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1.
Food Sci Nutr ; 12(3): 2182-2191, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38455177

RESUMEN

The effect of aqueous extract of Arctium lappa root (ALE) on the survival of Lactobacillus acidophilus La-5 and Bifidobacterium bifidum Bb-12 probiotic bacteria and sensory and physicochemical properties of synbiotic yogurt was evaluated during 4 weeks storage at 4°C. According to this study, using 0.5% and 1% ALE significantly affected the survival of La-5 and Bb-12 during storage. The results showed that 1% of ALE counting of La-5 and Bb-12 has been reached from 6.96 and 8.14 Log CFU/g to 7.3 and 7.30 Log CFU/g after 28 days of storage. Moreover, adding 1% ALE to yogurt enhanced antioxidant activity and phenolic content to 1299.8 mg gallic acid/kg and 392.8 mg BHT eq./kg compared with the control (without extract) after storage, respectively. In general, in yogurt containing ALE, a decrease in Syneresis, undesirable changes in taste, texture, and appearance, and reduced overall acceptances were observed compared to the control. In conclusion, using this prebiotic compound (ALE) can improve nutritional properties and probiotic protection in yogurt during long time storage; thus, it is a good choice for application in the dairy industry.

2.
Int J Biol Macromol ; 265(Pt 2): 131114, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38547954

RESUMEN

Nano-encapsulation of essential oils, a specific area of interest, can help overcome challenges associated with their commercial use. This study aimed to evaluate the effect of different concentrations of chitosan, Ziziphora clinopodioides L. essential oil (ZcEO), and Sodium-Tri Polyphosphate (TPP), both individually and in interaction, on several properties of EO-loaded chitosan nanoparticles. These properties include particle size (PS), zeta potential (ZP), and encapsulation efficiency (EE) using a two-stage emulsion-ionic gelation approach. The optimization of the parameters was done by response surface methodology using Box-Behnken design. The chemical composition of ZcEO was analyzed as well. The primary compounds in ZcEO were found to be pulegone (29.24 %), 1,3-dimethyl-2-(2-methylpropylidene) imidazolidine (9.05 %), piperitenone (6.65 %), thymol (5.38 %), and carvacrol (5.27 %). The PS ranged from 117.33 to 4934.1 nm, the ZP varied from -1.1 to -30.83 mV, and the EE spanned from 31.74 to 87.04 %. The results showed that an increase in the initial EO content led to a decrease in PS and ZP, but an increase in EE. Moreover, increasing the TPP concentration resulted in an enhancement in PS, ZP, and EE, whereas increasing the Chs concentration led to a slight increase in PS, ZP, and EE. Furthermore, the results of this study proved the interaction effect of different parameters on the responses investigated. Under optimized conditions, the optimal concentrations of chitosan, ZcEO and TPP were attained at 6.768, 6.078, and 7.595 mg/mL respectively. This resulted in a PS of 117.331 nm, a ZP of -20.949 mV, and an EE of 75.385 %. In conclusion, the results suggest that adjusting the concentrations of Chs, EO, and TPP is an effective approach to controlling the properties of NPs and optimizing their performance.


Asunto(s)
Quitosano , Lamiaceae , Nanopartículas , Aceites Volátiles , Quitosano/química , Lamiaceae/química , Nanopartículas/química , Tamaño de la Partícula
3.
Polymers (Basel) ; 13(21)2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34771348

RESUMEN

Among the main biodegradable food packaging materials, poly-lactic acid (PLA) is a commercially successful polymer used notably in the food packaging industry. In this study, active PLA films containing different percentage of anise essential oil (AE) (0, 0.5, 1 and 1.5% v/v) were developed, and characterized by physical, mechanical and antibacterial analysis. Based on physical examinations, thermal stability of PLA/AE films was greater than the neat PLA film, and the minimum water vapor permeability (WVP) was recorded for PLA/0.5AE film (1.29 × 10 11 g/m s), while maximum WVP was observed for PLA/1.5AE (2.09 × 1011 g/m s). Moreover, the lightness and yellowness of the composites were decreased by the addition of AE. For the PLA composites with 1.5% AE, the tensile strength decreased by 35% and the elongation break increased by 28.09%, comparing to the pure PLA. According to the antibacterial analysis, the minimum inhibitory concentrations of PLA/AE film were 5 to 100 mg/mL and the active composite could create visible inhibition zones of 14.2 to 19.2 mm. Furthermore, the films containing AE inhibited L. monocytogenes and V. parahaemolyticus in a concentration-dependent manner. The confirmation of the success of the incorporation of EOs into the PLA films was further evaluated using principal component analysis, where positive results were obtained. In this context, our findings suggest the significant potency of AE to be used as an antibacterial agent in active food packaging.

