Xenotransplantation in the 21st century.

Xenotransplantation, i.e. transplantation across species, is increasingly being viewed a potential solution to the problem of severe shortage of transplant donors. Clinical application of xenotransplantation is, however, limited in large part by the pre-eminent hurdle of the immune response of the recipient against the graft. This immunologic reaction is mediated initially by natural xenoreactive antibodies, complement and natural killer cells, and later by elicited humoral and cellular immune responses that ultimately lead to graft failure. Progress in understanding the cellular and molecular basis of xenograft rejection has characterized the past few years. Additional hurdles to xenotransplantation include physiologic incompatibility of the transplant and the risk of infections. The recent development of novel strategies to overcome xenograft rejection has brought about great optimism that xenotransplantation may be attainable in the near future.     

µ1‐Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post‐ictal antinociception

Generalised tonic and tonic–clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ₁‐opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post‐ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA‐mediated Cl^? influx antagonist, was intraperitoneally (IP) administered to induce tonic–clonic seizures in Wistar rats. The tail‐flick test was used to measure the nociceptive threshold. Microinjections of naltrexone (5.0 µg/0.2 µL), which is a non‐selective opioid receptor antagonist, in both dmPAG and vlPAG decreased the tonic–clonic seizure‐induced antinociception in seizing animals from 10 to 120 min after seizures. Furthermore, microinjections of the µ₁‐opioid receptor‐selective antagonist naloxonazine (5.0 µg/0.2 µL) into the dmPAG decreased post‐ictal antinociception immediately after convulsive reactions and from 10 to 90 min after seizures. However, vlPAG‐pretreatment with naloxonazine at the same concentration decreased the post‐ictal antinociception 30 min after the onset of tonic–clonic seizures and the nociceptive threshold returned to basal values 120 min after seizures. These findings indicate that µ₁‐opioid receptor‐signalling mechanisms in both dmPAG and vlPAG play a relevant role in the organisation of post‐ictal antinociception. In addition, µ₁‐opioid receptors in the dmPAG rather than in vlPAG seem to be more critically recruited during the antinociception induced by generalised tonic–clonic seizures.     

Poisoning by organophosphate insecticides. Epidemiology and prevention

In an agrarian environment, exposure to anticholinesterasic insecticides is a potential health problem. Acute or chronic intoxication may cause serious health problems due to its frequency or its severity. Extremadura is, as are other Spanish autonomous regions, mainly a rural environment which means that this problems carries special relevance there. In this article, the authors evaluate the number of cases of intoxication, the validity of the measures taken, and they describe the pedagogical programs which exist dealing with this problem. They review the physiopathological causes of this intoxication, its symptoms and its treatment. The authors reveal the results obtained from a questionnaire given to a group of Extremaduran farmers. Furthermore, the authors provide information to health professionals responsible for the treatment and prevention of this intoxication; the authors consider health education, especially in an agrarian environment, to be one of the most important action plans in order to prevent this intoxication and to reduce its mortality and chronic manifestations due to exposure to these agents.     

The Neuroprotective Effect of Erythropoietin in Docetaxel-Induced Peripheral Neuropathy Causes No Reduction of Antitumor Activity in 13762 Adenocarcinoma-Bearing Rats

Taxanes, including docetaxel (DOCE), are severely neurotoxic, causing disabling peripheral neuropathy. Co-treatment with neuroprotective agents has been proposed to prevent or reverse this. Besides its hemopoietic effects, erythropoietin (EPO) has neuroprotective and neurotrophic properties and when administered systemically it has a wide range of neuroprotective action in animal models of nervous system damage, including cisplatin-induced peripheral neurotoxicity. The present study investigated the effects of EPO on chemotherapy-induced peripheral neurotoxicity (CINP) by DOCE in vivo and whether it interfered with tumor growth or antitumor activity. Female Fischer rats bearing 13762 mammary carcinoma were randomly divided into four groups: untreated, treated with EPO, DOCE, or DOCE + EPO. DOCE was given once a week (5 mg/kg, i.v.) and EPO three times a week (50 μg/kg i.p.), for 4 weeks. Three other groups of rats without tumors were left untreated or given DOCE or DOCE + EPO. The rats were observed for 4 weeks after treatment. CINP and neuroprotection were evaluated by measuring nociception, electrophysiological, and biochemical parameters. EPO protected against CINP, and tumor growth in EPO-treated rats was the same as in controls. EPO significantly improved the thermal threshold, tail nerve conduction velocity, and intra-epidermal nerve fiber density. These benefits lasted through the follow-up period and EPO speeded-up spontaneous recovery after treatment withdrawal. EPO did not impair DOCE antitumor activity. Since CINP induced by DOCE reproduces the clinical utility of taxane in humans, the findings reported might provide a basis for investigating EPO as a neuroprotective agent in patients receiving therapy with DOCE.