Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

The directional effects of passive eye movement on the directional visual responses of single units in the pigeon optic tectum

We have investigated the visual responses of 184 single units located in the superficial layers of the optic tectum (OT) of the decerebrate, paralysed pigeon. Visual responses were similar to those reported in non-decerebrate preparations; most units responded best to moving visual stimuli, 18% were directionally selective (they had a clear preference for a particular direction of visual stimulus movement), 76% were plane-selective (they responded to movement in either direction in a particular plane). However, we also found that a high proportion of units showed some sensitivity to the orientation of visual stimuli. We examined the effects of extraocular muscle (EOM) afferent signals, induced by passive eye movement (PEM), on the directional visual responses of units. Visual responses were most modified by particular directions of eye movement, although there was no unique relationship between the direction of visual stimulus movement to which an individual unit responded best and the direction of eye movement that caused the greatest modification of that visual response. The results show that EOM afferent signals, carrying information concerning the direction of eye movement, reach the superficial layers of the OT in the pigeon and there modify the visual responses of units in a manner that suggests some role for these signals in the processing of visual information.     

Treatment of hypertension in nondiabetic renal disease

To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.     

Hydrogen peroxide in exhaled air is increased in stable asthmatic children

Exhaled air condensate provides a noninvasive means of obtaining samples from the lower respiratory tract. Hydrogen peroxide (H2O2) in exhaled air has been proposed as a marker of airway inflammation. We hypothesized that in stable asthmatic children the H2O2 concentration in exhaled air condensate may be elevated as a result of airway inflammation. In a cross-sectional study, 66 allergic asthmatic children (of whom, 41 were treated with inhaled steroids) and 21 healthy controls exhaled through a cold trap. The resulting condensate was examined fluorimetrically for the presence of H2O2. All subjects were clinically stable, nonsmokers, without infection. The median H2O2 level in the exhaled air condensate of the asthmatic patients was significantly higher than in healthy controls (0.60 and 0.15 micromol, respectively; p<0.05), largely because of high values in the stable asthmatic children who did not use anti-inflammatory treatment (0.8 micromol; p<0.01 compared to controls). We conclude that hydrogen peroxide is elevated in exhaled air condensate of children with stable asthma, and may reflect airway inflammation.     

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.     

Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)     

Isolation and Spectroscopic Characterization of Eu@C72

A new Eu-endohedral fullerene cage, namely, Eu@C₇₂, was synthesized, separated, and a single isomer, Eu@C₇₂-I, has been isolated by multi-step HPLC for the first time and characterized by LDI-TOF mass spectrometry, UV-Vis and EPR spectroscopy. Additionally, a second isomer, Eu@C₇₂-II, has been separated by HPLC and identified by LDI-TOF mass spectrometry.