Curcumin-based photosensitization inactivates Aspergillus flavus and reduces aflatoxin B1 in maize kernels.

Different methods have been applied in controlling contamination of foods and feeds by the carcinogenic fungal toxin, aflatoxin, but nevertheless the problem remains pervasive in developing countries. Curcumin is a natural polyphenolic compound from the spice turmeric (Curcuma longa L.) that has been identified as an efficient photosensitiser for inactivation of Aspergillus flavus conidia. Curcumin mediated photoinactivation of A. flavus has revealed the potential of this technology to be an effective method for reducing population density of the aflatoxin-producing fungus in foods. This study demonstrates the influence of pH and temperature on efficiency of photoinactivation of the fungus and how treating spore-contaminated maize kernels affects aflatoxin production. The results show the efficiency of curcumin mediated photoinactivation of fungal conidia and hyphae were not affected by temperatures between 15 and 35 °C or pH range of 1.5-9.0. The production of aflatoxin B1 was significantly lower (p < 0.05), with an average of 82.4 µg/kg as compared to up to 305.9 µg/kg observed in untreated maize kept under similar conditions. The results of this study indicate that curcumin mediated photosensitization can potentially be applied under simple environmental conditions to achieve significant reduction of post-harvest contamination of aflatoxin B1 in maize.

AAV9-mediated engineering of autotransplanted kidney of non-human primates.

Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the AAV9 capsid in 16 non-human primate tested sera. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an autotransplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. Results in non-human primates represent a step forward in maintaining the portability of this strategy into clinics.

Complement Alternative Pathway Deficiency in Recipients Protects Kidney Allograft From Ischemia/Reperfusion Injury and Alloreactive T Cell Response.

Despite the introduction of novel and more targeted immunosuppressive drugs, the long-term survival of kidney transplants has not improved satisfactorily. Early antigen-independent intragraft inflammation plays a critical role in the initiation of the alloimmune response and impacts long-term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive antigraft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we speculated whether selective blockade of AP could be a strategy for prolonging kidney graft survival. Here we showed that Balb/c kidneys transplanted in factor b deficient C57 mice underwent reduced IRI and diminished T cell-mediated rejection. In in vitro studies, we found that fb deficiency in T cells and dendritic cells conferred intrinsic impaired alloreactive/allostimulatory functions, respectively, both in direct and indirect pathways of alloantigen presentation. By administering anti-fB antibody to C57 wt recipients in the early post Balb/c kidney transplant phases, we documented that inhibition of AP during both ischemia/reperfusion and early adaptive immune response is necessary for prolonging graft survival. These findings may have implication for the use of AP inhibitors in clinical kidney transplantation.

Local gene therapy with indoleamine 2,3-dioxygenase protects against development of transplant vasculopathy in chronic kidney transplant dysfunction.

Chronic transplant dysfunction (CTD) is the primary cause of late allograft loss in kidney transplantation. Indoleamine 2,3-dioxygenase (IDO) is involved in fetomaternal tolerance and IDO gene therapy inhibits acute rejection following kidney transplantation. The aim of this study is to investigate whether gene therapy with IDO is able to attenuate CTD. Transplantation was performed in a rat Dark-Agouti to Wistar-Furth CTD model. Donor kidneys were incubated either with an adenovirus carrying IDO gene, a control adenovirus or saline. During the first 10 days recipients received low-dose cyclosporine. Body weight, blood pressure, serum creatinine and proteinuria were measured every 2 weeks. Rats were killed after 12 weeks. IDO had a striking beneficial effect on transplant vasculopathy at week 12. It also significantly improved body weight gain; it reduced blood pressure and decreased proteinuria during the follow-up. However, it did not affect the kidney function. In addition, IDO therapy significantly decreased the number of graft-infiltrating macrophages at week 12. The messenger RNA levels of forkhead box p3 and transforming grow factor-ß were elevated in the IDO treated group at week 12. Here we show for first time a clear beneficial effect of local IDO gene therapy especially on transplant vasculopathy in a rat model of renal CTD.

An unanticipated role for survivin in organ transplant damage.

