Reevaluating a non-conventional procedure to microencapsulate beneficial lactobacilli: assessments on yield and bacterial viability under simulated technological and physiological conditions.

BACKGROUND: Maintaining viability of beneficial microorganisms applied to foods still constitutes an industrial challenge. Many microencapsulation methodologies have been studied to protect probiotic microorganisms and ensure their resistance from manufacturing through to consumption. However, in many Latin-American countries such as Argentina there are still no marketed food products containing microencapsulated beneficial bacteria. The objectives of this work were: (i) to obtain microcapsules containing Lactobacillus fermentum L23 and L. rhamnosus L60 in a milk protein matrix; and (ii) to evaluate the viability of microencapsulated lactobacilli exposed to long-term refrigerated storage, mid-high temperatures and simulated gastrointestinal conditions. RESULTS: The method of emulsification/rennet-catalyzed gelation of milk proteins used in this study led to high encapsulation yields for both strains (98.2-99%). Microencapsulated lactobacilli remained viable for 120 days at 4 °C, while free lactobacilli gradually lost their viability under the same conditions. Microencapsulation increased the resistance of lactobacilli to mid-high temperatures, since they showed survival rates of 95-99.3% at 50 °C, and of 72.5-74.4% at 65 °C. Under simulated gastric conditions, the microencapsulated lactobacilli counts were higher than 8.5 log CFU mL-1 and showed survival rates between 96.61% and 97.74%. Furthermore, in the presence of bile (0.5-2% w/v) the survival of microencapsulated strains was higher than 96%. CONCLUSION: The microencapsulation process together with the matrix of milk proteins used in this study protected beneficial Lactobacillus strains against these first simulated technological and physiological conditions. These findings suggest that this microencapsulation method could contribute to secure optimal amounts of living lactobacilli cells able to reach the intestine. © 2021 Society of Chemical Industry.

Lactic acid bacteria with promising AFB1 binding properties as an alternative strategy to mitigate contamination on brewers' grains.

Adsorption of molecules to the cell walls of microorganisms plays an important role in helping to prevent animal exposure to the toxic and carcinogenic effects of aflatoxins (AFs). The aim of this study was to evaluate the ability of LAB strains, isolated from brewers' grains, to adsorb aflatoxin B1 (AFB1). All LAB were able to reduce the bioavailability of AFB1 from phosphate buffered-saline (PBS). In addition, the strains retained their effectiveness even after heat treatment. The AFB1-LAB complex stability was first evaluated through sequential washing steps. These assays demonstrated that a low percentage of AFB1 was released after consecutive washes. After subjecting the complex to different pH and bile salt treatments, the percentage of bound AF decreased, as compared to the control, but remained at high levels. Finally, to simulate the formation of the AFB1-LAB complex at conditions similar to those of the gastrointestinal tract, LAB and AFB1 were homogenized in PBS adjusted at acidic conditions or under different bile salt concentrations. In general, LAB strains showed the highest AFB1 adsorption at the lowest pH (2) and bile salt concentration (0.05%). In conclusion, the studied strains represent promising biocontrol agents for preventing and/or ameliorating the AFB1 contamination of feed.

Biological control of AFB1-producing Aspergillus section Flavi strains isolated from brewer's grains, alternative feed intended for swine production in Argentina.

The aim of the present study was to investigate the inhibitory activity of lactic acid bacteria (LAB) isolated from brewer's grains on Aspergillus section Flavi growth and aflatoxin B1 production. The Aspergillus strains tested were inhibited by all the LAB strains assayed. The isolates Lactobacillus brevis B20, P. pentosaceus B86, Lactococcus lactis subsp. lactis B87, L. brevis B131, and Lactobacillus sp. B144 completely suppressed the fungal growth and reduced aflatoxin B1 production. In conclusion, LAB isolated from brewer's grains show a high inhibitory activity on fungal growth and aflatoxin biosynthesis by Aspergillus flavus and Aspergillus parasiticus. Further studies must be conducted to evaluate the success of in vitro assays under food environment conditions and to elucidate the antifungal mechanism of these strains.

Bacteriocins and other bioactive substances of probiotic lactobacilli as biological weapons against Neisseria gonorrhoeae.

