Suitability of low-dosage oxytocin treatment to induce milk ejection in dairy cows.

Chronic use of high oxytocin (OT) dosages can cause a reduced response to endogenous OT. In this study the OT dosages used in the milking practice of 82 dairy cow farms were recorded. The OT dosages per cow used were high, especially when injected i.m. (23+/-2 IU) compared with i.v. (7+/-1 IU). In addition, the minimum OT dosages needed to obtain normal milk removal in cows with disturbed milk ejection were investigated. Seventeen cows routinely treated with OT during milking (group T) and 17 cows without previous OT treatment were used (group C). After cessation of spontaneous milk flow, both T and C groups were injected i.v. with a low dosage of OT (0.2 or 0.5 IU/cow). The time from injection until cessation of the OT-induced milk flow was recorded (response phase). The response phase and the amounts of removed milk by effect of the OT injection increased with increasing OT dosage. Values for 0.2 and 0.5 IU/cow of OT injected i.v. were (response phase and amount of milk removed) 198+/-27 and 302+/-18s and 3.4+/-0.7 kg and 6.5+/-1.3 kg, respectively, for the C group, and 157+/-15 and 221+/-16s and 3.2+/-0.5 and 5.5+/-1.0 kg, respectively, for the T group. Within 20 min of the OT injection, plasma concentrations returned to basal levels. The threshold OT concentration at cessation of milk flow after injection of 0.2 or 0.5 IU/cow of OT was calculated based on the OT plasma half-life. The threshold increased with increasing dosages of OT and was higher in group T (8+/-1 and 14+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively) than in group C (7+/-1 and 11+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively). In conclusion, desensitization of the udder toward OT occurs when the udder is exposed to elevated OT plasma concentrations, both short-term during the actual milking and long-term due to chronic high-dosage OT treatment. However, low-dosage OT treatments to induce normal milk removal can minimize the observed side effects.

Antineurotoxic activity of Galactia glaucescens against Crotalus durissus terrificus venom.

Ethanolic extract of leaves of Galactia glauscescens (GGE) at concentration of 100 and 500 microg/ml prevented the neuromuscular paralysis induced by Crotalus durissus terrificus venom on mouse phrenic nerve-diaphragm preparation.

Amplification of neuromuscular transmission by methylprednisolone involves activation of presynaptic facilitatory adenosine A2A receptors and redistribution of synaptic vesicles.

The mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A2A receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [(3)H]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A2A receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (0.3 mM)-induced transmitter release facilitation, because its effect was prevented by the A2A receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M2 and A1 receptors blocked by methoctramine (0.1 µM) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A2A receptors by endogenous adenosine leading to synaptic vesicle redistribution.

The study of tuberculosis-attributed deaths as a tool for disease control planning in Rio de Janeiro, Brazil.

SETTING: Two tuberculosis (TB) reference hospitals and three general hospitals in Rio de Janeiro (RJ). OBJECTIVE: To analyze TB-attributed deaths as a tool for evaluating the TB control program in RJ. DESIGN: Retrospective study based on 302 medical records selected from the 1998 death database. RESULTS: Of 1146 registered adult (>14 years) TB-attributed deaths in RJ, 328 occurred in five hospitals, and 302 records were analyzed. Median age was 47.5 (17-89) years; 237 (78.5%) were male. Median time elapsed from onset of symptoms until diagnosis was 60 (7-730) days; median hospitalization was 60 (0-517) days. Acid-fast bacilli sputum smears were performed in 200 (69%) of 290 cases of pulmonary disease. Among 32 (36%) smear-negative patients, culture was done in only one. The recommended regimen (RHZ) was used in 175 (58%). Among 125 re-treatment patients, 55 (44%) were on RHZ instead of RHZE. Notification to health authorities was recorded in 131 (43.4%) cases. CONCLUSION: In RJ, young people die from TB. Major issues identified in the public health system were poor detection and notification and a high default rate, perpetuating the spread of TB. Treating professionals do not follow guidelines, and political commitment is needed to ensure TB control in the state and in the country.

