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Biomedical subjects

J M Malacara

Publications and source records attributed to J M Malacara.

At least 19 recordsLinked to original sources

Telomerase activity, estrogen receptors (alpha, beta), Bcl-2 expression in human breast cancer and treatment response.

BACKGROUND: The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences, lost during replication by means of an intrinsic RNA component as a template for polymerization. Among the telomerase subunits, hTERT (human telomerase reverse transcriptase) is expressed concomitantly with the activation of telomerase. The role of estrogens and their receptors in the transcriptional regulation of hTERT has been demonstrated. The current study determines the possible association between telomerase activity, the expression of both molecular forms of estrogen receptor (ERalpha and ERbeta) and the protein bcl-2, and their relative associations with clinical parameters. METHODS: Tissue samples from 44 patients with breast cancer were used to assess telomerase activity using the TRAP method and the expression of ERalpha, ERbeta and bcl-2 by means of immunocytochemical techniques. RESULTS: Telomerase activity was detected in 59% of the 44 breast tumors examined. Telomerase activity ranged from 0 to 49.93 units of total product generated (TPG). A correlation was found between telomerase activity and differentiation grade (p = 0.03). The only significant independent marker of response to treatment was clinical stage. We found differences between the frequency of expression of ERalpha (88%) and ERbeta (36%) (p = 0.007); bcl-2 was expressed in 79.5% of invasive breast carcinomas. We also found a significant correlation between low levels of telomerase activity and a lack of ERbeta expression (p = 0.03). CONCLUSION: Lower telomerase activity was found among tumors that did not express estrogen receptor beta. This is the first published study demonstrating that the absence of expression of ERbeta is associated with low levels of telomerase activity.

Adult↗

Advanced glycosylation end products in skin, serum, saliva and urine and its association with complications of patients with type 2 diabetes mellitus.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) has a key role in the pathophysiology of diabetes complications. Comparison of AGEs measurement in serum, skin, saliva and urine has not been reported. AIMS: To compare AGEs in serum, skin, saliva and urine in patients with Type 2 diabetes mellitus, with complications at different stages. MATERIALS AND METHODS: We examined 50 patients with Type 2 diabetes mellitus (40 women and 10 men) grouped according to the progression of neuropathy, nephropathy and retinopathy. The AGEs content in serum, skin, saliva and urine was measured by spectrofluorometry HPLC. RESULTS: The patients had a mean age of 56.5 +/- 7.7 yr and 12.8 +/- 6.7 yr since diagnosis. AGEs in skin correlated with years since diagnosis (p = 0.0005). AGEs in serum, skin and saliva increased with the progression of complications, nevertheless, in urine a trend to diminution was found. In the group with end-stage renal disease (ESRD), AGEs in serum increased in greater proportion. In order to account for the decreased AGEs clearance, we corrected the values for creatinine levels, and AGEs in skin gave a better association with complications. CONCLUSIONS: The AGEs measurement in skin, serum and saliva are useful to evaluate diabetes complications. AGEs in skin are associated with years since diagnosis of diabetes. Correction for renal function might discriminate AGEs in situ formation from accumulation.

Adult↗

Gonadotropins at menopause: the influence of obesity, insulin resistance, and estrogens.

UNLABELLED: Obese, postmenopausal women have lower FSH levels. To determine whether this is due to higher estrogen exposure, we compared feedback gonadotropin sensitivity and its relation to insulin resistance in four groups of obese and lean, postmenopausal women. Group one was treated with 400 mg troglitazone (TG) daily for two weeks; 150 clomiphene citrate (CC) was added daily for the second week. Group two received 150 mg CC daily for a week. Group three received 1000 mg metformin (MET) daily for two weeks, with 120 mg raloxifene (RAL) added during the second week. Group four received 120 mg RAL for a week. Before and after each period, a serum pool was obtained from samples taken every minute during a 10 ml interval. The women recruited for this study were categorized as obese or lean based on BMI >/= 29 or BMI < 29, respectively. Obese, menopausal women had lower FSH (45.5 IU/l) and LH (16.2 IU/l) values than those of lean (64.1 IU/l and 23.0 IU/l), but the obese menopausal women had higher leptin, DHEAS, glucose, insulin, and HOMA-IR levels. Log [FSH] was associated with BMI (r = -0.53, P < 0.000001) and number of pregnancies (r = -0.37, P = 0.0009). TG treatment did not change HOMA-IR or gonadotropin levels, but DHEAS and androstenedione levels decreased significantly. CC alone or together with TG, diminished FSH (-7.9 and -9.2) and LH (-2.5 and -3.6) concentrations, with a greater reduction in lean women. MET reduced glucose and the HOMA-IR index without affecting gonadotropin or steroid levels. CONCLUSIONS: obese, menopausal women have lower FSH levels due to greater estrogen exposure, by mechanisms unrelated to insulin resistance.

