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Biomedical subjects

C Neves

Publications and source records attributed to C Neves.

13 recordsLinked to original sources
PubMed2004

Hydration of an amphiphilic excipient, Gelucire 44/14.

The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate and PEG dilaurate), and finally glycerides (trilaurin). At each stage, the remaining crystals are in equilibrium with an interstitial solution made of water and the dissolved components. In this range of hydrations, the total uptake is close to the sum of the equilibrium hydrations of the components. In the pharmaceutical formulation, the active ingredient could dissolve in the liquid phase. At larger hydrations, obtained through addition of liquid water, the state of Gelucire 44/14 differs from those of its components. Gelucire 44/14 forms a lamellar phase and this phase melts at 30 degrees C whereas the pure PEG esters form hexagonal and cubic mesophases. The cubic mesophases do not melt until the temperature exceeds 40 degrees C. At body temperature, all crystals in Gelucire 44/14 melt to an isotropic fluid as soon as the total water content exceeds 5%. Therefore the formulation of amphiphilic excipients can be optimized to avoid the formation of mesophases that impede dissolution of the excipient at body temperature.

Body Fluids↗
PubMed1999

Coupling of a targeting peptide to plasmid DNA by covalent triple helix formation.

The nuclear localization signal (NLS) of the SV40 large T antigen efficiently induces nuclear entry of proteins. We have developed a strategy for covalent coupling of one or a controlled number of NLS peptides to plasmid DNA at a specific site by triple helix formation. A psoralen-oligonucleotide-NLS peptide conjugate was synthesized and characterized by proteolysis with trypsin. This conjugate was used to covalently associate one NLS peptide to plasmid DNA by triple helix formation and photoactivation. The oligonucleotide-NLS peptide conjugate interacted with the NLS-receptor importin alpha. The reporter gene was expressed after transfection of the modified plasmid in NIH 3T3 cells, indicating no loss of the gene expression functionality of the plasmid. On the other hand, no increase in expression was observed as a result of the NLS peptide. This site-specific coupling technology can be used to couple to a plasmid other ligands targeting to a specific receptor.

Antigens, Viral, Tumor↗
PubMed1999

Intracellular fate and nuclear targeting of plasmid DNA.

One of the major steps limiting nonviral gene transfer efficiency is the entry of plasmid DNA from the cytoplasm into the nucleus of the transfected cells. The nuclear localization signal (NLS) of the SV40 large T antigen is known to efficiently induce nuclear targeting of proteins. We have developed two chemical strategies for covalent coupling of NLS peptides to plasmid DNA. One method involves a site-specific labeling of plasmid DNA by formation of a triple helix with an oligonucleotide NLS peptide conjugate. After such modification with one NLS peptide per plasmid molecule, plasmid DNA remained fully active in cationic lipid-mediated transfection. In the other method, we randomly coupled 5-115 p-azidotetrafluorobenzyllissamine-NLS peptide molecules per plasmid DNA by photoactivation. Oligonucleotide-NLS and plasmid lissamine-NLS conjugates interacted specifically with the NLS-receptor importin alpha. Plasmid-lissamine-NLS conjugates were not detected in the nucleus, after cytoplasmic microinjection. Plasmids did not diffuse from the site of injection and plasmid-lissamine-NLS conjugates appeared to be progressively degraded in the cytoplasm. The process of plasmid DNA sequestration/degradation stressed in this study might be as important in limiting the efficiency of nonviral gene transfer as the generally recognized entry step of plasmid DNA from the cytoplasm into the nucleus.

3T3 Cells↗
PubMed1998

[Modern ethics. Various considerations, particularly based on hospital experience].

The four basic principles of modern medical ethics are presented and discussed. The historic evolution of the hospital is analysed concerning the organisation and the social function of the hospital. The author presents some considerations about the relation between the patient and the hospital, clinical investigation and informed consent, confidentiality and technological progress. The problems of the end-of-life of the hospitalised patient is discussed, with an overview of the do-not-resuscitate orders.

Clinical Trials as Topic↗
PubMed1995

[Acute pancreatitis of biliary etiology. The case histories of the Department of General Surgery of S. Francisco Xavier Hospital (1990-1993)].

Gallstones and alcohol are the most important causes of acute pancreatitis, accounting for 80% of cases. One hundred and four cases of Acute Gallstone Pancreatitis were retrospectively studied, representing 39.5% of all cases of Acute Pancreatitis that have been treated between 1990-93. Abdominal ultrasound, demonstrating gallstones in 95% of the cases, was a very useful examination in the initial study of these patients. ERCP with sphincterotomy was performed in 25 patients: 6 in a urgent basis and the others as elective procedure. Gallstones have been treated during the initial admission in 80.6% of the cases and the others at a second admission: ERCP with sphincterotomy in 14 patients as the only etiologic treatment, open cholecystectomy in 50 cases and laparoscopic cholecystectomy in 29 cases. The overall mortality rate was 3.8%--four cases.

Acute Disease↗
PubMed1983

Management of massive hemoptysis by bronchial artery embolization.