Ischemia/reperfusion (I/R) injury is a major determinant of graft survival in kidney transplantation. Survivin, an inhibitor of apoptosis that participates in the control of mitosis and cell cycle progression, has been implicated in renal protection and repair after I/R injury; however, no study has been performed in the transplant setting. We investigated the role of survivin in modulating posttransplant I/R injury in syngeneic and allogeneic kidney grafts, and studied whether protection from I/R injury impacted on the recipient immune system, on chronic allograft nephropathy and rejection. We used genetically engineered mice with survivin haploinsufficiency and WT mice in which survivin over-expression was induced by gene-delivery. Survivin haploinsufficiency in syngeneic grafts was associated with exuberant I/R tissue injury, which triggered inflammation eventually resulting in graft loss. Conversely, survivin over-expression in the grafts minimized I/R injury and dysfunction in syngeneic grafts and in a clinically relevant fully MHC-mismatched allogeneic combination. In the latter, survivin over-expression translated into limited anti-donor adaptive immune response and less long-term allograft injury with protection from renal parenchymal damage. Our data support survivin over-expression in the graft as a novel target for protocols aimed at limiting tissue damage at the time of transplant ultimately modulating the recipient immune system.

The impact of perioperative transfusion of blood products on survival after pediatric liver transplantation.

Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after LT in adult patients. This relationship in pediatric patients has not been studied in depth, and its analysis is the scope of this study. Forty-one variables associated with outcome, including blood product transfusions, were studied in a cohort of 243 pediatric patients undergoing a cadaveric LT between 2002 and 2009 at the General Hospital of Bergamo. Multivariate stepwise Cox proportional hazards models were adopted with adjustment by propensity scores to minimize factors associated with the use of blood products. Median age at transplant was 1.37 yr. In uni- and multivariate analyses, perioperative transfusion of FFP and RBC was an independent risk factor for predicting one-yr patient and graft survival. The effect on one-yr survival was dose-related with a hazard ratio of 3.15 for three or more units of RBC (p = 0.033) and 3.35 for three or more units of FFP (p = 0.021) when compared with 1 or no units transfused. The negative impact of RBC and FFP transfusion was confirmed by propensity score-adjusted analysis. These findings may have important implications for transfusion practice in the LT pediatric recipients.

Dietary risk assessment of selected organophosphorus and pyrethoid pesticide residues in fresh harvested tomatoes at Makambako Town, Njombe region, Tanzania.

This study aimed to assess the levels of selected pesticides residues in harvested tomatoes and their associated dietary risks to consumers at Makambako Town in Njombe region, Tanzania. Forty-two fresh tomatoes were sampled among tomato farmers during harvesting season and extraction of analytes was done using QuEChERS method and analysed by Gas Chromatography-Mass Spectrometer. Residues of chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin were alternatingly detected in 78.51% of samples. The average concentrations of residues were 0.014, 0.056, 0.003 and 0.2 mg/kg for chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin and were all below their respective Codex MRLs. The highest concentration was 0.718 mg/kg for cypermethrin, above the Codex MRL of 0.2 mg/kg. The hazard indexes indicate no potential health hazards to the general population due to the lifetime consumption of fresh tomatoes from the study area. Periodic monitoring of residue levels of pesticides in vegetable fruits, including tomatoes, is recommended.

The Influence of Weather on the Occurrence of Aflatoxin B1 in Harvested Maize from Kenya and Tanzania.

A study was conducted using maize samples collected from different agroecological zones of Kenya (n = 471) and Tanzania (n = 100) during the 2013 maize harvest season to estimate a relationship between aflatoxin B1 concentration and occurrence with weather conditions during the growing season. The toxins were analysed by the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Aflatoxin B1 incidence ranged between 0-100% of samples in different regions with an average value of 29.4% and aflatoxin concentrations of up to 6075 µg/kg recorded in one sample. Several regression techniques were explored. Random forests achieved the highest overall accuracy of 80%, while the accuracy of a logistic regression model was 65%. Low rainfall occurring during the early stage of the maize plant maturing combined with high temperatures leading up to full maturity provide warning signs of aflatoxin contamination. Risk maps for the two countries for the 2013 season were generated using both random forests and logistic regression models.

Thromboxane A2 receptor blocking abrogates donor-specific unresponsiveness to renal allografts induced by thymic recognition of major histocompatibility allopeptides.

