Inhibitors of human collagenase, MMP1

Different common drugs (Meloxicam, Tenoxicam and Piroxicam, and sodium alendronate) were tested both experimental and theoretically as inhibitors of interstitial human collagenase, also known as matrix metalloproteinase 1 (MMP-1). The in vitro collagenase activity, alone and in the presence of inhibitors, was quantified by the reaction with a fluorescent synthetic substrate and measuring the change of emission. Collagenase-inhibitor interaction was studied theoretically by computational calculations. Three among the four tested substances showed moderate inhibiting activity against the human collagenase.

Humic substances from sediments of Lobos Pond (Argentina). Isolation, characterization and limnological implications

Humic substances (HS) were isolated from the sediments of Lobos Pond (Argentina) using mild conditions to preserve their native structure. The HS (humic and fulvic acids) were characterized by means of elemental analysis and FTIR spectroscopy. Also a by-product obtained during fulvic acids (FA) fractionation (an amorphous white solid residue) was analyzed. Results revealed possible interactions between FA and inorganic-organic substances that may have implications referring to bioavailability. Other limnological implications, such as autochtonous origin of HS linked with the hydrology, and change of pH during stormy weather that affects HS interactions, are discussed.

Impact of the substitution of reference annual streamflow by monthly streamflow on the potential use of water resources

The consideration of the streamflow seasonality has a high potential to improve the water use. In order to give subsidies to the optimization of water use, it was evaluated the impact of the change of reference annual streamflow by the monthly streamflows in the potential water use throughout the hydrography of Paracatu sub-Basin. It was evaluated the impact on Q7,10 (lowest average streamflow during a 7-day period with an average recurrence of 10 years) and on Q95 (permanent flow present 95% of the time). The use of monthly streamflow to substitute the annual streamflow had a high potential of improvement of water resources use in the sub-Basin studied. The use of monthly Q 7,10 in substitution of annual Q 7,10 increases the potential water use that vary from about 10% in the months of lower water availability to values exceeding 200% in the months with higher availability of surface water resources. The use of monthly Q95 in substitution of the annual Q95 implies in changes oscillating from reduction of 37% in months of higher water restriction to values exceeding 100% in the months of higher availability, so the use of monthly Q95 instead of the annual Q95 enables the more rational and safe use of water resources.

Chronic subdural hematoma: epidemiological and prognostic analysis of 176 cases

Objective : To characterize patients with chronic subdural hematoma undergoing surgery and to identify prognostic indicators. Methods : We conducted a retrospective analysis of patients diagnosed with chronic subdural hematoma (CSDH) undergoing surgical treatment. We analyzed: age, period from trauma to diagnostic imaging, pre and postoperative Glasgow coma scale, type of surgery, associated comorbidities, use of postoperative drainage and outpatient treatment. Results : The sample consisted of 176 patients, 126 male and 50 female patients (ratio 2.5 : 1), ages ranged from six months to 97 years, with an average of 59.3 years. CSDH was caused by trauma in 52% of patients, with the time from trauma to imaging averaging 25.05 days; 37.7% were hypertensive patients and 20% had a neurological disease. Eighty-five (48.3%) patients were elderly and altered consciousness was present in 63% of cases. Of the 91 (51.7%) non-elderly patients, 44% presented with headache, altered consciousness occurred in 40% and motor abnormalities in 27.5%. The CSDH was located on the right in 41%, left in 43% and bilaterally in 16% of patients. Conclusion : the change of consciousness was the most common clinical alteration in the elderly and headache in non-elderly. The most associated comorbidity was the arterial hypertension and the most frequent cause, head trauma. The trepanation with two oriffices associated with a closed drainage system was the most used operating, with high efficacy and low complication rate.

