Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

Transgenic Citrange troyer rootstocks overexpressing antimicrobial potato Snakin-1 show reduced citrus canker disease symptoms.

Citrus canker is a major disease caused by Xanthomonas citri pv. citri. Snakin-1 is an antimicrobial peptide, which was previously shown to be effective against different bacterial and fungal diseases in potato, wheat and lettuce when expressed in transgenic plants. We generated transgenic Citrange Troyer citrus rootstocks constitutively expressing this peptide and 5 different transgenic lines were challenged against virulent X. citri isolates. Challenge assays conducted in vitro using detached leaves and in planta by infiltration revealed a significant reduction of the number and size of canker lesions in some of the transgenic lines.

Effect of Chronic Consumption of Sweeteners on Microbiota and Immunity in the Small Intestine of Young Mice.

The consumption of sweeteners has increased as a measure to reduce the consumption of calories and thus combat obesity and diabetes. Sweeteners are found in a large number of products, so chronic consumption has been little explored. The objective of the study was to evaluate the effect of chronic sweetener consumption on the microbiota and immunity of the small intestine in young mice. We used 72 CD1 mice of 21 days old, divided into 3 groups: (i) No treatment, (ii) Group A (6 weeks of treatment), and (iii) Group B (12 weeks of treatment). Groups A and B were divided into 4 subgroups: Control (CL), Sucrose (Suc), Splenda® (Spl), and Svetia® (Sv). The following were determined: anthropometric parameters, percentage of lymphocytes of Peyer's patches and lamina propria, IL-6, IL-17, leptin, resistin, C-peptide, and TNF-α. From feces, the microbiota of the small intestine was identified. The BMI was not modified; the mice preferred the consumption of Splenda® and Svetia®. The percentage of CD3+ lymphocytes in Peyer's patches was increased. In the lamina propria, Svetia® increased the percentage of CD3+ lymphocytes, but Splenda® decreases it. The Splenda® and Svetia® subgroups elevate leptin, C-peptide, IL-6, and IL-17, with reduction of resistin. The predominant genus in all groups was Bacillus. The chronic consumption of sweeteners increases the population of lymphocytes in the mucosa of the small intestine. Maybe, Bacillus have the ability to adapt to sweeteners regardless of the origin or nutritional contribution of the same.

Effect of Supplementation with n-3 Fatty Acids Extracted from Microalgae on Inflammation Biomarkers from Two Different Strains of Mice.

BACKGROUND: Diabetes mellitus is considered a chronic noncommunicable disease in which inflammation plays a main role in the progression of the disease and it is known that n-3 fatty acids have anti-inflammatory properties. One of the most recent approaches is the study of the fatty acids of microalgae as a substitute for fish oil and a source rich in fatty acids EPA and DHA. OBJECTIVE: To analyze the effect of supplementation with n-3 fatty acids extracted from microalgae on the inflammatory markers from two different strains of mice. METHODS: Mice of two strains, db/db and CD1, were supplemented with n-3 fatty acids extracted from microalgae in lyophilized form and added to food; the experiment was carried out from week 8 to 16 of life. Flow cytometry was performed to determine the percentage of TCD4+ cells producing Th1 and Th2 cytokines. RESULTS: Supplementation with microalgae fatty acids decreased the percentage of TCD4+ cells producing IFN-γ and TNF-α and increased the ones producing IL-17A and IL-12 in both strains; on the other hand, supplementation decreased percentage of TCD4+ cells producing IL-4 and increased the ones producing TGF-ß. CONCLUSIONS: Microalgae n-3 fatty acids could be a useful tool in the treatment of diabetes as well as in the prevention of the appearance of health complications caused by inflammatory states.