4.
Food Sci Nutr ; 9(10): 5536-5545, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34646523

RESUMEN

In this study, the effect of aqueous extract of green tea on the viability of probiotic bacteria including Lactobacillus acidophilus and Bifidobacterium bifidum and the sensory and physicochemical and functional properties of synbiotic yogurt was investigated during 4 weeks of storage. L. acidophilus and B. bifidum counts did not significantly change in yogurt containing 0.5% and 1% of the extract during storage. Also, the addition of the extract to yogurt highly increased the phenolic compounds, since the amount of phenolic compounds in yogurt containing 0.5% and 1% extract was 660 and 1,123 mg gallic acid/kg, respectively. In addition, a significant increase in the antioxidant activity of yogurt containing green tea extract was observed in comparison with the control. The amount of antioxidant activity increased during 4 weeks of storage, which reached to 4,193 and 7,337 mg BHT eq./kg in probiotic yogurt containing 0.5% and 1% extract, respectively. The acidity increased during 4 weeks of storage, while the pH decreased. Addition of the extract significantly increased the acidity of probiotic yogurt compared with the control (p < .05). In addition, in all studied groups, an increase in syneresis was observed during the study, and the syneresis was greater in yogurt containing aqueous extract of green tea, compared with the control group. Although adding the green tea extract to probiotic yogurt impaired taste, texture, and appearance compared with the plain yogurt, the overall acceptability of these samples was yet above the acceptable level. In conclusion, the results of the study showed that the addition of aqueous extract of green tea increased the antioxidant properties and the amount of phenolic compounds in yogurt, while the viability of probiotic bacteria was not changed. Therefore, the simultaneous use of green tea extract and probiotics in yogurt is recommended as an effective functional food formulation.

5.
Vet Res Forum ; 12(2): 235-240, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34345392

RESUMEN

In this study, 22 Lactobacillus plantarum strains isolated from Siahmazgi traditional cheese were evaluated using different tests including resistance to low pH (1.50 and 2.50) and bile salt (0.50 and 1.00%), growth kinetic at low pH values and survival under simulated gastric and intestinal fluids. All the strains retained their viability at pH 2.50. However, the survival of all of the isolates was decreased at pH 1.50. Ten out of 22 strains which were able to tolerate low pH were selected for further investigations. All the selected isolates were able to grow at low pH. Strain F2 showed the highest specific growth rate. Five out of 10 isolates showed a significant decrease in bacterial count varied from 2.00 to 7.00 log CFU mL-1 during 3 hr exposure to 0.50% bile salt, while five isolates represented resistance to 0.50% bile during 3 hr. A significant reduction was observed in survival of all of the isolate at 1.00% bile salt concentration. Furthermore, viability of the selected isolates was lowered during 1 hr incubation under gastric conditions, while it remained unchanged within next 2 hr. Although, no significant changes were seen in bacterial count of the selected isolates during 1 hr of exposure to simulated intestinal condition, the survival of the isolates was relatively reduced after 3 hr. In conclusion, five out of 22 examined L. plantarum isolates showed appropriate resistance properties, therefore, could be good candidates for further examinations including functional and safety evaluation supporting their use as probiotics.