Neurological teleconsultation for general practitioners.

A neurology teleconsulting network was implemented between a university hospital in Lisbon and five nearby health centres. PCs equipped for videoconferencing were installed, connected by ISDN lines at 128 kbit/s. Fifty-three general practitioners (GPs) were surveyed. The survey showed that the GPs had difficulties in using computers, but they had definite intentions to use teleconsultation for neurology cases and 83% of the respondents stated that they would probably use the technique. During the study, 90 neurology teleconsultations took place over 55 weeks. The average consultation rate was 1.6 teleconsultations per week (SD 1.3, range 0-6). The conferences lasted 10-45 min. Longer teleconsultations were mainly due to technical difficulties in using computers on the part of users with a low level of computer literacy. The patients were 42 males and 46 females, with a mean age of 38 years (SD 20, range 1-84); two patients were discussed twice. The benefits consisted mainly of advice on patient medication, diagnosis and the prevention of unnecessary specialist consultations or laboratory examinations. Doctor-doctor teleconsultation allows the rapid resolution of queries which otherwise cause stress to patients and increase the cost and complexity of care.

Polymorphisms at the five exons of the growth hormone gene in the algarvia goat: possible association with milk traits.

The present preliminary study attempts to establish associations between milk production traits and genetic polymorphisms at the GH gene in the Algarvia goat. The DNA of 108 goats of the indigenous Portuguese Algarvia breed was evaluated. Single-strand conformation polymorphisms (SSCP) were identified at the five exons of the goat growth hormone (gGH) gene. Two conformational patterns were found in each of exons 1 and 2, four in exon 3, six in exon 4 and five in exon 5. An association between these SSCP patterns with milk, fat and protein production, and fat and protein content was examined. Patterns F/F of exon 4 and A/A of exon 5 were positively associated with milk production (P<0.05). The results demonstrated that the gGH gene could be exploited as a candidate gene for marker-assisted selection in goat breeds.

[Teleconsulta en neurology in a health unit: preliminary approach]. / Teleconsulta em neurologia na unidade de saúde a: abordagem preliminar.

This paper begins by discussing the influence of neurological diseases in the practice of general practitioners. A thorough review of the literature allows us to conclude that the frequency of neurological complaints in general practice varies between 7% and 15% and that complaints of sleep disorders reach about 26% in those cases. However, general practitioners do not refer all these neurological cases to a neurologist. They screen the cases and refer only 9% of all observed patients. Next, we briefly analyse the impact of telemedicine in general practice. Given this technique's novelty, we present a predictive model for the utility of teleconsultation, which we are currently developing and testing. We then summarise the current status of general practitioners' referrals to our hospital's neurological outpatient clinic, given previous measures that targeted waiting list reduction and adequate referral. After this overview, we present our methodology, which includes the development and implementation of the technologies needed for teleconsultation and the discussion and application of medical protocols for clinical data, benefits and costs. Simultaneously, we investigated the real need for teleconsultation in Neurology according to the literature and to several, more or less optimistic, models of acceptance. Based on this method, teleconsultation began its regular operation in July 1998. We discuss the result of the first 14 weeks of operation. We observed that referral developed according to calculated predictions and that there were clear advantages regarding diagnostics, medication, exam requests, cost avoidance and patient trips to the central hospital. The data collected predicts that this method is useful, efficient and able to substantially reduce costs.

Neuromuscular activity of BaTX, a presynaptic basic PLA2 isolated from Bothrops alternatus snake venom.

