Antidiabetic Sterols from Peniocereus greggii Roots.

The roots of the cactus Peniocereus greggii, which grows in Northern Mexico and in the south of Arizona, are highly valued by the Pima to treat diabetes and other illnesses, such as breast pain and common cold. As part of our chemical and pharmacological investigation on medicinal plants used for treating diabetes, herein we report the hypoglycemic and antihyperglycemic action of a decoction prepared from the roots of the plant. The active compounds were a series of cholestane steroids, namely, peniocerol (2), desoxyviperidone (3), viperidone (4), and viperidinone (5). Also, a new chemical entity was obtained from an alkalinized chloroform extract (CE1), which was characterized as 3,6-dihydroxycholesta-5,8(9),14-trien-7-one (6) by spectroscopic means. Desoxyviperidone (3) showed an antihyperglycemic action during an oral glucose tolerance test. Compound 3 was also able to decrease blood glucose levels during an intraperitoneal insulin tolerance test in hyperglycemic mice only in combination with insulin, thus behaving as an insulin sensitizer agent. Nevertheless, mitochondrial bioenergetic experiments revealed that compounds 3 and 6 increased basal respiration and proton leak, without affecting the respiration associated with ATP production in C2C12 myotubes. Finally, an ultraefficiency liquid chromatographic method for quantifying desoxyviperidone (3) and viperidone (4) in the crude drug was developed and validated. Altogether, our results demonstrate that Peniocereus greggii decoction possesses a hypoglycemic and antihyperglycemic action in vivo, that sterols 2 and 6 promotes insulin secretion in vitro, and that desoxyviperidone (3) physiologically behaves as an insulin sensitizer agent by a mechanism that may involve mitochondrial proton leak.

Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

[Portal and mesenteric thrombosis associated with protein S deficiency]. / Trombosis portal y mesentérica asociada al déficit de la proteína S.

INTRODUCTION: liver cirrhosis is the main cause of portal thrombosis (PT), while hypercoagulability syndromes are rarely found as the etiology of PT. We report a case of portal and mesenteric thrombosis secondary to protein S deficiency. CASE REPORT: a 74-year-old woman was admitted with melena secondary to upper gastrointestinal bleeding. She reported mild, diffuse abdominal pain in the last 2 weeks. Endoscopy revealed ruptured esophageal varices. Doppler ultrasonography and CT demonstrated a heterogeneous liver, splenomegaly and ascites, and complete non-occlusive PT involving the hilum and portal branches, as well as the superior mesenteric vein, with portosystemic collaterals. At this point a complete study for cirrhosis etiologies was negative, including a liver biopsy that showed nonspecific architectural changes secondary to diminished blood flow, which suggested non-cirrhotic portal hypertension. The search for hypercoagulability states determined a deficiency of S protein, with total pS = 107% and free pS = 56%. The patient was started on anticoagulant treatment and no other thrombotic events occurred. DISCUSSION: PT usually manifests without specific symptoms. The most common presentation is upper gastrointestinal bleeding, as occurred in our patient. Liver cirrhosis is one of the most frequent cause of PT. Up to 65% of these patients present an associated prothrombotic state, including protein S deficiency. Our case reminds us of the importance of a systematic search for hipercoagulability syndromes in patients with TP, even when the etiology can be conferred to liver cirrhosis.

Trombosis portal y mesentérica asociada al déficit de la proteína S / No disponible

Introducción: la causa más frecuente de trombosis portal (TP)es la cirrosis hepática, mientras que los estados hipercoagulables sonraramente identificados como etiología de la TP. Presentamos uncaso de TP y mesentérica secundaria al déficit de la proteína S (pS).Caso clínico: paciente mujer de 74 años, que debuta con dolorabdominal difuso de 2 semanas de evolución y hemorragia digestivaalta tipo melena secundaria a varices esofágicas. En el estudiose objetiva un hígado heterogéneo, esplenomegalia y ascitis,así como una trombosis portal completa no oclusiva del hilio hepáticoy de sus ramas y de la vena mesentérica superior con circulacióncolateral. El estudio etiológico de hepatopatía fue negativo,incluyendo una biopsia hepática que mostraba cambios arquitecturalessecundarios al flujo hemático disminuido compatible conhipertensión portal no cirrótica. El estudio de hipercoagulabilidadfue positivo para un déficit de proteína S. pS libre 56%, pS total107%. Desde entonces se inició tratamiento anticoagulante sinpresentar descompensaciones posteriores.Discusión: la trombosis portal suele manifestarse con síntomasinespecíficos, siendo la forma de presentación más frecuentela hemorragia digestiva alta como el caso que nos ocupa. La cirrosises una de las causas más frecuentes de trombosis portal, sinembargo existe hasta un 65% de estos pacientes que tienen unaenfermedad protrombótica asociada, como es el déficit de proteínaS. Nuestro caso remarca la importancia de realizar estudios defactores trombogénicos en pacientes con TP, incluso cuando laetiología se puede atribuir a una cirrosis