Recent in vitro studies have documented that thromboxane (Tx)A2 induces thymocyte apoptosis by acting on specific receptors abundantly expressed on the surface of immature T lymphocytes. No information is available on the in vivo relevance of this observation in development of self- or acquired tolerance. We and others have previously documented that injection of donor cells into adult thymus of experimental animals induced specific systemic unresponsiveness to allografts in the rat and mouse models. More recently, we have shown that intrathymic injection of synthetic class II major histocompatibility complex (MHC) allopeptides resulted in donor-specific unresponsiveness to renal allografts. The induction of unresponsiveness was abrogated by recipient thymectomy within the first week. We now report the effect of TxA2 blockade on acquired thymic tolerance to renal allografts induced by intrathymic injection of synthetic class II MHC allopeptides in the Wistar-Furth (WF) to Lewis rat strain combination. Administration of the TxA2 receptor blocker prior to transplantation or 2 wk postengraftment completely abrogated the unresponsive state. In addition, inhibiting the TxA2-forming enzyme by aspirin or dexamethasone also abolished the induction of acquired thymic tolerance. Evidence is also provided for a critical "dose" of peptides to be injected into the thymus to induce systemic unresponsiveness to renal allografts. These data, coupled with observations that activated peripheral T cells can circulate through the thymus, provide evidence that TxA2/TxA2 receptor interaction in the thymic microenvironment, leading to anergy/programmed cell death of activated T cells, may play an important role in the development of acquired unresponsiveness in vivo.

Adenoviral-mediated gene transfer restores plasma ADAMTS13 antigen and activity in ADAMTS13 knockout mice.

ADAMTS13 is a plasma metalloprotease that regulates the size of the von Willebrand factor (VWF) multimers. Genetic or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP) in humans. Plasma infusion is the treatment of choice for patients with congenital ADAMTS13 deficiency. However, this practice exposes patients to the risk of infections, allergies and fluid volume overload. The search for alternative treatments is required. Here, we tested the ability of systemically administered adenovirus encoding human ADAMTS13 to restore the deficient protein in the circulation of Adamts13(-/-) mice. Injection of the adenovirus efficiently transduced the liver, kidney, lung, heart and spleen, resulting in the secretion of ADAMTS13 into plasma. A reduced area of thrombi was observed when blood from Ad-ADAMTS13-treated mice was perfused over a collagen-coated surface in a parallel plate flow chamber compared with blood of Ad-betaGal-treated controls. The secreted ADAMTS13 protein was functionally active even after 2 months from injection. The data provide the proof of principle for developing a novel therapy for the correction of ADAMTS13 deficiency in patients with hereditary TTP.

Endothelin receptor selectivity in chronic renal failure.

Chronic kidney diseases are increasing worldwide at an alarming rate, and they are emerging as a major public health problem. Treatments that slow the progression of chronic kidney disease are needed. Endothelin-1 (ET-1) is a potent vasoconstrictor with proinflammatory, mitogenic and profibrotic effects that is closely involved in both normal renal physiology and pathology. Increasing evidence suggests that ET-1 and its cognate receptors are involved in a variety of progressive renal disorders to the extent that renal ET-1 expression correlates with disease severity and renal function impairment. Endothelin receptor antagonists have been used in renoprotection studies owing to their capacity of improving renal hemodynamics and reducing proteinuria. Whether selective ET(A) or non-selective ET(A)/ET(B) receptor antagonists are preferable is still a matter of debate. As angiotensin II blockers are not invariably effective in retarding disease progression when treatment is started late in the course of the disease, it is foreseeable that an ET-1 antagonist in addition to angiotensin-converting enzyme inhibitors could represent a combined treatment for progressive nephropathies. The focus of this review is to examine the role endothelin-1 plays in kidney diseases and to determine the ideal setting for antagonizing its biological activity in chronic nephropathies.

The use of desflurane or propofol in combination with remifentanil in myasthenic patients undergoing a video-assisted thoracoscopic-extended thymectomy.

BACKGROUND: Although several studies of the use of desflurane in anesthesia have revealed many desirable qualities, there are no data on the use and effects especially on the neuromuscular function of desflurane on myasthenia gravis (MG) patients. The purpose of this study was to evaluate the use of either desflurane or propofol, both combined with remifentanil, in patients with MG undergoing a video-assisted thoracoscopic-extended thymectomy (VATET). METHODS: Thirty-six MG patients who underwent VATET were enrolled. Nineteen patients were anesthetized with remifentanil and propofol infused with a target-controlled infusion plasma model, and 17 patients with desflurane and remifentanil. No muscle relaxant was used. The intubating conditions, hemodynamic and respiratory changes, neuromuscular transmission and post-operative complications were evaluated. RESULTS: Neuromuscular transmission was significantly decreased in the desflurane group (6.7%, from 3% to 9% during anesthesia P=or<0.05). The intubating conditions were good in all 36 patients and 35 patients were successfully extubated in the operating room. The time-to-awakening, post-operatory pH and base excess were significantly different in the two groups, with a decreasing mean arterial pressure in the group administered with desflurane. No patients required reintubation due to myasthenic or cholinergic crisis, or respiratory failure. No other significant differences between the two groups studied were observed. CONCLUSION: Our experience indicates that anesthesia with desflurane plus remifentanil in patients with MG could determine a reversible muscle relaxation effect, but with no clinical implication, allowing a faster recovery with no difference in extubation time and post-operative complications in the two groups.

Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclooxygenase defect.

A qualitative platelet abnormality and a bleeding tendency are frequently associated with renal failure and uremia. We demonstrated previously that uremic patients display an abnormal platelet aggregation to arachidonic acid and reduced malondialdehyde production in response to thrombin and arachidonic acid. The objectives of this investigation were: (a) to compare platelet prostaglandin (PG) and thromboxane (TX) production in whole blood and in platelet-rich plasma (PRP) of 21 uremic patients and 22 healthy subjects; (b) to evaluate the concentration and activity of platelet PG- and TX-forming enzymes; (c) to assess the functional responsiveness of the platelet TXA(2)/PGH(2) receptor; (d) to explore the hemostatic consequences of partially reduced TXA(2) production.Platelet immunoreactive TXB(2) production during whole blood clotting was significantly reduced, by approximately 60%, in uremic patients as compared to age- and sex-matched controls. Exogenous thrombin (5-30 IU/ml) failed to restore normal TXB(2) production in uremic platelets. Uremic PRP produced comparable or slightly higher amounts of TXB(2) than normal PRP at arachidonate concentrations 0.25-1 mM. However, when exposed to substrate concentrations >2 mM, uremic PRP produced significantly less TXB(2) than normal PRP. To discriminate between reduced arachidonic acid oxygenation and altered endoperoxide metabolism, the time course of immunoreactive TXB(2) and PGE(2) production was measured during whole blood clotting. The synthesis and release of both cyclooxygenase-derived products was slower and significantly reduced, at all time intervals considered. Furthermore, PGI(2) production in whole blood, as reflected by serum immunoreactive 6-keto-PGF(1alpha) concentrations, was significantly reduced in uremic patients as compared with healthy subjects. PGH synthase levels, as determined by an immunoradiometric assay, were not significantly different in platelets from uremic patients as compared to control platelets. A single 40-mg dose of aspirin given to five healthy volunteers reduced their serum TXB(2) to levels found in uremic patients. This was associated with a significant increase of threshold aggregating concentrations of ADP and arachidonic acid and prolongation of bleeding time. Substantially similar threshold concentrations of U46619, a TXA(2) agonist, induced aggregation of normal and uremic platelets. Prostacyclin induced a significant elevation of uremic platelet cyclic AMP, which was suppressed by U46619, further suggesting normal responsiveness of the TXA(2)/PGH(2) receptor. WE CONCLUDE THAT: (a) an abnormality of platelet arachidonic acid metabolism exists in uremia, leading to a reduced TXA(2) production; (b) the characteristics of this abnormality are consistent with a functional cyclooxygenase defect; (c) reduced TXA(2) production may partially explain the previously described abnormality of platelet function in uremia.

Tools for Defusing a Major Global Food and Feed Safety Risk: Nonbiological Postharvest Procedures To Decontaminate Mycotoxins in Foods and Feeds.

Mycotoxin contamination of foods and animal feeds is a worldwide problem for human and animal health. Controlling mycotoxin contamination has drawn the attention of scientists and other food and feed stakeholders all over the world. Despite best efforts targeting field and storage preventive measures, environmental conditions can still lead to mycotoxin contamination. This raises a need for developing decontamination methods to inactivate or remove the toxins from contaminated products. At present, decontamination methods applied include an array of both biological and nonbiological methods. The targeted use of nonbiological methods spans from the latter half of last century, when ammoniation and ozonation were first used to inactivate mycotoxins in animal feeds, to the novel techniques being developed today such as photosensitization. Effectiveness and drawbacks of different nonbiological methods have been reported in the literature, and this review examines the utility of these methods in addressing food safety. Particular consideration is given to the application of such methods in the developing world, where mycotoxin contamination is a serious food safety issue in staple crops such as maize and rice.

Metabolism of arachidonic acid in isolated glomeruli from pig kidney.

Arachidonic acid metabolism in isolated glomeruli from pig kidney was investigated. Arachidonic acid metabolism via cyclooxygenase was studied by three different methodological approaches: radioimmunoassay (RIA), high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). By all these techniques, the major prostaglandins (PG) formed by pig glomeruli appeared to be 6-keto-PGF1 alpha and PGF2 alpha, the former being the most abundant. RIA and GC-MS also detected lower amounts of thromboxane B2 (TxB2) and PGE2. This emphasises the similarity with human glomeruli, in which the main cyclooxygenase product has indeed been reported to be 6-keto-PGF1 alpha. The lipoxygenase activity in isolated pig glomeruli, as studied by HPLC, generated 15-HETE, 12-HETE and 5-HETE. These data demonstrate that isolated glomeruli from pig kidney possess cyclooxygenase as well as lipoxygenase activity. Since a marked functional similarity exists between human and pig kidney, the pig can be regarded as a good model for studying the influence of arachidonic acid metabolites on glomerular pathophysiology.

