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Biomedical subjects

F Castro

Publications and source records attributed to F Castro.

At least 55 records · Page 3Linked to original sources

Age-linked changes in the activity of enzymes of the tricarboxylate cycle and lipid oxidation, and of carnitine content, in muscles of the rat.

The activities of citrate synthase, NAD-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase were measured in homogenates of soleus, diaphragm and heart muscles of the rat, in an attempt to define potential tricarboxylate cycle activity and its response to aging. Activities were significantly decreased in 24-month animals versus 6-month controls in every case (except 2-oxoglutarate dehydrogenase in heart muscle). Age-linked decrements were greatest in the soleus and least in heart. Cytochrome oxidase was measured as an index of total respiratory chain activity and decreased significantly in each case, with the smallest decrease in the heart. Acyl-CoA dehydrogenase and 3-hydroxyacyl-Co-A dehydrogenase were measured as an index of beta-oxidative activity; the former decreased in soleus and diaphragm, the latter in soleus and heart, with the decrease in the soleus being the greater. Carnitine acetyl- and palmitoyltransferases were measured, together with the muscle content of carnitine and acylcarnitine, as determining the potential rate of entry of acyl groups into the mitochondria for oxidation. Carnitine acetyltransferase activity was decreased with age in each of the muscles, but to the greatest extent in the heart. Carnitine palmitoyltransferase was decreased in both soleus and diaphragm. Carnitine content was decreased most in the soleus and the heart and to a lesser extent in the diaphragm. It is concluded that there is a generalized decline in oxidative activity in all of these muscles with age, on the basis of wet weight; this occurs to the greatest extent in the soleus and to the least extent in the heart. There is, in addition, a specific deficiency in the ability to oxidize fatty acids, relative to other substrates, in heart muscle.

Aging↗

Effect of senescence on Ca2+-ion transport by heart mitochondria.

Both the rate of uptake of Ca2+ into isolated rat heart mitochondria and the rate of release of Ca2+ by a separate, Na+-dependent, pathway were shown to be diminished in senescence (24-month relative to 6-month animal). These processes were studied at lower concentrations of Ca2+ and loads of Ca2+ per mg of mitochondrial protein than those generally employed, and it is argued that these are more appropriate physiologically. In addition, Ca2+ release was characterized in terms of the sum of the added Ca2+ and the endogenous Ca2+ of the mitochondrial preparation; the endogenous Ca2+ content was found to be unchanged with age. The decrements in rates of transport are not caused by altered rates of substrate oxidation and are inferred to reflect decreased carrier-protein content or activity. The buffering of extramitochondrial free Ca2+ concentration by heart mitochondria was studied and found to be less than complete at mitochondrial Ca2+ loads inferred to be physiological. No change was shown in senescence, in keeping with the essentially equal age-linked decrements in the activity of mitochondrial Ca2+ uptake and release.

Aging↗

Effects of micromolar concentrations of free calcium ions on the reduction of heart mitochondrial NAD(P) by 2-oxoglutarate.

1. The reduction of mitochondrial NAD(P) by 2-oxoglutarate was monitored as a measure of 2-oxoglutarate dehydrogenase activity in its intramitochondrial locale. In the absence of ADP, steady-state reduction of NAD(P) by 0.5 mM-2-oxoglutarate in the presence of 0.5 mM-L-malate was markedly increased by extramitochondrial Ca2+, with 50% activation at pCa 6.58, when the Na+ concentration was 10 mM, the Pi concentration ws 5 mM and the added Mg2+ concentration was 1 mM. Omission of Pi resulted in 50% activation at pCa 6.77; omission of Mg2+ resulted in 50% activation at pCA greater than or equal to 7.3. 2. The activation of 2-oxoglutarate dehydrogenase could be reversed on addition of an excess of EGTA. The rate of inactivation was dependent on the concentration of Na+, with K0.5 2.5 mM, which is consistent with the rate of withdrawal of Ca2+ from the mitochondria being the limiting factor. 3. The steady-state reduction of cytochrome c by 2-oxoglutarate (0.5 mM) also showed a marked dependence on pCa in the absence of ADP; in the presence of an excess of ADP, no such effect of Ca2+ was detectable. 4. Mitochondria from the hearts of senescent rats showed an undiminished rate of dehydrogenase activation by Ca2+ but a rate of inactivation by excess EGTA that was diminished by 40%. Direct studies of Ca2+ egress with Arsenazo III confirmed a decrement in rate with old age. 5. Studies of 2-oxoglutarate dehydrogenase activity as a function of the mitochondrial context of Ca2+, as measured by atomic-absorption spectrophotometry, showed half-maximal activation at a mitochondrial content of 1.0 nmol of Ca2+/mg of protein, and saturation at 3 nmol/mg. 6. These findings support the model advanced by Denton, Richards & Chin [(1978) Biochem. J. 176, 899-906], of a control of the tricarboxylate cycle by intramitochondrial Ca2+, and demonstrate the range of mitochondrial Ca2+ content over which this may occur. In addition, they raise the possibility of a disturbance of this control mechanism in old age.

Animals↗

Schistosomiasis in the Republic of São Tomé and Principe: characterization of Schistosoma intercalatum.

