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Biomedical subjects

M Angulo

Publications and source records attributed to M Angulo.

At least 19 recordsLinked to original sources

Dental caries and caries-associated microorganisms in Uruguayan preschool children.

The prevalence of dental caries was studied in 3-5-year-old Uruguayan children (n = 76) living in 2 areas with different socioeconomic and cultural conditions. More children from the low socioeconomic area of Las Acacias had caries (68%) than children from the middle- to high-class neighborhood of Pocitos (19%). They also had poorer oral hygiene and a significantly higher caries prevalence (P < 0.05) than those from Pocitos. The occurrence of mutans streptococci and lactobacilli was determined in whole unstimulated saliva and compared with that in debris collected with a loop from the dorsum of the tongue. Mutans streptococci were detected in 42% of the children with significant correlations between the salivary levels of the microorganism and caries experience. Lactobacilli were recovered less frequently (18%). The detection of mutans streptococci in the tongue-loop samples was significantly correlated with that in whole saliva.

Child, Preschool↗

Thioredoxin redox control of cell growth and death and the effects of inhibitors.

Thioredoxin is a redox protein found over-expressed in some human tumors. Thioredoxin is secreted by tumor cells and stimulates cancer cell growth. Redox activity is essential for growth stimulation by thioredoxin. Cells transfected with thioredoxin cDNA show increased tumor growth and decreased apoptosis in vivo and decreased sensitivity to apoptosis induced by a variety of agents both in vitro and in vivo. Cells transfected with a redox-inactive mutant thioredoxin show inhibited tumor growth in vivo. Thus, thioredoxin offers an attractive target for anticancer drug development. A class of disulfide inhibitors of thioredoxin has been identified. These disulfides inhibit cancer cell growth in culture and have antitumor activity against some human tumor xenografts in animals.

Animals↗

Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2-imidazolyl disulfides.

The interactions of a series of 2-imidazolyl disulfide antitumor compounds with the thioredoxin reductase(TR)/thioredoxin (hTrx) redox system have been studied. Disulfides III-2 (n-butyl 2-mercaptoimidazolyl disulfide) and VI-2 (ethyl 2-mercaptoimidazolyl disulfide) were substrates for reduction by TR with Km values of 43 and 48 microM. Disulfides IV-2 (1-methylpropyl 2-mercaptoimidazolyl disulfide) and DLK-36 (benzyl 2-mercaptoimidazolyl disulfide) were competitive inhibitors of the reduction of hTrx by TR with Ki values of 31 microM. None of the disulfides were substrates for reduction by human glutathione reductase. The disulfides caused reversible thioalkylation of hTrx at the redox catalytic site as shown by the fact that there was no thioalkylation of a mutant hTrx where both the catalytic site Cys32 and Cys35 residues were replaced by Ser. In addition, the disulfides caused a slower irreversible inactivation of hTrx as a substrate for reduction by TR, with half-lives for III-2 of 30 min, for IV-2 of 4 hr, and for IX-2 (t-butyl 2-mercaptoimidazolyl disulfide) of 24 hr. This irreversible inactivation of hTrx occurred at concentrations of the disulfides an order of magnitude below those that inhibited TR, and involved the Cys73 of hTrx, which is outside the conserved redox catalytic site, as shown by the resistance to inactivation of a mutant hTrx where Cys73 was replaced by Ser. Electrophoretic and mass spectral analyses of the products of the reaction between the disulfides and hTrx show that modification of 1-3 Cys residues of the protein occurred in a concentration-dependent fashion. The disulfides inhibited the hTrx-dependent proliferation of MCF-7 breast cancer cells with IC50 values for III-2 and IV-2 of 0.2 and 1.2 microM, respectively. The results show that although the catalytic sites of TR and hTrx are reversibly inhibited by the 2-imidazolyl disulfides, it is the irreversible thioalkylation of Cys73 of hTrx by the disulfides that most probably accounts for the inhibition of thioredoxin-dependent cell growth by the disulfides.

Antineoplastic Agents↗

Partial growth-hormone insensitivity: the role of growth-hormone receptor mutations in idiopathic short stature.

