Effects of diazepam or haloperidol on convulsion and behavioral responses induced by bilateral electrical stimulation in the medial prefrontal cortex

1. Effects of diazepam (DZP) or haloperidol (HAL) on convulsions and behavioral responses (locomotion, circling, spying and head shaking) induced by bilateral electrical stimulation in the medial prefrontal cortex (mPFC) were examined. 2. Male Wistar rats were electrically stimulated (ten 30-sec trains, 60 Hz, 80-100 microA) bilaterally in the mPFC and their behavior was simultaneously observed in an open field in daily session. 3. DZP and HAL dose-response curves (0, 0.5, 1.25, 2.5 and 5 mg/kg, i.p., 30 min before electrical stimulation session) were determined after a baseline of behavioral responses was established. 4. DZP dose-dependently decreased head shaking and convulsions, had no effect in circling and spying behaviors, and increased locomotion except at the highest dose. HAL reduced locomotion, circling and spying behaviors in a dose-dependent manner, but did not affect convulsions or head shaking. 5. These results demonstrated that convulsion and behavioral responses induced by electrical activation of the mPFC were modified by DZP or HAL. Therefore, the mPFC is involved in the mediation of neural and/or behavioral activity that may be implicated in some central effects of psychoactive drugs.     

African horse sickness in Portugal: a successful eradication programme

African horse sickness (AHS) was diagnosed for the first time in southern Portugal in autumn 1989, following outbreaks in Spain. AHS virus presence was confirmed by virus isolation and serotyping. An eradication campaign with four sanitary zones was set up by Central Veterinary Services in close collaboration with private organizations. Vaccination began on 6 October. In February 1990, vaccination was extended to all Portuguese equines (170000 animals). There were 137 outbreaks on 104 farms: 206 of the equidae present died (16%) or were slaughtered (14%); 81.5% were horses, 10.7% were donkeys and 7.8% were mules. Clinical AHS occurred more frequently in horses than donkeys and mules. In the vaccinated population, 82 animals (62.2% horses and 37.8% mules and donkeys), died or were slaughtered due to suspected or confirmed AHS. One year after ending vaccination, December 1991, Portugal was declared free of AHS. Cost of eradication was US$1955513 (US$11.5/Portuguese equine).     

Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.     

A new method for monitoring the contamination of glycerol with diethylene glycol

A quartz crystal microbalance has been used to check the purity of glycerol. The experimental procedure involves no derivatization or other preliminary step except determination of water content. The protocol consists of the direct reading of the frequency of a quartz crystal with one face in contact with an aqueous solution of the glycerol to be tested. The method is inexpensive, simple, rapid, and highly sensitive; diethylene glycol contamination at the 3.61% level could be detected.     

Evaluation of in vitro toxicity of N,N-dimethyl-2-propen-1-amines isomers

The trypanocidal activities of cis-3-(4'-bromo[1,1'-biphenyl]-4-yl)- 3-(phenyl)-N,N-dimethyl-2-propen-1-amine (Vb) and cis-3-(4'-bromo[1,1'-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N-dimethyl-2- propen-1-anine (Vg) appeared 6.3 and 3.5 fold more active than the trans-isomers, respectively. Multi-endpoints for toxicity were also applied. Neutral red uptake (NRU), tetrazolium salt reduction (MTT), DNA content on V79 fibroblast cell culture and acute toxicity von E. coli were measured. The IC50 through DNA contents was lower for the cis-isomers in both series of compounds 5b: 7.8 microM and 5g: 5.2 microM). NRU values for derivative 5b in isomeric mixture shows the same value as the isolated isomers however, in the case of 5g a more significant toxicity of the cis-isomer was found. MTT values show that 5g is more toxic than 5b. In both cases, the acute toxicity of the trans-isomers was higher than that of the cis-isomers.     

TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus venom which acts on Ca2+-activated K+ channels.

The primary structure of TsTX-IV, a neurotoxin isolated from Tityrus serrulatus scorpion venom, is reported. Its amino acid sequence was determined by automated Edman sequential degradation of the reduced and carboxymethylated toxin and of relevant peptides obtained by digestion with Staphylococcus aureus strain V8 protease or trypsin and cleavage by CNBr. The complete sequence showed 41 amino acid residues, which account for an estimated molecular weight of 4520, and eight half-cystine residues which cross-link the toxin molecule with four disulfide bonds. The molecular weight determined by mass spectrometry was 4518. Comparison of this sequence with those from other scorpion toxins showed a resemblance with toxins which act on different types of K+ channels. TsTx-IV was able to block Ca2+-activated K+ channels of high conductance. TsTX-IV is the first four-disulfide-bridged short toxin from T. serrulatus so far completely sequenced.     

