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Biomedical subjects

G Moreno

Publications and source records attributed to G Moreno.

At least 55 records · Page 3Linked to original sources

[Considerations on the treatment of incipient diabetic nephropathy (lst of 2 parts)].

Diabetic nephropathy is the third cause of renal failure after pyelonephritis and glomerulonephritis. Lately, many efforts have been made for the early identification (on the silent stage) of patients with a high risk of developing this disease. On these initial stages, therapeutic attitude has changed very much, emphasizing nowadays the importance of glucose levels control, avoiding maintained conditions of hyperglycemia and maintaining blood pressure within the limits, by using the therapeutic store available, basically calcium antagonists and angiotensin-converting enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

[The treatment of incipient diabetic nephropathy (2nd of 2 parts)].

Besides diabetic patients are controlled with glycosylated hemoglobins not exceeding 7% and the normalization of blood pressure with some hypotensive drugs, it has been noted the important role of protein restriction in diet in order to retard nephropathy progression. For some years, various aldose reductase inhibitors (ARIs) have been used, which avoid the accumulation of sorbitol in tissues as well as complications. Platelet antiaggregants are also used for the treatment of diabetic nephropathy, but at a lower level.

Aldehyde Reductase↗

Temperature-induced changes in fluorescence properties as a probe of porphyrin microenvironment in lipid membranes. 1. The partition of hematoporphyrin and protoporphyrin in liposomes.

Temperature-induced fluorescence changes were studied for hematoporphyrin and protoporphyrin, incorporated into liposomes of dipalmitoylphosphoglycerocholine (Pam2GroPCho) or dimiristoylphosphoglycerocholine (Myr2GroPCho). In some cases, cholesterol or cardiolipin were added to the vesicles for better mimicking the lipid composition of biological membranes. The experimental conditions were appropriately chosen in order to reproduce different possible configurations of the porphyrin molecule in lipid membranes: namely, at the polar water/headgroups, headgroups/lipid and lipid/lipid interfaces. A peculiar feature observed in some of the above liposomal systems was the appearance of discontinuities in the Arrhenius plots of the fluorescence quantum yields, with relevant changes of the values of activation energies. These discontinuities were due to an increase of the fluorescence signal in a temperature range corresponding to the transition of the different lipids from the gel-to-liquid crystal state. The observed phenomena are consistent with the formation of non-covalent linear dimers or linear higher aggregates of the porphyrin molecules. The intermolecular contacts required for the formation of these species are favoured by at least three situations: disruption of the ordered lipid structure during the gel-to-liquid crystal phase transition; competition of other polar groups (e.g., the -OH group of cholesterol) with the porphyrin carboxylate groups for the polar phospholipid headgroups; and steric constraints due to overcrowding of porphyrin molecules in a restricted space.

1,2-Dipalmitoylphosphatidylcholine↗

Temperature-induced changes in fluorescence properties as a probe of porphyrin microenvironment in lipid membranes. 2. The partition of hematoporphyrin and protoporphyrin in mitochondria.

The temperature dependence of hematoporphyrin and protoporphyrin fluorescence quantum yields (phi F) was studied after delivery to whole mitochondria or isolated inner (IMM) and outer (OMM) mitochondrial membranes, obtained from liver of Wistar rats. These studies are very sensitive to variations of the porphyrin lipid environment. Before incorporation, the porphyrins were dissolved in 0.01 M sodium phosphate, 0.15 M NaCl, pH 7.4) NaCl/Pi (only hematoporphyrin) or dispersed into liposomes of dipalmitoylphosphoglycerocholine (Pam2GroPCho), sometimes enriched with cholesterol or cardiolipin. Whole mitochondria show higher incorporation capacity of hematoporphyrin and protoporphyrin than isolated IMM and OMM, probably because additional, energy-sensitive transport mechanisms for the porphyrin uptake occur in intact organelles. A small decrease in protoporphyrin uptake is observed in OMM in comparison with IMM; in contrast, the decrease in hematoporphyrin uptake by OMM is rather significant. A comparison between the results obtained with IMM, OMM and whole mitochondria show that both porphyrins, when released to the intact organelles, preferentially localize in the IMM, irrespective of the lipid carrier used. NaCl/Pi-dissolved hematoporphyrin probably interacts with some membrane proteins, due to the similarity of the Arrhenius plots with those obtained for liposome-entrapped human serum albumin/hematoporphyrin complexes which were used as models to mimic hematoporphyrin-membrane protein binding sites. Liposomal hematoporphyrin and protoporphyrin bind to lipid domains. Hematoporphyrin accumulates in specific, localized lipid regions, perhaps in the boundary lipids area surrounding some inner-mitochondrial carriers; protoporphyrin accomodates in more rigid, lipid areas. On these bases, the higher photoactivity of hematoporphyrin, previously observed in mitochondria, in comparison with protoporphyrin, can be easily explained. Formation of linear dimers/aggregates, endowed with higher phi F than that of the monomers, are postulated to occur for both porphyrins only in the inner mitochondrial membrane.

