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Biomedical subjects

M Medina

Publications and source records attributed to M Medina.

At least 19 recordsLinked to original sources

How healthy are clones and their progeny: 5 years of field experience.

There is considerable concern regarding the health of cloned cattle and their safety as a source of food. The objective was to summarize 5 years of commercial experience with cloning in three countries (United States, Argentina and Brazil). Overall, only 9% of transferred embryos resulted in calves; efficiency ranged from 0 to 45% (most were from 1 to 10%, but 24% of cell lines never produced live calves). There was no significant difference in pregnancy rate following transfer of one versus two embryos. Before 90 days of gestation, two ultrasound markers for embryo death were found, either crown rump length (CRL) or heart beat less than 7.5mm and 150bpm, respectively, were observed alone or together in 27% of clones that died. In addition, after 100 days of pregnancy, placental edema, hydrops fetalis and increased abdominal circumference size were used as ultrasound findings of a fetus at risk of loss. At 114 days of gestation, abdominal circumference in clones that died was statistically larger than in clones that survived alive to term and from MOET- and IVF-derived pregnancies (P<0.05). Since elective cesarean section (C-section) was partially replaced by natural or assisted parturition, C-section rates decreased from 100% in 2000 to 54% in 2005. On average, 42% of cloned calves died between delivery and 150 days of life; the most common abnormalities were: enlarged umbilical cord (37%), respiratory problems (19%), calves depressed/prolonged recumbency (20%) and contracted flexor tendons (21%). From 11 blood parameters evaluated during the first week of life, lactate decreased twice and glucose doubled its original value from 24h to 7 days. Adult cloned females had normal breeding and calving rates and cloned bulls produced good quality semen and had normal fertility when used for AI or natural mating. In conclusion, cloning had no risks qualitatively different from those encountered in animals involved in modern agricultural practices, although the frequency of the risks appeared to be increased in cattle during the early portions of the life cycle of cattle clones.

Animal Welfare↗

Point mutations in protein globular domains: contributions from function, stability and misfolding.

Several contrasting hypotheses have been formulated about the influence of functional and conformational properties, like stability and avoidance of misfolding, on the evolution of protein globular domains. Selection at functional sites has been suggested to be detrimental to stability or coupled to it. Avoidance of misfolding may be achieved by discarding misfolding-prone sequences or by maintaining a stable native state and thus destabilizing partially or fully unfolded states from which misfolding can take place. We have performed a hierarchical analysis of a large database of point mutations to dissect the relative contributions of function, stability and misfolding in the evolution of natural sequences. We show that at catalytic sites, selection for function overrules selection for stability but find no evidence for an anticorrelation between function and stability. Selection for stability plays a secondary role at binding sites, but is not fully coupled to selection for function. Remarkably, we did not find a selective pressure against misfolding-prone sequences in globular proteins at the level of individual positions. We suggest that such a selection would compromise native-state stability due to a correlation between the stabilities of native and misfolded states. Stabilization of the native state is the most frequent way in which natural proteins avoid misfolding.

Amyloid↗

Transrectal Doppler sonography for evaluation of uterine blood flow throughout pregnancy in 13 cows.

Once weekly from 30 to 270 days of gestation in 13 cows, Doppler ultrasound scanning (triplex Doppler system) was done to assess blood-flow parameters of both median uterine arteries. Resistance, velocity and volume indices were measured. Resistance index values were negatively correlated to all other blood-flow parameters (P<0.05), but there were positive correlations between velocity and volume indices (P<0.05). Resistance indices were lower, and velocity and volume indices were significantly higher in the median uterine artery ipsilateral versus contralateral to the fetus. Resistance indices decreased continuously during the first 36 weeks of pregnancy. Velocity values rose three-fold, whereas the area increased 20-fold and the volume increased 17-fold by the end of gestation (P<0.05). Birth weight of calves was positively correlated with blood-flow volume (r=0.34) but negatively correlated with the resistance index (r=-0.45). There were no significant differences between male versus female calves (at any stage of gestation) in the resistance, time-average maximum velocity, and volume indices (P>0.05). In conclusion, arterial blood flow was monitored with transrectal Doppler sonography in both median uterine arteries weekly throughout pregnancy in cattle; this could be very valuable for monitoring pregnancies at high risk for abnormalities of the placenta, fetus or both, e.g. cloned calves.