Pharmacological evaluation of ricinine, a central nervous system stimulant isolated from Ricinus communis.

The extract of the pericarp of castor bean (Ricinus communis) showed some typical central nervous system stimulant effects when administered to mice. The animals became exophthalmic, presented tremors and clonic seizures and died a few minutes after receiving larger doses of the extract. At lower doses the extract improved memory consolidation and showed some neuroleptic-like properties, such as a decrease in exploratory behavior and catalepsy. The memory-improving effect and the seizure-eliciting properties of the extract were also observed with the administration of ricinine, a neutral alkaloid isolated from the extract. However, the neuroleptic-like properties of the extract were not observed with ricinine. As the therapeutic index of ricinine is of the order of 200, the compound may be considered as a promising cognition-enhancing drug that may be used for the treatment of human amnesias.     

Effect of hydroquinone, hydroxocobalamin and carboxy-PTIO on non-adrenergic non-cholinergic nerve mediated relaxations of the rat duodenum

Relaxation induced by NANC-nerve stimulation is reduced by nitric oxide synthase (NOS) inhibitors but not by superoxide generators or NO scavengers, casting doubts on the precise nature of the neurotransmitter being released by these nerves. The lack of effect of superoxide anion generators to inhibit nitrergic nerve-mediated relaxations has been attributed to the protective action of high tissue levels of superoxide dismutase (SOD). The effects of hydroquinone, hydroxocobalamin and carboxy-PTIO, three NO inactivators which do not depend on superoxide anion generation, upon nitrergic nerve-mediated relaxations of the rat proximal duodenum were determined in order to elucidate whether they are mediated by free NO. GABA and nicotine caused relaxations of isolated segments of the rat proximal duodenum in a concentration-dependent manner that were abolished by tetrodotoxin (TTX). Similarly, transmural electrical stimulation (TES) caused frequency-dependent relaxations that were also abolished by TTX. The NOS inhibitors L-NAME and L-NOARG reduced in a concentration-dependent manner nerve-mediated relaxations elicited by TES, nicotine and GABA. The effect of NOS inhibitors was prevented by L-arginine but not D-arginine. NO caused concentration-dependent relaxations that were not affected by TTX or L-NOARG but were abolished by hydroquinone, hydroxocobalamin and carboxy-PTIO. In contrast, these compounds failed to affect TES-, nicotine- and GABA-induced relaxations. The lack of effect of hydroquinone, hydroxocobalamin and carboxy-PTIO upon nerve-mediated relaxations was unaltered by pretreatment with the SOD irreversible inhibitor DETCA. The present findings show that nitrergic nerve-mediated relaxations of the rat duodenum are unaffected by NO inactivators that do not generate superoxide anion. It is suggested that either a NO-containing molecule that is unreactive with the inactivators tested is the inhibitory neurotransmitter released by nitrergic nerves or that NOS activity fulfills another role in nitrergic nerves which could be related to the release of an still unidentified transmitter.     

Grossamide and N-trans-caffeoyltyramine from Annona crassiflora seeds

Grossamide, and N-trans-caffeoyltyramine, were isolated for the first time from the seeds of Annona crassiflora Mart, and in the Annonaceae family.     

Dizziness predicts initial worsening in panic disorder: an otoneurological investigation

Dizziness is a frequent complaint during the initial worsening of panic patients treated with clomipramine. In order to investigate the relationship between dizziness and initial worsening mechanisms, otoneurological tests were administered to 32 consecutive patients with panic disorder, with or without agoraphobia, before treatment, 36 h after the first dose of 25 mg clomipramine and after treatment and full remission of the panic and agoraphobic symptoms. A pretreatment complaint of 'dizziness during panic attacks' but not the occurrence of otoneurological abnormalities, predicted the occurrence of clinical worsening at the start of treatment. A specific pattern of otoneurological abnormalities was not found, but only three patients had normal results in all three sessions. The inconsistent test results suggest that functional vestibular pathology is frequently associated with panic disorder.