This paper reports the morphological and biochemical characterization of the species of Schistosoma infecting humans in the Republic of São Tomé and Principe. The eggs are typical in shape and size of S. intercalatum, measuring on average between 174.5 microns and 189.1 microns. The eggs are voided in the faeces and not the urine of infected people. The parasite experimentally develops in several different species of Bulinus belonging to the B. forskalii group, including B. forskalii, with a minimum prepatent period of 25 d, and also in snails of the B. reticulatus group (B. wrighti); it is incompatible with snails of the B. africanus and B. truncatus/B. tropicus complex. A survey of 5 different habitats at intervals of 2 weeks over a period of one year showed that populations of B. forskalii increased during the dry period of June, July and August in 1988, and in 3 of the habitats snails were present throughout the year. Hence transmission may take place in these habitats throughout the year. Preliminary evidence suggests that water velocity is a limiting factor confining Bulinus to the north-east of the island where the terrain is less mountainous. Development of schistosomes from São Tomé was followed in experimentally infected hamsters. The cross-over point (the point at which the paired male and female worms are of the same average length) occurred at about 49 d after infection: eggs were first seen in the uteri of the female worms 48 d after infection. The parasite from São Tomé developed in sheep and produced viable eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa, Western↗

Quality assurance in anatomic pathology: automated SNOMED coding.

This case study details the set-up and implementation of the PathNet autocoder (Cerner Corporation) in a busy anatomic pathology laboratory. After initial start-up, procedures were developed to improve the system's performance. Four classes of software coding errors were identified, and an index was developed to measure the number of cases between errors (CBE). Through modifications in the program, the CBE increased sharply by the end of the six-month study period. During the last three months of the study, the efficiency of case retrieval was tested by comparing manual and electronic methods on the same reference cases. This demonstrated significant time saving and removed the variability of manual coding. The technique employed in this study may assist other institutions seeking to implement such a coding system within their respective environments.

Clinical Laboratory Information Systems↗

Optimal interval for triple-lumen catheter changes: a decision analysis.

A survey of 53 university and community hospitals revealed that 73% of the institutions had no standard policy for the replacement of triple-lumen catheters (TLCs). Since the maintenance of a TLC in place for a prolonged period may lead to infectious complications, it appeared warranted that standards of management be developed. A decision-tree model was constructed for evaluating the optimal time for changing a TLC that would minimize infection. Cost estimates and health effects at three-, five-, and ten-day change intervals were considered for catheter insertion and complications resulting from such insertion. The results suggested that prophylactic catheter changes should occur no later than every five days, provided that there are no signs of infection. However, sensitivity analysis of several variables suggested that individual institutions should establish policy timing changes based upon careful interpretation of their own data. A model was developed to assist in determining the optimal time to change a TLC based upon such data.

Catheterization, Central Venous↗

Sequential test selection in the analysis of abdominal pain.

Numerous decision-making tools exist to assist physicians in diagnosis management. However, the accuracy of available clinical information is often ambiguous or unknown and current analytical models do not explicitly incorporate judgementally defined information. A model encompassing both physician judgment and probability analysis was developed to accommodate such data. A problem requiring sequential diagnostic testing was structured utilizing the analytic hierarchy process (AHP). The case presented involved a patient complaining of upper abdominal pain who, after initial evaluation, did not need immediate surgery. Physicians were faced with identifying the optimal sequence of diagnostic testing. The criteria used for test selection included minimizing risk, patient discomfort, and cost of testing and maximizing diagnostic capability. Although at the onset the "best" test choice was unknown, the clinical picture indicated four test alternatives: upper gastrointestinal series (GI), abdominal ultrasonography (US), abdominal computed tomography (CT), and upper gastrointestinal endoscopy (END). Based upon the relative preferences of the criteria utilized, the AHP analysis indicated that upper GI series was the optimal first test. Given a negative test, posterior probabilities were calculated using Bayes' theorem, resulting in a new estimate of diagnostic capability. The AHP analysis was reiterated, identifying abdominal ultrasonography as the optimal second test. This analysis may be repeated as many times as necessary. Sensitivity analysis demonstrated that changing criteria preferences may alter the choice of tests and/or their sequence.

Abdominal Pain↗

Treatment of early-stage breast cancer in the elderly: a health-outcome-based approach.

PURPOSE: To evaluate the post-lumpectomy treatment of a nonpalpable, stage I, T1b tumor, mammographically detected, in a 74-year-old woman without comorbidities. METHODS: A Markov process, through 120 monthly cycles, was used to model patient progression through a treatment program, employing literature data and a health-outcome utility. Treatments considered were: observation; radiation totaling 5,000 cGy over six weeks; tamoxifen, 20 mg/day, for five years; simple mastectomy; and radiation therapy plus tamoxifen. Health states included absence of disease (NED), loco-regional recurrence, distant metastasis, age-sex-race (ASR)-adjusted death, cancer mortality, treatment complications, and post-mastectomy death. Transition probabilities were established from the literature. Health-state utilities were determined from the responses of health care professionals to a basic reference gamble. RESULTS: Quality-adjusted life years (QALYs) were determined to be 8.19 for radiation plus tamoxifen, decreasing to 8.04 for mastectomy, a difference of only a 0.15 years (1.8 months). Sensitivity analysis, however, showed relative stability in the ranking among treatment options. CONCLUSION: Although the model showed little difference between QALYs with the treatments, the combination of radiation and tamoxifen provides the optimal therapy for this case.

Aged↗