Metformin and cancer: Technical and clinical implications for FDG-PET imaging

Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seem to involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway (the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083–6 h) with a Tmax at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies

Telocytes constitute a widespread interstitial meshwork in the lamina propria and underlying striated muscle of human tongue

Abstract Telocytes have recently emerged as unique interstitial cells defined by their extremely long, thin and moniliform prolongations termed telopodes. Despite growing evidence that these cells consistently reside in the stromal compartment of various organs from human beings, studies dealing with telocytes in structures of the oral cavity are scarce. Hence, the present morphologic study was undertaken to explore for the first time the presence and specific localization of telocytes within tissues of the normal human tongue, a complex muscular organ whose main functions include taste, speech, and food manipulation in the oral cavity. Telocytes were initially identified by CD34 immunostaining and confirmed by CD34/PDGFRα double immunofluorescence and transmission electron microscopy. CD34+/PDGFRα+ telocytes were organized in interstitial meshworks either in the tongue lamina propria or in the underlying striated muscle. Lingual telocytes were immunonegative for CD31, c-kit and α-SMA. Telopodes were finely distributed throughout the stromal space and concentrated beneath the lingual epithelium and around CD31+ vessels, skeletal muscle bundles/fibers, and intramuscular nerves and ganglia. They also enveloped salivary gland units outside the α-SMA+ myoepithelial cells and delimited lymphoid aggregates. These findings establish telocytes as a previously overlooked interstitial cell population worth investigating further in the setting of human tongue pathophysiology

STRATEGI EKONOMI PEMBANGUNAN PARIWISATA DI WILAYAH MAYORITAS MUSLIM UNTUK PARIWISATA BERKELANJUTAN

Pariwisata telah menjadi kontributor signifikan terhadap pertumbuhan ekonomi dan pembangunan di banyak negara. Namun, penting untuk memastikan bahwa pembangunan pariwisata berkelanjutan, dengan mempertimbangkan aspek budaya, sosial, dan lingkungan di destinasi tersebut. Tujuan penelitian ini adalah untuk mengeksplorasi strategi ekonomi yang diterapkan di wilayah mayoritas Muslim untuk mempromosikan pariwisata berkelanjutan. Metode penelitian yang digunakan adalah meta-etnografi, yang melibatkan analisis data penelitian pariwisata di Indonesia antara tahun 2014 hingga 2022. Penelitian ini mengidentifikasi beberapa strategi ekonomi penting, termasuk identifikasi dan pengembangan daya tarik wisata yang menarik bagi wisatawan Muslim, aksesibilitas dan keamanan menuju lokasi wisata, perawatan dan pemeliharaan daya tarik wisatawan, promosi efektif, dan penyediaan sarana ibadah. Hasil penelitian ini menunjukkan betapa pentingnya memperhatikan nilai-nilai dan kepekaan budaya Muslim setempat dalam mengembangkan pariwisata berkelanjutan. Pengembangan ekonomi pariwisata dalam konteks mayoritas Muslim mencakup aspek etika, moralitas, dan nilai-nilai yang sesuai dengan prinsip-prinsip syariah. Hasil penelitian ini dapat memberikan wawasan dan pemahaman baru tentang strategi pembangunan ekonomi pariwisata di wilayah mayoritas Muslim

Atrial natriuretic factor in essential hypertension : echocardiographic and humoral correlates

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH

Spatio and temporal spread of Plum pox virus infecting European plum (Prunus domestica L. cv. D'agen) orchard in Mendoza, Argentina

Sharka, caused by Plum pox virus (PPV), is considered one of the most serious viral diseases of stone fruits worldwide due to the great yield losses in orchards. In Rama Caída, Mendoza, a 5-year study (2007-2011) was conducted on the degree of disease dispersion in a European plum cv D?agen orchard using samples from leaves and DAS-ELISA assay against PPV in order to determine incidence over time and spatial spread. Incidence significantly increased between 2007 and 2009 and during the next two years the increase was not statistically significant. Spatial point pattern of PPV at the plot was characterized by the occurrence of some heterogeneous clusters of infected trees located up to 65 m in the west-east direction of the rows over the five years. Point pattern and correlation type-approaches were undertaken using joint-count and Ripley´s K function and showed that the detected infected plants had a disease aggregation pattern both in west-east and south-north directions, and within row and between rows across the plot. This short-distance local dispersion would be associated with diverse factors, such as vector aphids, that were not evaluated in this study. Hence, this work can serve as a basis for further studies in sharka dispersion in Cuyo region.Fil: Dal Zotto, Angélica. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Porcel, Laura Beatriz. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Marini, Diana Beatriz. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Picca, Cecilia Nélida. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Córdoba, Mariano. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Unidad de Fitopatología y Modelización Agrícola - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Fitopatología y Modelización Agrícola; ArgentinaFil: Teich, Ingrid. Instituto Nacional de Tecnología Agropecuaria; Argentin

Spatio and temporal spread of Plum pox virus infecting European plum (Prunus domestica L. cv. D'agen) orchard in Mendoza, Argentina = Distribución espacial y temporal del Plum pox virus en un monte de ciruelo europeo (Prunus domestica L cv D'agen) de Mendoza, Argentina

Sharka, caused by Plum pox virus (PPV), is considered one of the most serious viral diseases of stone fruits worldwide due to the great yield losses in orchards. In Rama Caída, Mendoza, a 5-year study (2007-2011) was conducted on the degree of disease dispersion in a European plum cv D’agen orchard using samples from leaves and DAS-ELISA assay against PPV in order to determine incidence over time and spatial spread. Incidence significantly increased between 2007 and 2009 and during the next two years the increase was not statistically significant. Spatial point pattern of PPV at the plot was characterized by the occurrence of some heterogeneous clusters of infected trees located up to 65 m in the west-east direction of the rows over the five years. Point pattern and correlation type-approaches were undertaken using joint-count and Ripley's K function and showed that the detected infected plants had a disease aggregation pattern both in west-east and south-north directions, and within row and between rows across the plot. This short-distance local dispersion would be associated with diverse factors, such as vector aphids, that were not evaluated in this study. Hence, this work can serve as a basis for further studies in sharka dispersion in Cuyo region.Sharka causada por Plum pox virus (PPV) es considerada la enfermedad más nociva de los frutales de carozo debido a las pérdidas que produce en los montes frutales. En Rama Caída (Mendoza) se estudió la dispersión del PPV en un monte de ciruelo europeo cv D’agen durante 2007 a 2011 a través del análisis de muestras de hojas de árboles individuales por DAS-ELISA, para determinar la incidencia y distribución espacial de virus. Entre 2007 y 2009, el aumento en la incidencia fue estadísticamente significativo mientras que en 2010 y 2011 este no resultó significativo. El PPV se distribuyó en el lote, como un patrón de puntos caracterizado por agrupamientos heterogéneos de árboles infectados, ubicados hasta los 65 m en dirección oeste-este de las filas. A través del análisis de patrones de puntos y de correlación de árboles infectados, mediante la función K de Ripley y el estadístico Joint-count, se comprobó que las plantas infectadas presentaron un patrón espacial agregado, tanto en sentido oeste-este (entre filas), como sur-norte (dentro de fila), indicando una dispersión a corta distancia. Este escenario puede responder a múltiples factores no estudiados, como la presencia de áfidos vectores, y constituir las bases de futuros estudios de dispersión de PPV en Cuyo.Instituto de Patología VegetalFil: Dal Zotto, Angelica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Porcel, Laura Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rama Caída; ArgentinaFil: Marini, Diana Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Junín; ArgentinaFil: Picca, Cecilia Nelida. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rama Caída; ArgentinaFil: Córdoba, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Estadística y Biometría; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Teich, Ingrid. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Fisiología y Recursos Genéticos Vegetales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Guaifenesin-Ketamine-Xylazine Infusion to Maintain Anesthesia in Mules Undergoing Field Castration

Many minor and surgical procedures can be performed in the field under sedation or general anaesthesia. Numerous drug combinations have been used for sedation, induction and maintenance. The purpose of this study was to determine if the combination of guaifenesin, ketamine and xylazine, commonly referred to as “triple drip”, produce safe and satisfactory total intravenous anaesthesia in mules undergoing field castration, premedicated with xylazine and induced with thiopental. Eight healthy adult intact male mules, aged 4 to 6 years and weighing 380 to 490, were anesthetized to performe field castration. Before anaesthesia a 14-gauge, 13–cm catheter was placed percutaneously in the external jugular vein. Mules were premedicated with 1.3 mg/kg xylazine IV and anaesthesia was then inducted with 6 mg/kg IV thiopental within 10 min after premedication, when the animals were at least moderately sedated. Additional xylazine was administered when the mules were inadequately sedated. Sedation was considered good when lowering of the head, drooping of the lower lip and drooping of the ears were present using a 4-point sedation score. Once the mules were recumbent, the infusion of guaifenesin (50 mg/ml) - ketamine (20 mg/ml) - xylazine (0.5 mg/ml) (GKX) was started to maintain general anaesthesia, approximately 1ml/kg/hr (based on monitoring eye signs, muscle relaxation of the neck, respiratory rate and pattern, and the responses to surgical stimulation. The spermatic cord of each testis was infiltrated with 5 ml of lidocaine to achieve local anaesthesia before the scrotum skin incision. The open technique of castration was applied to all mules for postoperative drainage. During anaesthesia heart rate (HR), respiratory rate RR), rectal temperature (RT) and hemoglobin saturation with oxygen (SpO2) were measured every 5 minutes. Times to sternal recumbency, lateral recumbency and standing were recorded. The data recorded were statistically analysed using simple one-way analysis of variance (ANOVA) and a pvalue>0.05 was considered significant. The qualities of anaesthesia were evaluated using induction, maintenance and recovery scores. The resultes suggest that the premedication using 1.3 mg/kg IV xylazine for mules undergoing thiopental anaesthesia was satisfactory and only one animal needed a supplemental dose of xylazine (0.3 mg/kg IV) to induce better sedation. The total IV amount of thiopental for induction was sufficient to achieve lateral recumbency in all animals. Furthermore, GKX provided adequate surgical plane of general anaesthesia to performe castration in all mules, without responses to the manuality or significant modification of HH, RR, RT, and SpO2 in comparison with the basal values and to maintain a satisfactory muscle relaxation. Recovery from anaesthesia was uneventful, smooth and clinically acceptable in all mules