Animals↗

Effect of a short contact time with lees on volatile composition of Airen and Macabeo wines.

Volatile compounds were analyzed in Airen and Macabeo wines at the end of the alcoholic fermentation and after a short time contact with wine lees. The concentration of 34 analyzed compounds, with the exception of hexyl acetate, linalool, ss-ionone and farnesol, increased significantly after contact with lees in Airen wines. Esters and terpenic compounds decreased significantly in Macabeo wines after contact with lees. The contact with lees could be considered as favourable in Airen wines to improve the aroma quality.

Cell Culture Techniques↗

Field evaluation of four novel enzyme immunoassays for Chagas' disease in Venezuela blood banks: comparison of assays using fixed-epimastigotes, fixed-trypomastigotes or trypomastigote excreted-secreted antigens from two Trypanosoma cruzi strains.

Many serological tests have been developed for the diagnosis of Chagas' disease, but few have been subjected to a rigorous field evaluation. We have recently described several novel enzyme immunoassays (EIAs) based on fixed-whole organisms or trypomastigote excretory-secretory antigens (TESA) from different Trypanosoma cruzi strains (Tulahuen or Brazil). This study evaluated the most promising of these novel assays (e.g. fixed-epimastigotes, fixed-trypomastigotes, TESA Brazil and TESA Tulahuen antigens) in a field study of Venezuelan blood bank specimens. The assays were tested in an operator-blinded fashion using 2038 blood bank samples obtained from low and high T.cruzi prevalence regions of Venezuela (n= 1050 and n= 988 from Bolivar and Portuguesa states, respectively). Based on National Laboratory for Chagas Immunodiagnosis (NLCI) 'gold standard' results, all novel EIAs were superior to the commercial kit currently used in Venezuela, achieving 100% sensitivity and >99% specificity at optimal cut-off values. The novel assays identified seven false-negative samples compared with the routine screening performed by the Venezuelan blood bank although two samples were also misclassified as positive. Minor differences in the performance of the four novel assays were observed at lower arbitrary cut-off values. This study confirms the potential utility of both the fixed-organism and the TESA-based assays in the diagnosis of T.cruzi infection.

Adolescent↗

Proteolysis of Hispanico cheese manufactured using lacticin 481-producing Lactococcus lactis ssp. lactis INIA 639.

Hispánico cheese was manufactured using lacticin 481-producing Lactococcus lactis ssp. lactis INIA 639, bacteriocin-nonproducing L. lactis ssp. lactis INIA 437, or a combination of both strains, as starter cultures. Lactobacillus helveticus LH 92, a culture of high amino-peptidase activity sensitive to lacticin 481, was added to all vats. Milk inoculation with the bacteriocin producer promoted early lysis of Lb. helveticus cells in cheese. Cell-free aminopeptidase activity in cheese made with the 3 lactic cultures was 1.8 times the level reached in cheese made only with L. lactis strain INIA 437 and Lb. helveticus, after 15 d of ripening. Proteolysis (as estimated by the o-phthaldialdehyde method) in cheese made with the 3 lactic cultures was twice as high, and the level of total free amino acids 2.4 times the level found in cheese made only with L. lactis strain INIA 437 and Lb. helveticus, after 25 d of ripening. Hydrophobic and hydrophilic peptides and their ratio were at the lowest levels in cheese made with the 3 lactic cultures, which received the lowest scores for bitterness and the highest scores for taste quality.

Amino Acids↗

Short communication: Inactivation of microbial contaminants in raw milk La Serena cheese by high-pressure treatments.

