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Biomedical subjects

M E Cruz

Publications and source records attributed to M E Cruz.

At least 19 recordsLinked to original sources

[Cognitive disorders in an Andean community located in a cysticercosis endemic zone of Ecuador].

Mini mental state tests (MMS) were administered to 227 adults over the age of 40 years living in an Ecuadorian urban Andean community known to be an endemic zone for Taenia solium taeniasis and cysticercosis. The overall prevalence of cognitive impairment was 8.4% (19/227). The prevalence of cognitive impairment was 23.5% (8 cases) in adults over 75 years (n=34). The Hachinski ischemic score for vascular dementia was abnormal in 4 of the 19 adults (21%) exhibiting cognitive impairment. This survey highlighted a high prevalence of dementia in comparison with industrialised countries. Parasitic encephalopathy that was present in one out of five persons in this Andean community could play a part in early damage of cognitive function.

Aged↗

Ovulation delay induced by blockade of the cholinergic system on dioestrus-1, is related to changes in dopaminergic activity of the preoptic anterior-hypothalamic area of the rat.

One hour after the injection of 100 mg/kg of atropine-sulphate at 1300 h of dioestrus-1, there was an abrupt increase of 17beta-oestradiol plasma level and a significant increase in dopaminergic neural activity in preoptic anterior-hypothalamic area, without changes in luteinizing hormone serum level, in comparison with the saline injected group. Animals injected with atropine-sulphate showed a second increase in dopaminergic neural activity in the preoptic anterior-hypothalamic at 1100 of dioestrus-2 (atropine-sulphate 0.471 +/- 0.7 vs. saline 0.241 +/- 0.03, p < 0.01). In this group of animals, the preovulatory surges of 17beta-oestradiol and luteinizing hormone occurred simultaneously at 1700 h of the expected day of oestrus; spontaneous ovulation was delayed until the expected day of dioestrus-1. Present results suggest that during dioestrus-1 there is a functional relationship between the cholinergic and dopaminergic systems in preoptic anterior-hypothalamic area, regulating the release of luteinizing hormone resulting in ovulation.

3,4-Dihydroxyphenylacetic Acid↗

Subcutaneous administration of superoxide dismutase entrapped in long circulating liposomes: in vivo fate and therapeutic activity in an inflammation model.

PURPOSE: We are exploring liposomal delivery with the aim to change the pharmacokinetics and biodistribution of SOD to increase its therapeutic activity. From a practical point of view, a convenient route of administration would be the subcutaneous (s.c.) route. Liposomal size has been shown to be the most important factor influencing the rate and extent of drainage of liposomes from the s.c. injection site. METHODS: To monitor the in vivo fate of the subcutaneous administered SOD-containing liposomes in rats with a chronic arthritis inflammation, the liposomes were labeled by the co-encapsulation of the 111In-DTPA complex in the internal water space. RESULTS: Over the initial 10h-observation period post-injection, the small-sized poly(ethyleneglycol)-liposomes (mean size about 110 nm) left the site of injection to a 2-fold higher extent (45% of the injected dose) as compared to large-sized poly(ethyleneglycol)-liposomes (mean size about 450 nm). Small-sized liposomes gave a 17-fold higher uptake in the inflamed foot than the large-sized liposomes. Comparing the localization in the inflamed foot with the non-inflamed foot, uptake was more than 15-fold higher for the small-sized liposomes as compared to the large-sized liposomes. After s.c. administration, small-sized SOD-liposomes showed substantial higher activity than large-sized SOD-liposomes. S.C. administration of small-sized SOD-liposomes is equally effective as i.v. administration of the same liposomes. I.V. administration of the large-sized SOD-liposomes yielded a significantly higher activity as compared to s.c. administration. CONCLUSIONS: These results indicate that small-sized poly(ethyleneglycol)-liposomes can be used for the targeting of SOD to arthritic sites after subcutaneous administration.

Animals↗

Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of infection.

Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of infection with a virulent Mycobacterium avium strain (strain P1581) and was compared with that of free rifabutin. The influences of the size of the liposomal rifabutin formulation, the administered doses, and the treatment schedules on the evolution of infection were studied. Two types of treatment schedules were assayed: therapeutic and prophylactic. The therapeutic treatment started 2 weeks after infection, while the prophylactic treatment began 1 day before the experimental infection with mycobacteria. Incorporation of rifabutin in liposomes resulted in a significant enhancement of activity against M. avium infection compared to that of rifabutin in the free form in both schedules. These results demonstrate that liposomal formulations of antibiotics such as rifabutin may be effective for the treatment or prophylaxis of infectious diseases.