The Influence of Education and Depression on Autonomy of Women with Chronic Pelvic Pain: A Cross-sectional Study

Objective Patient autonomy has great importance for a valid informed consent in clinical practice. Our objectives were to quantify thedomains of patient autonomy and to evaluate the variables that can affect patient autonomy in women with chronic pelvic pain. Methods This study is a cross sectional survey performed in a tertiary care University Hospital. Fifty-two consecutive women scheduled for laparoscopic management of chronic pelvic were included. Three major components of autonomy (competence, information or freedom) were evaluated using a Likert scale with 24 validated affirmatives. Results Competence scores (0.85 vs 0.92; p = 0.006) and information scores (0.90 vs 0.93; p = 0.02) were low for women with less than eight years of school attendance. Information scores were low in the presence of anxiety (0.91 vs 0.93; p = 0.05) or depression (0.90 vs 0.93; p = 0.01). Conclusions Our data show that systematic evaluation of patient autonomy can provide clinical relevant information in gynecology. Low educational level, anxiety and depression might reduce the patient autonomy in women with chronic pelvic pain.

Survey on control and management practices of equine helminthes infection

Twenty-nine stud farms were selected in the Medium Paraíba region of the Rio de Janeiro state, Brazil. After an interview with the person responsible for the animals, faecal samples were collected from mares and analyzed via the EPG technique, faecal cultures, Sedimentation-centrifugo-flotation, and modified Ueno and Baermann techniques. The prevalence of helminths in the mares and in the stud farms was calculated. The stocking rates of pasture, change of horse bedding, absence of pasture rotation, absence of technology in the property, and less frequent treatment of the animals were associated with a greater prevalence of helminths, showing that these variables must be considered in equine control programs. The intensity of the parasitism was also associated with the stocking rate of pasture, absence of dunghill, presence of the animals only in paddocks, lack of technology in the property, less frequent treatment of the animals, and absence of the use of rotation regarding the anthelmintic class.

Analysis of emergency braking performance with particular consideration of temperature effects on brakes

During vehicle deceleration due to braking there is friction between the lining surface and the brake drum or disc. In this process the kinetic energy of vehicle is turned into thermal energy that raises temperature of the components. The heating of the brake system in the course of braking is a great problem, because besides damaging the system, it may also affect the wheel and tire, which can cause accidents. In search of the best configuration that considers the true conditions of use, without passing the safety limits, models and formulations are presented with respect to the brake system, considering different braking conditions and kinds of brakes. Some modeling was analyzed using well-known methods. The flat plate model considering energy conservation was applied to a bus, using for this a computer program. The vehicle is simulated to undergo an emergency braking, considering the change of temperature on the lining-drum. The results include deceleration, braking efficiency, wheel resistance, normal reaction on the tires and the coefficient of adhesion. Some of the results were compared with dynamometer tests made by FRAS-LE and others were compared with track tests made by Mercedes-Benz. The convergence between the results and the tests is sufficient to validate the mathematical model. The computer program makes it possible to simulate the brake system performance in the vehicle. It assists the designer during the development phase and reduces track tests.

Primary and secondary development of Cyperus giganteus Vahl rhizome (Cyperaceae)

In Cyperus giganteus, like in other Monocotyledoneae, the protoderm, procambium, fundamental meristem and primary thickening meristem (PTM) are differentiated from the rhizome promeristem. The PTM produces the inner cortical parenchyma, endodermis, pericycle and amphivasal vascular bundles, which are formed by the procambium too. After the primary body differentiates, cellular divisions continue only in the pericycle, and originate an irregular vascular system with vessel elements shorter and more branched than those found in the primary growth. This change of activity in the pericycle defines a secondary growth, where the secondary thickening meristem (STM) is the pericycle itself.

Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period

Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks) of nutritional restriction by receiving the "regional basic diet" (RBD, with 8% protein) of low-income human populations of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD) was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23% protein, early malnourished rats showed deficits in body and brain weights (10% to 60% and 3% to 15%, respectively), as well as increases in velocity of SD propagation (10% to 20%). These effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 or 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD

Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress

In order to investigate whether prolonged stress interferes with the onset of sexual behavior at puberty and with fertility at adulthood, prepubertal male Wistar rats (40 days of age) were immobilized 6 h a day for 15 days (up to early puberty) or for 60 days (until sexual maturity). Pubertal stressed rats showed a two-fold increase in the latency for the first mount (probably due to repeated aversive experience in which a change of environment was always followed by immobilization) and a 2.5-fold increase in the frequency of thrusting (indicative of enhanced sexual performance). The apparently stimulatory effect of prolonged stress on the onset of sexual behavior is discussed in terms of increased testosterone level and interference with the complex interchanges between the neurotransmitters/neuropeptides involved in the central control of male sexual activity. Adult stressed animals were mated with normal females, which became pregnant but exhibited a more than two-fold increase in both pre-implantation and post-implantation loss, probably due to a smaller rate of fertilization and/or fertilization with damaged spermatozoa.

Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis

To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89% reduction in luminal diameter). In each study, dobutamine (5 to 40 µg kg-1 min-1 in 3-min stages) and pacing (20 bpm increments, each 2 min, up to 260 bpm) were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min). The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05) reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery). Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1) the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2) in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 ± 11%) and dipyridamole (-18 ± 16%) tests as compared to dobutamine (-9 ± 6%) (P = 0.05), but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery) (pacing: -16 ± 7%; dipyridamole: -25 ± 16%; dobutamine: -26 ± 10%; not significant), and 3) a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery stenosis. The pacing stress test was less sensitive, but the difference was not statistically significant. The magnitude of segmental left ventricular dysfunction induced by ischemia was similar in all stress tests evaluated.

Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

Are birth weight and maternal smoking during pregnancy associated with malnutrition and excess weight among school age children?

In the late 1980's child malnutrition was still prevalent in Brazil, and child obesity was beginning to rise in the richest regions of the country. To assess the extent of the nutritional transition during the period and the influence of birth weight and maternal smoking on the nutritional condition of schoolchildren, we estimated the prevalence of excess weight and malnutrition in a cohort of Brazilian schoolchildren from 1987 to 1989. We calculated the body mass index (BMI) of 8- to 10-year-old schoolchildren born in Ribeirão Preto in 1978/79. We considered children with a BMI <5th percentile (P5) to be malnourished, children with P5³BMIof these nutritional disorders with birth factors (infant weight, sex, preterm delivery, number of pregnancies, maternal smoking during pregnancy, marital status, and schooling) and type of school using nominal logistic regression. A total of 2797 schoolchildren were evaluated. There was a significant prevalence of malnutrition (9.5%) and excess weight already tended to increase (15.7%), while 6.4% of the children were obese. Excess weight was more prevalent among children attending private schools (odds ratio, OR = 2.27) and firstborn children (OR = 1.69). Maternal smoking during pregnancy protected against malnutrition (OR = 0.56), while children with lower birth weight were at higher risk for malnutrition (OR = 4.23). We conclude that a nutritional transition was under way while malnutrition was still present, but excess weight and related factors were already emerging.

Spectroscopic studies on the interaction of efonidipine with bovine serum albumin

Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters ΔH0 and ΔS0 were 68.04 kJ/mol and 319.42 J·mol-1·K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (θ) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85%, whereas for the NZ-105-BSA system, it is 53%, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine_BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.

Association of CYP7A1 -278A>C polymorphism and the response of plasma triglyceride after dietary intervention in dyslipidemic patients

We investigated the effect of the -278A>C polymorphism in the CYP7A1 gene on the response of plasma lipids to a reduced-fat diet for 6 to 8 weeks in a group of 82 dyslipidemic males with a mean age of 46.0 ± 11.7 years. Individuals who presented at least one high alteration in total cholesterol, low-density lipoprotein cholesterol or triglyceride values were considered to be dyslipidemic. Exclusion criteria were secondary dyslipidemia due to diabetes mellitus, renal, liver, or thyroid disease. None of the subjects were using lipid-lowering medication. Baseline and follow-up lipid concentrations were measured. The genotypes were determined by the digestion of PCR products with the BsaI restriction endonuclease. There were statistically significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations after dietary intervention. The minor allele C has a frequency of 43%. Carriers of the C allele had significantly lower triglyceride concentrations (P = 0.02) than AA homozygotes. After adjustment of covariates, subjects with the AC and CC genotypes showed a greater reduction in triglyceride concentrations compared to subjects with the AA genotype. Multiple linear regression analyses showed that the AC and CC CYP7A1 genotypes accounted for 5.2 and 6.2% of triglyceride concentration during follow-up and adjusted percent of change of triglyceride concentration, respectively. The present study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. This gene represents a potential locus for a nutrigenetic directed approach.