Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review

ObjectiveTo quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy.DesignSystematic review.Studies30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours.ResultsCannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: “high” 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11.ConclusionsIn selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

What is already known on this topic

Requests have been made for legalisation of cannabis (marijuana) for medical useLong term smoking of cannabis can have physical and neuropsychiatric adverse effectsCannabis may be useful in the control of chemotherapy related sickness

What this study adds

Oral nabilone and dronabinol and intramuscular levonantradol are superior to conventional antiemetics (such as prochlorperazine or metoclopramide) in chemotherapySide effects are common with cannabinoids, and although some may be potentially beneficial (euphoria, “high,” sedation), others are harmful (dysphoria, depression, hallucinations)Many patients have a strong preference for cannabinoids     

Understanding the changing value of natural resources: an integrated palaeoecological–historical investigation into grazing–woodland interactions by Loch Awe, Western Highlands of Scotland

Aim We aim to compare fine resolution pollen data from a former seasonal pasture with historical evidence for grazing and woodland use. We discuss the complexities and benefits of integrating qualitative and quantitative information, and the implications for studies of past wood–grazing interactions and their relevance to current conservation management. Location Corries is an abandoned farm township in Scotland's Western Highlands. Methods Two sources were used: (1) pollen evidence from a former seasonal pasture, analysed at c. 20‐year intervals and dated using ¹⁴C and ²¹⁰Pb, provides a c. 1100‐year local vegetation and land‐use history; (2) written sources document resource regulation and changing socio‐economic circumstances at local to national scales over the last c. 400 years. Results Each source records woodland and livestock management at different spatial and temporal scales: written evidence provides a clearer understanding of general (estate) rather than farm‐scale changes, while small pollen basins record localized woodland–grazing dynamics, which can be difficult to extrapolate to the landscape scale. Both sources indicate a dynamic wood–grazing balance and together provide clearer evidence for incentives and drivers controlling this relationship. The first palynological phase of woodland incursion (ad c. 1210–1490) pre‐dates the surviving written records, but a second (ad c. 1680–1760) occurs during a period of increasing market value for cattle, when farmers may have increased grazing despite regulations to protect woods. The site is not representative of grazing intensification associated with the introduction of extensive sheep farming because the farmer protected the woods (ad c. 1760–1880) until they were cleared (ad c. 1880–1920) for quarrying (ad 1885–1904), which accounts for the limited palynological evidence for grazing. Main conclusions Written evidence for past stocking levels is too fragmentary and ambiguous to allow long‐term quantitative analysis, but a local historical context is important for interpreting local pollen records. Management decisions that determined grazing–woodland interactions were shaped by changing values, markets, agricultural practices and regulatory structures, which can result in nonlinear relationships between stocking levels and woodland continuity. Many woods were managed for multiple purposes in the past and promoting natural processes or pursuing pre‐anthropogenic baselines will result in the erosion of cultural features that have shaped present landscape values.     

Cellulases and hemicellulases of the anaerobic fungus Piromyces constitute a multiprotein cellulose-binding complex and are encoded by multigene families

Abstract More than 80% of the extracellular Avicelase, endoglucanase, xylanase and mannanase activities of the anaerobic fungus Piromyces were associated with a cellulose-binding complex. The complex was composed of at least 10 polypeptides ranging in size from 190 kDa to 50 kDa, and contained numerous endoglucanases, xylanases and mannanases. Multiple genes encoding each of these activities were isolated from an expressing cDNA library.     

Interpreting soil ciliate biodiversity

The results of soil ciliate frequency studies of 47 field studies, from 12 ecosystem types, were combined with recent concepts and observations to assess the importance of soil ciliate biodiversity in ecosystem functioning. A few species typically furnish most of the individuals; increases in biodiversity, produced by less common species, alters soil ciliate communities. Soil ciliates were grouped according to position on the r/K continuum, with polyhymenophoran species as K, and colpodids as r organisms; and according to degree of soil affinity. Grasslands and hardwood forests were characterized by large numbers of K and intermediate species, whereas pine forests and more stressed ecosystems (e.g., arable lands, deserts) had more colpodid and fewer total species. Within these systems, certain species may become prominent, or be absent, suggesting that many soil ciliates exhibit widely overlapping niches, and that while a soil might function with a few species, high diversity allows systems to respond to changing seasons and climate.     

