A rat model of distractibility: effects of drugs modifying dopaminergic, noradrenergic and GABAergic neurotransmission.

A procedure for analyzing effects of drugs on distractibility is proposed. Rats are trained to traverse a straight runway with a sucrose solution as reinforcement. Once the response has been acquired, an additional runway ending in an empty box is connected. The time spent investigating this additional runway is the measure of distractibility. Amphetamine, 1 mg/kg i.p., increased distractibility. In rats that were never reinforced, amphetamine at a dose of 1 mg/kg reduced the time spent in the additional runway. This shows that the effects of amphetamine in the reinforced animals cannot be interpreted as enhanced exploration. Furthermore, the benzodiazepines diazepam (2 and 4 mg/kg, i.p.) and chlordiazepoxide (2.5, 5 and 10 mg/kg, i.p.), known to enhance exploration of novel environments, did not affect the time spent in the additional runway in sucrose-reinforced animals. It was concluded that the procedure indeed is a model of distractibility. The dopamine antagonist cis(Z)-flupenthixol, at a dose of 0.25 mg/kg, i.p., blocked the effects of amphetamine, 1 mg/kg. Flupenthixol itself, in doses of 0.25 and 0.5 mg/kg, did not affect the time spent in the additional runway. This suggests that enhanced dopaminergic activity indeed is responsible for the effects. This proposal is further supported by experiments showing that the noradrenaline precursor dihydroxyphenylserine (10 mg/kg + carbidopa, 50 mg/kg, both i.p.) and the noradrenergic neurotoxin DSP4 (50 mg/kg, i.p.) had no effect on distractibility. Moreover, amfonelic acid, a dopamine releaser with slight or no effect on noradrenergic neurotransmission, had effects very similar to those of amphetamine when given in doses of 0.25 and 0.5 mg/kg, i.p. A lower dose, 0.125 mg/ kg, was ineffective. Taken together, these data suggest that enhanced dopaminergic neurotransmission increases distractibility in the rat. However, both amphetamine and amfonelic acid may stimulate serotonin release. Until serotonergic drugs have been tested, a contribution of this transmitter cannot be ruled out. The distraction procedure may constitute an animal model of some kinds of disordered information processing.

Central nervous stimulants facilitate sexual behavior in male rats with medial prefrontal cortex lesions.

Male rats with lesions of the cerebral cortex near the midline in the frontal region destroying most of the cingulate cortex and producing some damage to adjacent frontal areas have very long mount and intromission latencies. Otherwise their sexual behavior is essentially normal. The dopamine releasers amfonelic acid, 0.5 mg/kg, and amphetamine, 1 mg/kg, reduced the mount and intromission latencies in males with such lesions. Caffeine, 30 mg/kg, had similar effects. None of the drugs modified sexual behavior in intact males. It has been suggested that medial prefrontal lesions reduce the animal's reactivity to environmental stimuli, and hence renders the activation of sexual behavior difficult. Present results show that stimulant drugs are capable of compensating for this reduced reactivity. The possible mechanisms behind this effect are discussed. The lesion had also a small but consistent effect on the intromission ratio, suggesting some motor impairment. The effect on intromission ratio was not reduced by the drugs, suggesting that the lesion's motor consequences are mediated by mechanisms different from those controlling behavioral reactivity. The noradrenaline precursor dl-threo-dihydroxyphenylserine, 10 mg/kg, in combination with carbidopa, 50 mg/kg, increased mount and intromission latencies in both intact and lesioned males. Thus, activation of noradrenergic neurotransmission had effects opposite to those found after activation of dopaminergic transmission. Noradrenergic stimulation cannot, therefore, be important for the effects of amphetamine or amfonelic acid.

Antibiotic resistance of Pseudomonas species.