In the search of new antimicrobial agents against Neisseria gonorrhoeae, the bacteriocins-producing probiotic lactobacilli deserve special attention. The inhibitory effects of biosubstances such as organic acids, hydrogen peroxide and each bacteriocin-like inhibitory substance (BLIS) L23 and L60 on the growth of different gonococcal strains were investigated. Different non-treated and treated cell-free supernatants of two probiotic lactobacilli containing these metabolites were used. The aims of this work were (i) to evaluate the antimicrobial activity of the biosubstances produced by two probiotic lactobacilli, estimating the proportion in which each of them is responsible for the inhibitory effect, (ii) to define their minimum inhibitory concentrations (MICs) and, (iii) to determine the potential interactions between these biosubstances against N. gonorrhoeae. The main antimicrobial metabolites were the BLIS-es L23 and L60 in comparison with other biosubstances. Proportionally, their contributions to the inhibition on the gonococcal growth were 87.28% and 80.66%, respectively. The MIC values of bacteriocins were promising since these substances, when diluted, showed considerable inhibitory activity for all gonococci. In the interaction between bacteriocins, 100% of synergism was found on the gonococcal growth. In summary, this study indicates that both L23 and L60 could potentially serve to design new bioproducts against N. gonorrhoeae.

Antifungal activity of two Lactobacillus strains with potential probiotic properties.

Aflatoxin (highly toxic and carcinogenic secondary metabolites produced by fungi) contamination is a serious problem worldwide. Modern agriculture and animal production systems need to use high-quality and mycotoxin-free feedstuffs. The use of microorganisms to preserve food has gained importance in recent years due to the demand for reduced use of chemical preservatives by consumers. Lactic acid bacteria are known to produce various antimicrobial compounds that are considered to be important in the biopreservation of food and feed. Lactobacillus rhamnosus L60 and Lactobacillus fermentum L23 are producers of secondary metabolites, such as organic acids, bacteriocins and, in the case of L60, hydrogen peroxide. The antifungal activity of lactobacilli strains was determined by coculture with Aspergillus section Flavi strains by two qualitative and one quantitative methods. Both L23 and L60 completely inhibited the fungal growth of all aflatoxicogenic strains assayed. Aflatoxin B (1) production was reduced 95.7-99.8% with L60 and 27.5-100% with L23. Statistical analysis of the data revealed the influence of L60 and L23 on growth parameters and aflatoxin B (1) production. These results are important given that these aflatoxicogenic fungi are natural contaminants of feed used for animal production, and could be effectively controlled by Lactobacillus L60 and L23 strains with probiotic properties.

Synergistic effect between two bacteriocin-like inhibitory substances produced by Lactobacilli Strains with inhibitory activity for Streptococcus agalactiae.

Group B streptococci (GBS) are bacterial species that colonize the vagina in pregnant women and as such may cause serious infections in neonates that passed through the birth channel. The objective of this work was to study the inhibitory activities produced by each bacteriocin-like inhibitory substance (BLIS) of Lactobacillus rhamnosus L60 and Lactobacillus fermentum L23, and the effects of the combined BLIS-es of these lactobacilli on GBS. The interactions between the BLIS-es were assessed by qualitative and quantitative methods on agar plates. The minimum inhibitory concentrations (MICs) and fractional inhibitory concentrations (FICs) were determined by a modification of the broth microdilution and checkerboard methods, respectively. Antibiotic susceptibilities of all S. agalactiae strains were assayed and the results of these tests were evaluated for statistical significance. A 7.5% of GBS isolates were recovered from 760 pregnant women and 91% of those strains were susceptible to each BLIS produced by L. fermentum, L. rhamnosus, and also to a mixture of them. The comparisons among the BLIS-es showed statistically significant differences, with a combination of the BLIS-es from the two Lactobacillus species being better than the BLIS of each one alone (P < 0.05) as GBS growth inhibitors. Synergistic activities between the BLIS-es were found on 100% of susceptible GBS strains, MICs ranges of BLIS of L23 and L60 were 80-160 and 160-320 UA ml(-1), respectively. By the checkerboard method, the BLIS-es combination showed synergistic effect on all sensitive strains tested, with values of FICs ranging from 0.131 to 0.218. The BLIS-es produced by these lactobacilli of vaginal origin were able to inhibit S. agalactiae isolates. The results indicate that these strains may have probiotic potential for the control of GBS in women and may consequently prevent GBS infections in newborns.