Chromans↗

Renal functional reserve in patients with recently diagnosed Type 2 diabetes mellitus with and without microalbuminuria.

BACKGROUND/AIMS: During the first 10 years, two thirds of the patients with type 2 diabetes mellitus (DM) have microalbuminuria (MA). Functional renal reserve (FRR) and its relationship with proteinuria and metabolic control are unknown at the early phases of disease. We investigated the frequency of MA in recently diagnosed type 2 DM patients, and its association with FRR. METHODS: We studied 181 type 2 DM patients with less than 6 months since diagnosis. Renal volume, MA, glomerular filtration rate (GFR) and renal plasma flow (ERPF) were evaluated before and after an acute oral protein load in 28 type 2 DM patients (14 with, and 14 without MA), and in 7 healthy subjects. RESULTS: A total of 10.6% of the patients had MA. MA patients had higher cholesterol and triglyceride levels than those normoalbuminuric. Twenty recently diagnosed type 2 diabetic patients showed high basal GFR. Twelve of them had MA and insulin resistance. After the acute oral protein load, the control subjects and the patients without MA increased their GFR and their ERPF. The group with MA did not. CONCLUSIONS: Seventy-five percent of the patients were hyperfiltering. Normoalbuminuric patients had larger increase in GFR and ERRPF than MB patients. We conclude that FRR measurement can be an important tool for the diagnosis of latent diabetic nephropathy.

Adult↗

Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: a randomized, placebo-controlled trial.

BACKGROUND: Alendronate (ALN) is an aminobisphosphonate commonly used for osteoporosis in postmenopausal women. We studied the effect of ALN on bone loss prevention in type 2 diabetes mellitus patients with periodontal disease. METHODS: In a controlled double-blind, randomized study we evaluated prospectively diabetic patients paired by gender and years since diagnosis for 6 months. The study included 40 patients (20 men and 20 women), 50 to 60 years old, with more than 5 years since diagnosis of diabetes and established periodontitis. They were randomly allocated to alendronate (10 mg/daily) or placebo treatment for 6 months. The endpoints of treatment were: the distance between the alveolar bone border and the cemento-enamel-junction (CEJ) evaluated by means of digital radiographic imaging, a biochemical marker of bone resorption (urine N-telopeptide) (Ntx), and periodontal parameters. Metabolic control was assessed at baseline and after 6 months. RESULTS: Baseline and 6-month glycated hemoglobin levels were similar in both groups. Alendronate induced a significant decrease in NTx at 6 months (P = 0.006). Periodontal parameters improved in both groups. However, they were significantly better for the ALN treated group. Alveolar bone border-CEJ distance increased in the placebo, but decreased in the ALN group (P = 0.0003). CONCLUSIONS: In type-2 diabetic patients, alendronate induced more improvement in alveolar bone crest height than control therapy. No differences in urinary N-telopeptide or glycated hemoglobin were observed in this short-term randomized controlled pilot trial.

Alendronate↗

Plasma epinephrine and norepinephrine response to stimuli in autonomic neuropathy of type 2 diabetes mellitus.

