For comparison, the total amount of carbon emitted due to tropical deforestation is estimated to be 1.5 Gt y -1 (or 20% of global anthropogenic emissions 1). ...the potential for emission reductions ...through improved forest management is at least 10% of that obtainable by curbing tropical deforestation. ...substantial occupational health and safety benefits can be achieved from training workers in one of the world's most dangerous professions.
The effects of immunosuppressive drugs on transplant tolerance have not been extensively studied, although their effect on rejection is well established.
We examined the effects of a short course of ...treatment with the immunosuppressive drug methylprednisolone (MP) on the survival of PVG liver allografts in Dark Agouti (DA) recipients that accepted the livers and in Lewis recipients that rejected the livers. Infiltration of liver allografts was examined by immunohistochemical staining of liver sections, and apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling.
A 5-day course of MP (days 0 to 4) led to rejection of four of six livers (mean survival time MST 99 days) in DA recipients compared with long-term survival (MST >100 days) in untreated animals. Delayed administration of MP (days 3 to 7) exacerbated rejection in DA recipients, and all eight animals rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not significantly prolong survival when administered from days 0 to 4 (MST 13 days), although delay of administration improved the outcome. Treatment from days 3 to 7 resulted in an MST of 21 days, whereas treatment from days 7 to 11 resulted in an MST of 41.5 days. MP treatment from day 3 to day 7 reduced T cells and interleukin 2 receptor-expressing cells but increased the numbers of apoptotic cells infiltrating both DA and Lewis strain allografts.
These results show that immunosuppression with MP inhibits both spontaneous tolerance and rejection of liver allografts in a rat model and question the efficacy of administering MP to all liver allograft recipients from the time of transplantation.
Though often perceived as an environmentally-risky practice, biological control of invasive species can restore crop yields, ease land pressure and thus contribute to forest conservation. Here, we ...show how biological control against the mealybug
(Hemiptera) slows deforestation across Southeast Asia. In Thailand, this newly-arrived mealybug caused an 18% decline in cassava yields over 2009-2010 and an escalation in prices of cassava products. This spurred an expansion of cassava cropping in neighboring countries from 713,000 ha in 2009 to > 1 million ha by 2011: satellite imagery reveals 388%, 330%, 185% and 608% increases in peak deforestation rates in Cambodia, Lao PDR, Myanmar and Vietnam focused in cassava crop expansion areas. Following release of the host-specific parasitoid
(Hymenoptera) in 2010, mealybug outbreaks were reduced, cropping area contracted and deforestation slowed by 31-95% in individual countries. Hence, when judiciously implemented, insect biological control can deliver substantial environmental benefits.
Fully allogeneic liver grafts from piebald virol glaxo to dark agouti rats are spontaneously tolerated, whereas kidney transplants between these strains are rejected. Liver tolerance is broken by ...donor irradiation or peritransplant corticosteroid treatment of recipient rats, both of which interfere with the activation of recipient cells.
In this study we used a combination of immunohistochemical staining, reverse transcription-polymerase chain reaction, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling and Annexin-V apoptosis assays to compare donor cell migration, cytokine profiles, and leukocyte apoptosis in grafts and lymphoid organs from tolerant liver and rejecting kidney recipients. We then examined the effect on apoptosis of treatments which abrogate liver tolerance.
Liver transplantation in this tolerant strain combination is accompanied by rapid migration of many passenger leukocytes to the recipient spleen and lymph node, concurrent with a marked but transient increase in the amount of mRNA for the cytokines interleukin-2 and interferon-gamma. Apoptotic cells appear promptly in the spleen, their numbers reaching a peak 2 days earlier than has been previously shown for the graft infiltrate. Both CD4+ and CD8+ T cells undergo apoptosis and apoptotic cells are most concentrated among CD25+ T cells. In contrast, renal transplant rejection is associated with limited donor cell migration to lymphoid tissues and significantly less up-regulation of interleukin-2 and interferon-gamma in the spleen. Few apoptotic cells are detected in spleen or graft infiltrate during rejection, whereas apoptotic renal tubular and glomerular cells are found from day 5. Either recipient steroid treatment or donor irradiation significantly reduced the number of apoptotic cells in liver graft infiltrates and recipient spleen.
Taken together, these findings suggest that a mechanism akin to activation-induced cell death, with apoptosis of alloreactive recipient cells may be responsible for the induction of spontaneous liver transplant tolerance.
Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for ...prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant–associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low‐dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow‐up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure–related deaths in this group. In group 3 patients, there was one death from graft‐versus‐host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low‐dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.
Liver transplants in rodents or pigs are often spontaneously accepted across a complete MHC mismatch. They induce tolerance to grafts of other organs or skin of liver donor strain and can even ...suppress ongoing rejection of heart grafts. It has not been established whether liver-induced tolerance is due to components of the liver or to passenger leukocytes within the liver. We depleted populations of passenger leukocytes from the transplanted liver by irradiation of the donor with 10 Gy, followed after 7 days by transplantation of the liver. Recipients of livers from irradiated donors had a median survival of 16 days compared with > 100 days for recipients of livers from normal donors. Examination of recipients of irradiated donor livers showed that allograft rejection was the cause of death. Syngeneic transplants of irradiated PVG donor to PVG recipient or of irradiated DA donor to DA recipient survived indefinitely. Parking of livers from irradiated PVG donors in normal PVG animals for 36 hr reconstituted tolerance when the livers were retransplanted to DA recipients. Livers from irradiated donors had greatly reduced passenger leukocyte numbers compared with normal or parked livers, with virtually complete loss of lymphocytes. These results show that spontaneous liver allograft acceptance is associated with populations of passenger leukocytes that are depleted by donor irradiation.
The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously ...tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.
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