Animals↗

Photodynamic action increases leakage of the mitochondrial electron transport chain.

Rat liver submitochondrial particles were treated with rose bengal or flavin mononucleotide and irradiated with visible or near UV light. In both cases, oxygen consumption is impaired after irradiation while O2-. production increases significantly. This suggests that exogenous or endogenous photosensitizers can induce more electron leakage in the mitochondrial respiratory chain. Photobiological implications in dermatology are discussed.

Animals↗

[Non-puerperal mastitis. Clinical study of 30 patients].

Non puerperal mastitis is an inflammatory disease that resembles carcinoma, the course is insidious and frequently this entity is misdiagnosed. The recurrence has been reported until 60%. This report is a prospective clinical investigation, of 30 patients with diagnosis of periductal mastitis, in these women were analyzed; age, marital stage, deliveries, breast feeding symptoms like tumour, inflammatory signs, mammary ductal fistula, mamography, cytology, bacteriology, histopathology, medical and surgical treatment. The middle age was 36 years old, 70% between 30 and 50 years old, 26 patients were multiparous, breast feeding were mentioned for 20 women. The tumor was palpable 70% of the cases, localized preferentially in the retroareolar segment, inflammatory changes were observed in 25 cases, 19 patients with fistula. The cytology was negative in 13 cases. In the bacterial culture were isolated, Staphylococcus aureus in 7 cases, Proteus vulgaris in 2 cases and seven cases resulted negative. Mamographic exams were realized in 23 patients; one case resulted adenocarcinoma. The medical treatment were with Eritromycin and Metronidazol and then, ducts resection surgery were performed in 16 cases, one case with adenocarcinoma was performed a modified radical mastectomy. The results were satisfactory 22 women improved, 6 cases with recurrence and two cases with spontaneous improvement.

Adenocarcinoma↗

[Impact of outdoor pollution on indoor air quality. The case of downtown Santiago (Chile)].

The influence of outdoor pollution on indoor air quality was studied in downtown Santiago(Bandera street). Carbon monoxide (CO), nicotine, particulate matter, respirable fraction (PM5) and total and carcinogenic polyaromatic hydrocarbons (PAHs) were simultaneously monitored indoors and outdoors in restaurants, offices and other places. The levels of CO changed simultaneously outdoors and indoors (r = 0.89) specially during traffic rush hours, demonstrating the importance of outdoor infiltration into the indoor air quality and masking the contribution of other CO indoor sources. The maximum CO concentrations were over 800% and over 1000% higher indoors and outdoors respectively than the 9 ppm CO National Ambient Air Quality. The PM 5 concentrations were very high and showed no significant differences (p > 0.05) from indoors to outdoors, or between indoor levels in restaurants, offices and other places. Total and carcinogenic PAHs levels were also very high outdoors and indoors, outdoor levels being generally higher than those indoors and no significant; differences (p > 0.05) were found for the indoor levels between restaurants, offices and other places. Nicotine levels showed significant differences (p < 0.05) between indoor and outdoor levels. In addition, great differences (p < 0.05) in indoor levels, were found between offices and restaurants, and offices and other places. Among indoor sources cigarette smoke seems to be a minor source since nicotine concentrations, being 2.3 times higher in restaurants and other places than in offices, do not contribute to enhance significantly PM5 and total and carcinogenic HAPs in the first ones. These results suggest that in downtown Santiago, infiltration might be the main source of indoor pollution. This is supported by two evidences: a) coronene, a tracer of vehicle emissions was found in high concentration indoors and b) in restaurants (in which PAHs emissions might be higher indoor) a correlation coefficient of 0.987 for the indoor and outdoor concentrations of carcinogenic PAHs was found. Furthermore a survey asking for different symptoms and effects probably related to air pollution was made to people working in Bandera and in a rural area located 40 Km from Santiago. The results showed that excluding smoking as a confoundend factor, people working in Bandera showed a significantly greater (p < 0.05) risk of ill effects on their health than people working in the rural area.

Air Pollutants↗

Interaction of phthalocyanines with lipid membranes: a spectroscopic and functional study on isolated rat liver mitochondria.

