Septic skin lesions: an uncommon manifestation of peripheral prosthetic vascular graft infection

Peripheral prosthetic vascular graft infection following lower limb surgical revascularization is a relatively rare but serious condition. A case of early infection and occlusion of a above-knee femoro-popliteal artery prosthetic bypass is here reported. It was accompanied by acute lower limb ischemia, fever and distally by embolic septic skin lesions

Sustainable management of the vine mealybug in organic vineyards

The vine mealybug (VMB), Planococcus ficus, is a major grapevine pest worldwide, whose chemical control is often unsatisfactory due to its cryptic behavior, insecticide resistance and high fecundity rate. Recently, increasing restrictions have been applied to insecticides used for managing VMB. This review discusses sustainable VMB management strategies in organic viticulture. Pheromone-mediated mating disruption has been proved to be effective in both organic wine and table-grape vineyards. Biocontrol projects carried out through the release of parasitoids and/or predators have often provided inconclusive results, ranging from effective reduction of mealybug infestation to a marginal impact of parasitoids on VMB density. The latter outcome is likely due to constraints affecting the parasitoid activity, such as the disrupting activity of mealybug-tending ants and broad-spectrum insecticides, or untimely release of parasitoids. Ant suppression should be associated with the release of beneficial organisms, as mealybug-tending ants can severely affect the parasitoid activity. Cultural and physical control and the employment of entomopathogens and natural products mitigate the buildup of VMB populations, but they are not widely applied. VMB control in organic viticulture requires the integration of different strategies, as application of single control tools as a stand-alone treatment may not be effective, especially for high pest infestation. Future research to determine the density action threshold below which sustainable methods are effective and calibrate efforts in relation with pest infestation is needed. A multi-disciplinary approach is required to define the most appropriate sustainable control protocols in different environmental conditions and promote a further spread of organic viticulture

Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres

Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previous study, we evaluated the analgesic activity of sumatriptan, an agonist of serotonin 5HT1B/D receptors, and some new chiral bioisosteres, using the hot plate test in the mouse. Interestingly, we observed that the analgesic effectiveness was not necessarily correlated to serotonin agonism. In this study, we evaluated whether sumatriptan and its congeners may inhibit heterologously expressed hNav1.7 sodium channels using the patch-clamp method. We show that sumatriptan blocks hNav1.7 channels only at very high, supratherapeutic concentrations. In contrast, its three analogs, namely 20b, (R)-31b, and (S)-22b, exert a dose and use-dependent sodium channel block. At 0.1 and 10 Hz stimulation frequencies, the most potent compound, (S)-22b, was 4.4 and 1.7 fold more potent than the well-known sodium channel blocker mexiletine. The compound induces a negative shift of voltage dependence of fast inactivation, suggesting higher affinity to the inactivated channel. Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors

Variabilit? genetica in popolazioni di Tortrix viridana L. (Lepidoptera, Tortricidae) associate alle diverse querce della Sardegna

A preliminary analysis of COI and COII gene variability was carried out in Sardinian populations of Tortrix viridana. The aim of the study was to investigate the genetic structure and mitochondrial haplotype variation in populations associated with deciduous (Quercus pubescens) and evergreen (Q. suber and Q ilex) oaks. Forty-four haplotypes out of 87 individuals were found: three haplotypes showed a high frequency (23%, 16% and 10%) and were largely shared among populations. Hierarchical AMOVA showed no significant differentiation grouping populations for geographic areas or oak species, in spite of significant divergences structuring populations for different duration in egg development (early- vs late-hatching). However a high haplotype diversity and a low nucleotide diversity have been observed

A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma

Thalidomide is a drug with interesting therapeutic properties but also with severe side effects which require a careful and monitored use. Potential immunomodulatory, anti-inflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma. Through an increase in the degradation of TNF alpha-mRNA, thalidomide reduces the production of TNF alpha by monocytes and macrophages stimulated by lipopolysaccharide or by T lymphocytes induced by mitogenic stimuli. The decreased level of TNF alpha alters the mechanisms of intracellular transduction by preventing the activation of NF-kB and by decreasing the synthesis of proteins, in particular IL-6, involved in cell proliferation, inflammation, angiogenesis and protection from apoptosis. Furthermore, thalidomide affects VEGF levels by down-regulating its expression. Nowadays, new safer and less toxic drugs, analogs of thalidomide, are emerging as beneficial for a more targeted treatment of multiple myeloma and several other diseases such as Crohn's disease, rheumatoid arthritis, sarcoidosis, erythema nodosum leprosum, graft-versus-host disease

Molecular Insights into the Local Anesthetic Receptor within Voltage-Gated Sodium Channels Using Hydroxylated Analogs of Mexiletine

We previously showed that the β-adrenoceptor modulators, clenbuterol and propranolol, directly blocked voltage-gated sodium channels, whereas salbutamol and nadolol did not (Desaphy et al., 2003), suggesting the presence of two hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for impeding sodium channel block. To verify such an hypothesis, we synthesized five new mexiletine analogs by adding one or two hydroxyl groups to the aryloxy moiety of the sodium channel blocker and tested these compounds on hNav1.4 channels expressed in HEK293 cells. Concentration–response relationships were constructed using 25-ms-long depolarizing pulses at −30 mV applied from an holding potential of −120 mV at 0.1 Hz (tonic block) and 10 Hz (use-dependent block) stimulation frequencies. The half-maximum inhibitory concentrations (IC50) were linearly correlated to drug lipophilicity: the less lipophilic the drug, minor was the block. The same compounds were also tested on F1586C and Y1593C hNav1.4 channel mutants, to gain further information on the molecular interactions of mexiletine with its receptor within the sodium channel pore. In particular, replacement of Phe1586 and Tyr1593 by non-aromatic cysteine residues may help in the understanding of the role of π–π or π–cation interactions in mexiletine binding. Alteration of tonic block suggests that the aryloxy moiety of mexiletine may interact either directly or indirectly with Phe1586 in the closed sodium channel to produce low-affinity binding block, and that this interaction depends on the electrostatic potential of the drug aromatic tail. Alteration of use-dependent block suggests that addition of hydroxyl groups to the aryloxy moiety may modify high-affinity binding of the drug amine terminal to Phe1586 through cooperativity between the two pharmacophores, this effect being mainly related to drug lipophilicity. Mutation of Tyr1593 further impaired such cooperativity. In conclusion, these results confirm our former hypothesis by showing that the presence of hydroxyl groups to the aryloxy moiety of mexiletine greatly reduced sodium channel block, and provide molecular insights into the intimate interaction of local anesthetics with their receptor

The chemistry and pharmacology of citrus limonoids

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detai

Food, flavouring and feed plant traditions in the Tyrrhenian sector of Basilicata, Italy

BACKGROUND: Research was carried out in the years 2002–2003 into food, flavouring and feed folk traditions of plants in the Tyrrhenian part of the Basilicata region (southern Italy). This area was colonized in ancient times by Greeks. Data was collected through field interviews, especially of farmers. METHODS: Field data were collected through structured interviews. The informants, numbered 49, belonged to families which had strong links with the traditional activities of the area. RESULTS: 61 taxa are cited, belonging to 26 botanical families, amongst which 44 used as food or flavouring and 22 for animal alimentation. Besides 7 taxa are involved in rituals especially connected with agriculture and plant growth. CONCLUSION: The preservation of some rituals especially concerning agricultural plants is noteworthy in the area, together with a certain degree of continuity in food uses. Knowledge and rediscovery of recipes in human and animal diet could represent an economic potential for the area