Metabolism of thromboxane B2 in the isolated perfused rat kidney: mass spectrometric identification of urinary products.

The metabolism of thromboxane B2 (TXB2), the stable breakdown product of thromboxane A2, has been studied in isolated perfused kidney preparations using a recirculating system. In a first experiment, TXB2 was infused at a rate of 20 micrograms/kg per min. In a second experiment, a 1:1 mixture of TXB2 and octadeuterated TXB2 (0.4 microgram/kg per min each) was infused. Urinary samples collected during the infusion of TXB2 or vehicle were extracted on C18 cartridges and derivatized to methyl or pentafluorobenzyl ester, methyloxime, trimethylsilyl ether. Samples were analyzed by high-resolution gas chromatography-mass spectrometry in the electron impact and negative ion chemical ionization modes. Products of beta-oxidation, reduction of the delta 5,6 double bond and dehydrogenation at C-11 (2,3-dinor-TXB2, 2,3-dinor-TXB1, 2,3,4,5-tetranor-TXB1 and 11-dehydro-TXB2) were identified in addition to unmetabolized TXB2. 2,3,4,5-tetranor-TXB1 and 2,3-dinor-TXB1 were the most abundant metabolites.

Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.

Chronic nephropathies are associated with enhanced renal synthesis of endothelin (ET)-1. A recent study demonstrated that an ET(A) receptor antagonist given to diabetic rats at the moment of disease induction prevented the development of renal injury. Here we investigated whether an unselective ET(A)/ET(B) receptor antagonist, PD 142,893, was renoprotective when given to streptozotocin diabetic rats when animals were already proteinuric. The effect of PD 142,893 was compared with that of an ACE inhibitor, lisinopril, known to retard progressive renal disease in experimental and human diabetes. PD 142,893 normalized systemic blood pressure, reduced urinary protein and albumin excretion, and ameliorated renal blood flow in diabetic rats, but it did not affect such parameters in control rats. Lisinopril had a renoprotective effect comparable to PD 142,893, although lisinopril controlled systemic blood pressure better. Northern blot analysis of ET-1 mRNA revealed upregulation of ET-1 gene in the diabetic kidney. Similar results were obtained by in situ hybridization in glomeruli and tubuli of diabetic rats. Both treatments remarkably attenuated exaggerated renal ET-1 gene expression. These data suggest that ET-1 is a contributory mediator of kidney damage in diabetes and indicate that ET receptor antagonists may represent a new therapeutic mean for treatment of progressive diabetic nephropathy.

Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats.

The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6-8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P less than 0.01) in hyperglycemic diabetic (72.9 +/- 11.7 pg/ml) than in normoglycemic diabetic (44.8 +/- 8.6 pg/ml) or nondiabetic (40.0 +/- 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P less than 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 +/- 0.06-1.02 +/- 0.04; 2.87 +/- 0.25-2.40 +/- 0.10 ml.min-1.100 g-1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 +/- 0.07; RPF 2.27 +/- 0.13 ml.min-1.100 g-1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto-prostaglandin F1 alpha (220.6 +/- 62.8 ng/24 h) compared with nondiabetic rats (51.2 +/- 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 +/- 0.07 to 1.06 +/- 0.07 ml.min-1.100 g-1, P less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 +/- 0.05 to 0.88 +/- 0.05 and 2.84 +/- 0.10 to 2.22 +/- 0.06 ml.min-1.100 g-1, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. MATERIAL AND METHODS: Pre-, Intra- and Post-operative data were collected. Tumor necrosis factor (TNF), interleukine 6, procalcitonine (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. RESULTS: Thirty-eight patients included, 29 (76.3%) female. Mean/median PCI: 9.2/5. Primary malignancy: 5 colo-rectal (13.2%), 5 gastric (13.2%), 23 ovarian (60.5%) and 5 others (13.2%). CCR 0-1 reached in all patients. Cardiac Index, Heart rate and Central Venous Pressure, increased during the procedure while Stroke Volume Variation showed a decrease. Mean Arterial Pressure and Superior Vena Cava Oxygenation were stable through the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (p<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (p<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. CONCLUSION: The most significant variations are those of IL-6 and PCT. The cytokines level parallel the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock.