PubMed Health⌕ Search

Biomedical subjects

A T Silva

Publications and source records attributed to A T Silva.

13 recordsLinked to original sources

Group selection models in prebiotic evolution.

The evolution of enzyme production is studied analytically using ideas of the group selection theory for the evolution of altruistic behavior. In particular, we argue that the mathematical formulation of Wilson's structured deme model [The Evolution of Populations and Communities (Benjamin-Cumings, Menlo Park, 1980)] is a mean-field approach in which the actual environment that a particular individual experiences is replaced by an average environment. That formalism is further developed so as to avoid the mean-field approximation and then applied to the problem of enzyme production in the prebiotic context, where the enzyme producer molecules play the altruists role while the molecules that benefit from the catalyst without paying its production cost play the nonaltruists role. The effects of synergism (i.e., division of labor) as well as of mutations are also considered and the results of the equilibrium analysis are summarized in phase diagrams showing the regions of the space of parameters where the altruistic, nonaltruistic, and the coexistence regimes are stable. In general, those regions are delimitated by discontinuous transition lines which end at critical points.

Enzymes↗

Trophic actions of neurotrophin-3 on postnatal rat myenteric neurons in vitro.

A number of neurotrophic factors have been implicated in the prenatal development of the enteric nervous system. Although several of these factors continue to be expressed in the gut during postnatal life, their actions on postnatal enteric neurons are not understood. One such factor is the neurotrophin, NT-3. Both NT-3 and its high affinity receptor, trk C, are expressed in the postnatal gut at a time when changes in the density of intestinal innervation are occurring. We have therefore examined the effects of NT-3 on postnatal myenteric neurons, using dissociated cell cultures of ganglia isolated from 6-8 day postnatal rat small intestine. Effects of NT-3 on neurite outgrowth and neuronal and glial cell numbers were measured after 2 days in vitro. The proportion of neurons was increased in NT-3 treated cultures, as was the proportion of neurons that extended processes. NT-3 treatment, at concentrations of between 0.1 ng and 10 ng/ml, also resulted in a significant increase in mean total neurite length. These results indicate that NT-3 may play a role in the postnatal development of the enteric nervous system.

Animals↗

[Family planning in Brazil in the context of public health policies: important historical factors].

This study searches historical records for the formulation and implementation of public health policies in Brazil, focusing on those referent to family planning. Initial conclusions show that the policies were geared toward international controlling interests. Family planning today, though officially recognized as an inalienable right of every citizen, still reflects the contradictory political, economic and ideological interests of the ruling power.

Brazil↗

[Family planning policies in João Pessoa-PB: analysis of the contradictions between official and practical discourses].

This research project's main objective is to analyze the contradictions encountered between official and practical discourses referent to family planning in public health policies in João Pessoa, PB, Brasil, using as its reference, PAISM (Program for Assistance in Women's Health). The policy was analyzed according to its official intentions and its practical use through interviews with people linked to PAISM. It was concluded that, this program is being developed under a utilitarian ideal, negating the individual citizen's right to regulate one's own fertility.

Brazil↗

Colonic transit times and the effect of lactulose or lactitol in hospitalized patients.

OBJECTIVE: To investigate whether a small dose (10 g per day) of a laxative (liquid lactulose, crystallized lactulose, or crystallized lactitol) can prevent the slow colonic transit associated with the physical inactivity of hospitalization. DESIGN: Patients were randomly allocated to one of four groups: control, liquid lactulose, crystallized lactulose or crystallized lactitol, and the average of mean colonic transit times in these groups was compared. SETTING: Gastroenterologic Unit, Hospital dos Covoes, Coimbra, Portugal. PATIENTS: Patients with normal bowel movements, admitted to hospital for the investigation of conditions not associated with constipation or diarrhoea, were allocated to one of the four treatment groups and had their mean colonic transit times studied after hospitalization using radiopaque markers and abdominal radiographs. Each study group had 18 patients. During the study, each patient was given a normal diet and no drugs except the relevant laxative. RESULTS: The average of the mean colonic transit times in each of the four groups were: 52.16 h [95% confidence interval (CI) 39.42-64.84] for controls; 22.45 h (95% CI 13.84-31.06) in the liquid lactulose group; 24.05 (95% CI 12.13-35.97) in the crystallized lactulose group; and 35.95 (95% CI 23.82-48.08) in the crystallized lactitol group. The differences were statistically significant for the two lactulose groups. The study of the mean colonic regional transit times showed that these differences related to transit in the right colon. CONCLUSIONS: A small dose of lactulose (either liquid or crystallized) was effective in preventing slow colonic transit and constipation in hospitalized patients without causing unwanted symptoms. The slow transit affected mainly the right colon, and it was in this region that the laxative had effect.