Mutations in the GHR locus may play a role in the cause of idiopathic short stature (ISS) by impairing growth-hormone (GH) receptor (GHR) function. At one extreme, mutations that nullify the function of the GH receptor are linked to complete GH insensitivity syndrome, or Laron syndrome, and we hypothesized that less-disruptive mutations could contribute to partial GH insensitivity syndrome. Low levels of GH binding protein may indicate mutations in the extracellular domain of the receptor, and by focusing on 14 children with ISS who had low GH binding protein and insulin-like growth factor I levels, we found three heterozygotes and one compound heterozygote for mutations in the extracellular domain of the receptor. We have since extended our study to a broader spectrum of patients, adding 76 patients with ISS who were treated with GH in a phase II study of the safety and efficacy of recombinant human GH in ISS and also adding 10 patients who were ascertained as having ISS by pediatric endocrinologists in private practice. The GHR gene has thus been analyzed in 100 patients with ISS, eight of whom were found to carry mutations: four in our original study and four with normal or elevated levels of GH binding protein. The latter group consists of three carriers of heterozygous extracellular domain mutations and one carrier of a heterozygous intracellular domain mutation. Family data suggest that the carriers of these mutations have a range of phenotypes, supporting our hypothesis that the expression of these heterozygous mutations as partial GH insensitivity syndrome depends on the genetic makeup of the person.

Body Height↗

Selenium and the thioredoxin redox system: effects on cell growth and death.

Thioredoxin is a redox protein found overexpressed in some human tumors. Thioredoxin is secreted by tumor cells and enhances the sensitivity of the cancer cells to other growth factors. Redox activity is essential for stimulation of cell growth by thioredoxin. Cells transfected with thioredoxin cDNA show increased tumor growth and decreased apoptosis in vivo and decreased sensitivity to apoptosis induced by a variety of agents both in vitro and in vivo. Cells transfected with a redox-inactive mutant thioredoxin show inhibited tumor growth in vivo. Dietary selenium has been shown to prevent some forms of human cancer. Selenocysteine is an essential component of thioredoxin reductase, the flavoenzyme that is responsible for the reduction of thioredoxin. Selenium added to the culture medium increases thioredoxin reductase activity due to an increase in thioredoxin reductase protein but mostly due to an increase in the specific activity of the enzyme. Some diaryl chalcogenide (selenium and tellurium) compounds have been studied as inhibitors of thioredoxin reductase. The most active were diaryl tellurium compounds, which were noncompetitive inhibitors of thioredoxin reductase with Ki values of 2-10 microM. Several of the compounds inhibited cancer cell colony formation in vitro with IC50s as low as 2 microM.

Apoptosis↗

MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings.

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.

Adolescent↗

Developmental trends of sleep-disordered breathing in Prader-Willi syndrome: the role of obesity.

Polysomnographic recordings of 43 children and adults with Prader-Willi syndrome (PWS) were inspected and classified into 5 age groups. The effect of age and body mass index (BMI) on measures of breathing, oxygen saturation, and sleep efficiency were analyzed. Body mass index (BMI) increased significantly between early childhood and preadolescent groups. Subjecting the data to analysis of variance showed an overall significant effect of BMI but no age effect on breathing parameters and oxygen saturation. Increased BMI was associated with decreased oxygen saturation and with higher apnea/hypopnea index. Sleep efficiency index was significantly lower in adults than in young children, preadolescent, and adolescent groups. These findings emphasize the role of obesity in the development of sleep-related breathing abnormalities and nocturnal oxygen desaturation in patients with PWS.

Adolescent↗

Disinfection and sterilization practices in Mexico.