We have previously isolated a Lys49 phospholipase A(2) homolog (BaTX) from Bothrops alternatus snake venom using a combination of molecular exclusion chromatography and reverse phase HPLC and shown its ability to cause neuromuscular blockade. In this work, we describe a one-step procedure for the purification of this toxin and provide further details of its neuromuscular activity. The toxin was purified by reverse phase HPLC and its purity and molecular mass were confirmed by SDS-PAGE, MALDI-TOF mass spectrometry, amino acid analysis and N-terminal sequencing. BaTX (0.007-1.4 microM) produced time-dependent, irreversible neuromuscular blockade in isolated mouse phrenic nerve-diaphragm and chick biventer cervicis preparations (time to 50% blockade with 0.35 microM toxin: 58+/-4 and 24+/-1 min, respectively; n=3-8; mean+/-S.E.) without significantly affecting the response to direct muscle stimulation. In chick preparations, contractures to exogenous acetylcholine (55 and 110 microM) or KCl (13.4 mM) were unaltered after complete blockade by all toxin concentrations. These results, which strongly suggested a presynaptic mechanism of action for this toxin, were reinforced by (1) the inability of BaTX to interfere with the carbachol-induced depolarization of the resting membrane, (2) a significant decrease in the frequency and amplitude of miniature end-plate potentials, and (3) a significant reduction (59+/-4%, n=12) in the quantal content of the end-plate potentials after a 60 min incubation with the toxin (1.4 microM). In addition, a decrease in the organ bath temperature from 37 degrees C to 24 degrees C and/or the replacement of calcium with strontium prevented the neuromuscular blockade, indicating a temperature-dependent effect possibly mediated by enzymatic activity.

Children and adolescents infected with Wuchereria bancrofti in Greater Recife, Brazil: a randomized, year-long clinical trial of single treatments with diethylcarbamazine or diethylcarbamazine-albendazole.

In filariasis-endemic areas beyond sub-Saharan Africa, the World Health Organization's recommended strategy for interrupting transmission of the causative parasites is annual, single-dose, mass treatment with a combination of diethylcarbamazine (DEC; given at 6 mg/kg) and albendazole (ALB; given at 400 mg) for 4-6 years (the minimum estimated life-span of the adult parasites). In an open, hospital-based, randomized and controlled trial, with a blinded evaluation of outcome, 82 children and adolescents from Recife, all with Wuchereria bancrofti microfilaraemias, were given either DEC alone (6 mg/kg) or the same dose of DEC combined with ALB (at 400 mg/patient). Every 90 days for 1 year after the single treatment, each patient was checked for microfilaraemia by the filtration of up to 5 ml of venous blood collected at night. One year post-treatment, 16 (39%) of the 41 patients given DEC alone and 20 (49%) of the 41 given DEC-ALB were found microfilaraemic (relative risk=0.8, with a 95% confidence interval of 0.49-1.31) and the corresponding geometric mean levels of microfilaraemia were 2.0% and 1.8% of the levels recorded immediately pre-treatment, respectively (P>0.05). In terms of the prevalences and intensities of microfilaraemia, therefore, the addition of ALB to the DEC appeared to offer no significant benefit.

Ophthalmic and anesthetic evaluation of topical 1 percent tetracaine and 0.5 percent proparacaine in dogs / Ação anestésica e oftálmica da administração de colírio de tetracaína 1 por cento e proparacaína 0,5 por cento em cães

The aim of this study was to establish the action of 1 percent tetracaine eye drops in combination with 0.1 percent phenylephrine in two different posologies and their effects on the eye compared to the 0.5 percent proparacaine drops in dogs. 22 animals were divided into two groups: TG (11 animals), received 1 percent tetracaine associated with 0.1 percent phenylephrine eye drops, one drop instilled in the left eye and two drops, with one-minute interval between each, instilled in the right eye; PG (11 animals) received 0.5 percent proparacaine eye drops following the same dosage. The average duration of the observed anesthetic action was 25 minutes for tetracaine and 15 minutes for proparacaine. The instillation of two drops increased anesthetic time in five minutes. No changes in intraocular pressure, pupil diameter and tear production was observed. The drops of tetracaine triggered chemosis in four (36.4 percent) animals. Topical anesthesia with proparacaine eye drops showed no adverse reactions and is thus recommended preferentially.