Adult↗

Effect of anti-TNF-alpha treatment in an antibiotic treated murine model of shock due to Streptococcus pyogenes.

Experimentally, Gram-negative septic shock can be prevented by the prophylactic use of an anti-TNF-alpha monoclonal antibody. The clinical similarity between Gram-negative and Gram-positive septic shock suggested that anti-TNF-alpha therapy might have a wide application. Increased levels of TNF-alpha were seen in a murine model of septic shock due to Streptococcus pyogenes but administration of an anti-TNF-alpha monoclonal antibody had no beneficial effect on the outcome.

Animals↗

Observations on the role of tumor necrosis factor-alpha in a murine model of shock due to Streptococcus pyogenes.

OBJECTIVE: To examine the effect of a monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) in a murine model of shock due to Streptococcus pyogenes. DESIGN: Prospective, multiexperimental, randomized, controlled trial. SETTING: University hospital research laboratory. INTERVENTIONS: An LD90 murine model of Gram-positive shock using S. pyogenes, associated with the presence of significant concentrations of TNF-alpha in the circulation. Prophylactic administration of antibody with concomitant saline controls. A 500-micrograms TN3-19.12 (hamster monoclonal antibody to recombinant murine TNF), or saline, by intravenous injection was administered. MEASUREMENTS AND MAIN RESULTS: Administration of 0.3 mL of 6 x 10(8) colony-forming units/mL of S. pyogenes H250 to mice resulted in 90% to 100% mortality rates in 72 hrs. Serum TNF-alpha concentrations peaked at 2 hrs after bacterial challenge and were 67.7 +/- 18.6 ng/mL. Treatment with anti-TNF-alpha monoclonal antibody abolished the serum TNF-alpha concentrations but did not affect the mortality rate. Serum endotoxin concentrations were < 50 pg/mL before challenge and at 0.5, 1, 2, 5, and 24 hrs after challenge. CONCLUSIONS: Pretreatment with an anti-TNF monoclonal antibody was not protective in this model of S. pyogenes sepsis, despite the presence of significant amounts of TNF in the circulation. These data suggest that TNF-alpha may not play such a crucial role in the pathogenesis of shock due to S. pyogenes.

Animals↗

Role of interferon-gamma in experimental gram-negative sepsis.

To study the role of interferon-gamma (IFN-gamma) in gram-negative shock, mortality was compared in mice receiving either a monoclonal antibody to IFN-gamma (H22) or an irrelevant monoclonal antibody (L2-3D9) before or after an LD90 dose of Escherichia coli O111:B4. H22 given either 1 h before or 0.5 h after bacterial challenge protected mice from death (mortality at 48 h, 28% vs. 83%, P less than .001). Serum tumor necrosis factor-alpha (TNF alpha) levels and bacterial counts in blood and organs (liver, spleen, heart, and brain) were similar in H22-treated animals and controls. The peak serum TNF alpha levels were 95.7 +/- 16.4 ng/mL and 80.7 +/- 14.9 ng/mL in the H22 and control groups, respectively. These results indicate that IFN-gamma plays a significant role in the pathogenesis of gram-negative sepsis.

Animals↗

Prophylactic and therapeutic effects of a monoclonal antibody to tumor necrosis factor-alpha in experimental gram-negative shock.