7.
J Ethnopharmacol ; 266: 113428, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33011368

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The application of the herb Ziziphora clinopodioides Lam. in folk medicine and as a food additive has been recommended due to its many claimed bioactivities. Regardless of the plant benefits, its safety considerations are largely unknown. AIM OF THE STUDY: The aim of the present research was to determine the chemical compositions and cytotoxicity, genotoxicity, and mutagenicity potentials of the ethanolic extract of Ziziphora clinopdioides Lam. (EEZC). MATERIALS AND METHODS: GC-MS and LC-MS analysis were used for chemical composition determination. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion dye assays were used for cytotoxicity and the Comet assay was employed for genotoxicity assessment on human blood lymphocytes. Also, the Ames Salmonella/microsome test was carried out for the evaluation of mutagenicity. RESULTS: Pulegone was the main component of the n-hexane fraction. Different phenolic acids and flavonoids were detected by LC-MS. The cytotoxicity study indicated a conspicuous decline in human lymphocyte viability ranging from 52% to 100% as showed by the MTT assay and 67% up to 100% by the trypan blue assay, at 1 and 10 mg/mL, respectively. The Comet assay results revealed a dose dependent genotoxicity, in so much as 90% and 98% of the cells were screened as damaged at concentrations of 5 and 10 mg/mL, respectively. An incidence rate of 8% and 13% of grade 4 damage was observed at 5 and 10 mg/mL, respectively. Additionally, the DNA damage index (DI) was elevated dose-dependently by a rising concentration of the extract, wherein the DI at 10 mg/mL concentration was 2.22, which was 22 times greater than that of negative control, and even more than positive control. The Ames test exhibited no signs of mutagenicity for neither Salmonella typhimurium TA98 nor TA100 strains, accompanied or unaccompanied by S9 metabolic activation. CONCLUSION: Results indicated a dose-dependent cytotoxicity and genotoxicity potential of the EEZC on human lymphocytes, suggesting that this plant should be used with caution by consumers, even in the food and pharmaceutical industries. Since the plant usage in daily life continues to increase due to its ever growing phytotherapical and phytonutritional properties, it may pose a health risk by its high concentration's uptake. Although no mutagenicity of this extract was observed in this study, further research is recommended to clarify the mutagenic risks of this herb.


Asunto(s)
Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Linfocitos/efectos de los fármacos , Extractos Vegetales/toxicidad , Adulto , Cromatografía Liquida , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lamiaceae/química , Espectrometría de Masas , Pruebas de Mutagenicidad , Fitoquímicos/análisis , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química
10.
Food Sci Nutr ; 8(2): 1254-1263, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32148831

RESUMEN

The effect of Auricularia auricula aqueous extract (AAE) on the survival of Lactobacillus acidophilus La-5 and Bifidobacterium bifidum Bb-12, and on chemical and sensory properties of yogurt was investigated during 28 days of storage at 4°C. The use of 0.05% of AAE improved the survival of L. acidophilus La-5 and B. bifidum Bb-12 about 0.35 and 0.58 log CFU/g, respectively. However, AAE in 0.1% concentration enhanced the survival of L. acidophilus La-5 and B. bifidum Bb-12 about 0.43 and 0.51 log CFU/g, respectively. Moreover, 0.1% concentration of AAE drastically increased antioxidant activity and total phenolic content to 115.30 mg BHT eq./kg and 1,057.6 mg Gallic acid/kg after 28 days, respectively. Addition of AAE to the yogurt significantly decreased sensorial acceptance while increased syneresis compared to the control group (p < .05). In conclusion, the results of this study showed that addition of AAE improved probiotic protection and functional properties of the yogurt recommending its application in symbiotic yogurt.

11.
Biotechnol Rep (Amst) ; 25: e00432, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32099822

RESUMEN

The survival rate of free and encapsulated L. acidophilus and L. rhamnosus into Doogh beverage and simulated gastrointestinal conditions during 42-day were studied. Microencapsulation considerably protected both L. acidophilus and L. rhamnosus in Doogh beverage storage and in gastrointestinal conditions. Microencapsulation provided better protection to L. acidophilus than to L. rhamnosus during Doogh storage. In beverages containing the free form of bacteria, pH and acidity changes were greater than those of microencapsulated and control groups. More activity of the free probiotic bacteria (during a 42-day period especially after 21-day) produced more acid and metabolites inside the product, thereby reducing the organoleptic properties scores, However, acidity, pH and organoleptic characteristics of Doogh containing microencapsulated bacteria did not change considerably. In conclusion, this study suggests that the encapsulation and double coating of L. acidophilus and L. rhamnosus can increase the viability of them in Doogh beverage and in simulated GI conditions.

12.
Food Chem ; 310: 125848, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-31846793

RESUMEN

Major databases were searched until January 2019 and 77 eligible studies were included in the meta-analysis to estimate the overall mean of AFM1 in milk in Iran. The mean of AFM1 levels was obtained 55.97 ng/kg (95% CI: 50.09-61.84). However, the pooled estimated mean of AFM1 levels in milk were 94.58 (95% CI: 70.24-118.92), 59.19 (95% CI: 51.84-66.54) and 35.23 ng/kg (95% CI: 31.53-38.92), considering 4, 55 and 18 TLC, ELISA and HPLC-based studies (including 354, 9224 and 2606 samples), respectively. Also, there is a wide variation of AFM1 levels among different geographical regions which were the highest in northern (88.77 ng/kg). The AFM1 contamination of milk taken from the areas with humid climate was higher than the arid climate. AFM1 Levels were the highest in winter (48.70 ng/Kg). The level of AFM1 in pasteurized, raw, and UHT milk were 49.76, 55.08 and 94.81 ng/kg, respectively.