Surveillance of Aflatoxin and Microbiota Related to Brewer's Grain Destined for Swine Feed in Argentina.

Córdoba province in the center of Argentina is an important area of swine production. The use of industry by-product (brewer's grain) as feedstuff for swine is a regular practice and increases animal performance on these animals production. The occurrence of aflatoxin contamination is global, causing severe problems especially in developing countries. No reports on aflatoxin B(1) production, micoflora, and potential aflatoxin B(1) producing microorganism from brewer's grain are available. The aims of this study were (1) to isolate the microbiota species from brewer's grain, (2) to determine aflatoxin B(1) natural contamination levels, and (3) to determine the ability of Aspergillus section Flavi isolates to produce aflatoxins in vitro. Physical properties, total fungal counts, lactic acid bacteria, and fungal genera distribution were determined on this substrate. In 65% of the samples, fungal counts were higher than recommended by GMP, and lactic bacterium counts ranged from 1.9 × 10(5) to 4.4 × 10(9) CFU g(-1). Aspergillus spp. prevailed over other fungal genera. Aspergillus flavus was the prevalent species followed by A. fumigatus. Aflatoxin B(1) levels in the samples were higher than the recommended limits (20 ng g(-1)) for complementary feedstuffs. Several Aspergillus section Flavi strains were able to produce aflatoxin B(1) in vitro. Inadequate storage conditions promote the proliferation of mycotoxin-producing fungal species. Regular monitoring of feeds is required in order to prevent chronic and acute toxic syndromes related to this kind of contamination.

Vaginal colonization and activity of the probiotic bacterium Lactobacillus fermentum L23 in a murine model of vaginal tract infection.

A strain of Lactobacillus, identified as Lactobacillus fermentum L23, was selected from among 100 strains isolated from vaginal swabs of healthy, non-pregnant, pre-menopausal women. L. fermentum L23 was chosen on the basis of its bacteriocinogenic ability and its properties relevant to colonization, i.e. self-aggregation, adherence to vaginal epithelial cells and co-aggregation with bacterial pathogens. The antimicrobial preventative and curative effects produced by the probiotic L. fermentum L23 administered locally against Escherichia coli in a murine vaginal tract infection model were studied. One dose of the human strain L23 containing 10(8) c.f.u. ml(-1) colonized and persisted in the vaginal tract of the female BALB/c mice for 5 days. Infection with the pathogen at 10(6) c.f.u. ml(-1) in the vaginal tract was maintained for more than 7 days. A single dose of L23 administered 24 h pre-infection inhibited E. coli growth on day 3 post-infection, showing the preventative effect displayed by this Lactobacillus strain. Treatment with L. fermentum L23 during the post-infection period showed complete inhibition of pathogen growth from day 5. Thus, this in vivo study indicated that the probiotic bacterium L. fermentum L23 produced both preventative and curative effects on E. coli growth. The beneficial properties and the production of antimicrobial metabolites may act in situ to inhibit a pathogenic micro-organism within the vaginal environment. Strain L23 could be a good natural alternative to other therapies used for genital infections.

Antimicrobial activity, inhibition of urogenital pathogens, and synergistic interactions between lactobacillus strains.

Lactobacillus fermentum strain L23 and L. rhamnosus strain L60 were selected as an alternative treatment to prevent or treat urogenital infections based on their probiotic properties and production of bacteriocins. The objectives of the present work were to study the inhibitory activities of these two bacteriocin-producing strains, and to analyze the interactions between pairs of bacteriocins that inhibit urogenital pathogens. Antimicrobial activity tests of L23 and L60 were performed by a diffusion method with 207 bacterial strains, isolated from female patients presenting a urogenital infection. Inhibitory substances interaction tests were carried out by using a streak-diffusion method on agar plates. One hundred percent of the clinical isolates showed sensitivity to the antimicrobial substances produced by L23 and L60. The selected lactobacilli produced larger inhibition halos when compared to several antibiotics commonly used for treating these infections. Synergistic interactions and indifferent interactions were recorded in 68.6% and 31.4% of the cases, respectively. No antagonistic interactions were observed. In conclusion, the bacteriocin-producing strains L23 and L60 are potential candidates for probiotic prophylaxis and treatment of urogenital disorders in women.

