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Biomedical subjects

C Aguirre

Publications and source records attributed to C Aguirre.

At least 37 records · Page 2Linked to original sources

Luteinizing hormone (LH) stimulates both intracellular calcium ion ([Ca2+]i) mobilization and transmembrane cation influx in single ovarian (granulosa) cells: recruitment as a cellular mechanism of LH-[Ca2+]i dose response.

The gonadotropic hormones, LH and FSH, activate adenylyl cyclase in their respective target cells and thereby initiate many biochemical responses. In addition to stimulating cAMP production, both LH and FSH promote agonist-specific increases in the cytoplasmic concentration of free calcium ions ([Ca2+]i) in gonadal cells. Here, we have applied single cell fluorescence video microscopy with the Ca2+-sensitive dye fura-2 to investigate the mechanism(s) by which LH induces a rise in the [Ca2+]i in individual (swine) granulosa cells collected from single Graafian follicles. Stimulation with LH induced a rapid onset, biphasic, spike- and plateau-like [Ca2+]i signal in responsive granulosa cells. The cellular mechanisms mediating this biphasic LH-stimulated increase in [Ca2+]i were examined by external Ca2+ removal and via the manganese (Mn2+) quench technique, which showed that LH triggers initial intracellular Ca2+ mobilization followed by delayed transmembrane Ca2+ influx. Single cell Ca2+ assessment of the LH dose-response mechanism(s) revealed that higher concentrations of LH progressively recruit a larger number of responding individual granulosa cells. Further analyses disclosed a marked [Ca2+]i response heterogeneity among individual granulosa cells harvested from the same Graafian follicle. In addition, the percentage of cells responding to LH [but not to an alternative putative agonist of the phospholipase C (PLC) pathway, viz. endothelin-1] with a biphasic [Ca2+]i rise increased with maturational development of the follicle. Pretreatment of granulosa cells with a specific PLC inhibitor, U-73122 (but not with its inactive congener U-73343), significantly reduced the percentage of cells responding to a LH challenge from 78% to 25% (P < 0.0001) and prolonged the time required to achieve a half-maximal value of the [Ca2+]i transient, viz. from 22 +/- 1.5 sec (n = 27 cells) to 39 +/- 7.2 sec (n = 12 cells; P = 0.002). In cell population studies, LH stimulated in a concentration- and time-dependent manner the accumulation of inositol phosphate in porcine granulosa cells. In summary, the present single cell investigations in mature granulosa cells demonstrate that LH drives initial intracellular Ca2+ mobilization followed by transmembrane divalent cation influx. The PLC inhibitor U-73122 antagonizes this action of LH. By analyzing [Ca2+]i responses in individual living granulosa cells, we further show that, despite within-follicle diversity, the LH dose biphasic [Ca2+]i response arises via the recruitment of a larger number of responding gonadal cells rather than by increased [Ca2+]i signal amplitude. Finally, the percentage of individual LH (but not endothelin-1)-responding granulosa cells increases with follicular maturation. Collectively, these data highlight the potential importance of the LH-stimulatable, PLC-transduced [Ca2+]i signaling mechanism in the later stages of granulosa cell differentiation.

Animals↗

High Cryptosporidium prevalences in healthy Aymara children from the northern Bolivian Altiplano.

The prevalence of Cryptosporidium infection was determined in four Aymara communities in the Bolivian Altiplano, between the city of La Paz and Lake Titicaca, at an altitude of 3,800-4,200 meters. Single stool specimens were randomly collected from 377 5-19-year-old students, all apparently asymptomatic. The total prevalence (31.6%) is possibly the highest reported among healthy humans (a maximum of 9.8% and 2.0% in coprologic surveys in underdeveloped and developed countries, respectively) and one of the highest even in symptomatic subjects. No significant age and sex differences were observed. Such an infection prevalence is probably related to the poor sanitation conditions, contaminated water supplies, overcrowding, and close contact with domestic animals. Continuous exposure to the parasite could be associated with protection against parasite-related symptoms in the children examined.

Adolescent↗

Balantidiasis in Aymara children from the northern Bolivian Altiplano.

