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Biomedical subjects

J Castro

Publications and source records attributed to J Castro.

At least 127 records · Page 7Linked to original sources
PubMed1992

Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities.

Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.

Adolescent↗
PubMed1992

The effects of repetitive community-wide ivermectin treatment on transmission of Onchocerca volvulus in Guatemala.

The effects of biannual ivermectin treatment at the community level on transmission of Onchocerca volvulus during the dry season were measured over a 30-month period in Guatemala. In the Los Tarrales Transmission Zone, an area encompassing three villages, significant changes occurred in both the prevalence and quantity of infection in the Simulium ochraceum vector population. These included a 76% reduction in females with infective stage larvae (L3S) and an 80% reduction in number of L3S per 1,000 parous flies. Significant reductions in both the mean infective biting density (IBD) and mean transmission potential (TP) also occurred. In Santa Emilia, the prevalence of infection with L3S in S. ochraceum was significantly reduced by 77% from the baseline value. The number of O. volvulus L3S per 1,000 parous flies was also reduced by 92%. Changes in both the IBD and TP were substantial but not significant due to the high degree of variance in the occurrence of O. volvulus L3S in the vector population. This was due, in part, to the movement of infected migrant workers into the finca (coffee farm). In Los Andes, four recurrent treatments successfully blocked transmission of infective stage larvae. Prevalence (flies with all stages of developing larvae) in the vector population was reduced by 89% over the two-year period; yearly reductions in both the IBD and TP were also highly significant, ultimately ending in zero values. This finding is particularly striking since prior to treatment, Los Andes exhibited the highest IBD of the three study locations and the second highest TP.

Animals↗
PubMed1991

Condition: critical.

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Cost Control↗
PubMed1991

Okadaic acid stimulates carnitine palmitoyltransferase I activity and palmitate oxidation in isolated rat hepatocytes.

Okadaic acid parallely increased carnitine [corrected] palmitoyltransferase I activity and the rate of palmitate oxidation in isolated rat hepatocytes. Nevertheless, okadaic acid had no significant effect on the rate of octanoate oxidation. Maximal effects of okadaic acid were similar and non-additive to those of dibutyryl-cAMP, forskolin and glucagon. Results indicate that carnitine palmitoyltransferase I activity may be controlled by a mechanism of phosphorylation/dephosphorylation.

Animals↗
PubMed1991

Properties of the mitochondrial membrane and carnitine palmitoyltransferase in the periportal and the perivenous zone of the liver. Effects of chronic ethanol feeding.

Rats were fed for 35 days a high-fat diet containing either 36% of total calories as ethanol (ethanol group) or an isocaloric amount of carbohydrate (control group). Then, mitochondria were isolated from the periportal and the perivenous zone of the liver in order to study the acinar heterogeneity of the effects of prolonged ethanol administration upon the properties of carnitine palmitoyltransferase I (CPT-I) and its membrane environment. Chronic ethanol ingestion selectively decreased CPT-I activity in periportal hepatocytes but equally increased enzyme sensitivity to malonyl-CoA and enzyme energy of activation in the two zones of the liver. In control animals, mitochondrial membrane showed higher fluidity and lower degree of saturation of phospholipid fatty acyl moieties in periportal than in perivenous hepatocytes. Prolonged ethanol feeding (i) decreased mitochondrial membrane fluidity; (ii) increased the proportion of palmitic acid and decreased that of arachidonic acid in mitochondrial phosphatidylcholine and phosphatidylethanolamine, whereas it drastically reduced the content of linoleic acid and concomitantly increased that of saturated and monoenoic fatty acids in cardiolipin; (iii) suppressed the disordering effects of the addition of ethanol to mitochondrial suspensions. All these ethanol-induced alterations of membrane fluidity and fatty acyl composition were not significantly different between periportal and perivenous mitochondria. In conclusion, chronic ethanol feeding changes the activity of CPT-I in a zone-selective manner but modifies both the regulatory properties of the enzyme and the properties of its lipid environment in a non-zone-selective manner. Hence factors in addition to the properties of the mitochondrial membrane seem to be involved in the ethanol-induced alterations of the CPT-I enzyme.

