Toxicity of topically applied drugs beyond skin irritation: Static skin model vs. Two organs-on-a-chip.

Skin model cultivation under static conditions limits the observation of the toxicity to this single organ. Biology-inspired microphysiological systems associating skin with a liver in the same circulating medium provide a more comprehensive insight into systemic substance toxicity; however, its advantages or limitations for topical substance toxicity remain unknown. Herein, we performed topical (OECD test guideline no. 439) and systemic administration of terbinafine in reconstructed human skin (RHS) vs. a RHS plus liver model cultured in TissUse' HUMIMIC Chip2 (Chip2). Aiming for a more detailed insight into the cutaneous substance irritancy/toxicity, we assessed more than the MTT cell viability: lactate dehydrogenase (LDH), lactate and glucose levels, as well as inherent gene expressions. Sodium dodecyl sulfate (SDS) was the topical irritant positive control. We confirmed SDS irritancy in both static RHS and Chip2 culture by the damage in the morphology, reduction in the lactate production and lower glucose consumption. In the static RHS, the SDS-treated tissues also released significantly high LDH (82%; p < 0.05) and significantly lower IL-6 release (p < 0.05), corroborating with the other metabolic levels. In both static RHS and Chip2 conditions, we confirmed absence of irritancy or systemic toxicity by LDH, glucose or lactate levels for topical 1% and 5% terbinafine and systemic 0.1% terbinafine treatment. However, topical 5% terbinafine treatment in the Chip2 upregulated IL-1α in the RHS, unbalanced apoptotic and proliferative cell ratios in the liver and significantly increased its expression of CYP1A2 and 3A4 enzymes (p < 0.05), proving that it has passed the RHS barrier promoting a liver impact. Systemic 0.1% terbinafine treatment in the Chip2 increased RHS expression of EGFR, increased apoptotic cells in the liver, downregulated liver albumin expression and upregulated CYP2C9 significantly (p < 0.05), acting as an effective hepatotoxic terbinafine control. The combination of the RHS and liver model in the Chip2 allowed a more sensitive assessment of skin and hepatic effects caused by chemicals able to pass the skin (5% terbinafine and SDS) and after systemic 0.1% terbinafine application. The present study opens up a more complex approach based on the microphysiological system to assess more than a skin irritation process.

Molecular biosignatures reveal common benthic microbial sources of organic matter in ooids and grapestones from Pigeon Cay, The Bahamas.

Ooids are sedimentary grains that are distributed widely in the geologic record. Their formation is still actively debated, which limits our understanding of the significance and meaning of these grains in Earth's history. Central questions include the role played by microbes in the formation of ooids and the sources of ubiquitous organic matter within ooid cortices. To address these issues, we investigated the microbial community composition and associated lipids in modern oolitic sands at Pigeon Cay on Cat Island, The Bahamas. Surface samples were taken along a transect from the shallow, turbulent surf zone to calmer, deeper water. Grains transitioned from shiny and abraded ooids in the surf zone, to biofilm-coated ooids at about 3 m water depth. Further offshore, grapestones (cemented aggregates of ooids) dominated. Benthic diatoms and Proteobacteria dominated biofilms. Taxa that may promote carbonate precipitation were abundant, particularly those associated with sulfur cycling. Compared to the lipids associated with surface biofilms, relict lipids bound within carbonate exhibited remarkably similar profiles in all grain types. The enhanced abundance of methyl-branched fatty acids and ß-hydroxy fatty acids, 1-O-monoalkyl glycerol ethers and hopanoids bound within ooid and grapestone carbonate confirms a clear association of benthic sedimentary bacteria with these grains. Lipids bound within ooid cortices also contain molecular indicators of microbial heterotrophic degradation of organic matter, possibly in locally reducing conditions. These included the loss of labile unsaturated fatty acids, enhanced long-chain fatty acids/short-chain fatty acids, enriched stable carbon isotopes ratios of fatty acids, and very high stanol/stenol ratios. To what extent some of these molecular signals are derived from later heterotrophic endolithic activity remains to be fully resolved. We speculate that some ooid carbonate forms in microbial biofilms and that early diagenetic degradation of biofilms may also play a role in early stage carbonate precipitation around ooids.