Balantidium coli infection was coprologically studied in 2,124 Aymara children 5-19 years of age from the schools of 22 communities of the northern Bolivian Altiplano over a five-year period. Infection with B. coli was found in 11 of the communities surveyed, with prevalences of 1.0-5.3% (overall prevalence=1.2%). The prevalences observed are some of the highest reported and did not differ significantly among the various age groups or between boys and girls. These prevalences, the apparent absence of symptoms or signs of illness due to this parasite in the schoolchildren surveyed at the time of stool sampling, and the consistency of stool samples of the infected students suggest that they are apparently asymptomatic carriers. Infection with B. coli must be considered as an endemic anthropozoonosis in the area studied. A relationship between B. coli infection and Altiplanic pigs is suggested.

Adolescent↗

Presence of very high prevalence and intensity of infection with Fasciola hepatica among Aymara children from the Northern Bolivian Altiplano.

Coprological studies of school children from four communities in the Northern Bolivian Altiplano were carried out in order to estimate the prevalences and intensities of Fasciola hepatica infection. Single stool specimens were collected at random from 558 school children (308 boys and 250 girls) aged 5-19 years old. Nineteen different parasite species (13 protozoan and six helminths) were detected. Of the children examined, 98.7% (96.5-100%) presented infection with at least one parasite species. The mean prevalence of 27.6% by Fasciola hepatica (range, 5.9-38.2%) was the highest not only with respect to the helminth species found in the Northern Bolivian Altiplano but also among the fasciolosis prevalences reported in children in other parts of the world to date. Prevalences were significantly different among the communities surveyed and was significantly higher in the 9-12 years age group. There were, however, no significant differences between sexes. Among the 154 children presenting F. hepatica eggs in stools, intensities ranged from 24-5064 eggs per gram of faeces (epg), with arithmetic and geometric means of 474 and 201 epg, respectively. Significant differences in mean egg output were detected between communities, sexes and age groups. Individual fasciolosis infections coexisting with other pathogenic parasite species (Entamoeba histolytica and/or E. dispar, Giardia intestinalis, Balantidium coli, Dientamoeba fragilis, Cryptosporidium sp., Hymenolepis nana, Taenia spp., Trichuris trichiura, Ascaris lumbricoides and Enterobius vermicularis) were detected. A significant positive association with F. hepatica was only found in the case of G. intestinalis. This coprological study not only verifies the existence of high prevalences of F. hepatica among humans in the Northern Bolivian Altiplano, but also demonstrates the need to expand the Southern boundaries of this high endemic zone to include the Southeastern region of Lake Titicaca.

Adolescent↗

A population-based coprological study of human fascioliasis in a hyperendemic area of the Bolivian Altiplano.

The community of Chijipata Alta, at an altitude of 3850 m, near the southern coast of Lake Titicaca in the northern Altiplano of Bolivia, was surveyed for human fascioliasis. The global prevalence (66.7%) and intensity (eggs per gram of faeces--epg: range: 24-4440; arithmetic mean: 1001; geometric mean: 390) proved to be the highest known in the world by means of coprological techniques. These results suggest the existence of highly hyperendemic subzones among the large human fascioliasis-endemic zone of the Bolivian northern Altiplano. Despite the decrease in prevalence and intensity from children (75.0%, 24-4440 epg) to adults (41.7%, 144-864 epg), our findings show that in an hyperendemic zone adult subjects either maintain the parasites acquired when young or are newly infected as the consequence of inhabiting a zone of high infection risk.

Adolescent↗

Serum protein binding of propofol in critically ill patients.

