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Biomedical subjects

J M Martins

Publications and source records attributed to J M Martins.

At least 19 recordsLinked to original sources

Degradation in soil and water and ecotoxicity of rimsulfuron and its metabolites.

The degradation and ecotoxicity of sulfonylurea herbicide rimsulfuron and its major metabolites were examined in batch samples of an alluvial sandy loam and in freshwater. An HPLC-DAD method was adapted to simultaneously identify and quantify rimsulfuron and its metabolites, which was successfully validated by GC-MS analysis. In aqueous solutions, pure rimsulfuron was rapidly hydrolyzed into metabolite 1 (N-(4,6-dimethoxypyrimidin-2-yl)-N-(3-(ethylsulfonyl)-2-pyridinylurea)), which itself was transformed into the more stable metabolite 2 (N-((3-(ethylsulfonyl)-2-pyridinyl)-4,6-dimethoxy-2-pyrimidineamine)), with half-life (t(1/2)) values of 2 and 2.5 days, respectively. Hydrolysis was instantaneous under alkaline conditions (pH = 10). In aqueous suspensions of the alluvial soil (pH = 8), formulated rimsulfuron had a half-life of 7 days, whereas that of metabolite 1 was similar to that in water (about 3.5 days). The degradation of the two major metabolites was also studied in soil suspensions with the pure compounds at concentrations ranging from 1 to 10 mg l(-1). The half-life of metabolite 1 ranged from 3.9 to 5 days, close to the previous values. Metabolite 2 was more persistent and its degradation is strongly dependent on the initial concentration (C0): half-life values ranged from 8.1 to 55 days at 2-10 mg l(-1), respectively. These values are higher than those determined from the kinetics of metabolite 1 transformation into metabolite 2 (t(1/2) = 8-19 days). The ecotoxicity of the three chemicals was evaluated through their effect on Daphnia magna and Vibrio fischeri (Microtox bioassay). No effect was observed on D. magna with 24 and 48 h acute toxicity tests. Similarly, no toxic effect was observed with the Microtox test for the three chemicals in the range of concentrations tested that included the field application dose. Thus, being of low persistence and lacking acute toxicity, these chemicals present a low environmental risk. However, chronic effects should be studied in order to confirm the safety of rimsulfuron and its major metabolites.

Animals↗

Psychoneuroendocrine characteristics of common obesity clinical subtypes.

OBJECTIVE: To relate psychological profiles, cerebral asymmetry and the hypothalamus-pituitary-adrenal axis (HPA) reactivity to clinical characteristics of common obesity. METHODS: Sixty consecutive adult female overweight and obese patients attending the outpatient endocrine department were included in this study. Clinical evaluation specifically selected a priori the following indexes: obesity age of onset, parenthood obesity, carbohydrate craving, binge eating with purging, obesity degree (defined by the body mass index (BMI)--weight (kg)/height (m(2))), body fat distribution (defined by the abdominal--thigh ratio (A/T)) and initial weight loss after medical treatment. Psychological evaluation was performed with the Minnesota Multiphasic Personality Inventory (MMPI). In the last 30 patients, the Edinburgh Inventory of Manual Preference (EIMP) and the corticotrophin-releasing hormone (CRH) test were also performed. RESULTS: Clinical characteristics defined a priori were independent variables as evaluated by contingency table analysis. Factorial analysis of variance (ANOVA) revealed a significantly different MMPI profile, according to parental obesity, with post-hoc significantly higher scores on the hypochondriasis (Hs), paranoia (Pa), psychasthenia (Pt) and schizophrenia (Sc) scales in patients with obese parents. Obese patients presented significantly higher dichotomized manual preference indexes in relation to overweight patients. Parental obesity, binge eating behaviour with purging, body fat distribution and the dichotomized manual preference index were independent significant factors for the ACTH response in the CRH test, together explaining 41% of the response variability. Age of onset of obesity and the dichotomized manual preference index were independent and significant factors for the cortisol response, together explaining 37% of its variability. A non-normal distribution was found for the ACTH response: high- and low-responders presented significantly different MMPI profiles, with high-responders presenting higher scores on all clinical scales except masculinity/femininity (Mf). CONCLUSION: Overweight/obese subjects with parental obesity present a distinctive personality profile and a higher ACTH response in the CRH test. Cerebral asymmetry may be a relevant factor for obesity development and is associated with the HPA reactivity. HPA reactivity is a sensitive index integrating clinical, psychological and neural asymmetric factors. International Journal of Obesity (2001) 25, 24-32

Adipose Tissue↗

Dissolution of omeprazole from delayed-release solid oral dosage forms.