A record of recent change in terrestrial sedimentation in a coral-reef environment, La Parguera, Puerto Rico: a response to coastal development?

Increased sediment flux to the coastal ocean due to coastal development is considered a major threat to the viability of coral reefs. A change in the nature of sediment supply and storage has been identified in a variety of coastal settings, particularly in response to European colonization, but sedimentation around reefs has received less attention. This research examines the sedimentary record adjacent to a coastal village that has experienced considerable land-use change over the last few decades. Sediment cores were analyzed to characterize composition and sediment accumulation rates. Sedimentation rates decreased seaward across the shelf from 0.85 cm y(-1) in a nearshore bay to 0.19 cm y(-1) in a fore-reef setting. Data reflected a significant (up to 2x) increase over the last approximately 80 years in terrestrial sediment accumulating in the back-reef setting, suggesting greater terrestrial sediment flux to the area. Reef health has declined, and increased turbidity is believed to be an important impact, particularly when combined with additional stressors.

Successful pregnancy and delivery after pulmonary autograft operation (Ross procedure) for rheumatic aortic valve insufficiency.

A young woman with aortic valve insufficiency secondary to rheumatic heart disease underwent replacement of her diseased aortic valve with her own pulmonary valve and replacement of her pulmonary valve with an aortic cadaver homograft, the Ross procedure. She went on to conceive and deliver a normal infant. The Ross procedure is the operation of choice in a young woman with aortic valve disease, since it avoids anti-coagulation fetal loss, valve deterioration and other maternal risk from pregnancy associated with other valve replacement options.

Successful pregnancy and delivery after pulmonary autograft operation (Ross procedure) for rheumatic aortic valve insufficiency

A young woman with aortic valve insufficiency secondary to rheumatic heart disease underwent replacement of her diseased aortic valve with her own pulmonary valve and replacement of her pulmonary valve with an aortic cadaver homograft, the Ross procedure. She went on to conceive and deliver a normal infant. The Ross procedure is the operation of choice in a young woman with aortic valve disease, since it avoids anti-coagulation fetal loss, valve deterioration and other maternal risk from pregnancy associated with other valve replacement options

[Intrauterine growth in full-term twins without risk factors]. / Crecimiento intrauterino en gemelos de término sin factores de riesgo.

Twins are analysed according to the intrauterine growth curve constructed for single fetus. The relationship of twins with length, weight, head circumference and the weight length-index is studied. Twins over 36 weeks gestation age, without maternal or fetal pathologies were selected. It is concluded the twins pregnancy "per se" constitutes on its own, a risk factor regarding the intrauterine growth curve, particularly in relation with the weight curve.

[Neonatal autoimmune purpura: laboratory study of 5 cases]. / Purpura aloinmune neonatal: estudio de laboratorio en cinco casos.

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia. We report our experience in the study of five cases with severe neonatal-thrombocytopenia. Using an ELISA with antigen capture and other serologic tests on platelets, we investigated the sera of the five mothers. Sera from four mothers contained a platelet-specific alloantibody, anti-HPA-1a (PlA1) whereas the platelets typed as HPA-1b/b. In one case despite extensive serological investigation and clinically unequivocal diagnosis of AINT, no antibodies were demonstrated. The use of monoclonal antibodies for antigen immobilization, showed to be a reliable and sensitive test for the detection and identification of platelet antibodies in AINT. These techniques could also be used in the follow-up of patients at risk (e.g. pregnant HPA-1b/b women) and in the screening of blood donors lacking of certain antigens, whose platelets are collected to be transfused in patients with platelet-specific antibodies.

Ciguatera toxins in the food chain revealed by stable isotopes.