VALORACIÓN DE ENERGÍA DIGESTIBLE DE LA GLICERINA CRUDA PROVENIENTE DE ACEITE DE PALMA -Elaeis guineensis- PARA CERDOS EN CRECIMIENTO EN FUNCIÓN DEL NIVEL DE ALMIDÓN DE MAÍZ EN LA DIETA / VALUATION OF DIGESTIBLE ENERGY OF CRUDE GLYCERIN FROM PALM OIL -Elaeis guineensis- FOR GROWING PIGS BASED ON DIETARY CORN STARCH LEVEL

Para determinar la energía digestible aparente (EDA) de la glicerina cruda (GC) proveniente del aceite de palma (Elaeis guineensis) en cerdos se realizaron dos experimentos (E). En E1 se determinó la EDA para GC con la técnica de la bolsa móvil de nailon (TBMN) utilizando ocho cerdos castrados con cánula duodenal. En E2 se determinaron la EDA y la energía metabolizable aparente (EMA) para GC, por el método convencional con indicador (MCI), con 10 cerdos castrados ubicados en jaulas metabólicas. En E1 y E2 se evaluaron, en un arreglo factorial 2 x 5, dos niveles de almidón de maíz (NA) en la dieta, 10% (NA10) y 12% (NA12), y cinco niveles de sustitución con GC (0%, 2,5%, 5,0%, 7,5% y 10%) en E1 en un diseño completo al azar y en E2 en un diseño de cuadrado latino. Para TBMN y MCI los datos se analizaron mediante regresión lineal múltiple y el metabolismo del nitrógeno en MCI como un diseño de cuadrado latino utilizando los módulos REG y GLM del paquete SAS. Por TBMN no hubo efectos (P > 0,05) del NA sobre la EDA de GC. La EDA de GC se calculó en 3.251 kcal/kg MS. La EDA de GC en MCI dependió de NA (P < 0,001) estimándose en 4.427,3 y 3.769,3 Kcal/kg MS para NA10 y NA12, respectivamente. Hubo interacción (P < 0,001) entre NA y GC para la cantidad de nitrógeno digestible, se redujo cuando GC aumentó en NA12 y aumentó en NA10. Otros parámetros del metabolismo nitrogenado no se vieron afectados (P > 0,05). Los resultados de EDA corregidos por NA con MCI mostraron correlación alta (R2 = 0,82) con TBMN. Con MCI se pudo establecer que el aumento en NA en la dieta reduce la EDA de GC.

To determine the apparent digestible energy (EDA) of crude glycerin (GC) from palm oil (Elaeis guineensis) in pigs two experiments (E) were performed. In E1, EDA was determined to GC, with the technique of mobile nylon bag (TBMN) using eight barrows with duodenal cannula. In E2, EDA, EMA to GC was determined by the conventional method with indicator (MCI) with 10 barrows placed in metabolic cages. In E1 and E2 were evaluated in 2 x 5 factorial arrangement, two levels of corn starch (NA) in the diet, 10 (NA10) and 12% (NA12), and five levels of replacement by GC (0%, 2.5%, 5%, 7.5% and 10%), in E1 as a completely randomized design and in E2 as a Latin square design. For MCI and TBMN, data were analyzed using multiple linear regression and nitrogen metabolism in MCI as a Latin square design using the GLM and REG modules of SAS. By TBMN there was no effect (P > 0.05) in the NA on the EDA of GC. EDA of GC was calculated at 3251 kcal/kg DM. EDA of GC in the MCI depended NA (P < 0.001), estimated at 4427.3 and 3769.3 Kcal/kg MS for NA10 and NA12, respectively. Interaction (P < 0.001) between NA and GC for the amount of digestible nitrogen was observed, was reduced when GC increased by NA12 and increased by NA10. Other nitrogen metabolism parameters were not affected (P > 0.05). The results of EDA corrected by NA with MCI showed high correlation (R² = 0.82) with TBMN. By MCI was established that increased in NA reduced the EDA of GC.

Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients.

The efficacy of primary prophylaxis with atovaquone in preventing Toxoplasma reactivation and disease in hematopoietic cell transplant (HCT) recipients is unknown. We describe 2 cases of atovaquone prophylaxis failure in pre-HCT Toxoplasma-seropositive (pre-HCTSP) recipients who underwent allogeneic HCT (allo-HCT) and review the literature on atovaquone prophylaxis in HCT recipients.

Introduction and Establishment of Pissodes castaneus (Coleoptera: Curculionidae) in the Andean Patagonia of Argentina.