The objective of this study was to examine epinephrine and norepinephrine plasma levels in patients with clinical type 2 diabetes mellitus, at different stages of autonomic neuropathy. Eighteen patients were classified in groups without (n = 6) and with early (n = 6), definite (n = 3) and severe (n = 3) neuropathy. Blood catecholamine levels were measured after the Valsalva maneuver, cold exposure and orthostatic tests. The norepinephrine basal levels were lower in patients with severe neuropathy (0.4 +/- 0.2 nmol/l), compared with the group with no neuropathy (1.3 +/- 0.5 nm/l, p = 0.034), or with early neuropathy (1.3 +/- 0.7 nm/l, p = 0.035). After the Valsalva maneuver, no increase was found in the group with severe alteration. In patients without neuropathy, cold exposure induced a peak of norepinephrine at 5 min (delta = 1.9 +/- 1.6 nmol/l). The increase was lower in groups with definite and severe damage. In patients with definite or moderate neuropathy, the orthostatic test induced minimal or no response. The epinephrine response to the maneuvers was not significant, and no differences were found among the groups. Norepinephrine basal levels and cold responses are diminished in patients with definite and severe autonomic neuropathy. This provides further evidence on their impaired response to stress. The comparable epinephrine levels in patients with or without autonomic neuropathy indicates that adrenal medullar function is not significantly altered.

Autonomic Nervous System Diseases↗

Contribution of HLA class II genes to end stage renal disease in mexican patients with type 2 diabetes mellitus.

To analyze the contribution of MHC class II genes in type 2 diabetes mellitus (DM) with end stage renal disease (ESRD), we examined the distribution of HLA-DRB1, DQA1, DQB1 loci in Mexican Mestizos of Central Mexico, using PCR-SSOP and PCR-SSP. Three groups were included: 47 type 2 diabetic ESRD patients; 42 patients with ESRD and 50 type 2 DM patients with no kidney complication. The results were compared with those of 101 controls of the same area. The median since DM was first diagnosed, was 18 years prior to the onset of ESRD. The frequencies of DRB1*1502 and DQB1*0501 were increased in DM patients with ESRD (p = 0.004; RR = 7.4, CI = 1.5-37; EF = 0. 13; p = 0.007; RR = 2.9, CI = 2.3-3.5, EF = 0.21, respectively). In contrast, DRB1*0407 was decreased in the same group (p = 0.0008, RR = 0.2; CI = 0.035-0.70, PF = 0.19). Diabetic patients with DRB1*1502 are 8.8 times more likely to develop ESRD, independently of the duration time of DM. DRB1*1502 contributes to the susceptibility to ESRD while DRB1*0407 is involved in protection. The residue at DRB1-74 differs in these alleles: DRB1*0407 has glutamic acid and DRB1*1502 has an alanine, suggesting that this substitution may be important for both, peptide anchoring and for presentation to the T cells.

Adult↗

Denial of disease in Type 2 diabetes mellitus: its influence on metabolic control and associated factors.

AIMS: We have investigated denial of disease in patients with Type 2 diabetes mellitus (DM) and its possible association with metabolic control, and with psychosocial variables: satisfaction with medical care, perceived stress, social support, knowledge of diabetes and belief in conventional medicine. METHODS: We studied 160 patients in a cross-sectional design, in two groups: with (70) and without social security coverage (90). The mean age for the total group was 53.6 years, with a known diabetes duration of 8.1 years. RESULTS: Denial of disease was similar in those with < or = 5 years since diagnosis (73 patients) and with > 5 years (87). The group without social security had higher scores of perceived stress, and lower scores of social support, knowledge about diabetes and belief in conventional medicine; denial, however, was similar in the two groups with or without social security. Multiple regression analysis showed that denial of disease was positively associated with HbA1c in the total group (P < 0.001), in the groups with < or = 5 and > 5 years since diagnosis, as well as in the groups with or without social security. Denial was also associated with years since diagnosis (P = 0.009) for the group with < or = 5 years since diagnosis. CONCLUSIONS: We concluded that, in patients with Type 2DM denial of disease increases with time during the first 5 years of evolution of diabetes; is associated with poor metabolic control; but is not associated with knowledge of diabetes, belief in conventional medicine, social support or perceived stress.

Cross-Sectional Studies↗

Age at menopause in women with type 2 diabetes mellitus.