Massive hemoptysis is a major clinical and surgical problem with a mortality of 80%, which is most often related to asphyxiation. Thirty-three patients with massive hemoptysis underwent selective bronchial arteriography and treatment by embolization or surgery. Lasting control of hemoptysis was achieved in 27 of 33 patients (81.8%) at follow-up ranging from one to 24 months. Hemoptysis recurred in six of 33 patients (18.2%). Mortality related to hemoptysis was three of 33 patients (9.0%), and overall mortality was six of 33 patients (18.2%). Seven patients underwent surgical treatment in addition to bronchial artery embolization. Patients with mycetoma suffered the highest relapse of bleeding and the highest mortality in this series. In these patients, bronchial artery embolization may be effective in the control of acute bleeding, but permanent control of hemoptysis is achieved only by later surgery. Bronchial artery embolization is an effective way to control massive hemoptysis with a low recurrence rate and reduced mortality among severely ill patients. Although we have had no unfavorable sequelae, reports of neurological damage following bronchial angiography indicate care in avoiding obstruction of the artery of Adamkiewicz.

Adult↗
PubMedDate not supplied

Novel method for covalent fluorescent labeling of plasmid DNA that maintains structural integrity of the plasmid.

We have developed a chemical strategy for covalent coupling of fluorophores to plasmid DNA. A p-azido-tetrafluoro-benzyl-lissamine conjugate was synthesized and purified. This conjugate was used to covalently associate fluorescent molecules to plasmid DNA by photoactivation. In contrast to nick-translated plasmid DNA, plasmid-lissamine conjugates appeared on gel as supercoiled DNA. Reporter gene was expressed after transfection of the plasmid-lissamine conjugates in NIH 3T3 cells, although gene transfer efficiency was decreased by 60% as compared with unlabeled DNA. Intracellular traffic of plasmid-lissamine conjugates was studied in transfected cells. After cytoplasmic microinjection, fluorescent plasmid did not diffuse from the site of injection and appeared to be progressively degraded in the cytoplasm.

3T3 Cells↗
PubMedDate not supplied

Clinical correlations in HIV-1 and HIV-2 infected patients.

In Portugal, the prevalence of human immunodeficiency virus type 2 (HIV-2) seropositivity is higher than in other European countries or North America. Recent literature data points out a possible difference on the pathogenic potential and on the natural history of HIV-1 and HIV-2, suggesting a lower virulence of HIV-2. Facing these hypothesis and the increasing number of HIV-2 cases, we analysed two infected groups HIV-1 and HIV-2, trying to correlate the ophthalmologic lesions present in both populations and searching for a difference in the clinical presentation of the ocular disorder. We studied prospectively 214 patients with HIV infection at several stages, 83% HIV-1 and 17% HIV-2. Ocular manifestations were present in both populations with a significant prevalence in HIV-1 (48%), compared to HIV-2 (19%) (p < 0.005). The ophthalmologic pathology found, particularly noninfectious retinopathy, infectious retinitis and neuro-ophthalmic disorders, were considered important for the disease's diagnosis and prognosis. All these ophthalmic findings were present in the HIV-1 population. In the HIV-2 group the most frequent lesion was noninfectious retinopathy. Within each group, HIV-1 and HIV-2, the comparison of the survival between AIDS patients with and without ocular lesions, revealed a significant shorter survival time in those with ocular pathology (p < 0.001 and p < 0.05). There seems to exist a certain analogy in clinical expression in both groups, although it is possible to admit a lower severity in ocular involvement in patients infected by HIV-2.

AIDS-Related Complex↗
PubMedDate not supplied

[Donovanosis in Pará].

From 1954 to 1990 granuloma inguinale was diagnosed in 259 patients al the dermatology service of the Universidade Federal do Pará in Belém, Brazil. Among them, 56 cases had occurred in the twenty-year period 1954-1974 and as many as 133 cases were seen during the last five years only. Greater sexual liberty, poor social and economic conditions, and especially increasing homosexual behavior were implicated by the authors as chief determinants for this augmented incidence of the disease.

Brazil↗
PubMedDate not supplied

[Visual screening in children].

The Early Visual Screening (EVS) before verbal communication and, certainly, before one year old, is essential to prevent strabismus and/or amblyopia. We consider the PREFERENTIAL LOOKING (PL) for visual acuity determination and screening of the amblyopia and the PHOTOREFRACTION (VIDEO-REFRACTION: VPR-1) for refractive screening, adequated methods for Early Visual Screening. We suggest that these two technics are used as EVS methods, four times in childhood (newborn, 6-8 weeks, 6-8 months, 18-24 months) performed by an Ophthalmologist at a Pilot Health Center of the National Health Service. The classic methods of visual screening such as: child's reaction to the eye occlusion, pursuit movements, STYCAR balls and miniature toys, Cover test, Hirschberg test, red fundus reflex, anterior segment examination, each of these used according to the child's age, must be performed by an Ophthalmologist. We think they are a positive alternative until we are able to use the PREFERENTIAL LOOKING and VIDEO-REFRACTION in Early Visual Screening. In the kindergarten and primary school the ASTENOPIC complaints due to hipermetropia, minor astigmatism and convergent deficit as well as chronic inflammation of the anterior segment eyelids and anexus, can be related with poor school performance more than with strabismus or myopia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Thermal colorectal lesions].

A case report of thermal burns of the rectum and colon in a 94-year-old woman. The thermal lesions were caused by a scalding water enema. Flexible sigmoidoscopy was useful in documenting the extension of the lesions and histology was helpful in documenting the diagnosis. The authors review the enema's complications.

Aged↗