Lactobacillus rhamnosus L60, a potential probiotic isolated from the human vagina.

The vagina has been increasingly viewed as an "ecosystem" whose normal microflora help protect it from invading pathogens, including those that cause urinary tract infections and sexually transmitted diseases. We tested new strains of lactobacilli as potential probiotics for maintenance of urogenital tract health, as well as prevention and therapy of urogenital infections. A strain of lactobacilli isolated from the vagina of nonpregnant, healthy, premenopausal women was identified as Lactobacillus rhamnosus L60 by 16S rDNA sequence homology. L60 was evaluated for antimicrobial activity, in vitro antibiotic resistance, autoaggregation, surface hydrophobicity, co-aggregation with other bacterial species, hydrogen peroxide (H(2)O(2)) production, and bacterial adherence. It displayed a wide spectrum of antimicrobial activity against urogenital pathogens, and resistance to antibiotics commonly prescribed for infections caused by these pathogens. L60 produced H(2)O(2), adhered to vaginal epithelial cells, co-aggregated with Escherichia coli and Candida albicans, and displayed self-aggregation. In view of these characteristics, L60 is considered a potential probiotic, and will be further evaluated for preventive and therapeutic application locally in the vaginal tract.

Purification and partial characterization of novel bacteriocin L23 produced by Lactobacillus fermentum L23.

Lactobacillus fermentum strain L23 produced a small bacteriocin, designated bacteriocin L23, with an estimated molecular mass of < 7000 Da. Isolation, purification, and partial characterization of bacteriocin L23 are described. It displayed a wide inhibitory spectrum including both Gram-negative and Gram-positive pathogenic strains and two species of Candida. The antibacterial activity of cell-free culture supernatant fluid was not affected by catalase or urease but was abolished by the proteolytic enzymes trypsin and protease VI. Bacteriocin L23 was heat stable (60 min at 100 degrees C) and showed inhibitory activity over a wide pH range (4.0 to 7.0). The proteinaceous compound was isolated from cell-free culture supernatant fluid and purified. Crude bacteriocin sample was prepared by a process of ammonium sulfate precipitation, gel filtration, thin-layer chromatography, bioautography, and reversed-phase HPLC.

Lactobacillus species isolated from the vagina: identification, hydrogen peroxide production and nonoxynol-9 resistance.

BACKGROUND: Lactic acid production is considered to be the major protection mechanism of lactobacilli against vaginal infections due to genital pathogens. Some species of Lactobacillus are also hydrogen peroxide (H(2)O(2)) producers. Nonoxynol-9 (N-9) is a nonionic detergent and is the active component of many spermicidal preparations. It immobilizes sperm by disrupting the cell membrane and is believed to act similarly on a number of bacteria and viruses. It is known that N-9 inhibits Lactobacilli in vitro at concentrations of 0.1% to 1%. PURPOSE: The present study was conducted to identify the species of Lactobacillus isolated from vaginal fluids of reproductive-age women and to characterize the H(2)O(2)-producing and N-9-resistant strains in an Argentine population. RESULTS: We identified Lactobacillus acidophilus, L. fermentum, L. gasseri, L. jensenii, L. casei subsp. casei, L. brevis and L. delbrueckii subsp. delbrueckii as the most frequent species. In this Argentine, South American population, 62% of women had H(2)O(2)-producing vaginal lactobacilli. We found a high number of sensitive strains. Sixty-two H(2)O(2)-producer strains were detected, 50 (80.6%) strains were sensitive to N-9 and 12 (19.4%) strains were resistant to the inhibitory effect of N-9. DISCUSSION: The vaginal microecologic findings are comparable to those found in other populations and suggest that (1) vaginal microecologic conditions are likely to be similar among Argentine women as in other countries, and (2) N-9 may have deleterious effects as in other populations.

Photoinactivation of Escherichia coli using porphyrin derivatives with different number of cationic charges.