OBJECTIVE: Considering that chronic diseases such as diabetes mellitus (DM) may determine premature ovarian failure by various mechanisms, we studied the age at menopause in women without diabetes and in women with type 2 DM. DESIGN: We studied 409 women without diabetes and 404 patients with type 2 DM, selected from 45 to 55 years of age, for analysis with the status quo method. The age at menopause was calculated with a logistic regression on the proportions of menopausal women for each age group. RESULTS: In the groups, 172 women without diabetes and 207 women with diabetes had menopause. The regression procedure gave a median age of 49.7 +/- SD 1.7 years for the whole group, 49.6 +/- 1.6 years for the nondiabetic group, and 49.8 +/- 1.7 years for women with diabetes. Women without diabetes were 1.4 years younger, but this factor did not have an influence on the results. Smoking habits, vegetarianism, and somatometric variables were similar in both groups, except for waist/hip and abdomen/hip ratios, larger in the group of women with diabetes. The mean for years since diagnosis in patients < 45 years of age was 4.9 years. For older patients, the figure increased to 8.9 years. CONCLUSIONS: No difference for age at menopause was found between women without diabetes and women with type 2 diabetes who were 5 to 8 years since the diagnosis was made.

Age Distribution↗

Factors associated with the sexual experiences of underprivileged Mexican adolescents.

This study investigated factors associated with the sexual experiences of 523 underprivileged Mexican adolescents. Approximately 41% of the males and 24% of the females were sexually active, with more than half not using contraceptives. Multivariate logistic regression analysis revealed that sexual activity was strongly associated with age, knowledge about sexually transmitted diseases, and attitudes toward sexuality. Positive affective responsiveness in the family was associated with sexual activity and number of sexual partners. Family problem solving and roles were also associated with sexual activity. The use of contraceptives was negatively related to affective involvement between parents, and being a victim of sexual abuse was negatively associated with number of persons in the family. These findings support the notion that affective environment within the family is a factor in adolescent sexuality.

Adolescent↗

High-frequency FSH and LH pulses in obese menopausal women.

We studied the pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretory patterns, at early or intermediate years of menopause in seven normal women with different degrees of obesity, taking blood samples every minute for 40 min to 2 h. The hormones were assayed with an immunoradiometric assay (IRMA) system, analyzing with the cluster pulse algorithm. All women showed hormone pulses every 8-10 min. In five of them were found periods of discrete pulses with oscillations of high amplitude alternating with periods of pulses of low amplitude. In two cases, the high-frequency oscillatory pattern with low amplitude was found around low mean levels of 22.8 and 25.7 IU/L. The LH oscillatory pattern also had a high frequency, but at a lower level, giving a high FSH/LH ratio. The coincidence index of FSH with LH peaks was 76.6%. We concluded that at menopause, the frequency of FSH and LH secretion increases with a high FSH/LH ratio. Obese menopausal women may have the same high-frequency oscillatory patterns, but at low levels.

Body Mass Index↗

Menopause in normal and uncomplicated NIDDM women: physical and emotional symptoms and hormone profile.

OBJECTIVE: To compare the physical characteristics, emotional symptoms and metabolic conditions of menopausal women with and without non insulin dependent diabetes mellitus (NIDDM). METHODS: We studied 100 menopausal women 45-72 years of age, 51 with and 49 without NIDDM, in a cross-sectional design. Biological characteristics were collected and emotional symptoms were assessed with a modified Hamilton and Bech-Rafaelsen scale, scoring depression, anxiety, non specific symptoms of depression (NSSD) and the empty nest syndrome (ENS). Weight, body mass index (BMI), waist/hip and abdomen/hip ratios and percent of body fat were registered. The sulfoconjugated form of the dehydroepiandrosterone (DHEAS), follicle stimulating hormone (FSH), cortisol and fasting, as well as postprandial insulin/glucose ratios, were measured in blood. RESULTS: Women with NIDDM had earlier mean age for menopause, more central obesity and less peripheral fat; they had also more prevalent emotional symptoms than non diabetic menopausal women. In women with NIDDM, symptoms were associated with years since diagnosis and with BMI. In non diabetic menopausal women schooling and attitudes to sexuality were associated with symptoms. FSH was inversely associated with BMI in both diabetic and non diabetic women; postprandial insulin/glucose ratio was correlated with central obesity in the group without NIDDM and cortisol with sitting systolic blood pressure (SBP) in the group with NIDDM. CONCLUSION: The diagnosis of NIDDM and its metabolic conditions were associated with an increased frequency of some symptoms in menopausal women.

