Desarrollo embriológico e importancia clínica de la membrana amniótica: revisión narrativa de literatura / Embryological development and clinical significance of the amniotic membrane: narrative literature review

La membrana amniótica (MA), ubicada en el lado interno de la placenta fetal, ha sido objeto de múltiples investigaciones para intentar dilucidar su papel embriológico y su potencial celular terapéutico. Actualmente las limitaciones del estudio en fetos humanos hacen que parte de su funcionamiento sea una incógnita, sin embargo algunos estudios clínicos y básicos nos dan luz sobre su papel en la médica moderna. Se realizó una revisión bibliográfica de la literatura desde 1960 hasta 2022, empleando bases de datos como PubMed, SciELO y Scopus, siendo incluidos un total de 50 artículos y dos textos de embriología. El objetivo de esta revisión narrativa fue sintetizar la información sobre la angiogénesis y su importancia clínica. La información recopilada permitió evidenciar que las propiedades de curación de la piel del feto se deben a factores intrínsecos del feto, y a que las células epiteliales amnióticas humanas poseen una diferenciación similar a las células madre embrionarias, con la capacidad de diferenciación similar al de las células mesenquimales, resaltando su importancia clínica por sus características regenerativas. En conclusión, el desarrollo embrionario humano sigue siendo relativamente inexplicable, pero su conocimiento ha permitido grandes avances, que podrían ser útiles en terapias de regeneración, reparación de tejidos y órganos lesionados.

The amniotic membrane, located on the inner side of the fetal placenta, has been the subject of multiple investigations to try to elucidate its embryological role and its therapeutic cellular potential. Currently, the limitations of the study in human fetuses mean that part of its functioning is unknown, however, some clinical and basic studies shed light on its role in modern medicine. A bibliographic review of the literature was carried out from 1960 to 2022, using databases such as PubMed, SciELO and Scopus, including a total of 50 articles and two embryology texts. The objective of this narrative review was to synthesize information on angiogenesis and its clinical importance. The information collected made it possible to show that the healing properties of the fetal skin are due to intrinsic factors of the fetus, and that human amniotic epithelial cells have a differentiation similar to embryonic stem cells, with the differentiation capacity similar to that of mesenchymal cells, highlighting their clinical importance due to their regenerative characteristics. In conclusion, human embryonic development remains relatively inexplicable, but its knowledge has allowed great advances, which could be useful in regeneration therapies, repair of injured tissues and organs.

Comportamiento de la amoxicilina en agua mediante métodos de solvatación implícita y explícita

El comportamiento molecular de la amoxicilina en agua fue explorado con solvatación implícita y explícita mediante dos estrategias que combinan diferentes técnicas de simulación molecular para evaluar el alcance de estos procedimientos. Con estas dos estrategias de cálculo computacional, la conformación molecular de la amoxicilina fue determinada en fase acuosa. En la primera estrategia se utilizó el generador de conformaciones Ballon-v1.8.2 y la estabilidad de las conformaciones en agua fue evaluada utilizando la energía libre de solvatación determinada con el método de solvatación implícita SMD. En la segunda estrategia, con la dinámica molecular tipo NVT fue evaluado el arreglo espacial de esta molécula en agua y, además, la interacción molecular entre la amoxicilina y el agua fue evaluada en esta simulación. Los resultados obtenidos muestran que la conformación de la amoxicilina más estable en fase acuosa es la plegada. Además, los valores de energías de solvatación de -121,42 y -14,58 kJ/mol obtenidos con solvatación implícita y dinámica molecular sugieren que esta molécula tiene una alta afinidad por el agua. Las funciones distribución radial y espacial sugieren que se forman 3 capas de solvatación alrededor de la amoxicilina y que esta molécula tiene una región altamente hidrofílica. Finalmente, la estrategia usando dinámica molecular permite obtener mejores conformaciones en equilibrio que la estrategia de simulación usando el generador de conformaciones Ballon-v1.8.2.

The molecular behavior of amoxicillin in water was explored with implicit and explicit solvation using two strategies that combine different molecular simulation techniques to assess the scope of these procedures. With these two computational calculation strategies, the molecular conformation of amoxicillin was determined in aqueous phase. In the first strategy, the conformation generator Ballon-v1.8.2 was used and the stability of the conformations in water was evaluated using the solvation free energy determined with the SMD implicit solvation method. In the second strategy, with NVT-type molecular dynamics, the spatial arrangement of this molecule in water was evaluated and, in addition, the molecular interaction between amoxicillin and water was evaluated in this simulation. The results obtained show that the most stable conformation of amoxicillin in the aqueous phase is the folded one. In addition, the solvation energy values of -121.42 and -14.58 kJ/mol obtained with implicit solvation and molecular dynamics suggest that this molecule has a high affinity for water. The radial and spatial distribution functions suggest that 3 solvation shells form around amoxicillin and that this molecule has a highly hydrophilic region. Finally, the strategy using molecular dynamics allows to obtain better equilibrium conformations than the simulation strategy using the Ballon-v1.8.2 conformation generator.