BACKGROUND: Disease-induced modifications in the level of serum proteins may change the degree of binding of drugs highly bound to serum proteins. METHODS: The serum protein binding of propofol, an intravenous anaesthetic agent was studied in vitro in samples of serum from healthy volunteers (n=28) and from critically ill patients (n=17). The free fraction was obtained by the ultrafiltration technique and was measured by high-performance liquid chromatography. Concentrations of serum albumin, alpha1-acid-glycoprotein and free fatty acids were also measured in all samples. RESULTS: The percentage of free propofol was significantly increased (P<0.001) in critically ill patients (1.31 (1.06-2.25)%) vs control subjects (1.07 (0.49-1.47)%). Albumin levels were significantly decreased (P<0.001) in patients (16.3 (8.8-24.6) g x l(-1) vs 45.8 (31.4-55.5) g x l[-1]), while levels of alpha1-acid-glycoprotein were increased (P<0.001) (1.9 (0.9-2.8) g x l(-1) vs 0.9 (0.5-1.4) g x l[-1]), as were levels of free fatty acids (0.68 (0.50-1.14) mmol x l(-1) vs 0.37 (0.11-1.05) mmol x l(-1); P<0.05 ). No correlation was found between levels of alpha1-acid-glycoprotein or free fatty acids and the bound/free ratio of propofol. However, a linear relationship was found between levels of albumin and the bound/free ratio (r2=0.25; P<0.001). CONCLUSION: In conclusion, in these critically ill patients, an increase in the percentage of free propofol occurs. The significance of this observation remains uncertain, but may be validated in future studies. However, the observation supports the common idea that potent drugs should be given with great care in critically ill patients.

Adult↗

Stability and chemical modification of xylanase from Aspergillus sp. (2M1 strain).

The 2M1 strain of Aspergillus sp., which showed high extracellular xylanolytic activities in a pre-screening, was studied. Oat-spelt, birch, eucalyptus and pine xylans were used as xylanolytic inductors. The following activities were found at 50 degrees C in the presence of 1% xylan: 120 units/ml (oat-spelt xylan), 132 units/ml (birch xylan), 107 units/ml (eucalyptus xylan), 67 units/ml (pine xylan) and 137 units/ml (larch-wood xylan). Xylanase induced by pine xylan exhibited a higher stability than those induced by the other xylans. The stability was improved by addition of glycerol. In the crude extract, reagents which were found to affect xylanase activity were 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide for amidation of carboxylic groups and N-bromosuccinimide at a concentration of 0.5 mM for indole oxidation. Methylene Blue, butane-2,3-dione, N-acetylimidazole, chloramine-T and iodoacetate had little effect on the enzyme activity (more than 97% of the original activity remained).

Aspergillus↗

[Otomastoiditis caused by Aspergillus in AIDS].

BACKGROUND: Aspergillus otomastoiditis is an infrequent infection that occurs in most cases in immunocompromised hosts. Although fungal infections are common in AIDS patients, few cases of Aspergillus otomastoiditis have been reported. METHODS: Two clinical cases of AIDS patients with Aspergillus otomastoiditis are reported, and a review of the literature is performed. RESULTS: Clinical presentation in both cases was similar to those of other diseases involving middle and internal ear. Infection was linked to severe immunosuppression (C3 group). CONCLUSIONS: Aspergillus otomastoiditis is an infrequent infection in AIDS patients. Different routes by which Aspergillus obtains access to the middle ear have been proposed (tympanogenic, meningogenic, hematogenous and direct spread from paranasal sinuses or external auditory canal). Otorrhea, otalgia, hearing loss and facial nerve involvement are common findings. Bone destruction and invasion of brain or skull base may occur. CT or MRI are necessary to evaluate the extent of the disease. Etiologic diagnosis requires histopathologic confirmation on deep tissue biopsy or isolation from blood cultures or fistula exudates, because Aspergillus is a common saprophytic fungus in external auditory canal. Concurrent infections (i.e. Pseudomonas aeruginosa) frequently delay the correct diagnosis. Aggressive surgical resection and intravenous antifungal chemotherapy (amphotericin B or itraconazole) are the main therapeutic options. Outcome is poor as a consequence of severity, delay of etiologic diagnosis and difficulty of aggressive surgical approach in compromised patients. In patients with AIDS a low CD4 cell count would favour invasive Aspergillus infection, implying a worse outcome.

AIDS-Related Opportunistic Infections↗

The effect of changes in gastric pH induced by omeprazole on the absorption and respiratory depression of methadone.