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.

Administration, Oral↗

Transient hyperandrogenemia and its relation to ovulation.

OBJECTIVE: To study serum androgen levels in relation to ovulation. DESIGN: Prospective, controlled clinical study. SETTING: Outpatient endocrine department of a public central hospital. PATIENT(S): Forty-eight consecutive young, nonobese, hirsute women. INTERVENTION(S): Endocrine evaluation between days 2 and 5 and between days 22 and 25 of a spontaneous menstrual cycle. MAIN OUTCOME MEASURE(S): Levels of FSH, LH, E2, P, androstenedione (A), total testosterone (T), DHEAS, and 17alpha-hydroxyprogesterone (17-OHP). RESULT(S): Hyperandrogenemia occurred equally in a persistent (56%) or a transient form (44%). Transient hyperandrogenemia was more common in the early follicular phase in ovulatory cycles and in the second phase in delayed or anovulatory cycles (63% and 37% versus 10% and 90%, respectively). In delayed or anovulatory cycles, A, total T, and DHEAS increased significantly during the delayed follicular phase. CONCLUSION(S): In delayed or anovulatory cycles, transient hyperandrogenemia occurs late in the follicular phase because of previous ineffective steroidogenesis. In contrast, in ovulatory cycles, transient hyperandrogenemia occurs mainly in the early follicular phase. After ovulation, effective aromatization attenuates the condition. During evaluation and medical treatment of hirsutism, physicians should consider the common occurrence of transient hyperandrogenemia and its relation to ovulation.

Adult↗

Uniformity of dosage units--comparative study of methods and specifications between Eur. Pharm. 3rd and USP 23.

Methods and specifications of Eur. Ph. 3rd Ed. and USP 23 for the evaluation of the uniformity of dosage units were compared, in relation to: (i) allowed dispersion of the sample; and (ii) adequability to control the individual contents of active ingredient in relation to the labelled amount. Using the characteristics of the normal distribution curve, we calculate: (1) the highest dispersion allowable, represented by the relative standard deviation of the uniformity of mass of single-dose preparations of Eur. Ph. 3rd Ed., (results were 3.4, 5.1 and 6.8% for L1 = 5, L = 7.5 and L = 10, respectively); and (2) for all the methods studied the allowable units frequency for different intervals of the labelled amount. Differences between the tests of Eur. Ph. 3rd Ed. and USP 23 can lead to acceptance samples with very different individual contents variability, namely if the limit specifications for the strength was +/- 10%. The main reasons for that are: (1) in Eur. Ph. 3rd Ed., the limits are set with reference to the average content of the sample, and in USP 23, they are set with reference to the labelled amount of the active ingredient; and (2), the USP 23 calculates the content of active ingredient in each tablet from the result of the assay, when the weight variation method was used. Taking +/- 5% of label claim as the specification for the strength of the product, according EEC requirements, the maximum percentage of units outside the range 95-105% of label claim allowed by Eur. Ph. 3rd Ed. and USP 23 tests are similar.

Chemistry, Pharmaceutical↗

Dyslipidaemia in female overweight and obese patients. Relation to anthropometric and endocrine factors.

OBJECTIVE: To characterize serum lipid abnormalities in overweight and obese female patients and to quantify the relative importance of associated factors. METHODS: Cross sectional study at the first visit to the out-patient department. 237 consecutive overweight and obese female patients (age 31 +/- 14 y, body mass index (BMI) 34.2 +/- 6.0 kg/m2) were studied. Evaluation included a questionnaire-based assessment of dietary and physical activity habits, determination of anthropometric indexes (BMI, abdominal/thigh ratio (A/T) and conicity index (CI)) and endocrine evaluation. Statistical analysis by factorial ANOVA and multiple regression. RESULTS: Dyslipidaemia was present in 46% of the patients, with hypercholesterolaemia (35%) being more frequent than hypertriglyceridaemia (10%). Age but not dietary habits or physical activity patterns was significantly related to serum lipid concentrations, independently accounting for 6-10% of their variability. Pharmacological drug use resulted in increased serum triglyceride concentrations, explaining less than 5% of their variability. Serum cholesterol concentrations were not significantly related either to anthropometric or to endocrine indexes. For serum triglyceride concentrations, anthropometric indexes accounted for 6% of their variability and endocrine indexes-postprandial insulin, serum cortisol, testosterone and androstenedione together accounted for 32%. CONCLUSION: In mild to moderate female obesity of the peripheral type, dyslipidaemia is common. However the most common abnormality, hypercholesterolaemia is not significantly related to anthropometric or endocrine indexes, while these together account for more than one third of variability in serum triglyceride concentrations.