Administration, Oral↗
PubMed1991

Treatment with anabolic steroids increases the activity of the mitochondrial outer carnitine palmitoyltransferase in rat liver and fast-twitch muscle.

Treatment of male rats with the anabolic steroids fluoxymesterone or methylandrostanolone increased the activity of the outer carnitine palmitoyltransferase in liver and fast-twitch muscle mitochondria. This effect was not potentiated by physical exercise and was not observed in heart and slow-twitch muscle mitochondria. Anabolic steroids did not affect the sensitivity of the liver enzyme to inhibition by malonyl-CoA. The data presented herein suggest that androgens may have an important physiological role in the regulation of fatty acid oxidation in liver and fast-twitch muscle mitochondria. In addition, our results are at odds with the notion that (most of) the metabolic effects of anabolic steroids on muscle are only evident when physical training is parallely performed.

Anabolic Agents↗
PubMed1991

Adjuvant treatment in stage I and II malignant melanoma: a randomized trial between chemoimmunotherapy and immunotherapy.

A randomized trial comparing chemoimmunotherapy (bacillus Calmette-Guérin + chemotherapy) and immunotherapy (bacillus Calmette-Guérin alone) was carried out in high-risk stage I and II malignant melanoma patients. Eight-two evaluable patients were included. The follow-up median duration was 11 years. Recurrent melanoma developed in 28 patients (34%). The overall survival rate was 76% at 5 years and 65% at 10 years. There were no statistical differences in survival probability or disease-free survival (DFS) probability between the two treatment groups. Survival and DFS were also analyzed in relation to various prognostic factors. Statistically significant differences were only seen in a subset of 33 patients with lower limb malignant melanoma, the prognosis being better for the chemoimmunotherapy group in this location. Because of the small number of patients in each group, a week positive effect of either of these two treatments cannot be ruled out. Chemoimmunotherapy only seems to improve the prognosis of stage I or II malignant melanoma of the legs.

Adult↗
PubMed1991

Comparison of the effects of a single dose and of four six-monthly doses of ivermectin on adult Onchocerca volvulus.

Adult Onchocerca volvulus worms, extracted from nodules of Guatemalans by collagenase digestion, were examined whole and by histological techniques. One group of persons received a single 150 micrograms/kg dose of ivermectin; two other groups (one with older and one with younger nodules) received four similar doses of ivermectin at 6-month intervals. For each group, there were comparable untreated controls. All nodules were removed six months after the last dose. After a single dose, the only significant difference from the controls was in the decreased proportion of female worms producing live microfilariae. After four doses, there were significant increases in the proportions of moribund/dead female worms and of live uninseminated females, when compared with the corresponding controls. There were also fewer male worms present, but this difference was not significant. Six months after the conclusion of the 4-dose regimen, the proportion of female worms producing live microfilariae was significantly lower than in the groups that had received a single dose.

Animals↗
PubMed1990

Simultaneous stimulation of fatty acid synthesis and oxidation in rat hepatocytes by vanadate.

When added to the hepatocyte incubation medium, vanadate increased the rate of fatty acid synthesis de novo as well as the activity of acetyl-CoA carboxylase, whereas it had no effect on the activity of fatty acid synthase. On the other hand, and despite elevating the intracellular levels of malonyl-CoA, vanadate diverted exogenous fatty acids into the oxidation pathway at the expense of the esterification route. This was concomitant to an increase in carnitine palmitoyltransferase I activity. All these effects were not significantly different between periportal and perivenous hepatocytes and were also evident in cells incubated in Ca2(+)-free medium. Nevertheless, Ca2+ ions enhanced carnitine palmitoyltransferase I activity in isolated liver mitochondria. In addition, the effects of vanadate on acetyl-CoA carboxylase and carnitine palmitoyltransferase I were only evident in a permeabilized-cell assay, disappearing upon cell disruption and isolation of the corresponding cell subfraction for enzyme assay. Results show that vanadate exerts specific insulin-like and non-insulin-like effects on hepatic fatty acid metabolism, and suggest that the intracellular concentration of malonyl-CoA is not the only factor responsible for the regulation of the fatty-acid-oxidative process in the liver.

