Circulating immune complexes in pre-eclampsia.

Serum samples from 20 non-pregnant women, 30 women with normal pregnancy and 50 women with pregnancy associated with pre-eclampsia were tested for circulating immune complexes using the polyethyleneglycol precipitation method. A highly significant positive correlation was found between circulating immune complexes and severe pre-eclampsia (BP greater than 140/90 mm Hg, albuminuria greater than 0.25 g/l). In contrast to this the difference in immune complex levels between non-pregnant subject, normal pregnancy cases and patients with mild pre-eclampsia was not statistically significant. A significant positive correlation was found between the level of circulating immune complexes and the severity of albuminuria. These findings suggest that circulating immune complexes, though not seeming to play an aetiological role in pre-eclampsia may very well be involved in its pathogenesis.     

Histamine receptors in isolated guinea pig duodenal muscle: H3 receptors inhibit cholinergic neurotransmission.

A series of histamine H3 receptor agonists and the H3 receptor antagonist thioperamide were tested in the isolated guinea pig duodenum, to investigate the role of this new receptor subtype in the intestinal contractility. At the same time the selectivity of the different compounds for the various histamine receptor subtypes was investigated. In the presence of famotidine (10(-6) M) and thioperamide (10(-5) M), histamine, N alpha-methylhistamine (NMH) and (R)-alpha-methylhistamine (alpha-MH) exerted a concentration-dependent contractile effect through activation of H1 receptors; the ratio of potency was histamine = NMH greater than alpha-MH (this last compound was approximately 500 times less potent). In the presence of pyrilamine (10(-6) M) and thioperamide (10(-5) M), histamine, dimaprit and impromidine caused a slight contractile effect, showing a high degree of tachyphylaxis; this effect was abolished by tetrodotoxin (10(-6) M) and by famotidine (10(-6) M). alpha-MH was ineffective up to 10(-4) M. The H2 receptor agonists dimaprit (10(-4) to 10(-3) M) and impromidine (10(-6) to 10(-5) M) caused a relaxant effect on the contraction elicited by acetylcholine (ACh), BaCl2 and electrical stimulation. This effect, which was unaffected by famotidine, was not mimicked by alpha-MH and not reversed by thioperamide (10(-5) M). In the presence of pyrilamine (109-6) M) and famotidine (10(-6) M), histamine, NMH and alpha-MH inhibited the twitch responses to electrical stimulation, with EC50 values of 1.17 x 10(-7), 6.76 x 10(-8) and 2.45 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Different behavioral deficits are induced by anoxia/hypoxia in neonatal and senescent rats: blockade by MK-801

Rats exposed on their first postnatal day to 100% nitrogen for 25 min developed hyperactivity and lower performance in passive avoidance task during development. Administration of MK-801 (0.5 mg/kg i.p.) 1 h before anoxia or (0.25 and 0.5 mg/kg) 1 h after completely reversed this behavioral impairment. Senescent rats (24-26 months) exposed to hypoxia (92% N2 + 8% O2) for 5 h failed in their performance in C.A.R., 30 days later. Pretreatment with MK-801 (1 mg/kg i.p.) completely reversed this impairment. These data suggest that activation of endogenous NMDA receptors produces different behavioral consequences in neonatal and senescent rats and that MK-801 administration close to exposure of animals to anoxia or hypoxia can prevent such damage, thus preventing behavioral impairments in postnatal as well as in senescent rats.     

Detection of optic pathway misrouting in the human albino neonate.

The diagnosis of albinism is indicated by the presence of visual pathway misrouting in which temporal retinal fibers erroneously decussate at the optic chiasm disrupting the normal topographical distribution of retinal geniculate-cortical projections. Detection of misrouted fibers is effected by non-invasive electrophysiological assessment of the topographical representation of the visual evoked potential (VEP) following full field monocular stimulation. By combining appropriate state defined neonatal recording procedures with the albino VEP test paradigm, the presence of aberrant optic pathway projections was detected in a five-day-old full-term infant. The electrophysiological signature pathognomonic to albinism was observed within a long (300 ms) latency window of an otherwise normal neonatal luminance flash response. The results of this study indicate that the VEP misrouting test can be extended to reliable albino diagnosis within the neonatal period.     

Response to treatment in panic disorder with associated depression

Thirty outpatients with panic disorder (PD) were treated at an anxiety clinic using a symptom-focused approach. Thirteen (43%) had no history of major depressive disorder (MDD), 12 (40%) had a history of secondary MDD, and 5 (17%) had history of primary MDD. The outcome was equally good in patients with no history of MDD (77% had good or excellent outcomes) and patients with a history of secondary MDD (83% had good or excellent outcomes). Patients with a history of primary MDD had the worst outcomes. These findings agree with earlier studies showing that secondary MDD does not adversely affect prognosis of patients presenting for treatment of PD.     

Management of pediatric pontine gliomas

We present 36 consecutive patients with intrinsic glioma of the pons. Tumors with exophytic expansion were excluded. There were 16 females and 20 males, ranging in age from 2 to 13 years, median 6 years. The most common presenting symptoms were cranial nerve dysfunction. unsteadiness of gait, and hemiparesis. Computed tomography (CT) showed a hypodense (17/21) or isodense (4/21) expansion of the pons. Five tumors had areas of contrast enhancement. Following information about prognosis and possible types of management, parents decided for or against radiation therapy: twentyfour children underwent irradiation and 12 did not. Median survival among children receiving a full course of irradiation was 280 days, compared to 140 days in an equivalent group of non-irradiated children. Hemiparesis presenting without cranial nerve symptoms and contrast enhancement on CT scan were poor prognostic factors, whereas sex, age, and duration of symptoms at diagnosis were unrelated to prognosis.     

Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.     

Single-channel K+ currents recorded from the somatic and dendritic regions of cerebellar Purkinje neurons in culture

Voltage-sensitive K+ channels were studied in rat cerebellar Purkinje neurons in culture using the single-channel recording technique. Recordings in the cell-attached and outside-out configuration revealed multiple voltage-sensitive K+ channel types in patches from both the somatic and the dendritic regions. K+ channel types were present in all patches studied. The same channel types were observed in somatic and dendritic recordings. Channel types were identified by reversal potential, single-channel conductance, voltage sensitivity, and patterns of activity. In cell-attached patches recorded under physiological conditions, 3 channel types were identified. Mean single-channel conductances were 92, 57, and 12 pS. All 3 channel types were activated by membrane depolarization. Similar channel types were identified in inside-out and outside-out patches recorded under physiological conditions. Two additional channel types were identified in the outside-out patches, with mean single-channel conductances of 41 and 26 pS. In cell-attached recordings under symmetrical K+ conditions, 6 channel types were identified. Mean single-channel conductances were 222, 134, 39, 25, 14, and 15 pS. Channel types with mean conductances of 222, 134, and 39 pS required membrane depolarization for activation. A comparison of channel properties indicated that these channel types correlated with the 3 channel types observed in cell-attached patches under physiological conditions. The 3 smaller-conductance channel types (25, 14, and 15 pS) were active at potentials around rest or at hyperpolarized membrane potentials. Two K+ channel types (39 and 25 pS) were commonly associated with the late phase of extracellularly recorded spontaneous spike events, suggesting a functional role in the repolarizing phase of somatic and dendritic action potentials. These results demonstrate that voltage-sensitive K+ channels are a prominent component of both the somatic and the dendritic membrane of the cerebellar Purkinje neuron and support the view that multiple voltage-sensitive K+ channel types contribute to the membrane functions of both cellular regions in this CNS neuronal type.