Animals↗

Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis.

Rheumatoid arthritis (RA) is a prevalent and debilitating autoimmune disease that affects the joints. RA is characterized by an infiltration of the affected joint by blood-derived cells. In response to activation, these cells generate reactive oxygen species, resulting in an oxidative stress situation. One approach to counteract this oxidative stress situation is the use of antioxidants as therapeutic agents. The free radical scavenger enzyme superoxide dismutase (SOD) may be used as a therapeutic agent in rheumatoid arthritis, but its rapid elimination from the circulation is a major limitation. Targeted delivery of SOD may overcome this limitation. In this study, the utility of PEGylated liposomes (PEG-liposomes) for targeting SOD to arthritic sites was explored. The targeting of SOD to arthritic sites following intravenous administration of both PEG-liposomes and positively charged liposomes lacking PEG but containing stearylamine (SA-liposomes) in rats with adjuvant arthritis was studied. At 24 h post injection, the blood levels of long circulating liposomes with a mean size of 0.11 micrometer and 0.20 micrometer were 8- and 3-fold higher, respectively, as compared to the SA-liposomes. The majority of SOD administered in liposomal form remains within the liposomes when they circulate in the bloodstream. The highest target uptake was observed with PEG-liposomes with a mean size of 0.11 micrometer and the lowest uptake with the SA-liposomes. These results demonstrate that SOD can be targeted to inflamed sites most efficiently via small-sized PEG-liposomes. Small-sized PEG-coated liposomes are to be preferred if prolonged circulation and enhanced localization of SOD at arthritic sites are desired.

Animals↗

Epilepsy and neurocysticercosis in an Andean community.

BACKGROUND: Taenia solium neurocysticercosis (NCC) has been documented as one of the major causes of epilepsy in developing countries. However, methodological limitations have hindered the evaluation of the epidemiological relationship between cysticercosis and epilepsy at the community level. METHODS: We used the WHO protocol for epidemiological evaluation of neurological disorders to conduct a door-to-door survey among 2723 residents of San Pablo del Lago, an Ecuadorean rural community in which T. solium taeniasis/cysticercosis was known to be endemic. The WHO protocol was complemented by neuroimaging and immunological tests to confirm the diagnosis of this infection. RESULTS: In all 31 people suffering from active epilepsy were detected (prevalence 11.4 per 1000, 95% CI:7.7-15.4); 26 agreed to undergo a computer tomography (CT) examination, and 28 agreed to have blood drawn for serodiagnosis. Fourteen of the 26 (53.8%) had CT changes compatible with NCC and six of the 28 (21.4%) tested positive in the enzyme-linked immunoelectro-transfer blot (EITB) assay. In a seizure-free random sample of this population, 17 of 118 (144 per 1000) subjects examined by CT and 10 out of 96 (104 per 1000) examined by EITB had evidence of this infection. The differences between the epilepsy group and the random sample of the population were statistically significant (OR = 6.93, 95% CI: 2.7-17.5, P < 0.001) for CT diagnosis, but not for EITB results (OR = 2.75, 95% CI: 0.8-7.1, P > 0.12, NS). CONCLUSIONS: These findings confirm that T. solium NCC is a significant cause of epilepsy at the community level in Andean villages of Ecuador. It is important to initiate effective public health interventions to eliminate this infection, which may be responsible for at least half of the cases of reported epilepsy in Ecuador.

Adolescent↗

[Epidemiology of cerebral cysticercosis in an Andean community in Ecuador].

Taenia solium neurocysticercosis (NCC) has been documented to be an underlying cause of epilepsy, intractable headaches, hydrocephalus, dementia and other serious neurological conditions in many countries of Central and South America. However, methodological limitations had prevented the assessment of the true prevalence of this condition at the community level. We conducted a house-to-house neuroepidemiological survey of 6,118 residents of an Andean community. This information was used to target neuroimaging (CT-scan) and immunodiagnosis (enzyme-linked immunoelectrotransfer blot assay, EITB) tests in individuals suspected of harbouring Taenia solium NCC. In the rural population, NCC was confirmed in 8 out of 47 examined by CT-scan (17%) and in 6 of 42 examined by EITB (14%). In the urban population, NCC was confirmed in 35 of 147 examined by CT-scan (23.8%) and in 28 of 124 examined by EITB (22.6%). In a sample of relatives of patients with documented cerebral cysticercosis, 20 out of 81 examined by CT-scan (25%) and 12 of 79 (15%) examined by EITB had NCC. Finally, CT scans were performed for 83 school children from urban areas, and 9 (11%) were diagnosed as harbouring NCC. In a community-based study, cysticercosis appears to be much more frequent than initially thought, when CT examination is used as the "gold standard" for diagnosis.