La Serena cheese, a Spanish variety made from Merino ewes' raw milk, has a high pH value, low salt content, and high moisture, conditions that are all favorable for growth and survival of contaminating microorganisms, including pathogens. To improve its microbiological quality and safety, high-pressure treatments at 300 or 400 MPa for 10 min at 10 degrees C were applied to 2 batches of La Serena cheese on d 2 or 50 of ripening. Cheese treated on d 2 at 300 MPa showed viable aerobic counts that were 0.99 log units lower than those for control cheese on d 3 and showed counts of enterococci, coagulase-positive staphylococci, gram-negative bacteria, and coliforms that were 2.05, 0.49, 3.14, and 4.13 log units lower, respectively, than control cheese. For cheese treated on d 2 at 400 MPa, the respective reductions in counts were 2.02, 2.68, 1.45, 3.96, and 5.50 log units. On d 60, viable aerobic counts in cheese treated on d 50 at 300 MPa were 0.50 log units lower than those in control cheese, and counts of enterococci, gram-negative bacteria, and coliforms were 1.37, 2.30, and 4.85 log units lower, respectively. For cheese treated on d 50 at 400 MPa, the respective reductions in counts were 1.29, 1.98, 4.47, and > 5 log units. High-pressure treatments at 300 or 400 MPa on d 2 or 50 reduced significantly the counts of undesirable microorganisms, improving the microbiological quality and safety of La Serena cheese immediately after treatment and at the end of the ripening period.

Animals↗

Effect of high-pressure treatment and a bacteriocin-producing lactic culture on the proteolysis, texture, and taste of Hispánico cheese.

The effects of high-pressure treatment, by itself or in combination with a bacteriocin-producing culture added to milk, on the proteolysis, texture, and taste of Hispánico cheese were investigated. Two vats of cheese were manufactured from a mixture of cow and ewe milk. Milk in one vat was inoculated with 0.5% Lactococcus lactis ssp. lactis INIA 415, a nisin Z and lacticin 481 producer; 0.5% L. lactis ssp. lactis INIA 415-2, a bacteriocin-nonproducing mutant; and 2% of a commercial Streptococcus thermophilus culture. Milk in the other vat was inoculated with 1% L. lactis ssp. lactis INIA 415-2 and 2% S. thermophilus culture. After ripening for 15 d at 12 degrees C, half of the cheeses from each vat were treated at 400 MPa for 5 min at 10 degrees C. Ripening of high-pressure-treated and untreated cheeses continued at 12 degrees C until d 50. High-pressure treatment of cheese made from milk without the bacteriocin producer accelerated casein degradation and increased the free AA content, but it did not significantly influence the taste quality or taste intensity of the cheese. Addition of the bacteriocin producer to milk lowered the ratio of hydrophobic peptides to hydrophilic peptides, increased the free AA content, and enhanced the taste intensity. The combination of milk inoculation with the bacteriocin producer and high-pressure treatment of the cheese resulted in higher levels of both hydrophobic and hydrophilic peptides but had no significant effect on the free AA content, taste quality, or taste intensity.

Amino Acids↗

Skin tests in NSAIDS hypersensitivity.

Prick tests are more specific but less sensitive than ID which can give false positive results. 3 NSAIDS groups can be considered: Aspirin, diclofenac and metamizol with a higher percentage of positivity. For others NSAIDS including the newer coxibs positivity around 50%. Nimesulid and acetaminophen with a lower of positivity. Skin tests can be used in NSAIDS hypersensitivity to confirm clinical history but also to choose, case by case, a drug less prone to give hypersentivity reactions.

Anti-Inflammatory Agents, Non-Steroidal↗

Prevalence of drug allergy in an out-patient population.

The prevalence of drug allergy in an out-patient population has been studied, 448 cases were diagnosed mainly to NSAIDS and beta-lactams and local anesthetics, sulfa drugs, quinolones and others. Clinical history and skin tests are sufficient to diagnose most cases of drug allergy.

Anesthetics, Local↗

Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE.