Asunto(s)
Aflatoxina M1/análisis , Contaminación de Alimentos/análisis , Leche/química , Animales , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Clima , Ensayo de Inmunoadsorción Enzimática , Irán , Límite de Detección , Pasteurización , Estaciones del Año
13.
Food Addit Contam Part B Surveill ; 12(4): 236-244, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31088276

RESUMEN

Aflatoxin M1 (AFM1) is a 2B Group human carcinogens agent and introduces into the human diet by milk consumption. In the present study 257 raw, 143 pasteurized and 61 UHT milk samples were collected from markets in 117 cities throughout Iran, during winter 2017 and AFM1 contents were determined using a HPLC-FLD method after immunoaffinity clean-up. Mean recovery rates and relative standard deviations of the method were 90.6 ± 5.7%. AFM1 was detected in 252 of 461 (54.7%) samples (mean 31.3 ± 8.8 ng/L), ranging from <10 to 150 ng/L. Three samples (0.6%) exceeded the Iranian maximum limit of 100 ng/L. The mean AFM1 content was significantly higher in raw milk samples obtained from humid climate areas. The extrapolated concentration of AFB1 in dairy cattle feed based on the AFM1 value of milk was 1.96 µg/kg. The AFM1 contamination of milk seems not to be a serious public health concern in Iran.


Asunto(s)
Aflatoxina M1/análisis , Manipulación de Alimentos , Leche/química , Pasteurización/métodos , Animales , Bovinos , Cromatografía de Afinidad/métodos , Cromatografía Líquida de Alta Presión/métodos , Estudios Transversales , Irán , Límite de Detección
14.
Iran J Pharm Res ; 18(3): 1332-1340, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32641943

RESUMEN

Milk would be contaminated with Aflatoxin M1 (AFM1), if it was obtained from lactating animal which fed with feedstuffs containing Aflatoxin B1 (AFB1). AFM1 is classified as group 2B, possibly carcinogenic to humans and its exposure to AFM1 through milk consumption is a public concern. The purpose of this study was to determine the AFM1 exposure through liquid milk consumption for adult consumers in Tehran. Forty-five samples including raw, pasteurized, and UHT milk samples were collected from markets in different cities of Tehran province in January and February 2017. The AFM1 was determined by HPLC method after immunoaffinity column clean up. Also, the milk intake was calculated using household budget survey. Finally, the daily intake of AFM1 through milk consumption was estimated using a deterministic approach. From total 45 samples, AFM1 was detected in 36 (80%) samples, although none of the analyzed samples were exceeded Iran legal limit of 0.1 µg/kg. On the basis of the average milk intake, the mean daily exposure to AFM1 was estimated between 0.03 ng/ Kg BW per day (lower bound estimate) and 0.06 ng/ Kg BW per day (upper bound estimate) and the 95th percentile daily exposure was calculated at 0.14 ng/ Kg BW per day. According to these values, it should be expected that the adults of Tehran population are not exposed to a significant risk of Hepatocarcinoma associated with AFM1 intake through milk consumption.

15.
J Health Popul Nutr ; 32(3): 391-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25395902

RESUMEN

The aim of this study was to evaluate the bacterial and fungal quality of minimally-processed vegetables (MPV) and sprouts. A total of 116 samples of fresh-cut vegetables, ready-to-eat salads, and mung bean and wheat sprouts were randomly collected and analyzed. The load of aerobic mesophilic bacteria was minimum and maximum in the fresh-cut vegetables and fresh mung bean sprouts respectively, corresponding to populations of 5.3 and 8.5 log CFU/g. E. coli O157:H7 was found to be absent in all samples; however,  other E. coli strains were detected in 21 samples (18.1%), and Salmonella spp. were found in one mung bean (3.1%) and one ready-to-eat salad sample (5%). Yeasts were the predominant organisms and were found in 100% of the samples. Geotrichum, Fusarium, and Penicillium spp. were the most prevalent molds in mung sprouts while Cladosporium and Penicillium spp. were most frequently found in ready-to-eat salad samples. According to results from the present study, effective control measures should be implemented to minimize the microbiological contamination of fresh produce sold in Tehran, Iran.


