Secondary acute angle closure attack as an initial presentation of a novel type of systemic lupus erythematosus.

BACKGROUND: We report a rare case of secondary acute angle closure attack because of lupus choroidopathy and accompanying polyserositis, as an initial presentation of a novel type of systemic lupus erythematosus in a 44-year-old woman. CASE PRESENTATION: The patient complained of eyelid oedema and chemosis with bilateral severe loss of visual acuity. Systemic lupus erythematosus was diagnosed based on malar rash, polyserositis, proteinuria and positive antibody titers for antinuclear antibodies, anti-DNA, antinucleosome antibodies and ribosomal RNP. Subsequently, secondary bilateral acute angle closure caused by choroidal effusions with lupus choroidopathy was diagnosed. A month after steroid and immunosuppressive drug therapy, the patient's intraocular pressure and visual acuity returned to normal. During the subsequent year, the secondary acute angle closure did not recur and polyserositis remained under control. CONCLUSIONS: Bilateral, secondary acute angle closure attack due to SLE choroidopathy can be an initial presentation of SLE, which is often accompanied by polyserositis. Prompt and aggressive high doses of steroids and immunosuppressive therapy are strongly recommended.

Biphasic effects of 3-quinuclidinyl benzilate on spontaneous motor activity in mice.

Dose-response relationships for onset, duration, and magnitude of 3-quinuclidinyl benzilate (QNB) on spontaneous motor activity (SMA) were studied in mice. QNB was administered SC immediately before 2-h test sessions in dose levels differing by a factor of 0.5 log (range 0.1-10.0 mg/kg). For the total activity session of 2 h, QNB had a biphasic effect on SMA; at a low dose (0.1 mg/kg) it decreased, and at moderate to higher doses (0.3-10.0 mg/kg) it increased SMA in a dose-related fashion. The onset and duration of the significant decreasing or increasing effects were also dose dependent; at the low dose (0.1 mg/kg) it depressed SMA from 5 to 35 min postinjection, at moderate doses (0.3 and 1.0 mg/kg) it enhanced SMA from 5 to 45 min and 5 to 70 min, respectively, postinjection. At the higher doses (3.0 and 10.0 mg/kg) it increased SMA within 5 min and lasted for 100 and 120 min, respectively. The increase in SMA for the dose range from moderate to high doses of QNB (0.3-10.0 mg/kg) was linear with dose. In general, QNB appears to produce a biphasic effect on SMA responding in mice.

Effects of 3-quinuclidinyl benzilate on fixed-ratio responding and open field behavior in the rat.

The effects of 3-quinuclidinyl benzilate (QNB) in the rat were evaluated on a fixed-ratio (FR) schedule of water reinforcement and on open field behavior in a novel environment. QNB had a biphasic effect on FR-20 responding: at a low dose (0.01 mg/kg SC) it increased, and at moderate to higher doses (0.05-1.0 mg/kg SC) it decreased bar pressing in a dose-dependent manner. The effect of QNB on the multiple indices of open field activity showed that at the low dose (0.01 mg/kg SC) it depressed spontaneous motor activity (SMA), while at higher doses (0.5 and 1.0 mg/kg SC) it enhanced SMA: rearing and forelimb flicks were unaffected at low doses and increased at higher doses. In general, QNB appears to produce differential effects on operant responding and open field activity.

Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction.

There is growing evidence that mild cognitive impairment in early AD (Alzheimer's disease) may be due to synaptic dysfunction caused by the accumulation of non-fibrillar, oligomeric Abeta (amyloid beta-peptide), long before widespread synaptic loss and neurodegeneration occurs. Soluble Abeta oligomers can rapidly disrupt synaptic memory mechanisms at extremely low concentrations via stress-activated kinases and oxidative/nitrosative stress mediators. Here, we summarize experiments that investigated whether certain putative receptors for Abeta, the alphav integrin extracellular cell matrix-binding protein and the cytokine TNFalpha (tumour necrosis factor alpha) type-1 death receptor mediate Abeta oligomer-induced inhibition of LTP (long-term potentiation). Ligands that neutralize TNFalpha or genetic knockout of TNF-R1s (type-1 TNFalpha receptors) prevented Abeta-triggered inhibition of LTP in hippocampal slices. Similarly, antibodies to alphav-containing integrins abrogated LTP block by Abeta. Protection against the synaptic plasticity-disruptive effects of soluble Abeta was also achieved using systemically administered small molecules targeting these mechanisms in vivo. Taken together, this research lends support to therapeutic trials of drugs antagonizing synaptic plasticity-disrupting actions of Abeta oligomers in preclinical AD.

Behavioral toxicological assessment of oral pralidoxime methanesulfonate in the rat.

The behavioral toxicity of pralidoxime methanesulfonate (P2S) was examined in the rat by comparing standard measures such as conditioned taste aversion (CTA), drinking behavior and acute oral toxicity. P2S produced a weak CTA at doses of 0.4 and 0.8 g/kg (PO) and a profound CTA at the highest dose (1.6 g/kg) using a single sucrose-flavored conditioning trial with a one bottle test. The CTA produced by the highest dose of P2S was blocked by a specific, and exclusively peripheral, histamine-H2blocker, cimetidine (30 mg/kg, IP), which also has a cytoprotecting effect on gastric mucosal lesions. These data suggest that the H2 receptors may be involved in inducing the aversive effects of P2S through the inherent local irritating property of P2S on the rat gastric mucosa. There was no disruption of water drinking in thirsty rats with P2S at doses ranging from 0.2 to 1.6 g/kg. The survival time after an acute oral lethal dose of P2S (8-15 g/kg) was prolonged in non-fasted rats (16.5-38.5 min) compared to fasted ones (3.5-14.5 min), however the LD50's were identical (8.7 +/- 1.0 and 7.5 +/- 0.5 g/kg; respectively); indicating that P2S taken with food delays the lethal effects, but does not affect its lethal potency.

Adverse behavioral effects of the anticholinesterase poisoning protector pralidoxime methanesulfonate.

Pralidoxime methanesulfonate (P2S) has anticholinesterase protective properties, but it also has an array of gastrointestinal (GI) symptoms. Because such a symptom would be disadvantageous to occupational workers who handled and used organophosphorus anticholinesterase continuously, and to soldiers who have had oral pretreatment in a situation where anticholinesterase agent poisoning is a possibility, this question was investigated in rats using three behavioral paradigms to evaluate the feasibility of the oral prophylactic regimen. These are: (1) conditioned taste aversion (CTA), (2) operant behavior and (3) spontaneous locomotor activity (SMA); these three behavioral parameters are analogous to toxicant-induced gastrointestinal (GI) disturbances, performance of learned tasks and behavioral arousal, respectively. Dose-response studies of P2S in dose levels of 0.2, 0.4, 0.8 and 1.6 gm/kg (P.O.) were evaluated. The results consistently demonstrated that only the highest dose significantly produced marked decreases in consumption of flavored solution associated with its ingestion, suppressed keypress response maintained under a 20-response fixed-ratio schedule of water presentation, and inhibited SMA. By inference, if CTA, operant behavior and SMA are appropriate paradigms, P2S, on an acute single oral high dose level, would cause GI disturbances, impair task performance and induce sedation in man.