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Biomedical subjects

L Montenegro

Publications and source records attributed to L Montenegro.

18 recordsLinked to original sources
PubMed2006

PLA/PLGA nanoparticles for sustained release of docetaxel.

This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of DeltaH value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

A femorotibial joint swelling with popliteal lymph node enlargement in a Rottweiler.

A 9-year-old male Rottweiler was presented to the Veterinary Medical Hospital Montenegro, Porto, Portugal with a large mass medial to the left stifle and radiographic signs of bone lysis involving the proximal tibia, fibula, and distal femur. A fine-needle aspiration was obtained from left popliteal lymph node, which was markedly enlarged. Cytologic examination revealed a highly cellular sample consisting of pleomorphic cells with marked anisocytosis and anisokaryosis and other criteria of malignancy. Some cells contained intracytoplasmic, granular, dark brown material, consistent with hemosiderin. Histologic evaluation of the surgically-excised lymph node revealed a neoplastic proliferation of histiocytic cells, with marked pleomorphism; occasional cells were erythrophagocytic. Mitotic figures were frequently observed, and many were atypical. Histologic findings were consistent with malignant histiocytosis. Necropsy examination confirmed the diagnosis of malignant histiocytosis with systemic involvement affecting most organs examined. This case of malignant histiocytosis case had an atypical clinical presentation, mimicking a musculoskeletal disorder. It underlines the importance of cytology as a simple, inexpensive, rapid and noninvasive complementary exam in routine clinical practice that can permit early diagnosis of the disease and timely selection of the most adequate therapy.

Animals↗
PubMed2003

Enhancer effects on in vitro corneal permeation of timolol and acyclovir.

The aim of this study was to evaluate the ability of two non-toxic skin penetration enhancers, N-methylpyrrolidone (NMP) and a positively charged phospholipid mixture (PS), to increase in vitro corneal permeation of timolol maleate (TM) and acyclovir (AC) in comparison with two corneal absorption promoters, polyethylene glycol octadecyl ether (Brij 78) and sodium taurocholate (TA). In vitro experiments were performed on corneas from albino rabbits which were mounted in a perfusion apparatus. The concentrations of the enhancers being tested were: Brij 78 1%, PS 1%, TA 1%, NMP 5%, NMP 10%. The safety of the enhancers being tested was assessed in vitro by determining their effects on corneal hydration and in vivo by means of a modified Draize test. Calculating the amount of drug permeated at different time points (90 and 180 min) we observed that TA, PS and NMP 5% significantly increased the cumulative amount of AC permeated after 90 min but only PS was effective after 180 min. TA, Brij 78 and PS were able to increase significantly the amount of TM permeated after 90 min but after 180 min only Brij 78 retained its effect. TA, Brij 78 and NMP 10% significantly increased the percent hydration levels (% HL) compared to the control while PS and NMP 5% did not affect % HL. The results of in vivo ocular tolerability studies showed that the enhancers which caused an in vitro increase of % HL produced in vivo conjunctival and/or corneal damages. The results of this study suggest that PS could be regarded as a potential corneal enhancer to increase the intraocular bioavailability of AC and TM.

Acyclovir↗
PubMed2001

Classic Pick's disease type with ubiquitin-positive and tau-negative inclusions: case report.

We report on a patient presenting Pick's disease similar to the one reported by Pick in 1892, with ubiquitin-positive and tau-negative inclusions. His diagnosis was made on the basis of clinical (language disturbance and behavioural disorders), neuropsychological (progressive aphasia of the expression type and late mutism), neuroimaging with magnetic resonance (bilateral frontal and temporal lobes atrophy) and brain single photon emission computed tomography (frontal and temporal lobes hypoperfusion) studies. Macroscopic examination showed atrophy on the frontal and temporal lobes. The left hippocampus displayed a major circumscribed atrophy. The diagnostic confirmation was made by the neuropathological findings of the autopsy that showed neuronal loss with gliosis of the adjacent white matter and apearance of status spongiosus in the middle frontal and especially in the upper temporal lobes. There were also neuronal swelling (ballooned cell) and argyrophilic inclusions (Pick's bodies) in the left and right hippocampi. Anti-ubiquitin reaction tested positive and anti-tau tested negative.

Aged↗
PubMed2001

Development and optimization of polymerase chain reaction-based malaria diagnostic methods and their comparison with quantitative buffy coat assay.

