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Biomedical subjects

A Baptista

Publications and source records attributed to A Baptista.

At least 37 records · Page 2Linked to original sources

Lipases and esterases: a review of their sequences, structure and evolution.

This chapter aims to provide a brief review on the enzyme family of lipases and esterases. The sequences, 3D structures and pH dependent electrostatic signatures are presented and analyzed. Since the family comprises more than 100 sequences, we have tried to focus on the most interesting features from our perspective, which translates into finding similarities and differences between members of this family, in particular in and around the active sites, and to identify residues that are partially or totally conserved. Such residues we believe are either important for maintaining the structural scaf-fold of the protein or to maintain activity or specificity. The structure function relationship for these proteins is therefore of central interest. Can we uniquely identify a protein from this large family of sequences--and if so, what is the identifier? The protein family displays some highly complex features: many of the proteins are interfacially activated, i.e. they need to be in physical contact with the aggregated substrate. Access to the active site is blocked with either a loop fragment or an alpha-helical fragment in the absence of interfacial contact. Although the number of known, relevant protein 3D structures is growing steadily, we are nevertheless faced with a virtual explosion in the number of known or deduced amino acid sequences. It is therefore unrealistic to expect that all protein sequences within the foreseeable future will have their 3D structure determined by X-ray diffractional analysis or through other methods. When feasible the gene and/or the amino acid sequences will be analyzed from an evolutionary perspective. As the 3D folds are often remarkably similar, both among the triglyceride lipases as well as among the esterases, the functional diversities (e.g. specificity) must originate in differences in surface residue utilization, in particular of charged residues. The pH variations in the isopotential surfaces of some of the most interesting lipases are presented and a qualitative interpretation proposed. Finally we illustrate that NMR has potential for becoming an important tool in the study of lipases, esterases and their kinetics.

Amino Acid Sequence↗

[The effect of combined toxicity on the development of alcoholic pancreatic lesions. A long-term experimental trial].

The aim of this study was to evaluate the adverse effects on the exocrine pancreas of ethanol and ethanol with congeners which coexist in alcoholic beverages most commonly consumed by the Portuguese population. Eighteen male Wistar rats were divided into three groups and submitted to a daily intraperitoneal injection of a hydroalcoholic solution of ethanol (SHAE) and a hydroalcoholic solution of ethanol, acetaldehyde, methanol and higher alcohols (SHAF); the third group served as a control and received an equivalent volume of an isocaloric solution of dextrose. All the animals were sacrificed at the end of the 9th week of the experiment. The following histological lesions were considered: acinar cell necrosis and steatosis, ductal dilatation, intraluminal plugs, parenchymal inflammation, fibrosis, peripancreatic fat necrosis and inflammation. Their severity was graded by means of a scoring system. The histopathologic changes which characterize pancreatitis (acinar cell necrosis, parenchymal inflammation, fibrosis and peripancreatic fat necrosis and inflammation) were found in the majority of animals of both study groups, but in none of the control group. The lesions tend to be more frequent and severe in the group treated with ethanol and its congeners (SHAF) than in the SHAE group; these differences are statistically significant when necrosis, ductal dilatation and overall severity of lesions are considered. The results of this study suggest that in the pancreas the toxicity of ethanol is enhanced by interaction with other components of alcoholic beverages.

Acetaldehyde↗

[Diltiazem 180 mg in delayed release formulation in mild and moderate arterial hypertension].

INTRODUCTION: Having acknowledge the need to treat arterial Hypertension concomitantly effective, safe and easy to comply with. These issues are the mainstay for a good adherence to a treatment that is long. AIM: This clinical trial addresses the efficacy and safety of an extended release tablet of 180 mg of diltiazem, once daily, to treat mild to moderate hypertension. POPULATION AND METHODS: Forty-five patients with mild to moderate hypertension were included in a multicentric, open trial consisting of three periods: washout (one week), placebo (one week) and a treatment period of four weeks with 180 mg slow-release tablets of diltiazem. Arterial Blood Pressure (BP) was measured through ambulatory blood pressure monitoring (ABPM) at the end of the first, second and sixth weeks. The therapeutic response was evaluated in terms of decrease in mmHg and in terms of systolic and diastolic loads. Treatment was considered successful when there was a drop in the medium diastolic BP to 90 mmHg or less and/or a decrease of at least 10 mmHg. RESULTS: Twenty-three patients completed the trial. There was a significant decrease (p < 0.0001) in the medium diastolic and systolic 24-hour BP values. The efficacy parameters were met in 62.5% of the patients, nonetheless there was a drop of at least 5 mmHg in 82.6%. There was a statistically more significant response during the diurnal versus the nocturnal periods, according to both criteria. CONCLUSION: Diltiazem, 180 mg extended-release tablet taken one daily, proved to be effective, over 24 hours, in controlling Hypertension in 62.5% of the enrolled patients while decreasing the medium diastolic BP by at least 5 mmHg in 82.5%.

