GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa.

Phytochemical investigation of the lipids extracted from seeds of Cannabis sativa by GC-MS showed 43 cannabinoids, 16 of which are new. The extract is dominated by Δ9-tetrahydrocannabinolic acid (A) and its neutral derivative trans-Δ9-tetrahydrocannabinol-C5 (THC) Cis and trans-Δ9-tetrahydrocannabinol-C7 isomers with an ethyl-pentyl branched chain together with minor amounts of trans-Δ9-tetrahydrocannabinol with a methyl-pentyl C6 branched side chain were identified as new natural compounds. Four cannabichromene isomers with a C5 side chain are postulated to be derived from the double bond migration at the terminal isoprenyl unit. C7 cannabichromene together with the neutral and acidic forms of cannabinol-C7 were also detected. The mass spectrum of these homologues as trimethylsilyl (TMS) derivatives are presented, and the fragmentation patterns are discussed.

Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish prospective multicenter study (GECMP-CCR).

BACKGROUND: Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. PATIENTS AND METHODS: Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. RESULTS: A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. CONCLUSION: Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results.

Comparison of two HIV testing strategies in primary care centres: indicator-condition-guided testing vs. testing of those with non-indicator conditions.

OBJECTIVES: The aim of the study was to compare prospectively indicator-condition (IC)-guided testing versus testing of those with non-indicator conditions (NICs) in four primary care centres (PCCs) in Barcelona, Spain. METHODS: From October 2009 to February 2011, patients aged from 18 to 65 years old who attended a PCC for a new herpes zoster infection, seborrhoeic eczema, mononucleosis syndrome or leucopenia/thrombopenia were included in the IC group, and one in every 10 randomly selected patients consulting for other reasons were included in the NIC group. A proportion of patients in each group were offered an HIV test; those who agreed to be tested were given a rapid finger-stick HIV test (€6 per test). Epidemiological and clinical data were collected and analysed. RESULTS: During the study period, 775 patients attended with one of the four selected ICs, while 66,043 patients presented with an NIC. HIV screening was offered to 89 patients with ICs (offer rate 11.5%), of whom 85 agreed to and completed testing (94.4 and 100% acceptance and completion rates, respectively). In the NIC group, an HIV test was offered to 344 persons (offer rate 5.2%), of whom 313 accepted (90.9%) and 304 completed (97.1%) testing. HIV tests were positive in four persons [prevalence 4.7%; 95% confidence interval (CI) 1.3-11.6%] in the IC group and in one person in the NIC group (prevalence 0.3%; 95% CI 0.01-1.82%; P < 0.009). If every eligible person had taken an HIV test, we would have spent €4650 in the IC group and €396,258 in the NIC group, and an estimated 36 (95% CI 25-49) and 198 persons (95% CI 171-227), respectively, would have been diagnosed with HIV infection. The estimated cost per new HIV diagnosis would have been €129 (95% CI €107-153) in the IC group and €2001 (95% CI €1913-2088) in the NIC group. CONCLUSIONS: Although the number of patients included in the study was small and the results should be treated with caution, IC-guided HIV testing, based on four selected ICs, in PCCs seems to be a more feasible and less expensive strategy to improve diagnosis of HIV infection in Spain than a nontargeted HIV testing strategy.

Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development.

OBJECTIVE: To compare the MANKIN and OARSI cartilage histopathology assessment systems using human articular cartilage from a large number of donors across the adult age spectrum representing all levels of cartilage degradation. DESIGN: Human knees (n=125 from 65 donors; age range 23-92) were obtained from tissue banks. All cartilage surfaces were macroscopically graded. Osteochondral slabs representing the entire central regions of both femoral condyles, tibial plateaus, and the patella were processed for histology and Safranin O - Fast Green staining. Slides representing normal, aged, and osteoarthritis (OA) tissue were scanned and electronic images were scored online by five observers. Statistical analysis was performed for inter- and intra-observer variability, reproducibility and reliability. RESULTS: The inter-observer variability among five observers for the MANKIN system showed a similar good Intra-class correlation coefficient (ICC>0.81) as for the OARSI system (ICC>0.78). Repeat scoring by three of the five readers showed very good agreement (ICC>0.94). Both systems showed a high reproducibility among four of the five readers as indicated by the Spearman's rho value. For the MANKIN system, the surface represented by lesion depth was the parameter where all readers showed an excellent agreement. Other parameters such as cellularity, Safranin O staining intensity and tidemark had greater inter-reader disagreement. CONCLUSION: Both scoring systems were reliable but appeared too complex and time consuming for assessment of lesion severity, the major parameter determined in standardized scoring systems. To rapidly and reproducibly assess severity of cartilage degradation, we propose to develop a simplified system for lesion volume.