Adolescent↗

[Angiography in thoracic outlet syndrome].

The thoracic outlet syndrome is a changeable clinical syndrome caused by compression of the neurovascular bundle of the upper extremity, within the cervicoaxillary channel. From April 1980 through May 1995, 24 patients with clinical thoracic outlet syndrome were evaluated by selective arteriography. The diagnosis was confirmed in seven patients, in 14 the exam was normal and in the last three cases another arterial pathology was detected--subclavian artery occlusion, subclavian artery kinking and vertebral steal syndrome. The authors' aim is to emphasize arteriography as a diagnostic exam for thoracic outlet syndrome, very useful in the detection and localization of arterial compression. It also allows the diagnosis of other arterial entities.

Adolescent↗

[The use of endoprosthesis in superior vena cava syndrome caused by lung neoplasms].

We present six cases of superior vena cava syndrome caused by a malignant tumor that were treated by percutaneous endoprostheses. The technique is described and the results evaluated. In one case there was acute thrombosis of the endoprosthesis that was treated by urokinase. No other complications were observed. A patient died one month later due to progression of the tumor. The remaining cases were asymptomatic for longer than 6 months. It was concluded that endoprostheses for superior vena cava syndrome are efficient, with quick improvement of the symptomatology.

Adult↗

Microbial response to repeated applications of low concentrations of pentachlorophenol in an alfisol under pasture.

Columns of an Alfisol under permanent pasture were polluted by repeated additions of pentachlorophenol (PCP) (7 mg l-1) to levels of 102 and 510 mg Kg-1, to simulate a dynamic diffuse pollution. PCP was rapidly sorbed to the soil organic matter, and was only slightly degraded. Measurements of soil microbial biomass-C revealed a 25% decrease in total biomass-C caused by both leaching and PCP toxicity. Microbial biomass-C measurements performed on soil fractions showed that only microorganisms located in the outer compartment of the aggregates were affected. Microorganisms protected by soil micro-aggregates were not affected, suggesting that they were not in contact with PCP, which was thus unavailable for biodegradation. Three gram negative bacterial strains (Si, C3 and C2), able to use PCP as a sole carbon and energy source, were isolated after 0, 1 and 3 months of PCP enrichment respectively, and were identified as Pseudomonas (Si) and Acinetobacter (C3 and C2). In liquid degradation tests, the strains C2 and C3 degraded 60% of PCP within 26 days whereas the Pseudomonas degraded only 25%. A specific immuno-labeling of the three strains permitted to show that repeated PCP additions to soil had a positive, negative or absence of effect on the populations C2, C3 and Si respectively.

Acinetobacter↗

Acute modulation of active carrier-mediated brain-to-blood transport of corticotropin-releasing hormone.

The unidirectional brain-to-blood transport system for corticotropin-releasing hormone (CRH) across the blood-brain barrier could be instrumental in the homeostasis of central CRH. To characterize this system, the intracerebroventricular injection of 125I-CRH was used in mice. CRH was rapidly transported out of the brain with a half-time disappearance (t1/2) of 15 min, much faster than albumin (t1/2 = 50 min). Kinetic analysis revealed a saturable component with a low maximum velocity (apaproximately 0.020 nmol x min(-1) x brain(-1)) and low capacity (Michaelis constant approximately 1.4 nmol/brain). Transport was inhibited by verapamil, ouabain, and colchicine but not by cyclosporin. Transport was increased by corticosterone and inhibited by tumor necrosis factor-alpha and beta-endorphin. These results suggest that the specific unidirectional brain-to-blood transport system for CRH is dependent on energy and calcium channels, involves microtubules, is independent of the P-glycoprotein transporter, and is acutely modulated by adrenal steroids, cytokines, and endogenous opiates. This suggests its participation in the control of the stress response.

Adrenal Cortex Hormones↗

Transport of CRH from mouse brain directly affects peripheral production of beta-endorphin by the spleen.