The pine weevils that occur in plantations of Pinus spp. in Andean Patagonia of Argentina belong to the species Pissodes castaneus (De Geer), a Eurasian endemic species, according to the identification based on molecular and morphological characters. Sequences of the mitochondrial Cytochrome oxidase subunit I and nuclear genes (28 S rDNA and ITS2) were obtained for individuals of 13 afforestations, covering the entire distribution area of the established populations in the Andean Patagonia of Argentina. Sequence comparison with representative species of the genus (European, North American, and Chinese species) shows that Patagonian specimens are conspecific to those of P. castaneus sequenced from Europe. Phylogenetic analyses indicate that all terminals from Patagonia form a monophyletic unit without evident subclades, eliminating the possibility of existence of more than one species of Pissodes Germar in this area, including cryptic ones. Moreover, the very low genetic divergence between the Patagonian populations suggests that it is plausible that P. castaneus was introduced into Patagonia from just one location. Mitochondrial DNA analysis shows that Patagonian terminals group together with a French haplotype and are clearly separated from other P. castaneus individuals represented in our sample, and reveal that established populations in Andean Patagonia originated via a limited introduction.

Pollen:ovule ratio and its relationship with other floral traits in Papilionoideae (Leguminosae): an evaluation with Argentine species.

The pollen:ovule ratio (P/O) has traditionally been used as a rough estimator of plant breeding systems. It has been shown that plant breeding systems are associated with particular floral traits. In this study, we determined the P/O in 21 Leguminosae species from Argentina and explored relationships between P/O and taxonomic position, flower size, floral rewards, pollen presentation and pollination mechanisms. According to the results, 15 out of the 21 species classified were obligate xenogamous, although some of them have been recorded as facultative xenogamous in previous studies. There was a significant effect of taxonomic position (genus), reward type and pollination mechanism on P/O. Species offering only nectar as a floral reward (which were species with a brush mechanism) had a significantly lower P/O than species offering pollen or pollen and nectar. Species with the brush pollination mechanism had the lowest P/O, while species with valvular and pump mechanism had the highest P/O. However, pollen presentation (primary and secondary) and flower size did not have a significant effect on P/O. Our results demonstrate that P/O variability is determined by taxonomic position and pollination mechanism in this plant group.

The influence of a restrictive atrial septal defect on pulmonary vascular morphology in patients with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) with a restrictive atrial septal defect (ASD) is a form of congenital heart disease with considerable morbidity and mortality. This morphologic analysis assesses the pulmonary vasculature in this patient population. Pulmonary arteries, the persistence of high-resistance fetal arterioles, pulmonary veins, and lymphatics from multiple lung sections from each of five patients with HLHS and a restrictive ASD were compared to those of five patients with HLHS and nonrestrictive ASD. Lung sections from each patient were qualitatively graded in severity of pathology from 0 to 3 for each of the structures described previously, with the pathologist blinded to the status of the ASD. Patients with a restrictive ASD exhibited more significant pulmonary venous thickening and lymphatic dilatation (p = 0.02), with a tendency toward persistence of high-resistance fetal vessels (p = 0.2), compared to patients with a nonrestrictive ASD. These findings imply that patients with HLHS and a restrictive ASD possess pulmonary vascular abnormalities that place them at higher risk for the current surgical interventions available compared to patients with a nonrestrictive ASD.

Factores asociados con la mortalidad hospitalaria en pacientes admitidos en cuidados intensivos en Colombia / Factors associated with hospital mortality in patients admitted to the intensive care unit in Colombia

OBJETIVOS: Describir las características demográficas, las causas de ingreso y los factores asociados con la mortalidad hospitalaria en pacientes admitidos en cuidados intensivos en Colombia. MATERIAL Y MÉTODO: Cohorte de pacientes en una muestra de unidades de cuidados intensivos (UCI). De 89 UCI identificadas, 20 unidades en 10 ciudades de Colombia fueron invitadas a recolectar información sobre 200 pacientes consecutivos ingresados en cada unidad. RESULTADOS: Estuvieron disponibles para ser analizados 3.066 pacientes. El promedio de edad fue de 53 años, el 43 por ciento eran mujeres (p < 0,001). La causa más frecuente de ingreso fue no quirúrgica (63,9 por ciento), principalmente infarto miocárdico (7,1 por ciento). La gravedad de la enfermedad, medida por APACHE II y III, fue como promedio de 14,0 (DE, 6,9) y 48,3 (DE, 23,5), respectivamente. En el análisis multivariado, independientemente de la escala utilizada para ajustar por confusión por la gravedad de la enfermedad (APACHE II y III), los factores asociados con muerte hospitalaria fueron la necesidad de ventilación mecánica, la respuesta pupilar a la luz, el proceder del área médica (no quirúrgico) y el manejo por el grupo de UCI antes de la admisión en cuidados intensivos (p < 0,01). CONCLUSIÓN: La causa más frecuente de ingreso en cuidados intensivos en Colombia fue el infarto miocárdico. Además de la gravedad de la enfermedad, existen en Colombia otras variables dependientes de la atención médica que se asocian con mortalidad, como la ventilación mecánica invasiva. Aunque podrían ser marcadores residuales de gravedad de la enfermedad, más probablemente están asociadas con la calidad de la atención brindada (AU)