Continuous aqueous phase reforming of a synthetic brewery wastewater with Pt/C and PtRe/C catalysts for biohydrogen production.

This work investigates H2 production through aqueous phase reforming (APR) of synthetic brewery wastewater in a continuous fixed bed reactor with Pt and PtRe (3 wt %) catalysts supported on activated carbon. The influence of weight hourly space velocity (WHSV) and superficial Ar gas flow velocity (VAr) was assessed for the sake of optimisation, while reaction temperature and pressure were maintained at 225 °C and 28 bar, respectively. H2 production was found to be higher using the PtRe catalyst at the lowest WHSV (0.03 h-1) and highest VAr (0.8 cm s-1). The comparison of the maximum H2 production obtained in this work (27.9 µmol min-1) with other treatment processes shows the potential of the application of APR process for H2 production from brewery wastewater. Despite the different reaction conditions tested, the catalysts showed deactivation with time on stream, which was related to the formation of solid deposits on the surface of the catalysts. Therefore, future research should be related to the development of more stable catalysts, strategies that avoid deactivation by coking and regeneration processes.

Fresh osteochondral allografts for posttraumatic knee defects: long-term followup.

Fresh osteochondral allograft transplantation has been an effective treatment option with promising long-term clinical outcomes for focal posttraumatic defects in the knee for young, active individuals. We examined histologic features of 35 fresh osteochondral allograft specimens retrieved at the time of subsequent graft revision, osteotomy, or TKA. Graft survival time ranged from 1 to 25 years based on their time to reoperation. Histologic features of early graft failures were lack of chondrocyte viability and loss of matrix cationic staining. Histologic features of late graft failures were fracture through the graft, active and incomplete remodeling of the graft bone by the host bone, and resorption of the graft tissue by synovial inflammatory activity at graft edges. Histologic features associated with long-term allograft survival included viable chondrocytes, functional preservation of matrix, and complete replacement of the graft bone with the host bone. Given chondrocyte viability, long-term allograft survival depends on graft stability by rigid fixation of host bone to graft bone. With the stable osseous graft base, the hyaline cartilage portion of the allograft can survive and function for 25 years or more.

First Report of Fulvia fulva, Causal Agent of Tomato Leaf Mold, in Greenhouses in Southeastern Spain.

Tomato (Solanum lycopersicum L.) is produced in more than 9,000 ha of greenhouses in Almería (southeastern Spain). During 2006 and 2007, a new disease was observed on almost all plants in 37 greenhouses. Yellow spots on upper and lower leaf surfaces were accompanied by gray-to-dark brown mycelia, conidiophores, and conidia on lower leaf surfaces. Affected leaves became necrotic and withered. Six isolates grown on malt extract agar (MEA) were identified as Fulvia fulva (1). The one- to three-celled conidia ranged from 21.8 × 7.8 µm to 21.5 × 6.5 µm. On MEA, potato dextrose agar, and V8 juice agar, the pathogen grew slowly; colonies were only 1 cm in diameter after 30 days. Colony color was initially intense yellow but became dark brown with age. In a growth chamber (12,000 lux for 16 h per day, 23 to 28°C, and 60 to 95% relative humidity), six pots containing five tomato plants (cv. SanPedro) at the four-true-leaf stage were inoculated with a conidial suspension (103 CFU/ml) of F. fulva. Control plants were sprayed with water. The trial was repeated once. Immediately after inoculation, plants were sealed in plastic bags for 8 days. Symptoms of the disease and signs of the pathogen were observed on all inoculated plants 18 days after inoculation. To our knowledge, this is the first report of leaf mold of tomato in Almería and it is becoming common in the greenhouse industry in this region. Reference: (1) P. Holliday and J. L. Mulder. No. 487 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, UK, 1976.

Removal of PAHs from water using an immature coal (leonardite).