The Genome Sequence of Herpes Simplex Virus Type 2

The genomic DNA sequence of herpes simplex virus type 2 (HSV-2) strain HG52 was determined as 154,746 bp with a G+C content of 70.4%. A total of 74 genes encoding distinct proteins was identified; three of these were each present in two copies, within major repeat elements of the genome. The HSV-2 gene set corresponds closely with that of HSV-1, and the HSV-2 sequence prompted several local revisions to the published HSV-1 sequence (D. J. McGeoch, M. A. Dalrymple, A. J. Davison, A. Dolan, M. C. Frame, D. McNab, L. J. Perry, J. E. Scott, and P. Taylor, J. Gen. Virol. 69:1531–1574, 1988). No compelling evidence for the existence of any additional protein-coding genes in HSV-2 was identified.The complete 152-kbp genomic DNA sequence of herpes simplex virus type 1 (HSV-1) was published in 1988 (56) and since then has been very widely employed in a great range of research on HSV-1. Additionally, results from this most studied member of the family Herpesviridae have fed powerfully into research on other herpesviruses. In contrast, although a substantial number of individual gene sequences have been determined for the other HSV serotype, HSV-2, the complete genome sequence for this virus has not been available hitherto. In this paper we report the sequence of the genome of HSV-2, strain HG52.At a gross level the 155-kbp genome of HSV-2 is viewed as consisting of two extended regions of unique sequence (U_L and U_S), each of which is bounded by a pair of inverted repeat elements (TR_L-IR_L and IR_S-TR_S) (17, 66) (Fig. ​(Fig.1).1). There is a directly repeated sequence of some 254 bp at the genome termini (the a sequence), with one or more copies in the opposing orientation (the a′ sequence) at the internal joint between IR_L and IR_S (21). U_L plus its flanking repeats is termed the long (L) region, and U_S with its flanking repeats is termed the short (S) region. In individual molecules of HSV-2 DNA, the L and S components may be linked with each in either orientation, so that DNA preparations contain four sequence-orientation isomers, one of which is defined as the prototype (66). The sequences of the terminal and internal copies of R_L and of R_S are considered to be indistinguishable. Open in a separate windowFIG. 1Overall organization of the genome of HSV-2. The linear double-stranded DNA is represented, with the scale at the top. The unique portions of the genome (U_L and U_S) are shown as heavy solid lines, and the major repeat elements (TR_L, IR_L, IR_S, and TR_S) are shown as open boxes. For each pair of repeats the two copies are in opposing orientations. As indicated, TR_L, U_L, and IR_L are regarded as comprising the L region, and IR_S, U_S, and TR_S are regarded as comprising the S region. Plasmid-cloned fragments used for sequence determination are indicated at the bottom: BamHI and HindIII fragments are indicated by B and H, respectively, followed by individual fragment designations in lowercase; KH and HK indicate KpnI/HindIII fragments as described in the text.This paper presents properties of the HSV-2 DNA sequence and our present understanding of its content of protein-coding genes and other elements. We are also interested in comparative analysis of the HSV-1 and HSV-2 genomes to examine processes of molecular evolution which have occurred since the two species diverged, and we intend to pursue this topic in a separate paper.     

Heteromeric channel formation and Ca-free media reduce the toxic effect of the weaver Kir 3.2 allele

weaver mice have a severe hypoplasia of the cerebellum with an almost complete loss of the midline granule cells. Recent genetic studies of weaver mice have identified a mutation resulting in an amino acid substitution (G156S) in the pore of the inwardly rectifying potassium channel subunit K_ir 3.2. When expressed in Xenopus oocytes the weaver mutation alters channel selectivity from a potassium-selective to a nonspecific cation-selective pore. In this study we confirm by cell-attached patch-clamp recording that the mutation produces a non-selective cation channel. We also demonstrate that the cell death induced by weaver expression may be prevented by elimination of calcium from the extracellular solution as well as by coexpression with the wild-type K_ir 3.2 allele, or other members of the K_ir 3.0 subfamily. These results suggest that the weaver defect in K_ir 3.2 may cause cerebellar cell death by cell swelling and calcium overload. Cells which express the weaver subunit, but which normally survive, may do so because of heteromeric subunit assembly with wild-type subunits of the K_ir 3.0 subfamily.     

Gas chromatographic-mass spectrometric determination of ß2-agonists in postmortem blood: application in forensic medicine

A solid-phase extraction procedure is described for the simultaneous determination of terbutaline, salbutamol and fenoterol in human postmortem whole blood, using gas chromatography-electron impact mass spectrometry. The limit of quantitation in 1 ml of blood was 1 ng/ml for all analytes. A linear response was observed over the concentration ranges tested, covering both low and high concentration of each drug. The recoveries in postmortem blood were: terbutaline, 88%; salbutamol, 86%; fenoterol, 92%; orciprenaline (internal standard), 86%. Coefficients of variation for both intra-assay precision and inter-assay reproducibility ranged between 2.2 and 13.0% for all analytes. This method is sensitive and selective, and has been applied successfully to over 60 postmortem blood specimens.     

2-Oxoglutarate: Oxidation and Role as a Potential Precursor of Cytosolic Acetyl-CoA for the Synthesis of Acetylcholine in Rat Brain Synaptosomes

The possibility that 2-oxoglutarate may supply acetyl units for the cytosolic synthesis of acetylcholine in rat brain synaptosomes was investigated. The contribution of [14C]2-oxoglutarate to the synaptosomal synthesis of [14C]acetylcholine was found to be negligible despite evidence for its uptake and oxidation. The activity of the enzymes NADP-isocitrate dehydrogenase (EC 1.1.1.42), aconitate hydratase (EC 4.2.1.3), and ATP citrate-lyase (EC 4.1.3.8) were measured in the synaptosol. NADP-isocitrate dehydrogenase and aconitate hydratase are present at three- to 1.5-fold higher activities than ATP citrate-lyase. It seems likely that these enzymes contribute to the metabolism of citrate and prevent detectable formation of cytosolic acetyl-CoA from exogenously added 2-oxoglutarate (or citrate). The data further suggest that ATP citrate-lyase may in part be associated with the mitochondrial fraction.     

Bacteriophage λ-mediated transposon mutagenesis of phytopathogenic and epiphytic Erwinia species is strain dependent

Summary Using transformation and conjugal mobilization, plasmids carrying the lamB gene of Escherichia coli were transferred to a range of Erwinia strains. The resultant strains were infected with 467, and kanamycin resistant transductants were screened for various mutant phenotypes including auxotrophy and altered extracellular enzyme activities. Reversion analysis suggested that most mutant phenotypes were due to Tn5 insertion. The applicability of the techniques was highly strain dependent. However a rapid and simple route to mutant isolation was obtained, which could allow the use of other -related genetic techniques in several important species which, to date, have not been genetically manipulated.