Cirugía antirreflujo por laparoscopia y manifestaciones extraesofágicas / Laparoscopic antireflux surgery and extraesophageal manifestations

Introduccion; El reflujo gastroesofágico (RGE) es una enfermedad comun en la poblacion general. Es bien conocida su relacion con manifestaciones extraesofagicas como tos cronica, ahogos nocturnos, asma y otras de orden otorrinolaringologico que con el tratamiento farmacologico mejoran, pero con tendencia a recurrir una vez. este es suspendido. Con la cirugia se puede lograr un control completo. Además, ha probado ser segura, efectiva y de efectos durables, superiores a los del tratamiento medico. Metodologia; Se realizó un estudio prospectivo entre julio de 1997 y febrero de 2001, en 44 pacientes con reflujo gastroesofágico y manifestaciones extraesofagicas, que fueron operados con la tecnica laparoscopica de Nissen-Rossetti con el fin de evaluar su respuesta. Esta serie hace parte de otra de 118 pacientes operados con reflujo gastroesofágico. Resultados: Estos pacientes con manifestaciones extraesofagicas constituyen un poco más de la 1/3 parte de la serie total (37,2 por ciento). Hubo 24 hombres y 20 mujeres, para una relacion 1,2: 1. Las manifestaciones extraesofagicas más comunes fueron los espasmos gloticos, la tos, el asma, la carraspera y la disfonia. La mitad de los pacientes tenia algun grado de esofagitis (5 tenian esofago de Barret) a la endoscopia digestiva. Además de este metodo de examen, se utilizó la monitoria de pH esofágico de 24 horas para establecer el diagnostico. El seguimiento promedio fue de 15 meses (rango 1-41 meses). Se registro un porcentaje de éxito de 95,3 por ciento, pues 86,3 por ciento fueron clasificados como Visick I y 9 por ciento como Visick II. Conclusion: La cirugia antirreflujo tipo Nissen-Rosseti para el control de las manifestaciones extraesofagicas causadas por RGE patologico, presento muy buenos resultados en la serie motivo de este estudio.

Sociodemographic, behavioral, and clinical correlates of inconsistent condom use in HIV-serodiscordant heterosexual couples.

We examined sociodemographic, behavioral, and clinical characteristics associated with inconsistent condom use in a cross-sectional analysis of 145 sexually active HIV-serodiscordant heterosexual couples who participated in the California Partners Study II. All couples were aware of their HIV-serodiscordant status. Forty-five percent of couples reported having had unprotected vaginal or anal sex in the previous 6 months. In the multivariate couple-level analyses, factors independently associated with inconsistent (i.e., <100%) condom use in the previous 6 months included lower educational level, unemployment, African-American ethnicity, and practice of anal sex by the couple. Injection drug use was associated with inconsistent condom use among couples with younger HIV-infected partners. In addition, couples with HIV-infected partners who had higher CD4 cell counts and couples in which the HIV-infected male partner ever had sex with a man were more likely to use condoms inconsistently. Consistency of condom use did not depend on the gender of the HIV-infected partner or duration of sexual relationship. The findings suggest that many HIV-serodiscordant heterosexual couples remain at high risk of HIV transmission and may benefit not only from behavioral interventions but also from structural interventions aimed at improving their social and economic conditions.

Awareness and use of untested barrier methods by HIV-seropositive gay and bisexual men.