Acetyl-CoA Carboxylase↗
PubMed1990

[Primary malignant melanoma of the skin. Retrospective study of 375 cases. Clinical aspects and histology].

The clinical and histologic features of 375 cases of primary malignant melanomas of the skin diagnosed and/or treated in the Hospital Clinic i Provincial (Barcelona, Spain) over a seven years period (1981-1987) were evaluated. The analysis of data showed many differences between these cases and those previously reported by us or from other countries. Sex incidence showed an increased frequency in women (58%), and a high incidence on lower limb in female (26% of all cases). Superficially spreading melanoma was the most common type (58%), followed by nodular melanoma (27%), acral lentiginous melanoma (8%) and lentigo maligna melanoma (6%). 57% of cases were diagnosed when the tumor thickness indicated a moderate or high-risk.

Adolescent↗
PubMed1990

Zonal heterogeneity of the effects of chronic ethanol feeding on hepatic fatty acid metabolism.

Periportal and perivenous hepatocytes were isolated from rats fed a high-fat, ethanol-containing diet to investigate the acinar heterogeneity of the effects of prolonged ethanol administration on lipid metabolism. Chronic feeding of ethanol caused a rather selective accumulation of triacylglycerols in the perivenous zone of the liver. In control animals the rate of lipogenesis and the activity of acetyl-CoA carboxylase were higher in perivenous than in periportal hepatocytes, whereas the rate of fatty acid oxidation and the activity of carnitine palmitoyltransferase I were higher in periportal than in perivenous cells; however, no zonation was evident for very-low-density-lipoprotein-lipid secretion. Prolonged ethanol administration abolished the zonal asymmetry of the lipogenic process and inverted the acinar distribution of the fatty acid-oxidative process (i.e., in ethanol-fed animals the rate of fatty acid oxidation and the activity of carnitine palmitoyltransferase I were higher in perivenous than in periportal hepatocytes). Moreover, chronic feeding of ethanol led to a marked and selective inhibition of very-low-density-lipoprotein-triacylglycerol secretion by the perivenous zone of the liver. Nevertheless, no zonal differences were observed between control and ethanol-fed animals with respect to the effects of acute doses of ethanol and acetaldehyde on lipid metabolism. In conclusion, our results show that chronic ethanol intake produces important alterations in the acinar distribution of the different fatty acid-metabolizing pathways.

Alcohol Drinking↗
PubMed1990

Long-term results of helium ion irradiation of uveal melanoma.

Between 1978 and 1988, 307 patients with uveal melanoma were irradiated using helium ions at Lawrence Berkeley Laboratory. The length of follow-up ranged from 1-115 months (median 42 months). The 5-year actuarial treatment results were: local control rate, 96.8%, determinate survival rate, 81%, freedom from distant metastases, 76%, eye retention rate, 83%, and risk of developing neovascular glaucoma, 36%. Long-term vision outcome was analyzed in 81 patients with a minimum follow-up of 5 years. Forty-seven percent of patients retained vision of 20/200 or better. The median change in vision was a loss of four lines on the standard eye chart. Thirty-eight percent of patients had visual acuity either improve or remain within two lines of their pretreatment vision. A multivariate analysis identified tumor size as the only independently significant risk factor affecting survival, development of neovascular glaucoma, or the risk of enucleation; no risk factor correlated with local recurrence. Tumor size, tumor-fovea distance, and pretreatment visual acuity were independently significant risk factors influencing vision outcome. These results confirm that helium ion irradiation is an effective treatment for uveal melanoma which combines high rates of local control, survival, and eye retention with a substantial likelihood of long-term vision preservation.

Adult↗
PubMed1990

Alterations in the regulatory properties of hepatic fatty acid oxidation and carnitine palmitoyltransferase I activity after ethanol feeding and withdrawal.

