁻ and NH₄⁺ of the appropriate-for-date infants were measured on days 0–2 and on days 4–6 of life.

Extremely low birth weight (ELBW) infants showed higher urine pH than more than 1500 g birth weight infants. FEHCO₃ and HCO₃⁻ excretion were of high values in ELBW infants on days 0–2, but decreased on days 4–6. Urine NH₄⁺ excretion rate was lower in ELBW infants than in birth weight more than 1000 g on days 0–2 of life and still remained at a low rate on days 4–6.

These data indicated that insufficiency of NH₄⁺ excretion is the main cause for metabolic acidosis of ELBW infants in the early neonatal period.