Aged↗

The effect of hormone replacement therapy on blood pressure and cardiovascular risk factors in menopausal women with moderate hypertension.

OBJECTIVE: To assess the effect of injectable hormone replacement therapy (HRT) vs a placebo in hypertensive menopausal women. DESIGN AND METHODS: Prospective randomised double-blind study over 90 days. Fifty-five menopausal women with mild to moderate hypertension, stopped their antihypertensive medication and were studied for 2 weeks. Diastolic BP increased to over 105 mm Hg in five patients who were not included in the study. The remaining patients were randomly allocated to three groups: placebo (PL), estradiol valeranate 10 mg (E), and estradiol valeranate 4 mg plus prasterone enantate 200 mg (E+P). A further five patients were excluded from the study for different reasons. RESULTS: Standing and recumbent BP decreased in the PL group but did not change in the E and E+P patients. No change was observed in the serum levels of total cholesterol or low density lipoprotein (LDL)-cholesterol at the end of the trial. Plasma renin activity (PRA), aldosterone and insulin levels decreased during the study; PRA fell more significantly in the E+P group, the aldosterone reduction was highly significant in both hormone treated groups, specially the E+P group. Plasma insulin decreased in all groups and FSH levels were lower in the two treatment groups. CONCLUSIONS: In a randomised controlled trial no rise in BP was found after 90 days in hypertensive women with two forms of HRT. There was an unexpected fall in BP in those women allocated to placebo injections.

Aged↗

Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system.

We proposed a simple analytical procedure for measurement of serum advanced glycosylation end products (AGEs) based on simultaneous detection of low-molecular-mass peptides and AGEs with a flow system and two detectors connected on-line: spectrophotometric for peptides (lambda = 280 nm) and spectrofluorometric for AGEs (lambda ex = 247 nm, lambda em = 440 nm). Sample pretreatment was carried out in microcentrifuge tubes: Serum (20 microL) was deproteinized with trichloroacetic acid (480 microL, 0.15 mol/L) and lipids were extracted with chloroform (100 microL). Twenty microliters of the filtered aqueous layer was injected to the flow system and the relation between fluorescence and absorption signals was measured. A peptide-derived AGE calibrator was used for calibration. Within-day and between-day CVs were 6.7% and 9.1%, respectively, at an AGE concentration corresponding approximately to that in healthy individuals. Mean results (+/-SD) in 10 healthy individuals were 10.1% +/- 1.0%, in 21 patients with diabetes without complications 18.0% +/- 6.2%, in 25 patients with complications 24.1% +/- 15.4%, and in 12 diabetic patients in end-stage renal disease 92% +/- 30%. Comparison with an ELISA procedure (x, in arbitrary units/L) yields a regression equation y = 0.713x + 1.24 (Sy [symbol: see text] x = 6777, r = 0.8477, n = 41).

Diabetes Mellitus↗

Renal tubular acidosis in children with vesicoureteral reflux.

PURPOSE: We evaluated renal tubular acidosis in children with primary vesicoureteral reflux. MATERIALS AND METHODS: We studied 18 children 4 to 15 years old to determine age at onset, reflux intensity, and renal scars and volume as possible associated factors of renal tubular acidosis. Patients had normal glomerular filtration rates and no urinary infections for the last 12 weeks, and they had not undergone urological surgery. Urine acidification and alkalization tests were done, and the Mann-Whitney U test was used to assess differences between the groups with and without renal tubular acidosis. RESULTS: A total of 14 patients had unilateral and 4 had bilateral reflux, which varied in severity. All children except 2 had renal scarring. Bilateral renal volume was smaller in the renal tubular acidosis group. Nine patients had distal renal tubular acidosis, including 4 with short stature. CONCLUSIONS: Several patients with vesicoureteral reflux had renal tubular acidosis and some had growth failure. Grades of reflux and renal scarring were similar in patients with and without renal tubular acidosis. A single evaluation of reflux is of slight value for predicting future functional tubular impairment, and the duration of reflux and other associated factors may be more important. Renal tubular acidosis was the main explanation for growth failure in these patients.