We evaluated antisepsis, disinfection, and sterilization procedures at 22 hospitals in the state of Yucatan, Mexico, which provide services for approximately 80% of the population. The percentage of hospitals that followed standard recommendations for diverse antisepsis procedures were as follows: surgical scrub, 41%; surgical site preparation, 68%; central intravenous (iv) catheters, 61%; peripheral iv catheters, 86%; urinary catheters, 41%, and umbilical cord care, 5%. Inappropriate procedures typically involved the use of benzalkonium chloride and mercury compounds. Adequate sterilization procedures were observed for sharp surgical instruments in 9%, for blunt surgical instruments in 81%; for linen in 90%; for surgical brushes in 9%; for metal prostheses in 100%; for plastic prostheses in 57%; and for disinfection of endoscopes in 30%. The most common errors were the use of too short an exposure time in steam sterilizers or dry heat sterilizers, and the use of benzalkonium chloride as a sterilizing agent. Only 14% of hospitals used commercial spore preparations for autoclave monitoring. For the reuse of disposables, 50-94% of hospitals employed inappropriate sterilization or low-level disinfection procedures. Similar conditions are likely to exist in hospitals throughout the country. The establishment of strict regulations and hospital training programmes for disinfection and sterilization procedures, and the reuse of disposable devices is urgently needed in Mexico.

Cross Infection↗

Caries incidence, effect of preventive measures, and caries prediction in Uruguayan children.

In 1988, 100 12- to 13-year-old children from two neighborhoods in Montevideo with different standards of living were examined. Twenty-three children with large numbers of mutans streptococci, lactobacilli, or decayed surfaces or a combination of these factors were considered to be at high risk of developing caries. Twelve of these 23 children were selected for special preventive measures. A second examination was made 18 months later, at which 81 of the originally 100 children were studied. The clinical and microbiologic variables were tested for their ability to predict caries by calculating their sensitivity, specificity, the positive and negative predictive values. The incidence of new DMFS was significantly higher in the children from the low than in those from the high socioeconomic area. It was also significantly higher in the children considered being at high risk than in those at low risk at the start of the study. Preventive measures reduced the caries risk. The highest sensitivity was obtained with the clinical test, whereas the highest specificity was obtained with the combined clinical and microbiologic tests. The findings indicate that methods for identifying children at risk which started to be used in Scandinavia 20 years ago could be applied in the Uruguayan population of today. It is valuable to know this, as the resources for both treatment and prevention are very limited.

Adolescent↗

Dental caries and microbial and salivary conditions in Uruguayan children from two different socioeconomic areas.

Dental caries, microbial and salivary conditions, dietary habits, and socioeconomic conditions were studied in 100 12- to 13-year-old children from 2 different socioeconomic areas in Montevideo: Pocitos and Piedras Blancas. The residents of Pocitos had a higher educational level, better housing conditions, and occupations involving higher earnings than those of Piedras Blancas. The caries prevalence in the two areas was about the same, but the children in Piedras Blancas had more decayed surfaces and fewer filled surfaces than the children in Pocitos. The mean values for caries in Piedras Blancas and Pocitos were, DMFT, 4.2 and 4.2; DMFS, 8.1 and 7.8; DS, 4.7 and 2.5; and FS, 1.7 and 4.7, respectively. The differences in DS and FS were statistically significant. The frequency of sugar intake and the salivary secretion rate were similar, but the buffer capacity was significantly higher in Pocitos than in Piedras Blancas. The plaque index was the same, but the distribution of cariogenic microorganisms differed significantly. Fifty-eight per cent of the children in Piedras Blancas had more than 10(6) CFU of mutans streptococci per milliliter saliva, compared with 17% of the children in Pocitos. Similar differences were found with regard to the lactobacilli. The percentage of children with high numbers of mutans streptococci was higher in Piedras Blancas and lower in Pocitos than in previous epidemiologic studies in Scandinavia. It was, however, higher than that recently noted in Finland.

Adolescent↗

Male hypogonadism with gynecomastia caused by late-onset deficiency of testicular 17-ketosteroid reductase.