Absorption and emission spectroscopic studies on Zn(II)-phthalocyanine (ZnPc) incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine, sometimes added with cholesterol or cardiolipin, and released to rat liver mitochondria via the three types of liposomal vesicles indicated that: (a) ZnPc predominantly dissolves in all lipid domains of biological membranes with the exception of cardiolipin-containing regions; a partial localization of ZnPc in protein binding sites is also postulated; (b) the spectroscopic properties of ZnPc, although mainly determined by the aggregation state of the dye, are somewhat influenced by the physico-chemical characteristics of the lipid environment; (c) ZnPc-binding lipid domains in mitochondria are mainly localized in the outer membrane; this conclusion is clearly deduced from the trends of Arrhenius plots of the ZnPc fluorescence quantum yield in whole mitochondria and isolated inner or outer membrane in the temperature range -10 degrees C-(+)45 degrees C; (d) the nature of the ZnPc-binding site in mitochondria is not dependent on the chemical composition of the liposome carrier, contrary to what observed for other hydrophobic dyes, such as porphyrins. This has been also confirmed by photosensitization experiments. Actually, illumination of ZnPc-loaded mitochondria by 600-700 nm light causes a decline of the respiratory control ratio, which is essentially dependent on the amount of incorporated photosensitizer, irrespective of the composition of the carrier.

Animals↗

Hematoporphyrin derivative (Photofrin) photodynamic action on Ca2+ transport in monkey kidney cells (CV-1).

After 24 h incubation with Photofrin (PF), photodynamic action has been studied on Ca2+ transport in CV-1 cells. A moderate increase of the cytosolic free Ca2+ concentration [Ca2+]i is observed immediately after a dose of irradiation which yields a survival rate of less than 5% at 48 h. In parallel, studies on digitonin-permeabilized cells indicate that such a treatment inhibits endoplasmic reticulum Ca2+ uptake with few alterations of this process in mitochondria. In contrast, ADP-stimulated respiration is impeded and intracellular ATP level decreases. It is suggested that direct damage to endoplasmic reticulum as well as mitochondrial disturbance are the primary mechanisms responsible for a nontransient elevation of [Ca2+]i preceding cell death.

Adenosine Triphosphate↗

[The results after extensive radical resection of locally advanced colorectal carcinoma].

The results of extended resections for locally advanced colorectal cancer and the factors influencing the long term survival and recurrence rate are analyzed in 69 patients. All of them underwent radical en-bloc resection including the primary tumor and the adjacent affected structures. The existence of tumoral invasion was confirmed in 42 cases (60%). In the remaining, inflammatory adhesions were presents. Overall 5 year survival did not show significant differences between the groups of patients with benign or malignant infiltration (71% y 51% respectively). Within the same tumor stage, the results were similar for the two types of infiltration. Significant differences were found when lymph nodes metastases were considered: 65% 5 year survival in patients with negative lymph nodes versus 35% in patients with positive nodes. The probability of metastases and tumor recurrence was significantly higher in the group with malignant infiltration. Patients with positive lymph nodes showed lower disease-free interval rate. These data show that long term control of the tumor in locally advanced colorectal carcinomas can be achieved by an aggressive surgical approach. The presence of lymph mode metastases is a more useful prognostic factor influencing survival and relapse rate that the local infiltration by it-self.

Adult↗

Photosensitization of mitochondria by liposome-bound porphyrins.

We have compared the photodynamic activities of hematoporphyrin (HP) and protoporphyrin (PP) on isolated rat liver mitochondria by measuring the decline of the respiratory control ratio (RCR) after irradiation at 365 nm. Before addition to the respiratory medium, the dyes were dissolved in phosphate-buffered saline (PBS) or incorporated into unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC), sometimes enriched with cholesterol (Chol) or cardiolipin (Card), which are naturally present in mitochondrial membranes. Chol and especially Card strongly increase the porphyrin uptake by mitochondria. In all experimental conditions, PP is taken up by mitochondria to a higher extent than HP. Nevertheless, under conditions giving the same amount of mitochondria-bound dye, HP is a more efficient photosensitizer than PP. As the efficiency of singlet oxygen production has been shown to be equivalent for the two porphyrins in monomeric state, the resulting photobiological effects are explained in terms of different localization of HP and PP in the mitochondrial membranes. In particular, HP preferentially localizes in the protein-rich polar domains of the inner mitochondrial membrane, whereas PP dissolves in the lipid regions of the membranes.

Animals↗

4-Thiouridine incorporation into the RNA of monkey kidney cells (CV-1) triggers near-UV light long-term inhibition of DNA, RNA and protein synthesis.