Acidosis, Renal Tubular↗

Knowledge and attitudes toward sexuality in adolescents and their association with the family and other factors.

Family structure and function and their association with knowledge and attitudes toward sexuality, contraception, and sexually transmitted diseases (STD) were studied in 918 students and 312 adolescents working in factories. Unmarried workers reported higher rates of sexual activity than did students (30.9% vs. 21.8%, p = .04 for males; 12.9% vs. 6.0%, p = .005 for females). Among sexually active males, 33.3% of students and 30.7% of workers used contraception, compared with 27.5% of female students and 9.5% of female workers. Workers were from larger families than students, and the male and female workers had lower scores for knowledge on sexuality, contraception, and STD than did students. Multiple stepwise regression showed that age and schooling of the parents were associated with knowledge and attitudes in the students. In workers, the position of the child in the family was a negative regressor for attitudes and knowledge on sexuality in males, and for knowledge on contraception and STD in females. In regard to family function, the significant factors were compromise between the parents, positive affective response, communication within the family, problem solution, and control of behavior. It was concluded that female workers are at higher risk for unwanted pregnancies and STD. The factors associated with knowledge and attitudes were age, schooling of the parents, mother working out of home, position of the adolescent in the family, and the diverse aspects of family function.

Adolescent↗

Symptoms at perimenopausal period: its association with attitudes toward sexuality, life-style, family function, and FSH levels.

We studied the association of symptoms with attitudes toward sexuality, life-style, family functioning, and follicle-stimulating hormone (FSH) levels in perimenopausal women. We collected data on depression, anxiety, nonspecific index of depression, and the empty nest syndrome in 222 women with a mean age of 47.7 (47.2-48.2, 95% CI) years (102 of them were at menopause). Family functioning was evaluated with the McMaster model, and attitudes toward sexuality with questions about women's opinions on sexuality. Scores of depression were higher in women with more than 1 year of menopause. Attitudes to sexuality was significantly associated with all four symptoms. For family function, affective involvement, control of behavior, the roles of the members in the family, and communication were associated with some symptoms. Serum FSH was associated with body mass index, abdomen/hip ratio, and depression. We concluded that: (1) Attitudes toward sexuality was the main regressor for symptoms; (2) the function of the family is also associated with some symptoms; and (3) FSH levels may be lower in obese menopausal women and higher in women with depression or anxiety.

Adult↗

Symptoms at the menopausal and premenopausal years: their relationship with insulin, glucose, cortisol, FSH, prolactin, obesity and attitudes towards sexuality.

The symptoms of 81 premenopausal and 70 menopausal women were studied to determine the association with obesity, attitudes towards sexuality (ATS), and diverse hormone values: fasting and postprandial glucose (FG, PG) and insulin (FI, PI), cortisol, prolactin, follicle-stimulating hormone (FSH). The mean age of the women studied was 49.1 years. The frequency of symptoms was 35.4% for depression, 34.3% for nonspecific symptoms of depression (NSSD), 38.6% for empty nest syndrome (ENS), and 42.3% for anxiety. NSSD, ENS, FSH and cortisol levels all possessed higher values at late-menopausal stage. A multiple regression analysis revealed the following results; NSSD was associated to ATS (negative); sleep alterations were correlated to prolactin, FSH, PI/PG, FI/FG and waist/hip ratio; FSH was associated with both a decreased sexual interest and depression. In the study of hormone levels it was found that cortisol, insulin and FI/FG were associated with ATS; PI, cortisol, FI/FG and PI/PG were associated with body mass index (BMI) and FSH; prolactin and FI/FG were associated with age. We concluded that: (1) data indicative of insulin resistance correlated to both depression and sleep alterations; (2) overweight is related to NSSD, sleep alterations, and hormonal changes.

Adult↗