It has been studied an immature coal (leonardite) as an adsorbent for removing PAHs [fluorene, pyrene, benzo(k)fluoranthene, benzo(a)pyrene and benzo(g,h,i)perylene] from water. To determine the efficiency of leonardite as an adsorbent of PAHs, factors such as pH, contact time and equilibrium sorption were evaluated in a series of batch experiments. There were no significant differences in the removal percentages for the various pH values studied, except for fluorene. The adsorption of fluorene was higher at lower pH values. The equilibrium time was reached at 24h. At this time, more than 82% of the pyrene, benzo(k)fluoranthene, benzo(a)pyrene and benzo(g,h,i)perylene had been removed. During the first 2h, the adsorption rate increased rapidly. After that time, however, there was a minor decrease. Equilibrium data were fitted to Freundlich models to determine the water-leonardite partitioning coefficient. Physical adsorption caused by the aromatic nature of the compounds was the main mechanism that governed the removal process. The polarity of the humic substances in leonardite may also have influenced the adsorption capacity.

Distribution of polycyclic aromatic hydrocarbons in riverine waters after Mediterranean forest fires.

Extensive forest fires occurred in Catalonia, northern Spain, in 1994. In our study, concentrations and profiles of 12 parent polycyclic aromatic hydrocarbons (PAHs) were determined in riverine waters, ash and sediment samples at nine sampling sites (W1-W9) and at three sampling dates from Llobregat hydrographic basin: in August, 1994, one month after the extensive forest fires; in September, 1994, after the first heavy autumn rainfalls and in January, 1995, six months after forest fires. In August 1994, the total concentrations of 12 PAHs measured in riverine waters varied from 2 ng/l to 336 ng/l. In September 1994, the total PAH concentrations decreased to 0.2-31 ng/l and in January 1995, from 9 ng/l to 73 ng/l. In August, the composition pattern of PAHs showed a distribution dominated by 4-ring PAHs (pyrene, chrysene+triphenylene, benzo(a)anthracene) at W3-W6, W8 and W9 and 3-ring PAHs (phenanthrene) at W1, W2 and W7. In September, a preference by 3-ring PAHs (phenanthrene) at all sampling sites except W5 was shown and in January was clearly dominated by 4-ring PAHs (chrysene+triphenylene, pyrene, benzo(a)anthracene) at all sampling sites. In ash and sediment samples, the total concentrations of 12 PAHs ranged from 1.3 ng/g to 19 ng/g. The dominant compound was phenanthrene.

Espina de pescado alojada en la glándula tiroides / Fishbone lodged in the thyroid gland

Los cuerpos extraños alojados en la vía aéreodigestiva superior son un motivo de consulta frecuente para el otorrinolaringólogo. Uno de los más frecuentes son las espinas de pescado. En raras ocasiones, éstas migran hacia tejidos adyacentes y generan complicaciones importantes. Presentamos el caso de una paciente que tras la ingesta de pescado manifiesta sensación de cuerpo extraño faríngeo, odinofagia y dolor látero cervical derecho. Dada la ausencia de hallazgos a la exploración física y laringoscópica se realiza una tomografia computarizada cervical, visualizando un cuerpo extraño alojado en la glándula tiroidea. Se interviene mediante cervicotomía media, realizando la extracción de la espina sin complicaciones. El diagnóstico precoz y manejo adecuado es determinante para prevenir complicaciones en estos casos.

Foreign bodies in the aerodigestive tract are commonly confronted in otolaryngology practice. The most frequent are the fish bones. In rare cases they can move and cause numerous complications. We report the case of a patient that manifest the sensation of pharyngeal foreign body, after fish ingestion. She also referred odynophagia and right cervical pain. Physical and laryngoscopic examination were normal. A cervical CT was performed, where a foreign body lodged in the thyroid gland was visualized, median cervicotomy was done and the foreign body was extracted. Early diagnosis and adequate management are crucial to prevent complications in these cases.

Alkylating nucleosides 1. Synthesis and cytostatic activity of N-glycosyl(halomethyl)-1,2,3-triazoles. A new type of alkylating agent.

1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivatives by treatment with (C6H5)3P/CCl4, (C6H5O)3P/Br2, and (C6H5O)3P/I2, respectively. 1-Benzyl-4-(fluoromethyl)-1,2,3-triazole was obtained from 1-benzyl-4-(bromomethyl)-1,2,3-triazole by treatment with KF and 18-crown-6. Chloromethyl-, bromomethyl-, and iodomethyl-1,2,3-triazole derivatives inhibited the "in vitro" growth of HeLa cells. Some of these compounds increased the life span of mice bearing tumors.

Cytostatic quinones. 3. Synthesis of benzotriazolequinones by a new oxidation with m-chloroperbenzoic acid. Biochemical studies.

