Cause of Cambrian Explosion - Terrestrial or Cosmic?

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H-W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma. Such viruses are known to be plausibly associated with major evolutionary genomic processes. We believe this coincidence is not fortuitous but is consistent with a key prediction of H-W theory whereby major extinction-diversification evolutionary boundaries coincide with virus-bearing cometary-bolide bombardment events. A second focus is the remarkable evolution of intelligent complexity (Cephalopods) culminating in the emergence of the Octopus. A third focus concerns the micro-organism fossil evidence contained within meteorites as well as the detection in the upper atmosphere of apparent incoming life-bearing particles from space. In our view the totality of the multifactorial data and critical analyses assembled by Fred Hoyle, Chandra Wickramasinghe and their many colleagues since the 1960s leads to a very plausible conclusion - life may have been seeded here on Earth by life-bearing comets as soon as conditions on Earth allowed it to flourish (about or just before 4.1 Billion years ago); and living organisms such as space-resistant and space-hardy bacteria, viruses, more complex eukaryotic cells, fertilised ova and seeds have been continuously delivered ever since to Earth so being one important driver of further terrestrial evolution which has resulted in considerable genetic diversity and which has led to the emergence of mankind.

Diagnóstico prenatal ultrasonográfico de higroma quístico / Prenatal Ultrasonographic Diagnosis of Cystic Hygroma

El higroma quístico es el resultado de segmentos del saco linfático yugular que están fuera de sitio o de la falla de los espacios linfáticos para conectar con los principales canales linfáticos y constituye un tumor líquido claro, limpio y transparente; se diagnostica por ecografía en el primer trimestre del embarazo, porque se aprecia una masa que sobresale en la pared posterior o lateral del cuello, su aparición se asocia a cariotipos anormales, por lo cual es indispensable un estudio de cariotipo humano. El higroma quístico está asociado a trisomía 21, 18 y 13, entre otras. Se reportó el caso de una paciente con embarazo de 13,2 semanas, a la cual se le realizó marcador genético, detectándose un feto con una tumoración quística en la región cervical. Se decidió la interrupción de la gestación, mediante el uso de misoprostol, obteniéndose un higroma quístico como resultado anatomopatológico, que reafirmó el diagnóstico ultrasonográfico.

Cystic hygroma is a result of jugular lymph sac segments that are out of place or the failure of the lymphatic spaces to connect with the main lymphatic channels. It is a clear, clean and transparent liquid tumor, diagnosed by ultrasound in the first trimester of pregnancy, for a mass that protrudes in the back or side wall of the neck can be seen, its onset is associated with abnormal karyotypes, which is indispensable for a study of the human karyotype. Cystic hygroma is associated with trisomy 21, 18 and 13, among others. A case of a patient with pregnancy of 13.2 weeks, who underwent genetic marker, detecting a fetus with a cystic tumor in the cervical region was reported. Interruption of pregnancy was decided by using misoprostol, a cystic hygroma was revealed that confirmed the ultrasonographic diagnosis.

Identificación de necesidades de aprendizaje sobre atención básica de urgencias y emergencias médicas en la Atención Primaria de Salud / Identification of learning requirements on basic care of medical urgencies and emergencies in the primary health care

Se realizó una investigación descriptiva, en el campo de la educación de posgrado, con el objetivo de identificar las necesidades de aprendizaje sobre atención básica de las urgencias y emergencias médicas, de los médicos de la Atenció n Primaria de Salud en el Policlínico Universitario Mario Gutiérrez Ardaya de junio a diciembre de 2011. El sistema de métodos integró métodos empíricos, teóricos y de procesamiento estadísticos. Se empleó una guía de observación donde se evaluaron las habilidades específicas de los médicos, en la atención a las urgencias y emergencias. Se aplicó un cuestionario a 39 médicos, con el objetivo de conocer las temáticas con necesidades de capacitación en cuanto a la atención del paciente grave. Los temas sobre manejo de la vía aérea y ventilación, resucitación cardio-pulmonar-cerebral y el tratamiento del shock, fueron los de mayor relevancia. Se realizó una entrevista a 14 informantes clave y a 3 expertos, se definieron los temas de urgencias y emergencias que son de importancia para los médicos de la APS...

A descriptive research study of the postgraduate education was conducted from June to December 2011. The objective was to identify the learning requirements in the field of basic care to medical urgencies and emergencies of the primary health care physicians who work in Mario Gutierrez Ardaya university polyclinic. The system comprised empirical, theoretical and statistical processing methods. An observational guide was used to evaluate the specific skills of physicians in the care of urgencies and emergencies. Thirty nine physicians answered a questionnaire to detect the topics in which they need training as to the care of the critical patient. The most relevant topics were found to be management of airways and ventilation, cardiopulmonary and cerebral resuscitation, and shock treatment. Fourteen key informants and 3 experts were interviewed, which resulted in the definition of the most important urgency and emergency topics for the primary health care physicians...

Intrablastocyst injection with human CD34+/CD133+ cells increase survival of immunocompetent fumarylacetoacetate hydrolase knockout mice.