O comportamento da amoxicilina em água foi analisado com solvatação implícita e explícita mediante duas estratégias que combinam diferentes técnicas de simulação molecular para avaliar o escopo destes procedimentos. Com estas duas estratégias de cálculo computacional, a conformação molecular da amoxicilina foi determinada em fase aquosa. Na primeira estratégia, utilizou-se o gerador de conformação do software Ballon-v1.8.2 e avaliou-se a estabilidade das conformações em água a partir da energia livre de solvatação determinada pelo método de solvatação implícita SMD. Na segunda estratégia, avaliou-se o arranjo espacial da amoxicilina e sua interação com a água através de simulações de dinâmica molecular NVT. Os resultados obtidos mostram que a conformação dobrada é a mais estável em fase aquosa. Ademais, os valores de energía de solvatação de -121,42 e -14,58 kJ/mol obtidos com solvatação implícita e dinâmica molecular sugerem que esta molécula possui alta afinidade pela água. As funções de distribuição radial e espacial sugerem que se formam 3 camadas de solvatação ao redor da amoxicilina e que esta molécula possui uma região altamente hidrofílica. Finalmente, a estratégia usando dinâmica molecular permite obter melhores conformações de equilíbrio do que a estratégia de simulação usando o gerador de conformação do software Ballon-v1.8.2.

First report of suspected glycogen storage disease type 1a occurring in an adult dog.

A 4-year-old female border collie was presented with haemoabdomen following the rupture of a hepatocellular carcinoma. After referral for ongoing elevation of alanine aminotransferase and alkaline phosphatase, the dog was found to have marked vacuolar hepatopathy due to glycogen accumulation within the liver, fasting hypoglycaemia and hyperlactataemia, and a negative response to glucagon stimulation testing. These changes were strongly suggestive of glycogen storage disease type 1a. Based on our literature search, this report documents the first adult canine to be diagnosed with suspected glycogen storage disease type 1a.

Uma nova estratégia para PDT antimicrobiana em Endodontia / A new approach for antimicrobial Endodontic PDT

O presente estudo avaliou diferentes parâmetros como concentração do fotossensibilizador,tempo/energia de irradiação e uso de fibras ópticas, na a PDT para redução bacteriana intracanal.Avaliou-se, in vitro, em cubetas de quartzo contendo concentrações de 50, 100, 150 e 300μM de solução aquosa de Azul de Metileno (AM) a produção de espécies reativas de oxigênio (EROs) em irradiações adicionais de 30s com um laser de diodo emitindo em 660nm. Utilizando-se a mesma metodologia, foi avaliado os efeitos na produção de EROs com e sem o uso de fibra óptica. Concentrações de 50, 150 e 300μM de AM e análise por imagens, avaliaram a formação do fenômeno escudo óptico. Dez incisivos contaminados com P. Aeruginosas bioluminescentes, foram utilizados para analisar as energias/tempo para redução bacteriana intracanal. Imagens obtidas nos dentes avaliaram a contaminação inicial. Os canais foram preenchidos com o fotossensibilizador (PS) eirradiações de 2,4J foram realizadas. A cada irradiação, imagens foram obtidas e a redução bacteriana avaliada. A formação de EROs é maior em concentrações menores do PS, assim como a formação de escudo óptico. O uso de fibra aumenta a formação de ERO quando comparado a irradiação sem fibra. Irradiação com 7J impossibilitou a detecção de biofilme intracanal. A concentração do PS em que há maior eficiência na formação de EROs e menor formação de escudo óptico se encontra entre 50 a 100μM. O uso de fibras ópticas contribui para maior formação de EROs. Energia de irradiação mínima de 7J promove significativa redução bacteriana intracanal.