The photodynamic effect of meso-substituted cationic porphyrins, 5-[4-(trimethylammonium)phenyl]-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide 1, 5,10-di(4-methylphenyl)-15,20-di(4-trimethylammoniumphenyl)porphyrin iodide 2 and 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide 3, have been investigated in both homogeneous medium bearing photooxidizable substrates and in vitro on a typical gram-negative bacterium Escherichia coli. Absorption and fluorescence spectroscopic studies were compared in N,N-dimethylformamide. Fluorescence quantum yields (varphiF) of 0.10, 0.06 and 0.08 were calculated for porphyrins 1, 2 and 3, respectively. The singlet molecular oxygen, O2(1Deltag), production was evaluated using 9,10-dimethylanthracene yielding values of 0.66, 0.36 and 0.42 for porphyrins 1, 2 and 3, respectively. Guanosine 5'-monophosphate was used as biological substrate model. Similar decomposition of guanosine 5'-monophosphate was obtained using these cationic porphyrins as sensitizer. In biological medium, photosensitized inactivation of E. coli was analyzed using cells without and with one washing step. E. coli cultures were treated with sensitizer at 37 degrees C for 30 min in dark. In both procedures, a higher photoinactivation of cells (>99.999%) was found for cells treated with 10 microM of tricationic porphyrin 3 and irradiated for 5 min with visible light. Porphyrins 1 and 2 only show an important photodamage when the cells are irradiated without washing step. These results indicated that the tetracationic porphyrin 3 could be a promising sensitizer with potential applications in the photoinactivation of bacterial cells by photodynamic therapy.

Photodynamic studies and photoinactivation of Escherichia coli using meso-substituted cationic porphyrin derivatives with asymmetric charge distribution.

The photodynamic activities of novel asymmetrically meso-substituted cationic porphyrins, 5,10-di(4-methylphenyl)-15,20-di(4-trimethylammoniumphenyl)porphyrin iodide 1 and 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide 2 and its metal complex with Pd(II) 3, have been investigated in both homogeneous medium bearing photooxidizable substrates and in vitro on a typical gram-negative bacterium Escherichia coli. The amphiphilic character of porphyrin 2 was increased by the presence of a high-lipophilic trifluoromethyl group and its photophysical properties changed by forming a complex with Pd(II). Absorption and fluorescence spectroscopic studies were compared in different media. Fluorescence quantum yields (phi(F)) of 0.16 for 1 in tetrahydrofuran and 0.08 for 2 in N, N-dimethylformamide (DMF) were calculated, whereas no significant emission was detected for Pd(II) porphyrin 3. The singlet molecular oxygen, O(2)((1)Delta(g)), production was evaluated using 9,10-dimethylanthracene in DMF yielding relative values of 1, 0.55 and 0.47 for porphyrins 3, 2 and 1, respectively. A faster decomposition of l-tryptophan was obtained using Pd(II) porphyrin 3 as sensitizer with respect to the free-base porphyrins 1 and 2. In biological medium, the behavior of cationic porphyrins 1-3 were compared with that of 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin 4, which was used as a noncationic sensitizer. These porphyrins are rapidly bound to E. coli cells in 5 min and the amount of cell-bound sensitizer is not appreciably changed incubating the cultures for longer times. The recovered porphyrin 2 after one washing step reaches a value of approximately 2.9 nmol/10(6) cells and this amount remains high even after three washes, indicating that this sensitizer is tightly bound to cells. Photosensitized inactivation of E. coli was analyzed using cells without and with one washing step. In both cases, a higher photoinactivation of cells was found for tricationic porphyrin 2 and 3, causing a approximately 5.5 log (99.999%) decrease of cell survival, when treated with 10 microM of sensitizer. Under these conditions, a lower effect was found for porphyrin 1 (approximately 4 log) whereas sensitizer 4 did not produce appreciable photodamage. The results were also confirmed by growth delay experiments. These studies show that the amphiphilic tricationic porphyrin 2 and 3 bearing a trifluoromethyl group can be a promising model for phototherapeutic agents with potential applications in inactivation of bacteria by photodynamic therapy.

Cross-linguistic analysis of vocabulary in young children: spanish, dutch, French, hebrew, italian, korean, and american english.