Estudou-se a ação do colírio de tetracaína 1 por cento, em associação com a fenilefrina 0,1 por cento em duas posologias diferenciadas, bem como seus efeitos oculares, comparando-a com a do colírio de proparacaína 0,5 por cento em cães. Vinte e dois animais foram separados em dois grupos. Os do GT (n=11) receberam colírio de tetracaína 1 por cento associada à fenilefrina 0,1 por cento, sendo uma gota instilada no olho esquerdo e duas gotas, com intervalo de um minuto entre cada, instiladas no olho direito; e os do GP (n=11), receberam colírio de proparacaína 0,5 por cento seguindo a mesma posologia. A média de duração da ação anestésica observada foi de 25 minutos para a tetracaína e 15 minutos para a proparacaína. A instilação de duas gotas aumentou o tempo anestésico em cinco minutos. Não ocorreram alterações na pressão intra-ocular, no diâmetro pupilar e na produção lacrimal. O colírio de tetracaína desencadeou quemose em quatro (36,4 por cento) animais. Na anestesia tópica do olho com proparacaína não ocorreram reações adversas sendo, assim, recomendada preferencialmente.

Mutagenicity induced by the hydroalcoholic extract of the medicinal plant Plathymenia reticulata Benth

Plathymenia reticulata Benth has an anti-inflammatory effect and is capable of neutralizing the neuromuscular blockade induced by Bothrops jararacussu or Crotalus durissus terrificus venoms, probably by precipitating venom proteins (an effect caused by plant tannins). The present study aimed to evaluate the mutagenic activity of P. reticulata by using the Salmonella mutagenicity assay (Ames test) and the micronucleus test in CHO-K1 cells. P. reticulata extract concentrations of 2.84, 5.68, 11.37, and 19.90 mg/plate were assayed by the Ames test using TA97a, TA98, TA100 and TA102 bacterial strains, with (+S9) and without (-S9) metabolic activation. Concentrations of 5, 1.6 and 0.5 ìg/mL of P. reticulata extract were used for the micronucleus test. P. reticulata extract was mutagenic to TA98 (-S9) and showed signs of mutagenic activity in TA97a and TA102 (both -S9) strains. Micronucleus test CBPI values showed that the endogenous metabolic system increased the number of viable cells when compared to the non-activated samples and the micronucleus frequency increased when the cells were treated in the absence of S9. We concluded that P. reticulata extract may present direct mutagenic properties.

Neuromuscular activity of Bothrops neuwiedi pauloensis snake venom in mouse nerve-muscle preparations

The pharmacological effects of Bothrops neuwiedi pauloensis venom on mouse phrenic nerve-diaphragm (PND) preparations were studied. Venom (20 mug/ml) irreversibly inhibited indirectly evoked twitches in PND preparations (60 ± 10 percent inhibition, mean ± SEM; p<0.05; n=6). At 50 mug/ml, the venom blocked indirectly and directly (curarized preparations) evoked twitches in mouse hemidiaphragms. In the absence of Ca2+, venom (50 mug/ml), produced partial blockade only after an 80 min incubation, which reached 40.3 ± 7.8 percent (p<0.05; n=3) after 120 min. Venom (20 mug/ml) increased (25 ± 2 percent, p< 0.05) the frequency of giant miniature end-plate potentials in 9 of 10 end-plates after 30 min and the number of miniature end-plate potentials which was maximum (562 ± 3 percent, p<0.05) after 120 min. During the same period, the resting membrane potential decreased from - 81 ± 1.4 mV to - 41.3 ± 3.6 mV 24 fibers; p<0.01; n=4) in the end-plate region and from - 77.4 ± 1.4 to -44.6 ± 3.9 mV (24 fibers; p<0.01; n=4) in regions distant from the end-plate. These results indicate that B. n. pauloensis venom acts primarily at presynaptic sites. They also suggest that enzymatic activity may be involved in this pharmacological action.(AU)