A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. These new hybrids combined a tacrine, 6-chlorotacrine or acridine unit as catalytic binding site and indanone (the heterocycle present in donepezil) or phthalimide moiety as peripheral binding site of the enzyme, connected through a different linker tether length. One of the synthesised compounds emerged as a potent and selective AChE inhibitor, which is able to displace propidium in a competition assay. These results seem to confirm the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease. To gain insight into the molecular determinants that modulate the inhibitory activity of these compounds, a molecular modelling study was performed to explore their binding to the enzyme.

Acetylcholinesterase↗

Inactivation of Staphylococcus aureus in raw milk cheese by combinations of high-pressure treatments and bacteriocin-producing lactic acid bacteria.

AIMS: To investigate the combined effect of high-pressure treatments (HPT) and milk inoculation with bacteriocin-producing lactic acid bacteria (BP-LAB) on the survival of Staphylococcus aureus during ripening of raw milk cheese. METHODS AND RESULTS: Cheeses were manufactured from raw milk artificially contaminated with S. aureus at ca 5 log CFU ml(-1), a commercial starter culture and one of seven strains of BP-LAB, added as adjuncts at 0.1%. HPT of cheeses were performed on days 2 or 50 at 300 MPa (10 degrees C, 10 min) or 500 MPa (10 degrees C, 5 min). On day 3, S. aureus counts were 6.46 log CFU g(-1) in control cheese. Milk inoculation with different BP-LAB lowered S. aureus counts on day 3 when compared with control cheese by up to 0.46 log CFU g(-1), HPT at 300 MPa on day 2 by 0.45 log CFU g(-1) and HPT at 500 MPa on day 2 by 2.43 log CFU g(-1). Combinations of BP-LAB with HPT at 300 and 500 MPa on day 2 lowered S. aureus counts on day 3 by up to 1.02 and 4.00 log CFU g(-1) respectively. CONCLUSIONS: The combined effect of milk inoculation with some of the BP-LAB tested and HPT of cheese on S. aureus inactivation was synergistic. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of HPT at lower pressures with BP-LAB inoculation is a feasible system to improve cheese safety in case of deleterious effects on cheese quality caused by HPT at higher pressures.

Antibiosis↗

Biodiversity of rocky intertidal benthic communities associated with copper mine tailing discharges in northern Chile.

Copper mine tailings have been discharged around the city of Chanaral, in northern Chile, for more than 60 years. This report summarizes a 17-month long monitoring study of species richness and biodiversity at five intertidal sites around the point of the tailing discharge. Total dissolved copper in sites close to the point of discharge varied between 8.72 microg/l and 34.15 microg/l, showing that there has not been a significant reduction since 1994. However, species richness has increased, suggesting a possible recovery of the system. While diversity of sessile organisms correlates negatively with dissolved copper, diversity of mobile invertebrates did not correlate with the metal concentration. To explain the observed results we discuss the role of algal turf interference on the distribution of mobile invertebrates at reference sites, a top-down effect caused by the absence of carnivores at impacted sites, and an avoidance strategy by some species to reduce their contact with contaminated seawater.

Animals↗

Pulmonary involvement in tuberous sclerosis.

Tuberous sclerosis is a neurocutaneous syndrome involving many tissues. Pulmonary involvement is rare. Pulmonary cases are usually women of child-bearing age who present with spontaneous pneumothorax or progressive dyspnea. In childhood and, even more, in male patients, pulmonary involvement by tuberous sclerosis is exceptional. We report on a 4-year-old male patient diagnosed in the first months of life with tuberous sclerosis with predominantly respiratory symptoms (frequently with acute RDS criteria), in whom lung involvement was pathologically confirmed.

Child, Preschool↗

Assessing the risks to zooplankton grazers of continuous versus pulsed cypermethrin exposures from marine cage aquaculture.