BACKGROUND: 17-Ketosteroid reductase deficiency results in male pseudohermaphroditism because conversion of the weak androgen androstenedione to the more potent androgen testosterone is impaired. If a late-onset form exists, hypogonadism and gynecomastia caused by decreased testosterone production and increased estrogen production, respectively, would be expected as the major clinical manifestations in men. METHODS: We studied 48 male subjects, ranging from 14 to 26 years of age, who had idiopathic pubertal gynecomastia. Serum concentrations of gonadal and adrenal steroid hormones were measured before and after the administration of corticotropin and after the combined administration of chorionic gonadotropin and dexamethasone for three days. RESULTS: We identified three unrelated subjects (ages, 16, 17, and 26 years) with results indicative of a partial deficiency of testicular 17-ketosteroid reductase. The three subjects had gynecomastia as well as decreased libido and impotence. Their mean (+/- SD) base-line serum androstenedione and estrone concentrations were elevated as compared with the levels in the 45 subjects without this enzyme deficiency (androstenedione, 380 +/- 70 vs. 110 +/- 70 ng per deciliter [13 +/- 2 vs. 4 +/- 2 nmol per liter]; estrone, 138 +/- 12 vs. 46 +/- 9 pg per milliliter [511 +/- 44 vs. 170 +/- 33 pmol per liter]). After the administration of chorionic gonadotropin, the mean serum androstenedione concentration in these three subjects was 910 +/- 48 ng per deciliter (32 +/- 2 nmol per liter) and the mean serum estrone concentration was 260 +/- 16 pg per milliliter (962 +/- 59 pmol per liter). The mean serum testosterone concentration at base line was 210 +/- 80 ng per deciliter (7.4 +/- 2.8 nmol per liter) in the 3 subjects, as compared with a value of 410 +/- 12 ng per deciliter (14.4 +/- 0.42 nmol per liter) in the 45 other subjects, and it did not increase in response to the administration of chorionic gonadotropin. The concentrations of androstenedione and estrone in spermatic venous serum were 19 times higher and 73 times higher, respectively, than in normal men. The serum concentrations of follicle-stimulating hormone and luteinizing hormone in these three subjects were inappropriately low, suggesting the presence of hypogonadotropic hypogonadism. CONCLUSIONS: A late-onset form of testicular 17-ketosteroid reductase deficiency can cause gynecomastia and hypogonadism in men.

17-Hydroxysteroid Dehydrogenases↗

Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): effects of age and gender.

Patients with Prader Willi syndrome (PWS) often complain of daytime hypersomnolence. Because of reported daytime sleepiness and high prevalence of morbid obesity, these patients have been considered at risk for sleep related disordered breathing, but polysomnographic studies have been limited. We evaluated sleep and breathing polysomnographically in 24 PWS patients including 15 adults and 9 children. All adult patients completed MSLT testing on the day following the nocturnal sleep study. Both adult and children groups showed little or no sleep apnea, but REM related oxygen desaturation was quite common, its severity significantly correlated with increased obesity. Sleep patterns in both groups showed abnormal REM sleep cycles with variable REM latency (at times significantly shortened) and fragmented REM sleep with multiple brief REM periods. REM sleep abnormalities were still present in some patients without REM related desaturation. As a group, patients with PWS demonstrated pathological somnolence as measured by MSLT, which correlated with nocturnal sleep efficiency but not with nocturnal REM latency. It is hypothesized that the abnormal sleep findings in PWS reflect an underlying hypothalamic dysfunction characteristic of this syndrome.

Adolescent↗

Elevated serum estradiol associated with increased androstenedione-testosterone ratio in adolescent males with varicocele and gynecomastia.

OBJECTIVE: To investigate the testicular function in adolescents with pubertal gynecomastia associated with varicocele before and after varicocelectomy. DESIGN AND PATIENTS: We have studied six male adolescents 15 to 19 years of age with bilateral gynecomastia. They were selected among other adolescents with gynecomastia because of the presence of visible varicoceles. All of them had normal physical examination and secondary sexual characteristics. This was prospective study of 3 months' duration. All the patients that were included finished the study. SETTING: All the patients were evaluated in the Endocrine Clinic of Winthrop-University Hospital, a tertiary care unit. INTERVENTION: Serum testosterone (T), androstenedione (A), and estradiol (E2) responses to the administration of human chorionic gonadotropin (hCG) 2,000 IU for 3 consecutive days before and 3 months after varicocelectomy were determined. RESULTS: Varicocelectomy did not cause any significant changes in the basal (pre-hCG) levels of the steroid. However, the increase in T levels achieved with hCG was significantly (P less than 0.005) higher after varicocelectomy (before T, 925 +/- 212 ng%; after T, 1,649 +/- 406 ng%). Simultaneously, the stimulated levels of E2 and A were significantly lower (P less than 0.005) after varicocelectomy (E2, 62 +/- 12 pg/mL; A, 326 ng% +/- 80 ng%) than before (E2, 106 +/- 13 pg/mL; A, 580 ng% +/- 95 ng%). CONCLUSION: The reciprocal effect on the levels of T and its immediate precursor, A, suggests an impairment of the 17-ketoreductase enzyme activity. The increased levels of E2 after hCG and its normalization after varicocelectomy suggests that varicoceles may play a pathogenetic role in the development of gynecomastia.