The effect of omeprazole (2 mg kg-1 i.v.) on respiratory depression induced in rats by acute oral methadone administration (5 mg kg-1) was examined and compared with control animals that only received methadone. Quantitative assessments of arterial Pco2,Po2, pH, and respiratory rate were employed as criteria for evaluation. Intragastric pH was measured in each rat immediately before and 2 h after methadone. Plasma concentration of methadone was measured for 3 h. The relationship between drug effect and the systemic bioavailability of methadone, measured as the area under the plasma concentration-time curve (AUC0-180), was also evaluated. The intensity of the methadone-induced respiratory depression was significantly greater in the omeprazole group than in control rats. A significant variation (p < 0.01) in all respiratory parameters was detected from 30 to 120 min after methadone. Omeprazole caused a significant increase in methadone levels (Cmax = 156 +/- 6.5 ng mL-1 against 51 +/- 5.8 ng mL-1 in control; p < 0.05). AUC0-180 was higher (p < 0.05) after omeprazole treatment (18.6 +/- 1.4 micrograms mL-1 min) than in control (6.8 +/- 0.6 microgram mL-1 min). Two hours after treatment with omeprazole, intragastric pH values were significantly elevated (4.7 +/- 0.1 against 2.2 +/- 0.04) and continued increasing, being 6.4 +/- 0.1 at the end of the experiment. Correlation was observed between intragastric pH and the area under the effect- (respiratory depression-) time curve (r = 0.74; p < 0.001). A relationship between plasma methadone levels at 120 min and gastric pH (r = 0.92; p < 0.001) was detected. A significant correlation between the area under the effect-time curve (0-120 min) and AUC0-180 has been also observed (r = 0.90; p < 0.01). These pharmacokinetic and pharmacodynamic changes could be gastric pH dependent because they were mimicked when gastric pH was experimentally modified by bicarbonate whereas opposite results were obtained with acidic pH2 solution.

Administration, Oral↗

Variable efficacy of bone remodeling biochemical markers in the management of patients with Paget's disease of bone treated with tiludronate.

The aim of this work was to evaluate the response of different biochemical bone markers to tiludronate administration in Paget's disease of bone. Ten patients (five men and five women), 56-77 years old (67 +/- 6.5), were treated for 3 months with tiludronate tablets (400 mg/day). Bone formation markers: alkaline phosphatase (AP), bone alkaline phosphatase (bAP), osteocalcin (BGP), and procollagen I carboxyterminal propeptide (PICP) in serum; and bone resorption markers: serum cross-linked carboxyterminal telopeptides of type I collagen (ICTP), urinary hydroxyproline/creatinine (Hyp/Cr), pyridinoline/Cr (Pyr/Cr), and alpha-1 collagen chain products degradation (CrossLaps) were assessed. Samples were taken before and at monthly intervals for 3 months after treatment began. The results of the present work show that serum AP and bAP are sensitive and reliable biochemical markers of bone formation in the follow-up of tiludronate in this disease. Serum PICP shows less sensitivity than serum AP, and serum BGP is not indicated as biochemical marker in these types of studies. Urinary hydroxyproline seems to be the most reliable biochemical marker of bone resorption. More studies should be performed with urinary Pyr and CrossLaps determinations. Serum ICTP is not adequate for the follow-up of tiludronate treatment in Paget's disease of bone.

Administration, Oral↗

Reversible bone marrow depression by high-dose piperacillin/tazobactam.

Bone marrow toxicity, mainly neutropenia, has been described as an uncommon secondary effect of most beta-lactams, and it is usually related to large cumulative doses. Although previously described for piperacillin, no cases of marrow depression caused by piperacillin/tazobactam have been reported to date. We report a case of reversible pancytopenia, with evidence of bone marrow depression, which occurred after a 17 d course of piperacillin/tazobactam. The drug was given to an underweight 18-year-old woman, at the usual dosage of 4/0.5 g three times a day. We stress the need for reducing the recommended dosage when treating underweight adult patients, and also of monitoring haematological parameters during prolonged treatments.

Adolescent↗

Pharmacokinetics and pharmacodynamics of penbutolol in healthy and cancer subjects: role of altered protein binding.