Survival responses of adult stages of the calanoid copepod A. tonsa during and after pulse exposures to cypermethrin were used to evaluate the environmental risks of cypermethrin treatments in the marine environment. To control sea lice, whole cages of salmon are exposed to cypermethrin over 1 h, after which the effluent is released into the environment and subsequently dissipates. Here we simulate this short presence of the chemical in the water column. The present study revealed that delayed toxicity in A. tonsa adults, here expressed as decreased survival, occurred following short term pulse exposures to cypermethrin. Persistent, sensitive responses to cypermethrin during and after pulse exposures of 24 h were similar to those reported in conventional acute tests, suggesting that damage caused by accumulated levels of cypermethrin during the first 24 h of exposure could explain long-term toxicity responses in A. tonsa. Delayed toxicity following 1 h pulse exposures to cypermethrin impaired male survival and therefore changed copepod sex ratios. The proposed delayed toxicity tests were considered sensitive and suggest potentially detrimental effects of cypermethrin on copepod populations within the vicinity of the cages. By monitoring toxic responses following pulsed exposures, delayed toxicity tests are especially suitable to assess environmental risks of poorly water-soluble substances that dissipate rapidly within the water column.

Animals↗

Analysis of the interaction of a hybrid system consisting of bovine adrenodoxin reductase and flavodoxin from the cyanobacterium Anabaena PCC 7119.

The mitochondrial steroid-hydroxylating system in vertebrates and the NADPH producing electron transfer chain in photosynthetic organisms contain structurally and functionally similar components. Examination of a potential hybrid reconstitution of the electron transfer chain between different components of both systems could help to improve our knowledge on protein-protein interaction and subsequent electron transfer. Here we analyzed the interaction between bovine adrenodoxin reductase and flavodoxin from the cyanobacterium Anabaena PCC 7119. Optical biosensor as well as steady state and fast kinetic experiments showed their ability to form distinct productive complexes. Compared with the corresponding physiological systems the electron transfer is rather slow, probably due to the lack of specificity at the interaction surface.

Animals↗

Changes in volatile compounds and aromatic series in sherry wine with high gluconic acid levels subjected to aging by submerged flor yeast cultures.

Volatile compounds of sherry wine containing gluconic acid under aging by submerged flor yeast cultures were analyzed. The aroma profile was obtained by grouping the compounds in nine aromatic series. The balsamic, fatty, herbaceous and empyreumatic series increased significantly as consequence of the increase of pantolactone, acids (butanoic, 2-methylbutanoic and 3-methylbutanoic), methionol and gamma-butyrolactone compounds, respectively. The decrease of higher alcohols promoted solvent series diminished. These changes are consistent with those observed in the production of commercial sherry wine using traditional biological aging.

Fermentation↗

A cost-effectiveness analysis of peginterferon alfa-2b plus ribavirin for the treatment of naive patients with chronic hepatitis C.

AIM: To estimate the cost-effectiveness of therapy and analyse the effect of therapy compliance in naive patients with chronic hepatitis C. METHODS: A decision analysis using the Markov model was performed for four different therapeutic strategies using peginterferon alfa-2b plus ribavirin or interferon alfa-2b plus ribavirin. Clinical data were obtained from available published reports and from the Spanish health system perspective. RESULTS: The incremental cost-effectiveness ratio of peginterferon alfa-2b plus ribavirin at a fixed dose, compared with interferon alfa-2b plus ribavirin, was 8478 euros per life year saved and 3737 euros per quality-adjusted life year gained. Good therapeutic compliance and weight-adjusted doses of ribavirin decreased the incremental cost-effectiveness ratio to 1636 euros per life year saved and 721 euros per quality-adjusted life year gained. In compliant genotype 1 patients, the incremental cost-effectiveness ratio decreased to 916 euros per life year saved and 404 euros per quality-adjusted life year gained, with an increase from 64 to 69 years in the threshold age at which therapy was cost-effective. The sensitivity analysis demonstrated that changes in the values of the most relevant parameters do not modify the study outcomes. CONCLUSION: From the clinical and pharmaco-economics perspective, the use of decision therapeutic analysis models suggests that the most effective therapy for chronic hepatitis C is peginterferon alfa-2b plus ribavirin adjusted to patient body weight and with good compliance, particularly in genotyped patients.

Adult↗