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.     

Etoposide in the treatment of six children with Langerhans cell histiocytosis (histiocytosis X)

Six children received etoposide as the single agent for treatment of Langerhans cell histiocytosis (LCH; histiocytosis X). Five were less than 2 years old at diagnosis. All had multiorgan involvement; one had liver and pulmonary dysfunction. Two infants also had clinical signs of immune deficiency. Complete response was observed in five. There was no major toxicity. Although three of four evaluable patients relapsed, the drug was considered useful in moving the children from a symptomatic to an asymptomatic clinical status. Etoposide may become a "first-line" drug in the treatment of systemic LCH, especially when the side effects of steroid therapy are considered unacceptable.     

The most frequent neurologic disturbances. A contribution to the definition of topics for the programmatic content to the program of neurology in medical graduation

INTRODUCTION: Knowledge accumulation is overfilling the thematic content of medical graduation. Medical Schools must be alert to define a minimal content related with the most frequent disturbs. We intent to suggest topics for the minimal content, to the program of Neurology in medical graduation. METHOD: 1. To identify the places where young doctors are working outside the School Hospital (SH): we analysed the answers of the letters sent to 6415 resident - doctors (RD) in S?o Paulo's State and we made personal interview with 201 RD. 2. To verify the most frequent neuropsychiatric disturbs (ND) in the population: we made the analysis of the patient's diagnostic records in emergency room of three institutions: Municipal of Taubaté-SP, Municipal of S?o José dos Campos-SP and Faculty of Medicine of S?o Paulo Santa Casa de Misericórdia. RESULTS: 1. The RD are young and, outside the SH, they work in other emergency services. 2. The most frequent diagnosis in institutions were listed: alcoholism, cerebrovascular disease, coma, cranial trauma, dementia, dizziness, epilepsy, facial paralysis, faint, headache, hemiplegia or paraplegia, meningitis, others paralysis, periferical neuropathy and psychiatric disorders. CONCLUSIONS: Those diagnostics most frequent are relevant topics of the programmatic content to the program of Neurology in medical graduation.     

Carpal tunnel syndrome: controversies regarding clinical and electrodiagnosis and its work-relatedness

The diagnosis of carpal tunnel syndrome (CTS) may be difficult because paresthesias and tingling in the upper limbs are commonly reported in the general population. These symptoms are poorly correlated with changes of nerve conduction studies of the median nerve. CTS should be diagnosed only when typical symptoms are associated with significant electrophysiological abnormalities. The association of CTS with work is highly controversial.     

The effects of hand preference and gender on finger tapping performance asymmetry by the use of an infra-red light measurement device

We used an infra-red device to study the effects of gender and handwriting preference on manual asymmetry in tapping rate and intertap variability. Our sample (n=102) consisted of approximately equal number of subjects with respect to gender (52 women and 50 men) and handedness (52 right-handers and 50 left-handers). Data on overall performance indicated that men performed more quickly and regularly than women. The index used for measuring manual asymmetry was the difference between the hands as a proportion of the total. Therefore, the asymmetry index was adjusted to remove the influence of overall performance. The analyses based on asymmetry scores indicated a significant handedness effect: right-handers showed greater manual asymmetries than left-handers for both tapping rate and intertap variability. In addition, right handers exhibited a significant greater asymmetry for intertap variability than tapping rate. Taken together, these data may reflect greater hemispheric differences in right-handers, specially for intertap variability.