Adolescent↗

Formulation of L-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release.

This paper describes the preparation and characterisation of poly(lactide-co-glycolide) (PLG) nanoparticles containing the enzyme L-asparaginase. L-Asparaginase was encapsulated in PLG nanospheres using a water-in-oil-in-water solvent evaporation technique. The effect of the copolymer molecular weight and the presence of carboxyl-end groups in the copolymer chain on the physicochemical and in vitro release properties of the nanoparticles was investigated. Results indicated that size, encapsulation efficiency and in vitro release properties (enzymatic activity retention and protein quantification) of the nanoparticles were affected by the PLG molecular weight. As expected, nanoparticles made of high-molecular-weight PLG had a larger size, a higher loading and la slower release rate than those made od a low-molecular-weight PLG. Nevertheless, the most relevant factor affecting the entrapment and release of L-asparaginase from PLG nanoparticles was the presence of free carboxyl-end groups in the PLG chain. The nanoparticles made of PLG with free carboxyl-end groups had a high protein loading (4.86%, w/w) and provided a continuous delivery of the active enzyme for 20 days. However, the enzyme loading was lower (2.65%, w/v) and no active enzyme was detected in the release medium after a 14-day incubation period when nanoparticles were made of PLG with carboxyl-end groups esterified. These results give evidence of the potential of PLG nanospheres for the continuous delivery of L-asparaginase for extended periods of time and show the effect of the PLG chain end-groups in the amount and activity of the enzyme loaded into the nanospheres.

Asparaginase↗

C-fos expression pattern in the hypothalamus and the preoptic area of the rat during proestrus.

c-fos gene expression in the hypothalamus, the preoptic area, the hippocampus and the frontal cerebral cortex of the rat was determined every two hours from 09:00 h to 19:00 h on the day of proestrus by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10 h light-dark cycle, with lights on at 06:00 h were used. We found a marked increase in c-fos gene expression in the studied regions but the hippocampus at 13:00 h, followed by a significant diminution in the subsequent hours of proestrus day. The high expression of c-fos gene at 13:00 could be associated to the increase in estradiol seric levels observed both at 11:00 h and at 13:00 h. Our results correlate with the increase in the number of FOS immunoreactive cells in some forebrain areas in proestrus afternoon related to gonadotropin releasing hormone secretion.

Animals↗

Differential effects of ovarian local anaesthesia during pro-oestrus on ovulation by the right or left ovary in normal and hemi-ovariectomized adult rats.

The effects on spontaneous ovulation in normal and hemi-ovariectomized cyclic rats of an injection of saline or a local anaesthetic (2-diethylamine-2',6'-acetoxilidide hydrochloride with adrenaline, Xylocaine; administered at 13:00 h) into the bursa ovarica, were studied to investigate the participation of ovarian innervation in the regulation of the response of ovarian follicles to endogenous gonadotrophins on the day of pro-oestrus. The injection of saline or Xylocaine into both ovaries did not affect ovulation by the right ovary. Bilateral injection of Xylocaine did not affect ovulation by the left ovary. However, when saline was injected into the right ovary and Xylocaine into the left ovary, the number of ova shed by the left ovary decreased significantly (0.9 +/- 0.7 versus 4.4 +/- 0.2, P < 0.01; Mann-Whitney U test). In hemi-ovariectomized animals, when the right ovary was anaesthetized, ovulation was similar to that in saline-treated animals, and when the right ovary was anaesthetized, ovulation was blocked (one of six animals ovulated). The injection of hCG at 14:00 h to hemi-ovariectomized rats did not restore ovulation, whereas all the rats ovulated when anaesthesia occurred at 18:00 h. The present results suggest that on the afternoon of the day of pro-oestrus, before the LH peak, a neural signal modulates the response of the left ovary to gonadotrophins.

Anesthetics, Local↗

Geographic distribution and clinical description of leishmaniasis cases in Peru.