A monoclonal antibody to recombinant murine tumor necrosis factor-alpha (TNF alpha), TN3-19.12, was used to explore pathogenetic mechanisms and therapeutic strategies in gram-negative shock. In mice receiving an LD90 dose of Escherichia coli O111, TN3-19.12 prevented death if given 1.5 h before or 30 min after challenge. Less protection was conferred if the antibody was given 2.5 h after challenge. In control mice receiving an irrelevant antibody, L2-3D9, TNF alpha levels rose (less than or equal to 185.1 +/- 26.1 ng/ml) by 90 min and had returned to baseline by 5 h. Mice receiving TN3-19.12 did not have this response. TN3-19.12 was of limited benefit in mice receiving Pseudomonas aeruginosa but had no protective effect in cyclophosphamide-treated mice receiving Klebsiella pneumoniae. In L2-3D9-treated mice, TNF alpha levels were elevated to 61.8 +/- 27.9 and 49.7 +/- 5.1 ng/ml by 90 min in the two models, respectively. TNF alpha levels in TN3-19.12-treated mice in these two models were very low (3.9-5.5 ng/ml). TNF alpha is a mediator in gram-negative shock; antibody to TNF alpha can be of value in prophylaxis and treatment, but its clinical use remains to be established.

Animals↗

Monoclonal antibody to endotoxin core protects mice from Escherichia coli sepsis by a mechanism independent of tumor necrosis factor and interleukin-6.

To study the role of cytokines as mediators of endotoxin-induced shock, the serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were compared in mice receiving either a monoclonal antibody to endotoxin core (clone 20), an irrelevant monoclonal antibody (A1), or culture media (DMEM/FCS) alone before lethal challenge with live Escherichia coli O111:B4. Clone 20 given 1.5 h before the bacterial challenge protected mice from death (mortality at 48 h 3% vs. 87%, P less than .001). The pattern of IL-6 release was indistinguishable in clone 20 recipients and controls: The area under the curve (AUC) for 5 h was 1.22 +/- 0.07 x 10(6), 1.03 +/- 0.17 x 10(6), and 1.22 +/- 0.07 x 10(6) units/ml for clone 20, A1, and DMEM/FCS, respectively. Similarly, the timing and extent of TNF release in the serum was virtually identical in clone 20 recipients that survived and control animals that died. AUC for 5 h was 30.8 +/- 4.0 x 10(3), 28.1 +/- 1.1 x 10(3), and 30.4 +/- 4.7 x 10(3) ng/ml in clone 20, A1, and DMEM/FCS recipients, respectively. Thus, TNF and IL-6 appear insufficient to cause death in this model of experimental gram-negative shock.

Animals↗

Effect of dietary lithium on cortical spreading depression.

The influence of lithium administration on cortical spreading depression (SD) was investigated in rats whelped by dams fed a diet containing lithium (1.5 g/kg) during the gestation or the lactation periods. Velocity of SD propagation was measured when the rats became adults and was similar to that of rats raised on a normal diet. A third group of adult rats received lithium during the three weeks preceding SD recordings and presented a significant reduction in SD velocity as compared to control rats. These data suggest that in adult rats a brief treatment with lithium impairs SD propagation, whereas much earlier treatment does not.

Animals↗

Use of particle-bound microbial enzyme activity to predict the rate and extent of fibre degradation in the rumen.

A method was developed for extracting enzymes from micro-organisms closely associated with ammonia-treated straw (NH3-S) that had been incubated in nylon bags in the rumen. Incubation of washed straw with 125 ml carbon tetrachloride/l and 20 micrograms lysozyme/ml for 3 h at 37 degrees gave carboxymethylcellulase (EC 3.2.1.4; CMCase) and NAD-linked glutamate dehydrogenase (EC 1.4.1.2; GDH) activities greater than those extracted by sonication. GDH associated with NH3-S increased with incubation time and was highest in sheep receiving a high-barley diet. Particle-bound CMCase activity reached a peak between 16 and 24 h and declined thereafter. Particle-bound GDH activity showed no correlation with dry matter (DM) degradation in the rumens of sheep fed on a range of diets. In contrast, CMCase activity after 24 h was highly correlated with DM degradability of the same samples at 24 h (r 0.98) and 48 h (r 0.94). It was concluded that GDH and CMCase can be used as indices of the total population of colonizing rumen micro-organisms and of the fibre-degrading population respectively, and that these enzymes can therefore be used to assess rapidly and with great sensitivity variations in the rumen environment that affect the rate of fibre breakdown.

Ammonia↗