Polymerase chain reaction (PCR)-based assays targeting the small-subunit rRNA were developed and evaluated, allowing for the simultaneous diagnosis of Plasmodium falciparum and Plasmodium vivax DNA in human blood samples. The PCR methods and quantitative buffy coat (QBC) were compared in 402 patients. The heminested PCR method showed a sensitivity of 97.4%, which was superior to the sensitivity of the QBC method (91.7%, P < 0.05), to simple PCR (84.6%, P < 0.001), and to PCR with digoxigenin labeling (PCR-DIG) (88.5%, P < 0.001). The PCR-DIG and QBC analyses were more sensitive than simple PCR (P < 0.003 and P < 0.05, respectively). There was no significant difference between the sensitivities of the QBC assay and the PCR-DIG assay. The specificity for the 3 PCR-based methods was 100%, superior to the specificity calculated for the QBC assay (88.95%, P < 0.009). The frequency of a positive result in groups from endemic areas but without detectable parasitemia increased, in order, from simple PCR, QBC test, PCR-DIG, to heminested PCR. An association between a positive PCR result and a history of malaria was also found. Taken together, these data suggest that this technology could be further developed to screen people with oligoparasitemia and to monitor malaria treatment.

Adolescent↗
PubMed1997

Anticonvulsive activity of a new GABA mimetic drug.

This study examines the pharmacological profile of a new GABA mimetic drug, 4-[(2H)-1,3-benzoxazine-2,4(3H)-dione]-butyric acid (BXDBA), using both a behavioral and an anticonvulsive study. The behavior elements considered were locomotor activity, motor coordination, catalepsy, behavior and antinociception. The anticonvulsive study was performed using the convulsive agent bicuculline. BXDBA [10, 20 and 40 mg/kg, intraperitoneally (i.p.)] did not significantly modify animal behavior or the nociceptive threshold of the animals. The anticonvulsive study indicated that BXDBA (10, 20 and 40 mg/kg, i.p.), injected 60 min before bicuculline (10 micrograms/intracerebroventricular (i.c.v.)/mouse) induced a dose-dependent and significant reduction of the convulsive activity of bicuculline whereas it was ineffective if injected immediately before the convulsive agent. Our data indicate that this new GABA mimetic drug possesses good anticonvulsive activity and its ability to block bicuculline-induced convulsions suggests that it could be a GABAA mimetic drug. Furthermore, since BXDBA is able to act after systemic administration, our data suggest that this new GABA mimetic drug crosses the blood-brain barrier.

Analgesics↗
PubMed1997

Synthesis, stability and anticonvulsant activity of two new GABA prodrugs.

4-(3,4-Dihydro-2,4-dioxo-2H-1,3-benzoxazin-3-yl)-butyric acid (7) and its ester 6, two potential gamma-aminobutyric acid (GABA) prodrugs, were synthesized and studied to determine their stability in aqueous buffer and their susceptibility to undergo enzymatic hydrolysis in vitro (mouse plasma). Both compounds were fairly stable in aqueous media, (t1/2 = 68.2 h and 25.7 h, respectively). The 3,4-dihydro-2,4-dioxo-2H-1,3-benzoxazine ring underwent enzymatic hydrolysis (t1/2 = 5.8 h) in compound 7, whereas in compound 6 it seemed not to be opened by mouse plasma esterases within the observation time (3h). Both compounds were tested for their anticonvulsant activity in pentetrazole (PTZ) treated mice, and showed significant activity. Compound 7, administered as sodium salt 8, was active at relatively low doses and can be considered a very interesting GABA prodrug.

Animals↗
PubMed1996

Transport of alpha-tocopherol and its derivatives through erythrocyte membranes.

PURPOSE: To investigate the transport of alpha-tocopherol (T), tocopherol succinate (TS) and tocopherol succinate-3-glucose (a newly synthetized, less hydrophobic T ester; TSG) through bovine erythrocyte membranes. METHODS: Our experiments were carried out on erythrocytes (obtained from heparinized fresh bovine blood), because they represent a suitable model for investigations of membrane transport. RESULTS: T was shown to reside almost completely in the suspension medium, while the greater part of TS disappeared from the suspension medium and was mainly incorporated into erythrocyte membranes. In comparison with T, a larger amount of TSG was incorporated into erythrocyte membranes and taken up by cells; however the TSG intracellular accumulation was significantly lower than that observed with TS. Furthermore, the transport of TS and TSG was partially inhibited by p-chloromercuribenzenesulfonate (which inhibits monocarboxylate uptake; PCMBS) and by maltose (a competitive inhibitor of glucose transport) respectively, with a concomitant increase in drug membrane incorporation. No significant change in drug transport was observed in the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonate, a selective and irreversible blocker of band 3 protein (DIDS). CONCLUSIONS: Our results show 1) the existence of large differences in membrane incorporation of T, TS and TSG (very likely caused by differing abilities to fill spaces in the lipid bilayer) and 2) a specific contribution of the monocarboxylate transport protein and of the glucose transport protein in the cellular uptake of TS and TSG, respectively. A tempting suggestion is that the unique cytoprotective properties of TS may be related to the differences in the transmembrane mobility observed between T and its succinate ester. Furthermore, T conjugation to a monocarboxylate or glycoside moiety could provide suitable substrates for active membrane transport, thus appearing as a promising pharmaceutical strategy for the improved delivery of tocopherol derivatives.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Synthesis and pharmacological evaluation of oligoethylene ester derivatives as indomethacin oral prodrugs.