Studies were conducted from 1986 through 1993 to further define the geographic distribution and relative importance of different species of Leishmania as a cause of leishmaniasis in Peru. Patients with a clinical diagnosis of cutaneous and/or mucosal or diffuse cutaneous leishmaniasis were enrolled at the Naval Medical Research Institute Detachment (NAMRID) Laboratory in Lima, the Tropical Disease Clinic at San Marcos University Daniel A. Carrión, the Central Military Hospital, and a Ministry of Health hospital in Cusco, Peru. Clinical features, lesion aspirates, and biopsy tissue were obtained from each patient. All specimens were collected and assayed separately, including multiple specimens from some of the same patients for Leishmania parasites by inoculating aliquots of either aspirates or biopsy tissue suspensions onto Senekji's blood agar medium. Stocks of Leishmania isolates were used to prepare promastigotes to produce extracts for identifying the Leishmania species by the cellulose acetate electrophoresis enzyme technique. A total of 351 isolates of Leishmania were obtained from 350 patients who were infected primarily in the low and high jungle of at least 15 different Departments of Peru. Of the 351 isolates, 79% were identified as L. (V.) braziliensis, 7% as L. (V.) guyanensis, 10% as L. (V.) peruviana, 2% as L. (V.) lainsoni, and 1.7% as L. (L.) amazonensis. The clinical form of disease varied depending on the species of Leishmania, with L. (V.) braziliensis being associated most frequently with cutaneous, mucosal ulcers and mixed cutaneous and mucosal disease, and L. (V) peruviana, L. (V.) guyanensis, L. (V.) lainsoni with cutaneous lesions. Leishmania (L.) amazonensis was isolated from six patients, three with cutaneous lesions, one with mucosal lesions, and two with diffuse cutaneous lesions. Among all of the leishmaniasis cases, males were affected more frequently, and cases occurred among patients less than 10 to more than 51 years of age. These data further defined the geographic distribution and the relative frequency of Leishmania species associated with different clinical forms of leishmaniasis in Peru.

Adolescent↗

An analytical methodology to quantify the incorporation of enzymes in polyalkylcyanoacrylate nanoparticles based on size exclusion chromatography.

The performances of different methods of quantification of protein (methods based on direct spectrophotometric and spectrofluorimetric analysis, chemical reactions and liquid chromatography) to quantify the amount of enzyme incorporated into polyalkylcyanoacrylate nanoparticles, were compared. A methodology based on size exclusion chromatography was selected. The performances of the analytical method to quantify the enzymes L-asparaginase and superoxide dismutase in different polymerization media of poly-isobutilcyanoacrylate, were evaluated. The quantification of superoxide dismutase in the presence of esterase, enzyme used to solubilize nanoparticles, was attempted. An adequate separation between enzyme and the other components of polymerization media was achieved, so the selectivity of the method is adequate to the quantification of an enzyme in polymerization medium, either before or after polymerization. Although lack of selectivity of the column to separate enzymes was observed. The retention time of L-asparaginase and superoxide dismutase in polymerization medium are, respectively, 7.4 and 7.5. Linear correlation between peak area and enzyme concentration were observed for both enzymes in the concentration range from 10 to 80 micrograms ml-1, either before or after polymerization and in different polymerization media. This SE-HPLC analytical methodology is adequate to determine the degree of incorporation of enzymes in polyalkylcyanoacrylate nanoparticles as evidenced by the linear responses of the chromatographic method, the reproductibility of repeated sample injections and the precision of the quantification of enzyme concentration.

Asparaginase↗

Prevalence of epilepsy in a migrant population near Quito, Ecuador.

A census, uniform screening questionnaire and simple screening neurologic examination were administered door to door to the 221 residents of Paluguillo, a rural migrant community near Quito, Ecuador. This protocol was pretested to assure a high level of sensitivity for detecting major neurologic diseases in both children and adults. Of the participants, 119 (54%) had responses or findings suggesting the presence of neurologic disease, and, in particular, 53 (24%) had responses suggestive of epilepsy. These individuals were then examined by neurologists using fixed diagnostic criteria. The prevalence ratio for epilepsy was found to be 22.6/1,000. The results of this survey support the conclusion that epilepsy has a higher prevalence in rural areas of socioeconomically deprived countries than it does in industrialized nations.

Adolescent↗

Asymmetrical effects of the unilateral implant of pilocarpine on the preoptic-anterior hypothalamic area on spontaneous ovulation of the adult rat.