Asunto(s)
Recuento de Colonia Microbiana , Comida Rápida/microbiología , Microbiología de Alimentos , Plantones/microbiología , Verduras/microbiología , Comercio , Escherichia coli O157/crecimiento & desarrollo , Contaminación de Alimentos/análisis , Manipulación de Alimentos/métodos , Hongos/crecimiento & desarrollo , Irán , Salmonella/crecimiento & desarrollo , Levaduras/crecimiento & desarrollo
16.
J Sci Food Agric ; 94(11): 2210-6, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24343670

RESUMEN

BACKGROUND: In this study, chitosan-coated alginate beads were produced with different concentrations of chitosan and alginate to evaluate the survival of encapsulated Lactobacillus rhamnosus GG during exposure to adverse conditions in gastrointestinal simulated juice and heat processing. RESULTS: The encapsulation yield of different encapsulation treatments was between 25 and 53.2%. Although there was a drastic decrease in pH within 48 h of incubation in MRS medium inoculated with free and encapsulated bacteria, no significant changes (P > 0.05) in bacterial count were observed among different encapsulation treatments. Moreover, the survival rate after gastrointestinal juice exposure of all prepared beads was 10-87 times greater than that of free cells and was significantly enhanced by increasing chitosan and alginate concentrations. The encapsulated bacteria survived significantly (P < 0.05) better than the free cells during heat exposure at 55, 60 and 65 °C: free cells experienced about 5 log cycles reduction after heat treatment at 65 °C for 30 min, whereas 40 g L(-1) alginate/10 g L(-1) chitosan-encapsulated L. rhamnosus was reduced by only 2.55 log cycles. CONCLUSION: Encapsulation effectively protected L. rhamnosus against heat treatment and gastrointestinal conditions, and this effect is important in delivering sufficient numbers of viable probiotic bacteria to the gastrointestinal tract.


Asunto(s)
Alginatos , Quitosano , Tracto Gastrointestinal/microbiología , Calor , Lacticaseibacillus rhamnosus , Viabilidad Microbiana , Probióticos/administración & dosificación , Cápsulas , Composición de Medicamentos/métodos , Jugo Gástrico/química , Tracto Gastrointestinal/química , Ácido Glucurónico , Ácidos Hexurónicos , Humanos , Microesferas
17.
Adv Biomed Res ; 3: 251, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25590029

RESUMEN

BACKGROUND: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. MATERIALS AND METHODS: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. RESULTS: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). CONCLUSION: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

18.
Foodborne Pathog Dis ; 7(3): 299-305, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19911935

RESUMEN

The effect of different concentrations of Zataria multiflora Boiss. essential oil (EO; 0%, 0.005%, and 0.015%), nisin (0, 0.125, and 0.25 microL/mL), and their combinations on the production of staphylococcal enterotoxin C (SEC) and alpha-hemolysin (alpha-toxin) by Staphylococcus aureus at different inoculation levels (10(3), 10(4), and 10(5) cfu/mL) in brain heart infusion broth during storage at 35 degrees C for up to 43 days was evaluated. The SEC production was significantly (p < 0.05) inhibited and the hemolysis due to alpha-toxin was significantly (p < 0.05) reduced by EO concentration at levels 0.015% and 0.005%, respectively. Significant (p < 0.05) inhibitory effect of EO on SEC production at level 0.005% was observed when it was used in combination with nisin = 0.125 microL/mL. The significant (p < 0.05) synergistic effect of EO = 0.005% and nisin = 0.125 microL/mL was also observed as more reduction of hemolysis due to alpha-toxin than EO = 0.005% alone. Further, EO significantly (p < 0.05) prevented SEC production by S. aureus during the manufacturing process of a traditional Iranian white brined cheese (as a food model) even at its lowest concentration (5 microL/100 mL), in this study.


Asunto(s)
Toxinas Bacterianas/biosíntesis , Enterotoxinas/biosíntesis , Proteínas Hemolisinas/biosíntesis , Lamiaceae/química , Nisina/administración & dosificación , Aceites Volátiles/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Toxinas Bacterianas/antagonistas & inhibidores , Queso/análisis , Queso/microbiología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Enterotoxinas/análisis , Enterotoxinas/antagonistas & inhibidores , Enfermedades Transmitidas por los Alimentos/microbiología , Enfermedades Transmitidas por los Alimentos/prevención & control , Proteínas Hemolisinas/antagonistas & inhibidores , Humanos , Irán , Olfato , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/metabolismo , Gusto
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