This study evaluates different approach such as photos sensitizer (PS) concentration, irradiation time/energy, and the use of optical fiber for intracanal microbial reduction. In a quartzcurvet, aqueous solution of Methylene blue at 50, 100, 150 and 300μM was tested for reactive oxygen species production (ROS) after successive irradiations of 30s with a diode laser (660nm,100mW). Using the same methodology, the ROS production was tested using an optical fiber. Image analyses evaluated the presence of optical shield in 3 different concentration of PS. Tencentral incisors were contaminated with bioluminescent P. aeruginosas to test the ideal energy/time for endodontic microbial reduction. Initial contamination was recorded by image after biofilm grown. The root canals were ful filled with Ps and irradiated with successive energiesof 2.4J. After every irradiation new images were recorded to compare the microbial reduction. ROS formation was improved using low concentration of PS, such as optical shield formation. The use of optical fiber did enhance the ROS formation when compared to irradiation with thelaser tip. Energy of 7J was the minimal energy to achieve lost of bioluminescent signal. For more efficient ROS production and minor optical shield presence, a concentration between 50 and 100μM seams to be ideal. The use of an optical fiber improves ROS production. Energy of 7J promotes significative intracanal de contamination.

Rubiaceae-Type Cyclopeptides from Galianthe thalictroides.

Two Rubiaceae-type cyclopeptides, 6-O-methylbouvardin (1) and the new cyclopeptide 5ß-hydroxy-RA-III (2), were isolated from the roots of Galianthe thalictroides. Employing the sulforhodamine B assay, compounds 1 and 2 were tested in vitro against three cancer cell lines--786-0 (kidney carcinoma), PC-3 (prostate carcinoma), and HT-29 (colon carcinoma)--and showed GI50 values ranging from 0.06 to 1.80 µg mL(-1). This is the first report on the isolation of Rubiaceae-type cyclopeptides from a genus other than Rubia or Bouvardia.

Seudomixoma peritoneal como causa infrecuente de ascitis mixta masiva / Peritoneal Pseudomyxomata tumor as uncommon cause of massive mixed ascites

Se presenta el caso clínico de una paciente de 32 años de edad con historia de aumento progresivo de volumen del abdomen, que le dificultaba la respiración y la alimentación, quien ingresa en el Servicio de Medicina Interna del hospital del instituto ecuatoriano del seguro social de la ciudad de Ibarra, con diagnóstico de ascitis para estudio. Al realizar la paracentesis se extrae líquido de aspecto gelatinoso, por lo cual se plantea la hipótesis de un seudomixoma peritoneal. Teniendo en cuenta estas características del líquido se recupera el informe de biopsia de la apendicectomía efectuada 2 años antes, donde se halló la presencia de un tumor mucinoso de apéndice. Se efectuó cirugía citorreductora sin hipertermia intraperitoneal y se confirmó la citada hipótesis(AU)

The case report of a 32 years patient with history of progressive increase in abdomen volume making difficult breathing and feeding is presented. She is admitted in the Internal Medicine Service of the Ecuatorian institute hospital of social insurance in Ibarra city, with ascites diagnosis to be studied. When carrying out the abdominal tap, a jelly-like liquid is extracted, reason why the hypothesis of a peritoneal pseudomyxomata tumor is stated. Taking into account these characteristics the biopsy report from an appendectomy made 2 years earlier is recovered, where the presence of an appendix mucinous tumor was found. Cytoreduction surgery was performed without intraperitoneal hyperthermia and the mentioned hypothesis was confirmed(AU)

Seudomixoma peritoneal como causa infrecuente de ascitis mixta masiva / Peritoneal Pseudomyxomata tumor as uncommon cause of massive mixed ascites

Se presenta el caso clínico de una paciente de 32 años de edad con historia de aumento progresivo de volumen del abdomen, que le dificultaba la respiración y la alimentación, quien ingresa en el Servicio de Medicina Interna del hospital del instituto ecuatoriano del seguro social de la ciudad de Ibarra, con diagnóstico de ascitis para estudio. Al realizar la paracentesis se extrae líquido de aspecto gelatinoso, por lo cual se plantea la hipótesis de un seudomixoma peritoneal. Teniendo en cuenta estas características del líquido se recupera el informe de biopsia de la apendicectomía efectuada 2 años antes, donde se halló la presencia de un tumor mucinoso de apéndice. Se efectuó cirugía citorreductora sin hipertermia intraperitoneal y se confirmó la citada hipótesis.

The case report of a 32 years patient with history of progressive increase in abdomen volume making difficult breathing and feeding is presented. She is admitted in the Internal Medicine Service of the Ecuatorian institute hospital of social insurance in Ibarra city, with ascites diagnosis to be studied. When carrying out the abdominal tap, a jelly-like liquid is extracted, reason why the hypothesis of a peritoneal pseudomyxomata tumor is stated. Taking into account these characteristics the biopsy report from an appendectomy made 2 years earlier is recovered, where the presence of an appendix mucinous tumor was found. Cytoreduction surgery was performed without intraperitoneal hyperthermia and the mentioned hypothesis was confirmed.

Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study.

BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression-free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options. METHODS: In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The primary endpoint was safety. All analyses were done on the safety population, which included all patients who received at least one dose of vemurafenib. This report is the third interim analysis of this study. This study is registered with ClinicalTrials.gov, number NCT01307397. FINDINGS: Between March 1, 2011, and Jan 31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at least one dose of vemurafenib (safety population). At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n=257; 152 [59%, 95% CI 53-65] and ten [4%, 2-7], respectively) than in those younger than 75 years (n=2965; 1286 [43%, 42-45] and 82 [3%, 2-3], respectively). INTERPRETATION: Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug. FUNDING: F Hoffmann-La Roche.

Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.

UNLABELLED: We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. STUDY DESIGN: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. RESULTS: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. CONCLUSION: We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

El alcoholismo en la adolescencia. Características y acciones para su prevención

Con el objetivo de conocer la incidencia de propensión al alcoholismo en los jóvenes de un área de salud, se estudiaron en una población de 400 adolescentes, los 60 varones que resultaron propensos a esta toxicomania, los cuales fueron divididos en dos grupos; experimental (30) y control (30). Fue diseñado un sistema de influencias basado en técnicas de la medicina preventiva y comuunitaria, que se ensayó en el grupo experimental. Transcurrido seis meses se hizó un corte evolutivo para comparar los resultados obtenidos en relación con el grupo control. En el grupo estudio se produjeron cambios favorables en cada una de las variables estudiadas, pues se observó una disminución en la frecuencia y cantidad de bebidas alcohólicas ingeridas. Este sistema puede constituir un método útil para prevenir el alcoholismo en los adolescentes

Effect of strain and age of the broiler breeder female on incubation time and chick weight.

Two experiments were conducted to evaluate effects of strain [five in Experiment (Exp.) 1 and six in Exp. 2)] and age (29, 47, and 57 wk in Exp. 1 and 29, 41, and 52 wk in Exp. 2) of commercial broiler breeders on incubation time and chick weight. Highly significant differences in egg weight were found among strains in both Exp. After adjusting for effects of egg weight, significant effects of strain, age, and their interactions were found on incubation time, egg weight at transfer, and chick weight at hatch in Exp. 1, but not in Exp. 2. Mean incubation times varied among strains from 496.6 to 498.8 h in Exp. 1 and from 499.3 to 501.9 h in the second experiment. In Exp. 1, incubation time decreased from 498.6 h when breeders were 29 wk to 494.8 at 47 wk, whereas in Exp. 2, it decreased from 510.5 h at 29 wk to 495.1 h at 41 wk. This decrease also resulted in a negative correlation between egg weight and incubation time. Differences due to strain and age were found for yolk and albumen percentage and yolk: albumen ratio. Percentage yolk was 27.2 and 32.7% and percentage albumen was 60.1 and 55.9% in eggs from 29 to 52 wk breeders, respectively. Shell percentage was significantly affected by strain. Strain by age interactions were found for each response in Exp. 1 but only for set and chick weight in Exp. 2. Differences among incubators were found only for incubation time; interactions of incubation time and strain and age were also detected. Results indicate that genotype, age of the female breeder, and incubator should be considered along with their interactions to obtain optimum hatching performance.

Low temperature effects on embryonic development and hatch time.

A series of experiments was conducted to estimate phenotypic correlations between incubation characteristics, and to evaluate the effects of cold stress and genotype during incubation on chick weight, egg weight loss, hatching time, and embryonic mortality. Eggs were cooled at 18 or 24 C, for 12, 24, 36, 48, or 72 h beginning on Day 8, 12, 14, 16, or 18 of incubation. Other eggs were cooled intermittently for 6 h every 48 h or 12 h every 96 h. A control group in each experiment was not cold stressed. Results indicated a low and negative correlation between hatching time and chick weight, and a low and positive correlation between hatching time and weight loss from transfer to hatching when variability due to egg weight was removed. Chick weights at hatching were lower in chicks from cooled eggs than those of chicks from eggs incubated under normal temperature. The chicks from cooled eggs were more susceptible to dehydration during holding in the hatcher. Incubation times were delayed approximately as long as the times of embryonic cooling. Embryonic mortality was significantly increased under continuous (single period) cold stress, but not under intermittent cooling (6 h every 48 h). Significant genotype by environment interactions were found in the response of embryos of various strains to cold stress. Exposure for 36 h or longer had detrimental effects on chick weight and embryo viability, but these effects were modified by interactions among the factors involved. The results indicated that embryos from cooled eggs lose more weight during incubation and that the neonatal chicks are more susceptible to dehydration during holding time, and have a longer incubation period, and a greater embryonic mortality.