The blood-brain barrier (BBB) regulates the passage of substances between the brain and the periphery. It has not been shown that the secretion from the brain of a small amount of a substance can directly affect the periphery by transport across the BBB. We found that central injection of radioactively labeled corticotropin-releasing hormone (CRH) resulted in the accumulation of intact CRH in the spleen. CRH also increased splenic beta-endorphin, an effect not blocked by pretreatment with dexamethasone. Inhibition of the secretion of CRH from the brain by colchicine resulted in decreased accumulation of CRH in the spleen and also decreased splenic beta-endorphin. Similar findings occurred in the pituitary gland. The results show that the passage of labeled CRH from the brain can directly affect a peripheral organ, thus emphasizing the regulatory function of the BBB.

Animals↗

Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone.

Corticotropin-releasing hormone (CRH) is produced and acts both within the central nervous system and at several peripheral sites. However, it is not known whether CRH is able to cross the blood-brain barrier (BBB) in either direction, or whether the central and peripheral compartments are independent. We studied the transport across the BBB of both human/rat CRH (hCRH) and ovine CRH (oCRH) using the native peptides labeled with 125I at the histidine residue, thereby avoiding the use of other synthetic modifications. No apparent transport of either hCRH or oCRH into the brain from blood was found, as measured by multiple-time regression analysis after intravenous injection of the labeled peptides. There were no significant differences between the two forms of the CRH peptide. However, both hCRH and oCRH were rapidly transported out of the brain after intracerebroventricular injection, with half-time (t1/2) disappearances of 11.1 (hCRH) and 15.1 min (oCRH); the transport rate was significantly different for the human and ovine forms. The transport of hCRH could be specifically inhibited by 5 nmol of unlabeled hCRH (t1/2 = 17.7 min) but not by the same dose of the synthetic analog alpha CRH12-41. The process could also be inhibited by pretreatment with aluminum chloride (t1/2 = 18.8 min). An indirect influence of the endogenous opiate modulating peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2, 5 nmol) was apparent by a change in the initial distribution within the brain. In conclusion, there is a specific unidirectional brain to blood transport system for CRH. This transport system in the mouse has a greater affinity for the human/rat than for the ovine form of the peptide, is inhibited by hCRH itself, and can be disrupted by pretreatment with aluminum. By facilitating the rapid clearance of central CRH, this transport system could be involved in the regulation of central CRH levels and could allow central CRH to reach the general circulation and act at peripheral sites.

Aluminum↗

[The transjugular intrahepatic portosystemic shunt].

The case of a 66-year-old woman with several episodes of hemorrhage by esophageal varices and ascites due to portal hypertension is presented. Despite 4 sessions of endoscopic sclerotherapy bleeding recurred. A transjugular intrahepatic portosystemic shunt was performed. In the 10 months following the intervention, there was no further hemorrhage, the ascites disappeared and the shunt is open.

Aged↗

[Renal artery angioplasty].

In the 59 hypertensive patients submitted to percutaneous transluminal angioplasty (PTA) of the renal artery, there was an immediate success in the blood pressure in 91.5% and a later one of 79.6%. In these patients we obtained better results: 81.4% in the unilateral lesions, more than in the bilateral ones--72.7%; 82.5% in the renal artery trunk lesions, more than in the ostium ones--71.4%; 88.9% in the lesions of fibromuscular origin, more than in the aterosclerotic ones--75%; 84.4% in up to 55 years old patients, more than in older ones--71.4%. These differences were not significant. The results of renal angioplasty in renovascular hypertension suggest this type of intervention as an alternative treatment.

Adult↗

Internal iliac artery: embolization to control hemorrhage from pelvic neoplasms.

The control of the massive and often fatal hemorrhage from pelvic neoplasms is a major therapeutic problem. Transcatheter embolization of the internal iliac arteries was performed in 108 patients with uncontrollable hemorrhage due to pelvic neoplasms (urinary bladder in 50, uterus in 39, ovary in 16, and prostate in three). Complete control of the hemorrhage was achieved in 74 patients, partial control in 23, and no control in 11. Seventy patients experienced postembolization syndrome (nausea, vomiting, gluteal pain, and fever due to tissue necrosis), and three had transient acute tubular necrosis caused by the contrast medium. It is important for success that the embolization be bilateral and that the embolic agent used be a permanent one.

Adult↗