Pseudomonas species are highly versatile organisms with genetic and physiologic capabilities that allow them to flourish in environments hostile to most pathogenic bacteria. Within the lung of the patient with cystic fibrosis, exposed to a number of antimicrobial agents, highly resistant clones of Pseudomonas are selected. These may have acquired plasmid-mediated genes encoding a variety of beta-lactamases or aminoglycoside modifying enzymes. Frequently these resistance determinants are on transposable elements, facilitating their dissemination among the population of bacteria. Mutations in chromosomal genes can also occur, resulting in constitutive expression of normally repressed enzymes, such as the chromosomal cephalosporinase of Pseudomonas aeruginosa or Pseudomonas cepacia. These enzymes may confer resistance to the expanded-spectrum beta-lactam drugs. Decreased cellular permeability to the beta-lactams and the aminoglycosides also results in clinically significant antibiotic resistance. The development of new drugs with anti-Pseudomonas activity, beta-lactam agents and the quinolones, has improved the potential for effective chemotherapy but has not surpassed the potential of the organisms to develop resistance.

Infecçäo urinária näo complicada: eficácia de norfloxacin em esquema de 72 horas: importância da pesquisa de bactérias revestidas por anticorpos / Non-complicated urinary infection: efficiency of norfloxacin in scheme of 72 hours; importance of the research of coated bacterias by antibodies

Foram analisadas 40 mulheres com sintomas de infecçäo urinária e tratadas com norfloxacin 400 mg a cada 12 horas, por 72 horas. Dezoito pacientes (45%) tiveram cultura de urina positiva e, destas, seis tinham pesquisa de bactérias revestidas de anticorpos positiva. Uma semana após o tratamento, apenas uma paciente permaneceu com cultura de urina positiva. O índice de cura para 18 casos submetidos a tratamento com norfloxacin por três dias foi de 94,4% e a incidência de efeitos colaterais foi de 2,5%

O norfloxacin no tratamento de infecçöes urinárias causadas por Pseudomonas aeruginosa / The norfloxacin in the treatment of urinary tract infections caused by Pseudomonas aeruginosa

Tratam-se com norfloxacin 20 pacientes adultos com infecçäo urinária causada por Pseudomonas aeruginosa. Muitos destes pacientes apresentaram fatores prognósticos negativos, como processos obstrutivos, litíase e cateterismo vesical. O medicamento foi administrado por via oral, na dose de um comprimido de 400 mg cada 12 horas, por 10 dias consecutivos. Controles de cura foram efetuados após cinco e 30 dias do final do tratamento, e todos os pacientes foram cuidadosamente observados no sentido de detectar possíveis efeitos colaterais da droga. Obtiveram cura 11 indíviduos (55%), quatro (20%) revelaram recaída no segundo exame de controle e somente em cinco (25%) houve falha terapêutica completa. Näo foram observados efeitos colaterais em qualquer um dos pacientes. Conclui-se ser este novo medicamento bastante promissor, pois permite o tratamento de infecçöes urinárias pelo bacilo piociânico por via oral, com excelente tolerância, e resultados considerados bons para este tipo de agente e pelas circunstâncias frequentemente associadas com seu aparecimento como agente etiológico de infecçöes do trato urinário

Estudio "in vitro" sobre la susceptibilidade a norploxacina y ácido nalidíxico de 200 cepas bacterianas / In vitro study of the susceptibility to norfloxazine and nalidixic acid of 200 bacterial strains

Con objetivo de evaluar la susceptibilidad in vitro de los gérmenes patógenos asilados con mayor frecuencia, así como investigar la incidencia de su resistencia natural, en el Hospital Universitario de la ciudad de Monterrey se llevó a cabo un estudio comparativo entre norfloxacina y ácido nalidíxico, en 200 cepas bacterianas procedentes de diferentes salas del hospital, en un periodo de 12 semanas. Los principales gérmenes identificados correspondieron, en primer lugar (55%) a E. coli, Klebsiella y Pseudomona; en segundo (30%): Enterobacter, Proteus indolnegativo y Staphylococus; en menor cantidad (15%). Serratia, Proteus indolpositivo, Providence, Acinobacter, Citronacter, Morganella y Alcaligenes. A una concentración mínima inhibitoria (CMI) <= 3.9 mcg, las cepas mostraron 90.5% de susceptibilidad a norfloxacina, y a esta misma concentración, sólo 21.5% de las cepas fueron inhibidas por ácido nalidíxico En este estudio se confirma que la norfloxacina es significativamente superior al ácido nalidíxico, en su acción sobre las bacterias más comuns en este hospital