Adolescent↗

Leydig cell function in adolescent boys with varicoceles.

The incidence of varicoceles in adolescent boys ranges from 5% to 19.5%. We studied five adolescent boys aged 17 to 20 years with visible left-sided varicoceles. All of them had public hair and testicular volumes between 20 to 25 mL and had achieved stage V of pubertal development. Serum gonadotropin response to the intravenous administration of 100 micrograms of gonadotropin-releasing hormone (GnRH) and testosterone response to the administration of 2,000 IU human chorionic gonadotropin (hCG) daily for 3 days before and 3 months after varicocelectomy were measured. Basal levels of both gonadotropins were in the pubertal range, and there was no significant difference between serum levels before and after varicocelectomy. Both gonadotropins, however, showed increased responses to the administration of GnRH (luteinizing hormone [LH]: basal, 12.0 +/- 5.1 mIU/mL; peak, 105.0 +/- 36.0 mIU/mL; follicle-stimulating hormone [FSH]: basal, 11.6 +/- 4.2 mIU/mL, peak, 60.0 +/- 18.0 mIU/ml) that decreased after varicocelectomy (LH: basal, 14.3 +/- 6.0 mIU/mL; peak, 58.6 +/- 12.0 mIU/mL; FSH: basal, 6.8 +/- 4.6 mIU/mL; peak, 38.0 +/- 8.1 mIU/mL). Serum testosterone response to hCG was also significantly improved by varicocelectomy (testosterone peak: before, 780 +/- 210 ng/dL; after, 1850 +/- 170 ng/dL). Testicular biopsy specimens showed no histologic abnormalities and normal spermatogenesis. Endocrine evaluation in adolescent boys with varicoceles could detect an early Leydig cell dysfunction that could be corrected by varicocelectomy.

Adolescent↗

[Comparative study of the adherence test and the Petry plaque count test of Streptococcus mutans in saliva].

The Streptococcus mutans counts--added to lactobacili depicting test--are an useful instrument in cariology when determining the risk groups. In studies concerning a large number of patients the S. Mutans count in saliva test are the most accesible. Nevertheless, they are very expensive and also complicate to carry out. Simplified techniques which depict S. Mutans on the basis of adherence tests have been perfected. The most suitable from them, taking into account our working conditions, is the Matsukubo test. We deemed it interesting to correlate this test and the Gold medium count. The study has been carried out with three different populations using both techniques at the same time. As per the correlation indices obtained we conclude that the Matsukubo technique and the count have a significant correlation between them. Due to its low cost, the simplicity of its realization, as well as its easy reading it can be effectively used as a primary procedure when studying populations large in number. Through this method selection will be made of the patients to be studied applying more precise microbiological techniques.

Adult↗

[Evaluation of oral health status of a preschool group with a predictive test based on mutans group and clinical studies].

A children's population, aged from 2 to 5 years, was studied for three years. Bacteriological and clinical criteria were followed, with a determination of the M. st level in non-stimulated saliva in the age-groups of 3, 4 and 5 years. We found, as Alaluusua did, a correlation between the M. st level in saliva and the number of caries. With this study, a large number of caries-free children had a low M. st level. The largest amount of caries appears in children with a high M. st level. The highest caries incidence in this population appears at the 4 year children group. It has to be remembered that this is an age-group with specific characteristics. Caries is a disease depending on many factors and the M. st level would be very significant to an early detection of risks, but should be evaluated considering all the parameters as a whole. Its predictive value is not sufficient by itself but it has an unquestionable value when detecting risk patients of an early age. Therefore, treatment has to be the result of an etiological diagnosis addressed to prevention after an evaluation of all the factors related with the caries disease.

Child, Preschool↗