A systematic review of the analgesic efficacy of cannabinoid medications in the management of acute pain.

BACKGROUND: Cannabinergic medications have been postulated to demonstrate efficacy in the management of pain. The aim of this systematic review was to assess the analgesic efficacy and adverse effects of cannabinoids when used for the management of acute pain. METHODS: A systematic review was performed by searching the MEDLINE, EMBASE and CENTRAL databases, and the World Health Organization International Clinical Trials Registry Platform for human randomized controlled trials that assessed the analgesic efficacy of cannabinoids compared to placebo or active comparators. The reported outcomes for analgesic efficacy and adverse effects in included studies were qualitatively analysed. RESULTS: Seven studies, including 611 patients were included in the systematic review. In five studies, cannabinoids were found to provide equivalent analgesia to placebo, in one study the analgesia provided by cannabinoids was superior to placebo, and in one study cannabinoids provided analgesia that was inferior to that provided by placebo. No synergistic or additive analgesic effect was observed when cannabinoids were used in combination with opioids. In five of the seven studies, certain adverse effects were more frequent with cannabinoid treatment than with placebo or active comparator. CONCLUSION: On the basis of the available randomized controlled trial evidence, cannabinoids have no role in the management of acute pain.

Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis.

Phosphoinositide 3-kinase γ (PI3Kγ) consists of a catalytic subunit p110γ, which forms mutually exclusive dimers with one of the regulatory subunits called p101 and p84/p87(PIKAP). Recently, PI3Kγ emerged as being a potential oncogene because overexpression of the catalytic subunit p110γ or the regulatory subunit p101 leads to oncogenic cellular transformation and malignancy. However, the contribution of the individual subunits to tumor growth and metastasis and the mechanisms involved are not understood. We therefore individually knocked down the PI3Kγ subunits (p84, p101 and p110γ) in MDA-MB-231 cells, which reduced in vitro migration of the cell lines. Knockdown of p110γ or p101 inhibited apoptosis, Akt phosphorylation and lung colonization in SCID mice. Similarly, the knockdown of p110γ and p101 in murine epithelial carcinoma 4T1.2 cells inhibited primary tumor growth and spontaneous metastasis, as well as lung colonization. In contrast, knockdown of p84 in MDA-MB-231 cells enhanced Akt phosphorylation and lung colonization. These findings are the first to implicate differential functions of the two PI3Kγ regulatory subunits in the process of oncogenesis, and indicate that loss of p101 is sufficient to reduce in vivo tumor growth and metastasis to the same extent as that of p110γ.

Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa.

Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.

Paracentric inversions in humans: a review of 446 paracentric inversions with presentation of 120 new cases.

We present a large review of 446 cases of paracentric inversions (PAI), including 120 new cases, to assess their incidence, distribution, inheritance, modes of ascertainment, interchromosomal effects, viable recombinant offspring, and clinical relevance. All 23 autosomes and sex chromosomes had inversions. However, none were identified in chromosome arms 18p, 19q, 20q, and Yp. PAI were most commonly reported in chromosomes 1, 3, 5, 6, 7, 11, and 14 and less frequently in chromosomes 4, 16, 17, 18, 19, 20, 21, 22, and Y. Inversions were most common in chromosome arms 6p, 7q, 11q, and 14q and observed least in chromosome arms 2p, 2q, 3q, 4q, and 6q. Frequently encountered breakpoints included 3(p13p25), 6(p12p23), 6(p12p25), 7(q11q22), and 11(q21q23). Ascertainment was primarily incidental (54.5%), mental retardation and/or congenital anomalies (22.2%), spontaneous abortions (11.4%), associations with syndromes (3.0%), and infertility (2.0%) accounted for the remainder. Ascertainment was neither related to the length of the inverted segment nor to specific inversions except for PAI of Xq which often presented with manifestations of Ullrich-Turner syndrome. Sixty-six percent of PAI were inherited while 8.5% were de novo. Recombination was observed in 17 cases, 15 of which resulted in a monocentric chromosomal deletion or duplication. No common factors were identified that suggested a tendency towards recombination. The incidence of viable recombinants was estimated to be 3.8%. This review documents that PAI are perhaps more commonly identified than suggested in previous reviews. Despite the possible bias of ascertainment in some cases, there may be associated risks with PAI that require further examination. Our data suggest that PAI carriers do not appear to be free of risks of abnormalities or abnormal progeny and caution is recommended when counseling.

Single cell translocations in couples with multiple spontaneous abortions.

Single cell translocations have been previously reported to occur in normal lymphocyte cultures. Comparison of the frequency of these in 140 individuals referred for a history of multiple miscarriages and 415 individuals referred for a history of multiple miscarriages and 415 individuals referred for other reasons showed a significantly greater number of single cell translocations in the former group. This group also had a significantly greater number of other types of single cell structural abnormalities. Increased chromosome instability, chromosome mosaicism, residual fetal trophoblasts, and immunological differences are discussed in considering the possible etiology.