The effects on ovulation at the next estrus after unilaterally implanting pilocarpine in the preoptic-anterior hypothalamic area (POA-AHA) of rats on each day of the estrous cycle were analyzed. Implantation on the left side of POA-AHA on the day of estrus blocked ovulation in all animals, whereas implantation on the right side did not (0/5 vs. 4/4, P < 0.05). Implantation on diestrus 1 or 2 on either side of the POA-AHA blocked ovulation. Implantation on the right side of the POA-AHA at the day of proestrus blocked ovulation (1/6 animals ovulated), while 10/12 with pilocarpine on the left side ovulated (P < 0.05). The administration of 3.7 micrograms of GnRH at 13:00 h on the expected day of proestrus induced ovulation in 36/42 treated animals. In rats with a pilocarpine implant, the injection of estradiol benzoate on diestrus 2 restored ovulation only in those animals with the pilocarpine implant placed in the left side of the POA-AHA, performed on the day of estrus. The results support the previous statements that in the adult rat POA-AHA, the cholinergic mechanism regulating preovulatory GnRH release, is lateralized. In addition, at the beginning of the estrous phase, the POA-AHA-cholinergic system needs to remain undisturbed for normal ovulation to take place at the next estrus.

Animals↗

Biological characterization of L-asparaginase liposomal formulations.

The biological properties of preselected liposomal formulations of L-asparaginase (L-ASNase) were studied. Pharmacokinetics studies showed that encapsulation in large liposomes (sDRV; median diameter 1,249 nm) decreased the circulation time of the enzyme, whereas encapsulation in small liposomes (VET: median diameter 158-180 nm) prolonged it by a factor of up to 10. Liposome encapsulation in either VET or sDRV prevents the induction of anti-asparaginase antibodies and mitigates the anaphylatic reaction, as no death occurred in animals presensitized and challenged with liposomal formulation, in contrast to animals treated with the free enzyme. The antitumor activity was also enhanced by liposome encapsulation. The survival of animals bearing P1534 tumors was prolonged by a factor of 2 after treatment with selected liposomal formulations as compared with free enzyme.

Animals↗

Neurocysticercosis: optimal dose treatment with albendazole.

Albendazole has been used successfully in the treatment of cerebral cysticercosis for several years. The published dosage schedule has varied from 15 mg/kg/day for 8 days to up to 30 days. Fifty three patients with neurocysticercosis received 8, 15 or 30 days treatment with 800 mg of albendazole daily. The present study demonstrates the effectiveness in clinical and radiological terms of albendazole 800 mg/day for 8 days for the majority of patients affected with cystic or encephalitic parenchymatous cysticercosis. There was no apparent advantage of continuation of treatment for 15 or 30 days in this series. The routine use of high dose steroids limited the effects of parasite destruction. No toxicity attributable to albendazole was encountered.

Adult↗

Parasitic infection in malnourished school children: effects on behaviour and EEG.

This paper describes a study of 194 children (aged 9-13) from a mountain village in Ecuador who were infected with one or more species of intestinal helminth or protozoan parasite. In addition to parasite load, the assessment consisted of a battery of psychological and neuropsychological tests, an EEG examination, measures of iodine level, presence of goitre and level of nutrition. We found that, in general, parasite infection, as measured at the baseline level, was not associated with cognitive impairment. The intensity of infection with A. lumbricoides, however, was correlated with the level of verbal ability and with inhibition-control aspects of cognitive behaviour. Multivariate analysis with level of nutrition, EEG status and parasite burden showed a consistent main effect of the degree of nutrition on neuropsychological performance, particularly the language, problem solving and inhibition-control dimensions.

Adolescent↗

Headache and cysticercosis in Ecuador, South America.

Intractable headaches have been described as the presenting complaint of many patients with T. solium neurocysticercosis. We conducted a house-to-house neuroepidemiological survey of 2,723 residents of an Andean community, known to be endemic for this infection. Migraine headaches were confirmed in 187 cases (68.7 per thousand), and tension headaches were diagnosed in 77 cases (28.3 per thousand). Fifty-seven migraine sufferers accepted computed tomography examination, and in 19 it revealed neurocysticercosis. In 11 out of 52 migraineurs who had their blood drawn, electron immunotransfer blot testing (EITB) was positive for anticysticercal antibodies. In a computer-generated random sample of this community, 109 headache-free individuals were examined by CT, and 87 had EITB. Of the 109 subjects examined by CT, 14 were positive for cysticercosis. Of the 87 individuals tested by EITB, 7 were positive. A statistically significant difference between the symptom-free general population and the migraine patients was obtained for both CT (odds ratio 3.39, P < 0.005) and EITB (odds ratio 3.07, P < 0.05) diagnosis of neurocysticercosis. Neurocysticercosis appears to be a significant risk factor for the presentation of migraine-type headaches in areas endemic for T. solium infection.

Adolescent↗