Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

Suppression of the immune system has been constantly reported in the last years as a classical side effect of opioid drugs. Most of the studies on the immunological properties of opioids refer to morphine. Although morphine remains the "reference molecule," other semisynthetic and synthetic opioids are frequently used in the clinical practice. The primary objective of this review is to analyze the available literature on the immunomodulating properties of opioid drugs different from morphine in preclinical models and in the human. A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "opioids," "Natural killer cells," "cytokines," and "lymphocytes." The results achieved concerning the effects of fentanyl, methadone, oxycodone, buprenorphine, remifentanil, tramadol, and tapentadol on immune responses in animal studies, in healthy volunteers and in patients are reported. With some limitations due to the different methods used to measure immune system parameters, the large range of opioid doses and the relatively scarce number of participants in the available studies, we conclude that it is not correct to generalize immunosuppression as a common side effect of all opioid molecules

Mixed-mode oscillations and interspike interval statistics in the stochastic FitzHugh-Nagumo model

We study the stochastic FitzHugh-Nagumo equations, modelling the dynamics of neuronal action potentials, in parameter regimes characterised by mixed-mode oscillations. The interspike time interval is related to the random number of small-amplitude oscillations separating consecutive spikes. We prove that this number has an asymptotically geometric distribution, whose parameter is related to the principal eigenvalue of a substochastic Markov chain. We provide rigorous bounds on this eigenvalue in the small-noise regime, and derive an approximation of its dependence on the system's parameters for a large range of noise intensities. This yields a precise description of the probability distribution of observed mixed-mode patterns and interspike intervals.Comment: 36 page

The antagonism of the prokineticin system counteracts bortezomib induced side effects: Focus on mood alterations

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL‐6 and TNF‐α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression‐like behavior in BTZ mice

Osservazioni sulla meiosi in cellule madri del polline di Vitis vinifera L. (cv. Barbera) diploide e tetraploide

Sono state osservate in Barbera diploide e mutato (tetraploide e chimera periclinale 2n-4n) le varie fasi della meiosi a partire dalle cellule madri del polline fino alla formazione del polline stesso.E' stata evidenziata una certa incidenza di appaiamenti anomali in entrambi i mutanti e, al termine della meiosi, si sono potuti osservare tetradi con granuli soprannumerari. Il polline delle piante mutate, presentante per lo più 4 pori, possiede una capacità germinativa ridotta rispetto al testimone.Investigations on meiosis in pollen mother cells of diploid and tetraploid Vitis vinifera L. cv. BarberaThe different stages of meiosis have been investigated in diploid and mutated Vitis vinifera cv. Barbera (a tetraploid and a periclinal chimera 2n-4n) concerning the pollen mother cells.Some incidence of anomalous coupling in both mutants has been pointed out, and tetrades with extra grains can be observed at the end of meiosis.Pollen grains from mutated plants have generally 4 pores and show with respect to the control a reduced germinability

Osservazioni su due casi di poliploidia indotta in Vitis vinifera L. (cv. Barbera)

Vengono descritti gli aspetti citologici ed istologici di due viti cv. Barbera irraggiate con CO60 e present anti fenotipo poliploide.Le analisi compiute hanno riguardato il conteggio dei cromosomi negli apici radicali, l'osservazione degli strati epidermico e subepidermico delle gemme ibernanti, dei granuli pollinici, degli stomi, delle cellule dell'epidermide degli acini.Da tali osservazioni è emerso che un individuo è totalmente tetraploide, mentre il secondo è una chimera periclinale del tipo 2n-4n.Investigations on two cases of induced polyploidy in Vitis vinifera L. (cv. Barbera)The authors describe cytological and histological aspects of two grapevine plants, cv. Barbera, previously irradiated with CO60 and showing polyploid phenotype.The number of chromosomes in the root tip cells, the two first meristematic layers of wintering buds, the size of pollen grains, stornata, and epidermal cells of berries were investigated.The results show that one of them is a tetraploid grape, while the other was found to be a 2n-4n periclinal chimera

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Hospital factors and patient characteristics in the treatment of colorectal cancer: a population based study

BACKGROUND: The present study focuses on the analysis of social, clinical and hospital characteristics that can lead to disparities in the management and outcome of care. To that end, indicators of the quality of initial treatment delivered to newly-diagnosed colorectal cancer patients in a North-Western Region of Italy, were investigated using administrative data. METHODS: The cohort includes all incident colorectal cancer patients (N = 24,187) selected by a validated algorithm from the Piedmont Hospital Discharge Record system over an 8-year period (2000–2007). Three indicators of quality of care in this population-based cohort were evaluated: the proportion of preoperative radiotherapy (RT) and of abdominoperineal (AP) resection in rectal cancer patients, and the proportion of postoperative in-hospital mortality in colorectal cancer patients. RESULTS: Among rectal cancers, older patients were less likely to have preoperative RT, and more likely to receive an AP resection compared to younger patients. The probability of undergoing preoperative RT and AP resection was reduced in females compared to males (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.64-0.93 and OR 0.78, 95%CI 0.69-0.89, respectively). However, there was a trend of increasing RT over time (p for trend <0.01). The probability of undergoing AP resection was increased in less-educated patients and in hospitals with a low caseload. A higher risk of postoperative in-hospital mortality was found among colorectal cancer patients who were older, male, (female versus male OR 0.71, 95%CI 0.60-0.84), unmarried (OR 1.32, 95%CI 1.09-1.59) or with unknown marital status. CONCLUSIONS: The study provides evidence of the importance of social, clinical and hospital characteristics on the equity and quality of care in a Southern European country with an open-access public health care system