The pharmacokinetic and pharmacodynamic profiles of penbutolol were examined in healthy volunteers and in cancer patients using a pharmacokinetic/pharmacodynamic (pk/pd) model. After receiving a 40 mg single oral dose of penbutolol, the absorption rate constant, apparent volume of distribution and serum clearance of penbutolol were found to be reduced in the cancer group. Changes in the disposition of the conjugate metabolite were also observed in the cancer patients. Penbutolol unbound fraction in serum was statistically decreased (p < 0.005) in the cancer group, according to the increase in the serum levels of alpha 1-acid glycoprotein seen in that group (p < 0.05). The pharmacodynamic effect of penbutolol was measured as the reduction in heart rate (HR); in healthy volunteers, a linear relationship (p < 0.01) between effect and penbutolol serum concentrations (total or unbound) was found. In contrast, in cancer patients, values of HR did not vary statistically in respect to baseline values. These results show that in cancer patients, a change in the pharmacokinetics of penbutolol occurs (associated with changes in drug protein binding), together with an alteration in the pharmacodynamics.

Adult↗

Characteristics of serum protein binding of felodipine.

The protein binding of felodipine in concentrations ranging from 3 to 65 nmol L-1 has been characterized in pooled serum, and in isolated human plasma proteins: albumin (HSA) and a1-acid glycoprotein (AAG). Protein binding was determined by an ultrafiltration technique using an Amicon Micropartition System. Serum protein binding of felodipine (16 nmol L-1) was measured in five groups of individuals: I: healthy subjects (n = 16). II: patients with chronic renal disease before and after dialysis (n = 10). III: patients with liver disease (n = 9). IV: diabetics Type I (n = 10) and Type II (n = 12) and V: cancer patients (n = 12). Concentrations of HSA, AAG, lipoproteins and non esterified fatty acids (NEFA) were also measured. The drug was extensively bound in pooled serum and the protein binding was essentially unchanged over the concentrations of felodipine studied (99.60 +/- 0.31% at 3 nmol L-1; 99.70 +/- 0.15% at 65 nmol L-1). In albumin solution (40 g L-1) felodipine was also highly bound. The mean of percentage bound was not significantly different from that in serum and was also independent of the felodipine concentrations (98.57 +/- 0.35 at 3 nmol L-1; 98.31 +/- 0.90 at 65 nmol L-1). The extent of binding to AAG was significantly lower than in serum (p < 0.01) and HSA (p < 0.01) and was independent of felodipine concentrations (85.64 +/- 2.25 at 3 nmol L-1; 85.68 +/- 2.3 at 65 nmol L-1). The percentage of bound felodipine in group II (before dialysis) was significantly lower than in group I (p < 0.001). The variability in the percentage of bound felodipine was greater in group II, before dialysis, than in the rest of the groups. After dialysis, protein binding was similar to that in group I. HSA did not change and AAG was increased. NEFA was significantly higher after dialysis when compared with group I (p < 0.01). In vitro carbamylation of serum did not change felodipine protein binding. HSA was decreased significantly in group III patients (p < 0.05). However, protein binding did not change. Binding of felodipine in the rest of the groups was not significantly different from that in group I. Linear regression analysis of the data for all individuals indicated that the binding of felodipine was related to serum lipoproteins and that age, HSA, AAG, and NEFA were not significant determinants of binding.

Adult↗

[Neodymium YAG laser in treating prostatic adenoma].

BACKGROUND: Conventional surgery and transurethral ablation are the treatments of choice for benign prostatic hyperplasia. AIM: To report our experience with Neodynium: YAG laser ablation of prostatic adenomas. PATIENTS AND METHODS: Revision of 182 patients subjected to Laser ablation of benign prostatic adenoma of whom 28 had a complete urinary retention and 50 were considered of high surgical risk. RESULTS: One hundred eighty patients had spontaneous voiding after surgery, there were no intraoperatory complications and were discharged 6 to 24 hours after the procedure. Urinary flow increased from 8 ml/sec in the preoperative period to 20 and 21 ml/sec, two and six months after surgery. Symptom score decreased from 12 to 1.2 points. Seven patients had late hematuria and two required vesical lavage and cystoscopic clot drainage. Ten patients had a positive urine culture. 12 had lack of ejaculation and 75%, had some degree of dysuria. CONCLUSIONS: Neodynium YAG laser ablation of benign prostatic adenoma seems to be efficient and safe.

Adult↗