Oxidation of N-1 and N-2 alkylbenzotriazoles with m-chloroperbenzoic acid afforded 1-alkylbenzotriazole 3-oxides and 2-alkylbenzotriazole-4,4-diones, respectively. The quinonic compounds inhibited the "in vitro" growth of both HeLa and KB cells, the synthesis of macromolecules (DNA, RNA, and proteins), and the uptake of glucose by Ehrlich carcinoma ascites cells. A possible mode of action is suggested.

Synthesis and antiviral evaluation of nucleosides of 5-methylimidazole-4-carboxamide.

Due to the antiviral activity of certain 5-substituted imidazole nucleosides related to ribavirin, 5-methylimidazole-4-carboxamide nucleosides having beta-D-ribofuranosyl, 2-deoxy-beta- and -alpha-D-ribofuranosyl, and (2-hydroxyethoxy)methyl moieties have been prepared and tested as antiviral agents. 1-beta-D-Ribofuranosyl-5-methylimidazole-4-carboxamide was obtained by deacetylation of the corresponding tri-O-acetyl nucleoside 11 or by deacetylation and ammonolysis of the blocked ethyl 5-methylimidazole-4-carboxylate nucleoside 10, which was prepared from the stannic chloride catalyzed condensation of the trimethylsilyl derivative of ethyl 4(5)-methylimidazole-5(4)-carboxylate. Glycosylation of 4(5)-methylimidazole-5(4)-carboxamide with 3,5-di-O-p-toluoyl-2-deoxy-D-erythro-pentofuranosyl chloride via mercuric cyanide method provided an anomeric mixture of the blocked 5-methylimidazole-4-carboxamide deoxynucleoside 14 along with an anomeric mixture of the 4-methyl 5-carboxamide isomer 15. Separation of compound 14 into the corresponding beta and alpha anomers was achieved by conversion to the 3',5'-di-O-acetyl derivatives 17 and 18, which after chromatographic separation were deacetylated to give 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-methylimidazole-4-carboxa mid e and its alpha anomer 20. 1-[(2-Hydroxyethoxy)methyl]-5-methylimidazole-4-carboxamide was prepared by alkylation of the imidazole 13 with (2-acetoxyethoxy)methyl bromide followed by treatment with methanolic ammonia. All these imidazole nucleosides were tested in HeLa cell cultures against type 1 herpes simplex and vesicular stomatitis viruses. The ribofuranosyl derivative 12 showed a significant activity against type 1 herpes simplex virus.

Uridine 5'-diphosphate glucose analogues. Inhibitors of protein glycosylation that show antiviral activity.

A series of analogues of uridine 5'-diphosphate glucose and uridine 5'-diphosphate glucosamine have been synthesized by reaction of 2,3,4,6-tetra-O-benzyl-, 2,3,4,6-tetra-O-benzoyl-, 2,3,4,6-tetra-O-acetyl-, and 2,3,4,6-tetra-O-palmitoyl-alpha-D-glucopyranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranose with chlorosulfonyl isocyanate and 2',3'-O-isopropylideneuridine. Isopropylidene and acetyl groups of the resulting 5'-O-[[[[(alpha-D-glucopyranosyl)oxy]carbonyl]amino]sulfonyl] -2',3'-O-isopropylideneuridine derivatives were removed by reaction with a TFA/water (5:1) mixture and methanolic ammonia, respectively. The 5'-O-[[[[(2",3",4",6"-tetra-O-benzyl-and 2",3",4",6"-tetra-O-benzoyl-alpha-D-glucopyranosyl)oxy]carbonyl] amino]sulfonyl]-2',3'-O-isopropylideneuridine (13 and 19) and the corresponding deisopropylidenated derivatives showed antiviral activity as determined by the inhibition of the cytopathic effect induced by HSV-1 replication and by the plaque assay method. Compound 13 inhibited glycosylation of proteins in HSV-1 infected HeLa cells.

Synthesis and antiviral activity of 3'-C-cyano-3'-deoxynucleosides.