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

PIP: Lactation, ovulation and conception were observed as part of an anthropological study of Amerindian Mopan Mayan women from the village of San Jose Hawaii in western Belize from March 1985-January 1987. Single blood samples from each subject were immunoassayed for prolactin, LH, FSH, hCG, placental lactogen, estrogen, progesterone and cortisol. Anthropomorphic data analyzed were body mass index (BMI), fat/weight percentage, total body water and lean body weight. 117 women had at least 1 child during the study; 91 were lactating; 51 reported no menstrual cycles. 50 submitted to blood testing. Almost all infants were breast fed for 18 months or longer, up to 3 years, typically at least 6 times per day and 3 times per night. Women averaged 9 live births and 8 surviving children, with a mean birth interval of 28 months. 25 of the 29 women known to be pregnant conceived while lactating. 16 lactating women were pregnant. Their culture requires them to have 3 menses before conception to nourish the fetus, yet forbids speaking about menstrual blood: women fabricated menstrual dates, but in confidence 51 of 81 stated that they did not menstruate before the last conception. Most often menses began 12 months postpartum. Lactating women had heightened prolactin levels even if supplementing their children's diet. Thus frequent lactation delayed onset of menses, but supplementation had no effect. Most of the women were within the normal range of BMI, but 13% were below normal. In lactating menstruating women there was a significant negative correlation between fat weight and postpartum month. The data suggest that the interval to conception or menstruation was inversely correlated with fat weight. Here suckling frequency rather than prolactin levels seems to postpone fertility. In this society, with 10-12 births and 9-10 children in the completed family, the largest in the world, prolonged frequent lactation has little effect on fertility. Instead, birth trauma, maternal mortality, fetal and infant mortality, and perhaps nutrition, have more effect on completed family size.

Noninfectious colitis associated with short gut syndrome in infants.

We describe noninfectious bloody diarrhea in 13 of 16 infants referred for management of short bowel syndrome and parenteral nutrition during a 33-month period. The condition was characterized by bloody, watery stools associated with carbohydrate malabsorption. Colitis occurred at a mean age of 4.2 months during periods of advancing enteral feedings of a hydrolyzed protein- or amino acid-containing formula. Sigmoidoscopy performed in nine patients revealed edema, patchy erythema, loss of normal vascular pattern, and mucosal friability without ulcerations or pseudomembranes. Colonic biopsy specimens demonstrated edema and mixed hypercellularity of the lamina propria, with prominent eosinophilia. Rectal bleeding ceased if formula feedings were decreased or withheld. Of multiple medications administered, sulfasalazine seemed to improve rectal bleeding most effectively in our patients and allowed for more rapid reintroduction of enteral feedings.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

The pharmacokinetics of amrinone at three dose levels in the rabbit.

Amrinone is a positive inotropic and vasodilatory compound being used to improve cardiocirculatory function in chronic cardiac failure. The linearity of the pharmacokinetics of amrinone was examined in New Zealand white rabbits given i.v. bolus doses of 1.5, 3.0, and 7.5 mg/kg amrinone. Blood samples were obtained serially for a period of 6 hours following amrinone administration. Serum concentration-time data were analyzed by nonlinear least squares regression, as well as non-compartmental techniques. There were no differences as a function of dose in the systemic clearance, elimination half-life, mean residence time, or average concentration of amrinone. The pharmacokinetics of amrinone appear to be linear in rabbits. The rabbit may be useful as an animal model to study various aspects of amrinone pharmacokinetics.

Genetic control and distribution of leucine aminopeptidase in the cultivated chenopods (Chenopodium) and related weed taxa.

Isozymes of leucine aminopeptidase (LAP) in leaf tissue of the cultivated chenopods (Chenopodium quinoa and C. nuttalliae) and their sympatric weedy relatives (C. hircinum and C. berlandieri) can be electrophoretically resolved into a sum total of five anodally migrating bands. These are the products of two unlinked gene loci which apparently reflect genetic duplication via allotetraploidy. Accessions from the Andean and Mexican areas of cultivation are characterized by a lack of electrophoretically detectable variation. Andean weed and cultigen accessions appear to be genetically identical at both Lap loci, as do weed and cultigen material from Mexico. The two cultigens, and their sympatric weeds, can be differentiated by variation at the Lap-B locus, whereas they are monomorphic at Lap-A. This locus is, however, highly polymorphic in weedy C. berlandieri populations of western North America.