Adult↗

The effect of permethrin-impregnated wall-curtains on malaria transmission and morbidity in the suburbs of Maputo, Mozambique.

The effect of nylon-netting wall-curtains impregnated with 0.5 g permethrin/m2 upon the biting rate of malaria vectors (Anopheles gambiae s.l. and An. funestus) and on the Plasmodium falciparum parasite rate, and morbidity due to malaria in children under five and between five and fourteen years was tested in the Maputo area. The curtains significantly lowered biting rates of both vector species inside curtained houses, but reduced inside resting and outside biting only in An. funestus. The percentage of children with falciparum parasitaemia fell significantly in curtained houses, and among their neighbours. However, parasite load and malaria morbidity in under fives was unaffected but malaria morbidity fell throughout the experimental area in 5 to 14-year-olds. This led to the speculation that malaria vectors inhibited from feeding in the vicinity of the curtains might have gone to feed in the adjacent control area.

Adolescent↗

The blind watchmaker and rational protein engineering.

In the present review some scientific areas of key importance for protein engineering are discussed, such as problems involved in deducting protein sequence from DNA sequence (due to posttranscriptional editing, splicing and posttranslational modifications), modelling of protein structures by homology, NMR of large proteins (including probing the molecular surface with relaxation agents), simulation of protein structures by molecular dynamics and simulation of electrostatic effects in proteins (including pH-dependent effects). It is argued that all of these areas could be of key importance in most protein engineering projects, because they give access to increased and often unique information. In the last part of the review some potential areas for future applications of protein engineering approaches are discussed, such as non-conventional media, de novo design and nanotechnology.

Animals↗

Interaction of the constituents of alcoholic beverages in the promotion of liver damage.

Little has been studied of the adverse effects of the exposure of the liver to the interaction of ethanol with its congeners and acetaldehyde, coexisting in the contents of alcoholic beverages. Twenty four male Wistar rats were divided into four groups. Two groups (SH/DA; SH/FA) were submitted to daily treatment with synthetic hydroalcoholic solutions containing ethanol, methanol, higher alcohols and acetaldehyde in the same proportions as those found in most common distilled and fermented alcoholic beverages; the third group (SH/EA) was treated with a hydroalcoholic solution of ethanol; the fourth group served as control and received an equivalent volume of an isocaloric solution of dextrose. All the animals were killed at the end of the 9th week of the experiment. The ratio between the liver weight and body weight was found to be lower in the treated animals than in the control group. The histology of the liver was altered in the three groups which were submitted to treatment with the hydroalcoholic solutions, with quantitative and qualitative differences between the groups. These results suggest that the hepatoxicity of ethanol in alcoholic beverages is enhanced by interaction with its congeners and acetaldehyde; they also suggest that alcoholic beverages are not equivalent in their potential to cause liver damage.

Alcoholic Beverages↗

[Homocysteinemia as a risk factor in early cerebrovascular disease].

PURPOSE: To determine whether hyperhomocysteinemia represents a risk factor of early thrombotic cerebrovascular disease. METHOD: In a group of patients under 55 years of age (n = 33, 19 males) which had suffered a stroke from 3 months to 1 year before the study, defined by clinical criteria and presence of cerebral infarction confirmed by tomography, without history or predisposition to embolic disease. The patients were matched with a group of normal controls of checkup program, in terms of age, and sex. Patients and controls with a history of alcoholism, clinical or laboratory signs of renal or hepatic insufficiency or with a history of recent ingestion of Group B vitamins were excluded since these conditions would influence homocysteinemia levels. We measured the plasmatic basal homocysteinemia of patients and controls (HC) and 6 hours later a methionine overload of 0.1 g/Kg body weight (LOAD HC). RESULTS: Patients; Controls; Signific.; Age 46.0 +/- 7.7; 45.9 +/- 7.8; NS; Basal HC. 10.1 +/- 3.4; 8.5 +/- 1.7; p < 0.05; Load HC 28.0 +/- 7.6; 22.7 +/- 5.5; p < 0.01. CONCLUSION: In this study hyperhomocysteinemia appears as a risk factor for thrombotic cerebrovascular disease before the age of 55;-The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement;-A larger number of patients and controls will be necessary to establish the relative importance of homocysteinemia among other vascular risk factors in cerebrovascular disease.