Introduction: liver cirrhosis is the main cause of portalthrombosis (PT), while hypercoagulability syndromes are rarelyfound as the etiology of PT. We report a case of portal andmesenteric thrombosis secondary to protein S deficiency.Case report: a 74-year-old woman was admitted with melenasecondary to upper gastrointestinal bleeding. She reported mild, diffuseabdominal pain in the last 2 weeks. Endoscopy revealed rupturedesophageal varices. Doppler ultrasonography and CT demonstrateda heterogeneous liver, splenomegaly and ascites, andcomplete non-occlusive PT involving the hilum and portal branches,as well as the superior mesenteric vein, with portosystemic collaterals.At this point a complete study for cirrhosis etiologies was negative,including a liver biopsy that showed nonspecific architecturalchanges secondary to diminished blood flow, which suggested noncirrhoticportal hypertension. The search for hypercoagulabilitystates determined a deficiency of S protein, with total pS = 107%and free pS = 56%. The patient was started on anticoagulant treatmentand no other thrombotic events occurred.Discussion: PT usually manifests without specific symptoms.The most common presentation is upper gastrointestinal bleeding,as occurred in our patient. Liver cirrhosis is one of the mostfrequent cause of PT. Up to 65% of these patients present an associatedprothrombotic state, including protein S deficiency. Ourcase reminds us of the importance of a systematic search forhipercoagulability syndromes in patients with TP, even when theetiology can be conferred to liver cirrhosis (AU)

Iris yellow spot virus: A New Onion Disease in Spain.

So far, only three viral diseases have been identified in onion crops grown in Spain. These are Tomato spotted wilt virus (TSWV), Onion yellow dwarf virus (OYDV), and Leek yellow stripe virus (LYSV). In September 2003, unusual virus-like symptoms including straw-colored, dry, tan, diamond-shaped lesions on the leaves and stalks, sometimes with necrotic lesions, curled leaves, and bulbs of reduced size, were observed on several onion plants (Allium cepa L.) in commercial fields in Albacete, Spain. Severely affected plants eventually died. To verify the identity of the disease found in the Spanish onions, double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was performed on leaf extracts of symptomatic onions using specific polyclonal antibodies against OYDV, LYSV, Cucumber mosaic virus (CMV) (Biorad Phyto-Diagnostics, Marnes-La Coquette, France), Iris yellow spot virus (IYSV), and TSWV (Loewe Biochemica, Sauerlach, Germany). All samples of infected onion tissue were positive for IYSV and negative for the other viruses tested. To confirm the ELISA results, viral RNA was extracted from five of the ELISA-positive onion samples, a healthy onion plant, and a positive control for IYSV (DSMZ, Braunschweig. Germany). The extracted RNA was used in a One-Step reverse transcription-polymerase chain reaction (RT-PCR) assay using SuperScript Platinum Taq (Invitrogen Life Technologies, Barcelona, Spain) in the presence of the IYSV1S and IYSV1A primers for the nucleocapsid gene of IYSV (1). The RT-PCR assay produced an amplicon of the expected size of 790 bp. No amplification products were observed when healthy plants or a water control were used as templates in the RT-PCR reaction. To establish the authenticity of the virus from onion, the PCR products were purified (High Pure PCR Product Purification Kit, Roche Diagnostics, Mannheim, Germany), sequenced, and the nucleotide sequences obtained were analyzed and compared with the published sequences in GenBank. The PCR product was 97% identical to the sequence of the IYSV nucleocapsid gene (Genbank Accession No. AB121026). IYSV, an emerging tospovirus that is potentially a devastating pathogen of onion, has been reported in many locations in Brazil, Japan, the Netherlands, Israel, Australia, the western United States, Slovenia, and Iran (2). IYSV is included in the European and Mediterranean Plant Protection Organization alert list of viruses (2), and to our knowledge, this is the first report of IYSV in Spain. This tospovirus is transmitted in a propagative manner by Thrips tabaci. Although the vector is present in large populations in the onion-growing areas in Spain, the efficiency of the Mediterranean ecotype in transmitting IYSV is not known. References: (1) B. A. Coutts et al. Australas. Plant Pathol. 32:555, 2003. (2) European and Mediterranean Plant Protection Organization. EPPO on-line publication at www.eppo.org/QUARANTINE/Alert_List/Viruses/irysxx.html .

Hepatitis C virus infection in Spanish volunteer blood donors: HCV RNA analysis and liver disease.