Mice harbouring a humanized liver represent a powerful tool for translating preclinical studies of drug metabolism and pharmacokinetics into humans, as well as the exploitation of basic studies on liver pathophysiology including hepatitis C virus (HCV) infection. Human adult stem cells injected into immunocompetent mice at preimmune stages of development, generate chimeric animals harbouring a liver with relatively discrete foci of human hepatocyte-like cells. In this study, we have evaluated whether similar protocol of xenotransplantation in the presence of selective pressure might lead to a higher human-into-mouse liver repopulation, leading to a relevant improvement of liver function. Human CD34(+)/CD133(+) cells were microinjected into blastocysts from genetically-modified mice committed to develop a lethal hepatopathy, due to the absence of the enzyme fumarylacetoacetate hydrolase (FAH). Following xenotransplantation, mouse survival was followed over time and histochemical evidence of liver chimerism was assessed. The survival expectancy of seven out of 21 intrablastocyst xenotransplanted FAH knockout (Fah-/-) mice was significantly higher as compared with non-xenotransplanted mice. Several nodules of human hepatocyte-like cells were revealed by immunohistochemistry in the liver of rescued mice. Our data positively support the hypothesis that preimmune xenotransplantation of human stem cells into immunocompetent mice harbouring a lethal hepatic disease might lead to a functionally relevant human-mouse liver chimerism and marks a significant advancement towards the establishment of a novel translational preclinical model for liver diseases.

Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells.

We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.

Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase.

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. Compounds that block replication of subgenomic HCV RNA in liver cells are of interest because of their demonstrated antiviral effect in the clinic. In followup to our recent report that indole-N-acetamides (e.g., 1) are potent allosteric inhibitors of the HCV NS5B polymerase enzyme, we describe here their optimization as cell-based inhibitors. The crystal structure of 1 bound to NS5B was a guide in the design of a two-dimensional compound array that highlighted that formally zwitterionic inhibitors have strong intracellular potency and that pregnane X receptor (PXR) activation (an undesired off-target activity) is linked to a structural feature of the inhibitor. Optimized analogues devoid of PXR activation (e.g., 55, EC(50) = 127 nM) retain strong cell-based efficacy under high serum conditions and show acceptable pharmacokinetics parameters in rat and dog.

Human hepatocytes in mice receiving pre-immune injection with human cord blood cells.

It is well established that certain subpopulations of human adult stem cells can generate hepatocyte-like cells when transplanted into adult immunosuppressed mice. In the present study, we wanted to explore whether xeno-transplantation of human cord blood CD34(+) (hCBCD34(+)) cells during pre-immune stages of development in immunocompetent mice might also lead to human-mouse liver chimerism. Freshly isolated hCBCD34(+) cells were xeno-transplanted into non-immunosuppressed mice by both intra-blastocyst and intra-fetal injections. One and four weeks after birth, immunostaining for different human-specific hepatocyte markers: human hepatocyte-specific antigen, human serum albumin, and human alpha-1-antitrypsin indicated the presence of human hepatocyte-like cells in the livers of transplanted animals. Detection of human albumin mRNA further corroborated the development of pre-immune human-mouse chimeras. The current report, besides providing new evidence of the potential of hCBCD34(+) cells to generate human hepatocyte-like cells, suggests novel strategies for generating immunocompetent mice harboring humanized liver.

p21(Waf1/Cip1/Sdi1) mediates shear stress-dependent antiapoptotic function.

OBJECTIVE: The antiapoptotic effect of p21(Waf1/Cip1/Sdi1) (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia. METHODS: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h. In vivo: Hindlimb ischemia was realized in mice by femoral artery ligation. SNP was acutely administered by subcutaneous injection or by Alzet osmotic pumps for a longer treatment. RESULTS: At T0, HUVEC were either exposed to SS (15 dyn/cm2/s(-1)), treated with SNP or kept in static condition (ST) for 1-12 h; after additional 12 h in ST, 30-35% of cells still alive at T0 had died. In this condition, both SS and SNP treatments markedly increased p21 levels and reduced apoptosis in HUVEC. Recombinant adenoviruses carrying p21 (AdCMV.p21) or antisense p21 (AdCMV.ASp21) cDNA revealed that AdCMV.p21-infected HUVEC were protected from death while AdCMV.ASp21 reduced SS- and SNP-dependent protection from apoptosis. In mice, apoptosis was detected in endothelial cells of ischemic hindlimbs as early as 8 h after femoral artery ligation. Treatment with SNP enhanced p21 expression and protected ischemic tissue from damage. Remarkably, direct in vivo injection of AdCMV.p21 significantly reduced the number of apoptotic nuclei in the presence of ischemia. CONCLUSIONS: The present study establishes that, under our experimental conditions, (a) p21 plays an important role in SS and nitric oxide antiapoptotic effect in vitro, and (b) p21 gene transfer prevents apoptosis in vitro and in vivo, following acute interruption of blood flow.