Five indomethacin oligoethylene ester derivatives (3-7) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity after oral administration. The molecular weight of the oligoethylene glycols used for synthesizing esters 3-7 ranged from 106 to 282. The chemical and enzymatic stabilities of esters 3-7 were evaluated in pH 7.4 and 2.0 buffers and in human plasma, respectively. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer, and they were readily hydrolyzed by human plasma. Esters 3-7 showed an anti-inflammatory activity, determined as the percent inhibition of carrageenan-induced edema, similar to that of indomethacin, although at higher doses. From writhing test results, we observed that all the prodrugs exhibited better or similar analgesic activity compared to indomethacin. Esters 3-7 were significantly less irritating to the gastric mucosa than indomethacin, after oral administration, and esters 3-5 did not show any ulcerogenic activity, although they were administered at higher doses than indomethacin.

Animals↗
PubMed1992

Bioavailability of two formulations of acetylsalicylic acid gums.

Bioavailability studies have been performed with ten healthy volunteers on different dosage forms of acetylsalicylic acid (ASA) in order to assess the bioavailability of two different ASA gums compared with commercial ASA tablets. The results of this study show that ASA is more readily absorbed and eliminated after administration of gum formulations than after administration of tablets, but the bioavailability obtained from the gums was lower than that observed from the tablets.

Adult↗
PubMed1991

Child pedestrian injury: a population-based collision and injury severity profile.

Linked multiple data sources were analyzed to provide a population-based collision and injury severity profile among pedestrians under 20 years of age struck by a motor vehicle during 1986-1987 in Hartford, Connecticut. Data sources included police accident reports, medical examiner records, and hospital charts. There were 234 motor vehicle-pedestrian collisions reported to the police in the study period. Of these, 213 were Hartford residents resulting in an annual age-specific pedestrian collision rate of 22.8 per 10,000 persons. A spot map of collision location reveals several well-defined geographic areas, which includes nearly half (45%) of the motor vehicle-pedestrian collisions. We reviewed 143 of 192 medical charts (75%) and 6 medical examiner records. The case fatality rate was 4.2% and the mean Injury Severity Score was 4.4. These findings will be useful for designing, implementing, and evaluating a targeted child pedestrian safety program.

Accidents, Traffic↗
PubMedDate not supplied

[When is the best time to perform upper digestive endoscopy to detect the presence of esophageal varices in patients with cirrhosis?].

INTRODUCTION: Variceal hemorrhage occurs in 25 to 35% of cirrhotic patients and is associated with significant morbidity and mortality and elevated hospital costs. Endoscopic exploration of gastroesophageal varices (GEV) in cirrhotic patients increases costs and involves a certain degree of invasiveness and discomfort for patients. The association between the presence of GEV and spleen size, liver function and platelet count is controversial. The aim of this study was to determine the correlation between liver function, evaluated by Child-Pugh (Ch-P) classification, platelet count (PC) and spleen volume index (SVI) with the presence of GEV in patients with cirrhosis managed in the outpatient setting. PATIENTS AND METHOD: Sixty-eight patients were included. In all patients, a medical history was taken and biochemical tests, mode B and Doppler abdominal ultrasonography, and upper digestive video-endoscopy were performed. RESULTS: A total of 76.47% of the patients were men and 23.53% were women. The median age was 52.8 12.4 years. More than half (54.41%) of the patients were Ch-P grade A, 41.18% were grade B and 4.41% were grade C. The most frequent causes of cirrhosis were alcohol in 52.95% and hepatitis C virus in 17.65%. Esophageal varices (EV) were found in 85.29% of the patients. The median SVI was 50.5 9.2 and the median PC was 150 26 x 109/L. A correlation was found between the presence of EV, SVI >or= 45 and PC < or= 100 x 109/L (r = 0.327; p = 0.006). No correlation was found between the presence of EV and Ch-P grade A. In the multivariate analysis, only the presence of EV was associated with SVI >or= 45 (OR 7.4; 95% CI, 1.30-77.7; p = 0.02). CONCLUSION: The presence of EV in cirrhotic patients managed in the outpatient setting was correlated with SVI >or= 45 and PC <or= 100 x 109/L.

Endoscopy, Gastrointestinal↗