A series of 3'-C-cyano-3'-deoxynucleosides have been synthesized and evaluated as antiviral agents. Reaction of 2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-erythro-pentofuranos- 3'-ulosyl derivatives of uracil, 4-N-acetylcytosine, and adenine with sodium cyanide gave a mixture of epimeric cyanohydrins, which after 3'-deoxygenation yielded the corresponding 3'-C-cyano-3'-deoxy-beta-D-xylo-pentofuranosyl derivatives 10. These compounds were epimerized to the corresponding beta-D-ribo-pentofuranosyl derivatives 11. Desilylation of 10 and 11 gave the deprotected 3'-C-cyano-3'-deoxy-beta-D-xylo- and -ribo-pentofuranosyl nucleosides. These derivatives of uridine, cytidine, and adenine, as well as the 3'-C-cyano-3'-deoxy-beta-D-xylo- and -ribo-pentofuranosyl, 3'-C-cyano-2',3'-dideoxy-beta-D-threo- and -erythro-pentofuranosyl, and 3'-C-cyano-2',3'-dideoxy-beta-D-glycero-pent-2'-enofuranosyl derivatives of thymine, were evaluated for their antiviral activity. None of the compounds proved active against the replication of retroviruses (human immunodeficiency virus, murine sarcoma virus) at concentrations that were not toxic to the host cells. However, the 3'-C-cyano-3'-deoxy-beta-D-xylo- (12e) and -ribo-pentofuranosyl (13e) derivatives of adenine showed activity against some DNA (i.e., vaccinia) and RNA (i.e., Sindbis, Semliki forest) viruses at concentrations well below the cytotoxicity threshold.

Distal aphalangia, syndactyly, and extra metatarsal, associated with short stature, microcephaly, and borderline intelligence: a new autosomal dominant disorder.

We report on 3 members of a Spanish family with partial aphalangia, syndactyly with duplication of metatarsal IV, microcephaly, dull intelligence, and short stature. The MCA pattern observed in this family appears to constitute a previously undescribed syndrome.

Antiviral activity of uridine 5'-diphosphate glucose analogues against some enveloped viruses in cell culture.

Twenty five analogues of uridine 5'-diphosphate glucose were screened against herpes simplex type 2, vaccinia virus, Sindbis virus and African swine fever virus. After screening, the compound 5'-[[[[(2",3",4",6"-tetra-O-benzoyl-alpha-D- glucopyranosyl)oxi]carbonyl]amino]sulfonyl]uridine (2), the synthesis of which has been reported (Camarasa et al., J. Med. Chem. 28, 40-46, 1985), was selected for further study. This compound showed in vitro activity against all viruses tested. The replication of herpes virus type 2 and African swine fever virus was completely inhibited at 100 micrograms/ml and 150 micrograms/ml respectively; vaccinia virus and Sindbis virus were inhibited to a lesser extent. The compound may inhibit several steps in the viral replication process.

Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Grupo Cooperativo de Carcinoma Broncogénico de la Sociedad Española de Neumología y Cirugía Torácica.

BACKGROUND: We prospectively analyzed the postoperative morbidity, mortality rate, and risk factors in 605 patients who underwent thoracotomy for bronchogenic carcinoma. METHODS: Patients were categorized by postsurgical tumor stage: I, 287 patients (47.4%); II, 49 patients (8.1%); IIIA, 154 patients (25.5%); IIIB, 80 patients (13.2%); IV, 16 patients (2.7%); unavailable, 19 patients (3.1%). Two hundred ninety-four patients (48.6%) underwent lobectomy, 172 (28.4%) pneumonectomy, 20 (3.3%) bilobectomy, 29 (4.8%) segmentectomy, 27 (4.5%) wedge resection, and 63 (10.4%) exploratory thoracotomy. The importance of the factors that influence the morbidity and mortality rates was calculated from their relative risks. Univariate and multivariate methods for a logistic regression model were used for this analysis. RESULTS: Postoperative complications developed in 196 patients (32.4%); there were 165 (27.3%) cases of operation-related complications and 152 (25.1%) cases of respiratory and cardiovascular complications. The morbidity rate was highest in patients with preexisting vascular disease (50.9%; odds ratio [OR], 2.20) or insulin-dependent diabetes mellitus (52.4%; OR, 2.77) and in patients who underwent pneumonectomy (40.1%; OR, 1.82). Forty patients (6.6%) died postoperatively, most commonly of respiratory failure (67.5%). The mortality rate was highest in patients with postoperative morbidity (OR, 31.9) or vascular disease (15.8%; OR, 2.83) and in patients who underwent pneumonectomy (13.4%; OR, 4.9). CONCLUSIONS: Postoperative complications are more likely to develop in patients with peripheral vascular disease or insulin-dependent diabetes mellitus, or both. Postoperative mortality was found to be significantly higher in patients with vascular disease and those who underwent pneumonectomy.