The stable carbon and nitrogen isotope contents of the meat tissues of 27 identifiable fish found in the gut contents of 70 ciguatoxic and non-ciguatoxic barracuda caught along the southwest coast of Puerto Rico have been analyzed. The isotope ratios of those fish found in the stomach contents of ciguatoxic barracuda were significantly different than ratios determined in those fish found in the stomachs of non-ciguatoxic barracuda. The isotope ratios of the toxic dinoflagellate Ostreopsis lenticularis, a presumed vector of ciguatera in the Caribbean were found to be extremely light, particularly for nitrogen. The lightened nitrogen ratios of the herbivore (Doctorfish) and carnivore (Squirrelfish) fishes found in the stomach contents of ciguatoxic barracuda suggest that the dinoflagellate was in the food chain of these barracuda. Results indicate that the trophic pathway of ciguatoxins through the marine food chain from the presumed primary trophic level (dinoflagellates/bacteria) to ciguatoxic barracuda appears to be different than the pathway to non-toxic barracuda. Stable isotope ratios may be a very useful tool for tracing ciguatoxins in the food chain and the identification of ciguatoxic fish.

[Ultrasonography in spinal dysraphism and tethered cord]. / Ultrasonografía en la disrafia espinal y la médula anclada.

Spinal dysraphism is relatively common in children and includes a wide spectrum of congenital anomalies in the normal closure of the posterior elements of the spine. The prognosis will depend mostly on early diagnosis and treatment. Occult spinal dysraphism may present without external anomalies and the diagnosis could be suspected lately, when neurological symptoms are present and often irreversible. Occult spinal dysraphism is frequently associated to a tethered cord, most commonly secondary to the presence of a lipoma. Ultrasonography has been proven highly sensitive in the detection of intraspinal anomalies, especially in the diagnosis of tethered cord, in children under two years of age due to lack of ossification of the posterior elements of the spine. Today ultrasonography should be the examination of choice in all those patients in whom some kind of spinal dysraphism is suspected. We report our experience with three infants with occult spinal dysraphism in whom diagnosis was initially made by US and later on proved by either computed tomography, magnetic resonance or myelography. All of them had corrective surgery and neurological abnormalities were not detected afterwards.

[Intrauterine growth in Chilean middle class newborn infants]. / Crecimiento intrauterino en recién nacidos chilenos de clase media.

Intrauterine growth of 11,543 newborn infants, liveborn between 1978 to 1987 that met prospective selection conditions (without intrauterine growth retardation risk) and their data are reported. MBW and weight percentiles 10, 25, 50, 75, 90 from 26 throughout 42 week of gestational age are reported. Selection of cases was important in obtaining adequate percentiles of birth-weight vs gestational age. The intrauterine growth pattern herein reported is recommended for evaluation of chilean newborns, because it is different to that of some foreign countries and the studied sample seems representative of chilean babies.

[Importance of iron for the recovery of malnourished infants]. / Importancia del hierro en la recuperación del desnutrido.

Thirty one infants with moderate and severe protein-calorie malnutrition whose blood hemoglobin concentrations were higher than 10 g/dl were managed with diet supplements containing iron fortified cereals for three months. In addition, 17 of them were given an extra daily dose of elementary iron (3 mg/kg/day). Mean weight gain was similar in both subgroups but mean hemoglobin concentration raised by 1,2 g/dl among extra iron infants in contrast with no increase or even decreased hemoglobin levels at the end of follow up in controls, thus demonstrating the importance of adding supplementary iron to these children during the recovery period of under nutrition, even it the diet provides the usually recommended 8 to 10 mg/day of iron.

Sindrome de la cimitarra. / Scimitar syndrome

Se presenta un caso clinico de drenaje venoso pulmonar anomalo derecho a la vena cava inferior (Sidrome de la Cimitarra).El cuadro clinico se caracterizo por ausencia de sintomas los primeros cinco dias de vida comenzando luego con polipnea, discreta retraccion y requerimientos de oxigeno variable. El diagnostico inicial fue de atelectasia de lobulo superior derecho, sin embargo la evolucion radiologica descarto esta posibilidad. Se envio al Hospital Calvo Mackenna para completar su estudio efectuandose un cateterismo cardiaco que confirmo el diagnostico de Sindrome de la Cimitarra