Adult↗

The galea frontalis myofascial flap in anterior fossa CSF leaks.

We report the clinical use of galea frontalis myofascial flaps in the treatment of anterior fossa cerebrospinal fluid leaks after trauma. This flap provides an adequately sized and vascularised barrier between the cranial and nasal cavities through which the cells of the inflammatory response reach the target area. This technique was used in 9 cases with complete success; in 5 out of 9 patients, repair of an anterior cranial base bone defect was also performed with split calvarial bone grafts, harvested from the frontal craniotomy bone. In all patients, neither recurrence of the CSF leakage nor postoperative meningitis or its recurrence were observed.

Adult↗

[Interaction of the contents of alcoholic beverages in the promotion of liver damage].

The adverse effects of the exposure of the liver to the interaction of ethanol with its congeners and acetaldehyde, coexisting in the contents of alcoholic beverages, have been little studied. Twenty four male Wistar rats were divided into four groups. Two groups (SH/DA; SH/FA) were submitted to daily treatment with synthetic hydroalcoholic solutions containing ethanol, methanol, higher alcohols and acetaldehyde in the same proportions as those found in most common distilled and fermented alcoholic beverages; the third group (SH/EA) was treated with a hydroalcoholic solution of ethanol; the fourth group served as control and received an equivalent volume of an isocaloric solution of dextrose. All the animals were killed at the end of the 9th week of the experiment. The ratio between the liver weight and body weight was found to be lower in the treated animals than in the control group. The histology of the liver was altered in the three groups which were submitted to treatment with the hydroalcoholic solutions, with quantitative and qualitative differences between the groups. These results suggest that the hepatoxicity of ethanol in alcoholic beverages is enhanced by interaction with its congeners and acetaldehyde; they also suggest that alcoholic beverages are not equivalent in their potential to cause liver damage.

Acetaldehyde↗

[The intrahepatic expression of the hepatitis B virus in chronic delta hepatitis].

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.

Adolescent↗

Choledochoenterostomy with an anti-reflux mechanism.

A new technique of choledochoenterostomy was devised to solve some of the problems of enterobiliary anastomosis with a normal calibre. The distal extremity of the common bile duct is completely surrounded by the bowel mucosa to a length of 3 cm after seromyectomy of a bowel wall rectangle of 4 x 1 cm. Experimental studies in rats and dogs demonstrated that this procedure prevents the risks of anastomotic disruption and functions like a mechanical unidirectional valve, which has great efficacy in stopping enterobiliary reflux. Studies in ten patients with obstructive jaundice with an extrahepatic biliary dilation less than 1.2 cm diameter submitted to this procedure confirmed the experimental results. All patients were asymptomatic, without jaundice and with normalization of the liver enzymes after 2 months. The permeability of the valvular anastomosis studied by cholangiography, the HIDA 99mTc test and manometry was quite similar to other classical biliary-enteric anastomosis. In contrast, anti-reflux efficacy was only demonstrated in patients with a valvular anastomosis.

Animals↗

[Collagenous colitis: clinical and histologic improvement after sulfasalazine and topical betamethasone].

We here by report a case of a 42 year-old white woman with an eight-year history of watery diarrhea where the rectal biopsies performed in endoscopically normal mucosa led to the diagnosis of collagenous colitis, characterized histologically by a thickening of the colonic subepithelial basement membrane. A brief review of the current etiopathogenic concepts of this entity is done and the importance of performing rectal biopsies in patients with unexplained diarrhea and normal appearing colon mucosa is stressed. A clinical improvement following therapy with Sulfasalazine and Beta-methasone enemas was found in this patient. We discuss the current views on the therapy and the difficulties of assessing responses to drugs in this condition.

Administration, Topical↗

Patch testing in children: a study of 562 schoolchildren.

562 schoolchildren from Oporto were patch tested with the standard series of the Portuguese Contact Dermatitis Group (GPEDC). 13.3% of the children had positive reactions, the most common being to neomycin, thimerosal, para-tertiary-butylphenol-formaldehyde (PTBPF) resin and fragrance-mix. Thus contact allergy in children seems not to be as unusual as previously thought.

Adolescent↗