The effects of prolonged ethanol feeding on the regulatory properties of both hepatic fatty acid oxidation and carnitine palmitoyltransferase I activity (CPT-I) were studied in rats fed a high-fat diet containing 36% of total calories as ethanol (ethanol group) or an isocaloric amount of carbohydrate (control group). Prolonged ethanol feeding progressively decreased CPT-I activity and increased enzyme sensitivity and sensitization to inhibition by malonyl-CoA in liver mitochondria. Similarly, long-term ethanol feeding progressively increased the sensitivity of CPT-I, as well as that of fatty acid oxidation, to inhibition by 4-hydroxyphenylglyoxylate. Short-term addition of ethanol or acetaldehyde to the incubations markedly increased the sensitivity of CPT-I to inhibition by malonyl-CoA in a subsequent assay in hepatocytes isolated from ethanol-treated rats, but not in cells from control animals. This effect may be mediated by the ethanol- or acetaldehyde-induced increase of intracellular malonyl-CoA levels. The present results show that ethanol feeding to rats leads to profound alterations in the regulatory properties of hepatic CPT-I, which seem to be determinant for the decreased capacity of fatty acid oxidation by the liver in this state. Nevertheless, all the above-mentioned alterations of the fatty acid oxidative system were reversible, disappearing after 2 to 4 days of ethanol withdrawal.

Acetaldehyde↗
PubMed1990

Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus.

This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted.

Animals↗
PubMed1990

[The admission and discharge criteria of a unit for critical patients].

Admission and discharge criteria for patients in an intensive care unit are controversial, especially in view of the fact that some patients derive no benefit from intensive care therapy while depriving others from a potential benefit. The general characteristics of patients in need of intensive care are discussed. Irreversibility of the underlying condition, the quality of "terminal patient" and other factors that may contraindicate admission to an intensive care unit are analyzed. Discharge criteria for patients not expected to derive further benefit from a prolonged stay in the unit are outlined.

Humans↗
PubMed1990

Ultrasonic forms of posterior staphyloma.

The most frequent deformations of the globe encountered in pediatric ophthalmology are staphylomas and colobomas. In this paper we reviewed 16 ultrasonographically diagnosed staphylomas and classified the ultrasonographic patterns produced by staphyloma cases into four types: (1) staphylomas involving the posterior pole but not the optic nerve head, (2) staphylomas involving the posterior pole and the optic nerve head, (3) peripapillary staphylomas, and (4) giant peripapillary staphylomas. Morphologic and ultrasonographic characteristics are described.

Eye Abnormalities↗
PubMed1989

Zonation of fatty acid metabolism in rat liver.

Fatty acid metabolism was studied in periportal and perivenous hepatocytes isolated by the method of Chen & Katz [Biochem. J. (1988) 255, 99-104]. The rate of fatty acid synthesis and the activity of acetyl-CoA carboxylase were markedly enhanced in perivenous hepatocytes as compared with periportal cells. However, the response of these two parameters to short-term modulation by cellular effectors such as the hormones insulin and glucagon, the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate and the xenobiotics ethanol and acetaldehyde was similar in the two zones of the liver. In addition, perivenous hepatocytes showed a higher capacity of esterification of exogenous fatty acids into both cellular and very-low-density-lipoprotein lipids. Nevertheless, no difference between the two cell sub-populations seemed to exist in relation to the secretion of very-low-density lipoproteins. On the other hand, the rate of fatty acid oxidation was increased in periportal cells. This could be accounted for by a higher activity of carnitine palmitoyltransferase I and a lower sensitivity of this enzyme to inhibition by malonyl-CoA in the periportal zone. No differences were observed between periportal and perivenous hepatocytes in relation to the short-term response of fatty acid oxidation and carnitine palmitoyltransferase I activity to the cellular modulators mentioned above. In conclusion, our results show that: (i) lipogenesis is achieved at higher rates in the perivenous zone of the liver, whereas the fatty-acid-oxidative process occurs with a certain preference in the periportal area of this organ; (ii) the short-term response of the different fatty-acid-metabolizing pathways to cellular effectors is quantitatively similar in the two zones of the liver.

Acetyl-CoA Carboxylase↗