Monkey kidney cells (CV-1) grown for 4 h in the presence of 0.1 mM 4-thiouridine (s4Urd) incorporate this photoactivable uridine analog in their RNA. A minor, 5-8%, thiolated RNA fraction can be isolated from bulk RNA by affinity chromatography. This RNA fraction contains 1.5-2.5 s4Urd residues per 100 nucleotides and exhibits a broad chain length distribution ranging from 700 to 7000 nucleotides. It is essentially of nuclear origin and amounts to 30% of the RNA synthesized during exposure of cells to s4Urd. Under the same s4Urd labeling conditions, no thiolated pyrimidine residues have been detected in DNA. Irradiation with 365 nm light (45 kJ/m2) of the cells immediately after s4Urd exposure triggers long-term inhibition of DNA, RNA and protein synthesis accompanied by a linear decline (50% in 2 days) in the total cell mass of cultured cells. In contrast, exposure to s4Urd alone results in moderate but reversible inhibitory effects. The available data suggest that s4Urd-induced photolesions in newly synthesized RNA such as RNA-RNA cross-links as well as RNA-protein bridges are directly involved in impairment of essential cellular functions.

Animals↗

Cytotoxic and photodynamic effects of Photofrin on sensitive and multi-drug-resistant Friend leukaemia cells.

To study cross-resistance to Photofrin (PF) photosensitization, a Friend leukaemia cell line (ADM-RFLC) with a high level of multi-drug resistance (MDR) and the parental sensitive cell line (FLC) have been used. PF uptake measured by HPLC shows a similar intracellular drug accumulation in both cell lines. The ID50s for cell growth inhibition by PF are also similar after exposure in the dark in the two cell lines, while after illumination they are slightly lower in ADM-RFLC than in FLC cells. Moreover, verapamil, known to reverse the MDR phenotype induced by P-glycoprotein over-expression (the drug efflux mechanism), affects equally ADM-RFLC and FLC cells sensitivity to PF. In addition, photodynamic treatment with PF did not reverse the resistance to rhodamine 123 and aclarubicin, but partly reverses resistance of ADM-RFLC cells to antitubulin drugs such as vinblastine or vincristine. These latter results could have clinical application in the treatment of tumours expressing the MDR phenotype.

Animals↗

Effects of rhodamine 123 in the dark and after irradiation on mitochondrial energy metabolism.

Isolated rat liver mitochondria have been used to study the mechanism of toxicity of Rhodamine 123 (Rho 123) in the dark and after irradiation with visible light. We report an inhibition of adenosine 5'-diphosphate phosphorylation which is increased after illumination. In the dark, the first steps of the phosphorylation process (i.e. the entry of substrates into the matrix, the electron transport to oxygen and the creation of the proton gradient) as well as ATPase activity are not significantly perturbed at Rho 123 concentration below 10 micrograms/mL. In contrast, the movements of the phosphate compounds are drastically impaired. Irradiation strengthens the detrimental effects in an oxygen dependent process. The nature of the noxious transient species is not clearly established, but it is suggested that singlet oxygen could be responsible for the observed damage.

Adenosine Diphosphate↗

Effects of anthralin on mitochondrial bioenergetics.

Isolated mitochondria were used to determine what causes anthralin inhibition of oxidative phosphorylation. In good agreement with other results, the rate of oxygen consumption was not modified by anthralin when mitochondria were first uncoupled with FCCP, suggesting that only the last steps of the process leading to ATP phosphorylation are implicated. No effects were found at the level of the ATPase and the Pi carrier in contrast with a competitive inhibition of the ADP/ATP translocator. These experiments suggest an atractyloside-like effect to explain the action of anthralin on mitochondria.

Adenosine Triphosphatases↗

Comparative in vitro activity of three cephalosporins against Staphylococcus aureus isolated from bovine mastitis.

This report compares the in vitro activity of three cephalosporins (cephalothin, cefoxitin and ceftriaxone) against 57 Staphylococcus aureus strains isolated from cows with clinical mastitis on the basis of the minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC). The majority of the S aureus strains showed resistance to cefoxitin and ceftriaxone and sensitivity to cephalothin. The highest MICs and MBCs were found for cefoxitin and ceftriaxone. Antimicrobial tolerance (MBC/MIC greater than or equal to 32:1) was observed in relation to cephalothin and ceftriaxone. The data suggest that these cephalosporins may not be effective for the treatment of staphylococcal bovine mastitis. The precise definition of their antimicrobial efficacies requires more detailed in vitro and in vivo studies.

Animals↗

Photosensitization of isolated mitochondria by hematoporphyrin derivative (Photofrin): effects on bioenergetics.

Isolated rat liver mitochondria were incubated in the presence of 6 micrograms/ml of Photofrin and irradiated at the wavelength of 365 nm. After 45 s irradiation (30 W/m2), coupling defined as stimulation of respiration by externally added adenosine 5'-diphosphate (ADP) is totally lost. In contrast, membrane potential created by addition of succinate or adenosine 5'-triphosphate (ATP) is only slightly affected. Similarly, the ADP/O ratio is not modified after 20 s irradiation. These data suggest that modification of the mitochondrial membrane potential is not a primary event after irradiation.

Animals↗