The composition of young children's vocabularies in 7 contrasting linguistic communities was investigated. Mothers of 269 twenty-month-olds in Argentina, Belgium, France, Israel, Italy, the Republic of Korea, and the United States completed comparable vocabulary checklists for their children. In each language and vocabulary size grouping (except for children just learning to talk), children's vocabularies contained relatively greater proportions of nouns than other word classes. Each word class was consistently positively correlated with every other class in each language and for children with smaller and larger vocabularies. Noun prevalence in the vocabularies of young children and the merits of several theories that may account for this pattern are discussed.

Diagnóstico microbiológico de vaginosis bacteriana / Microbiological diagnosis of bacterial vaginosis

Se estudiaron exudados vaginales de 360 mujeres con aumento del flujo vaginal. Las muestras fueron obtenidas de fondo de saco, endocervix y posteriormente procesadas. En las muestras endocervicales se investigó Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum, mientras que en las muestras de fondo de saco se investigaron otras bacterias, hongos y parásitos. El diagnóstico de vaginosis bacteriana (VB) se realizó teniendo en cuenta los criterios de Amsel: pH, prueba de las aminas (KOH 10 por ciento) y la observación de clue cells por coloración de Gram. Las cepas de Gardnerella vaginalis fueron aisladas por cultivo en placas de agar sangre humana al 5 por ciento e identificadas por pruebas bioquímicas. El 23,9 por ciento de los aislamientos correspondió a G. vaginalis, el 21,9 por ciento a Candida albicans, el 14,2 por ciento a Trichomonas vaginalis, el 11,7 por ciento a C. trachomatis, el 5,5 por ciento a N. gonorrhoeae, U. urealyticum el 4,2 por ciento y M. hominis el 2,7 por ciento. Por coloración de Gram se observó un 8,2 por ciento de formas compatibles con Mobiluncus spp. Las asociaciones más frecuentes de G. vaginalis fueron con C. albicans (14,3 por ciento), T. vaginalis (14,3 por ciento), C. trachomatis (14,3 por ciento). De las 360 mujeres estudiadas, 37 presentaron más de un microorganismo patógeno. La relación entre el aislamiento de G. vaginalis y presencia de clue cells fue del 95,2 por ciento, presentando una sensibilidad del 95,2 por ciento, especificidad del 100 por ciento y el valor predictivo positivo del 100 por ciento

Diagnóstico microbiológico de vaginosis bacteriana / Microbiological diagnosis of bacterial vaginosis

Se estudiaron exudados vaginales de 360 mujeres con aumento del flujo vaginal. Las muestras fueron obtenidas de fondo de saco, endocervix y posteriormente procesadas. En las muestras endocervicales se investigó Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum, mientras que en las muestras de fondo de saco se investigaron otras bacterias, hongos y parásitos. El diagnóstico de vaginosis bacteriana (VB) se realizó teniendo en cuenta los criterios de Amsel: pH, prueba de las aminas (KOH 10 por ciento) y la observación de clue cells por coloración de Gram. Las cepas de Gardnerella vaginalis fueron aisladas por cultivo en placas de agar sangre humana al 5 por ciento e identificadas por pruebas bioquímicas. El 23,9 por ciento de los aislamientos correspondió a G. vaginalis, el 21,9 por ciento a Candida albicans, el 14,2 por ciento a Trichomonas vaginalis, el 11,7 por ciento a C. trachomatis, el 5,5 por ciento a N. gonorrhoeae, U. urealyticum el 4,2 por ciento y M. hominis el 2,7 por ciento. Por coloración de Gram se observó un 8,2 por ciento de formas compatibles con Mobiluncus spp. Las asociaciones más frecuentes de G. vaginalis fueron con C. albicans (14,3 por ciento), T. vaginalis (14,3 por ciento), C. trachomatis (14,3 por ciento). De las 360 mujeres estudiadas, 37 presentaron más de un microorganismo patógeno. La relación entre el aislamiento de G. vaginalis y presencia de clue cells fue del 95,2 por ciento, presentando una sensibilidad del 95,2 por ciento, especificidad del 100 por ciento y el valor predictivo positivo del 100 por ciento (AU)

Diátesis hemorrágica a partir de aumento de la actividad fribrinolítica como manifestación primaria y precoz en la amiloidosis / Hemorrhagic diathesis from increased fibinolytic activity as primary and early manifestation in amyloidosis

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