OBJECTIVE: To evaluate in a large group of volunteer blood donors the prevalence of antibodies to hepatitis C virus (anti-HCV) and the relation of transaminase (ALT) levels and viraemia to liver damage. DESIGN: A prospective study. SETTING: Transfusion Centre of the Autonomous Community of Madrid and the Liver Unit of the Princesa University Hospital. PATIENTS: From a population of 55,587 volunteer blood donors, 160 seropositive cases were further evaluated for virological and histological assessment. METHODS: Anti-HCV was tested by ELISA-2 and RIBA-2 assays. HCV RNA was analysed by nested PCR. Liver biopsies were obtained in 35 volunteer blood donors with abnormal ALT levels. RESULTS: The prevalence of anti-HCV detected by ELISA-2 was 0.93%. Serum ALT was abnormal in 61 of the 160 volunteers (38.1%). Of these, RIBA-2 was positive in 96.7% and HCV RNA was detectable in 96.1%. Serum ALT was normal in the remaining 99, 70.7% being RIBA-2 negative and 98.3% HCV RNA negative. The majority of biopsies (85.6%) showed chronic hepatitis. CONCLUSION: This study demonstrates that in blood donors screening for anti-HCV, a positive ELISA-2 test, when associated with abnormal ALT levels, is effective in recognizing subjects with active infection detected by HCV RNA and liver disease. Concerning ELISA-2 positive volunteer blood donors with normal ALT, long-term studies are warranted to elucidate whether they are really infected by HCV.

[Tissue expression of antigenic recognition and intercellular adhesion molecules in chronic viral hepatitis]. / Expresión tisular de moléculas de reconocimiento antigénico y de adhesión intercelular en la hepatitis crónica vírica.

OBJECTIVE: To analyze the expression of different HLA class I antigens and cell adhesion molecules on frozen liver sections from patients with chronic active hepatitis, types B and C. EXPERIMENTAL DESIGN: Liver biopsy samples were divided into two parts, one for routine histological examination and another, after snap-freezing and storing at -80 degrees C, for immunohistochemical analysis. To carry out immunoperoxidase and immunofluorescence stainings, a panel of monoclonal antibodies specific for HLA class I light (beta 2-microglobulin) and heavy chain determinants, and for adhesion molecules such as intercellular adhesion molecule-1 and lymphocyte function associate antigen-3 was used. PATIENTS: Immunohistochemistry was performed in frozen liver biopsy sections from 25 patients with viral chronic active hepatitis, 10 type B and 15 type C. As controls, normal liver samples and liver specimens from patients with cholestasis or steatosis were also studied. RESULTS: HLA class I light and heavy chain determinants were expressed on hepatocytes, biliary duct epithelium, sinusoidal lining cells and lymphocytes from patients and controls; however, the beta 2-microglobulin conformational epitope was undetectable on hepatocytes from normal livers or with cholestasis or steatosis, but clearly positive on hepatocytes from patients with hepatitis. In addition, in liver sections from controls no adhesion molecules positivity was detected on hepatocytes; by contrast, hepatocytes from patients with hepatitis showed markedly enhanced membranous reactivity for both adhesion molecules in areas of piecemeal and lobular necrosis. CONCLUSIONS: Virus B and C infections could induce an increased hepatocellular expression of HLA-class I determinants, including the conformational epitope adequate for antigen presentation, and cell-cell adhesion molecules. These findings underline the role of cell mediated immune reactions in the pathogenesis of hepatic injury in viral chronic hepatitis.

[Lower digestive hemorrhage. Its etiology and the diagnostic efficacy of different explorations. A study of 2646 patients]. / Hemorragia digestiva baja. Etiología y rentabilidad diagnóstica de diversas exploraciones. Un estudio sobre 2.646 enfermos.

Lower gastrointestinal bleeding (LGB) is more frequent than upper gastrointestinal bleeding (UGB) with a better course and a more difficult diagnosis. We reviewed retrospectively 8544 cases from patients who were admitted at the Coloproctology Unit of Hospital de la Princesa. Those with the diagnosis of LGB with visible blood in stools (2646-31%) were outpatients, with a mean age of 43 years (range 9-91). Males represented 56.4% and females 43.6. All of them underwent at least sigmoidoscopic examination. The more frequent disorder was hemorrhoids (48.5%) and the bleeding source was found in the anus in 61%. Most of lesions (86%) could be reached with the short colonoscope and 92.7% of the bleeding sources were found with total colonoscopy. In 7.3% colonoscopy was not diagnostic and fiber gastroscopy identified the bleeding spot in 1.5% of the total. Barium studies were diagnostic in 0.5%, arteriography in 0.25% and radionuclide bleeding scan in 0.1%. Finally in 130 patients the bleeding source could not be found. We conclude that most of hemorrhagic lesions occur in the descending colon and that total colonoscopy can localize more than 92%. When total colonoscopy fails only 33% of the lesions can be found (2.35% from total) and 19% (1.5% from the total number) with UGB are identified with the fiber gastroscopic examination.