Little is known about HIV-seropositive men's awareness and use of untested barrier methods during anal intercourse. A sample of 240 HIV-seropositive men (69.2% men of color) completed a self-administered survey that included items on nonoxynol-9 (N-9), female condoms, and the simultaneous use of two male condoms (double bagging). Most participants (79.6%) had heard of N-9 being used to prevent HIV transmission during anal intercourse. Of these, 20.0% rated N-9 as more effective than condoms, and 14.6% had used N-9 instead of condoms. Fewer men (35.4%) were aware of female condoms being used during anal intercourse. Overall, few respondents (5.4%) had used female condoms; 53.8% of whom rated the device as more pleasurable than male condoms. Most men (69.6%) had heard of double bagging, and 35.2% had engaged in this practice. Of these, 45.1% rated the practice as less pleasurable than using a single condom. Few associations were observed between participant characteristics and the awareness or use of these barrier methods. The widespread use of these untested methods emphasizes the urgent need to further educate HIV-seropositive men about the potential risks of N-9 use and to test the effectiveness of other strategies that may serve as alternatives to male condom use.

The Ross/Konno procedure in neonates and infants: intermediate-term survival and autograft function.

BACKGROUND: The Ross procedure has been increasingly applied to neonates and infants. Addition of a modified Konno-type enlargement of the aortic annulus allows the application of this procedure to neonates and infants with significant annular hypoplasia. The potential for growth and the proven durability make the autograft an ideal aortic valve replacement. METHODS: Between March 1993 and December 2000, 10 patients under 1 year of age underwent a Ross/Konno procedure at our institution (range, 2 to 349 days; median 16). All patients had severe to critical aortic stenosis. All patients required aortic annulus enlargement for size mismatch between the aortic and pulmonary valves. RESULTS: There were no deaths at a median follow-up of 48 months (range, 1 to 74 months). All patients had none to mild aortic stenosis on Doppler echocardiography. Eight patients had a 0 to 1+ aortic insufficiency, 1 patient had a 2+ aortic insufficiency, and 1 patient had a 3+ aortic insufficiency. Aortic annular dilatation was not observed. Aortic sinus dilatation occurred initially (mean change in z-value: 0 to 12 months, +2.1) and then stabilized (mean change in z-value: 12 to > 36 months, +0.6). No patient required additional procedures for aortic valve disease. Two patients required three pulmonary allograft replacements. CONCLUSIONS: The Ross procedure with a modified Konno-type enlargement of the aortic annulus is an excellent approach to aortic valve disease in the neonate and infant. The procedure can be accomplished with low morbidity and mortality, and low rates of reoperation. The pulmonary autograft demonstrates durability without developing aortic stenosis, aortic insufficiency, or progressive dilatation. Enlargement of the aortic annulus parallels somatic growth.

G-protein signaling through tubby proteins.

Dysfunction of the tubby protein results in maturity-onset obesity in mice. Tubby has been implicated as a transcription regulator, but details of the molecular mechanism underlying its function remain unclear. Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxyl terminal "tubby domain." X-ray crystallography reveals the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidyl- inositol binding factors. Receptor-mediated activation of G protein alphaq (Galphaq) releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein 3 (TULP3) is similarly regulated. These data suggest that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G-protein signaling and the regulation of gene expression.

In vivo acceleration of heart relaxation performance by parvalbumin gene delivery.

Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.

N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains.

Omenn's syndrome is an autosomal recessive primary immunodeficiency characterized by variable numbers of T lymphocytes of limited clonality, hypereosinophilia, and high IgE levels with a paradoxical absence of circulating B lymphocytes. We have previously attributed this disorder to missense mutations that render the RAG1/RAG2 recombinase only partially active. Here we report seven Omenn's patients with a novel class of genetic lesions: frameshift mutations within the 5' coding region of RAG1. Interestingly, we demonstrate in transient expression experiments that these frameshift deletion alleles remain partially functional for both deletional and inversional recombination and can hence explain the partial rearrangement phenotype observed in these patients. The rearrangement activity is mediated by truncated RAG1 proteins that are generated by alternative ATG usage 3' to the frameshift deletion and that demonstrate improper cellular localization. Taken together, our results suggest a novel mechanism for the development of immunodeficiency in a subset of Omenn's syndrome patients.