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Highlights: [•] Effect of early diagenetic marine influence on oil potential of coals studied. [•] Total S content is a sensitive indicator of marine influence in coaly rocks. [•] Marine influence preserves H content and total oil potential of coaly rocks. [•] Cutinite controls the paraffinic oil generative potential of the coals. [•] Marine influence facilitates expulsion of paraffinic oil from coaly source rocks. [Copyright &y& Elsevier]

Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progres- sively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal era- nial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid Pulse Pressure timing. [ABSTRACT FROM AUTHOR]

Abstract: It remains arguable if an animal model can be of use in pre-eclampsia (PE) studies, as it is clearly a human disease not observed spontaneously in other species. The aim of this study was to investigate whether PE-like signs in mice inoculated with activated Th1 cells were accompanied by abnormal expression of molecules related to the regulation of blood pressure, viz. nitric oxide synthase enzymes (eNOS and iNOS) and angiotensin (Ang) II receptors (AT1R and AT2R), in order to analyse the relevance of this model for human disease. In this model, C57/BL6-mated BALB/c females received lymphocytes crosslined with anti-CD3 and cultured with interleukin (IL)-2 and IL-12 to mimic PE pathology. Control mice received PBS. eNOS, iNOS and AT1R but not AT2R expression was augmented in the kidneys of PE-mice compared with control pregnant mice. The expression of eNOS but not of iNOS was augmented at the fetal–maternal interface of PE-mice as compared with the controls. NOSs regulate the synthesis of NO, a blood pressure and parturition mediator. As its expression is increased in PE patients, our data suggest that the Th1 cells-induced signs in this model are due to similar mechanisms as in humans. AT1R and AT2R mediate the effect of Ang II, and particularly the AT1R appears to be involved in the pathogenesis of human PE. The increased AT1R expression in the kidneys of PE-mice reinforces the theory that Th1 cells elicit a pathological situation closely resembling the human PE. All together, our data support the use of this animal model to study mechanisms underlying clinically overt PE. [Copyright &y& Elsevier]

Abstract: Geochemical analyses of the fuel used for the motor driven sledges used by the explorer Robert Falcon Scott for his 1911/1912 quest to the South Pole indicate that it is a straight run gasoline. The presence of bicadinanes, oleanane and other oleanoid angiosperm markers indicate that the feedstock oil was likely to have been sourced from terrestrial source rocks of Tertiary age in the South East Asian region. The overall chemical composition of the fuel in its present state indicates that it may have been too heavy for usage in polar regions. [Copyright &y& Elsevier]

The ca. 1280 Ma dolerite sill within the Mesoproterozoic Roper Group in the Roper Superbasin, Australia, contains evidence for at least two episodes of hydrocarbon migration represented, respectively, by solid bitumen with a ketone-rich extract, and a mixture of a high maturity gas-condensate and a lower maturity oil within oil-bearing fluid inclusions. The ketone isomers are formed by flash pyrolysis of kerogen during the intrusion of the dolerite sill [Org. Geochem. 21 (1994) 829] and represent the first and oldest phase of hydrocarbon migration. The gas condensate and oil were subsequently trapped as a mixture within fluid inclusions at diagenetic temperatures and pressures of around 110 °C and 250 bars, significantly after cooling of the sill and likely during the Neoproterozoic reactivation of the Roper Superbasin. Either (1) these fluids migrated together and mixed in the reservoir or (2) an earlier oil charge was flushed by a later condensate charge and the oil-condensate mixture was trapped within single fluid inclusions. Oil inclusions occur chiefly within albitised zones of labradorite laths within the dolerite matrix, and within transcrystalline microfractures cutting vein calcite and rarely vein quartz. Oil inclusions trapped in the vein calcite are accompanied by hypersaline Ca/Mg brines. Gas chromatography–mass spectrometry of oil extracted from inclusions within the dolerite matrix shows that the oil is non-biodegraded and was therefore trapped relatively quickly within the host minerals. Trace amounts of biomarkers indicate that the inclusion oil is of a biogenic origin and excludes any abiotic processes that are apparent sources of hydrocarbons in many crystalline rocks. Monomethylalkanes, pentacyclic terpanes chiefly comprising hopanes and diahopanes, and very low concentrations of steranes and diasteranes indicate input from cyanobacterial organic matter with a minor contribution from eukaryotes. The hydrocarbons are likely derived from Proterozoic source rocks such as the directly overlying Velkerri Formation and/or the underlying Barney Creek Formation from the McArthur Group. The study has implications for the source of hydrocarbons in non-sedimentary rocks and suggests that fluid inclusions can be used not only to distinguish between biogenic and abiogenic sources of hydrocarbons but also to provide critical information about the composition of the biomass, fluid migration events, and conditions under which hydrocarbons in different geological settings are trapped. [Copyright &y& Elsevier]

In the brain, the efflux transporter P-glycoprotein (Pgp) is predominantly located on the luminal membrane of endothelial cells lining brain microvessels and forming the blood–brain barrier. Many lipophilic drugs, including antiepileptic drugs, are potential substrates for Pgp. Overexpression of Pgp in endothelial cells of the blood–brain barrier has been determined in patients with drug resistant forms of epilepsy such as temporal lobe epilepsy and rodent models of temporal lobe epilepsy and suggested to lead to reduced penetration of antiepileptic drugs into the brain. Expression of Pgp after seizures has also been described in astrocytes, whereas it is not clear whether neurons can express Pgp. In the present study, Pgp expression was studied by immunohistochemistry in rats 24 h after a status epilepticus induced by either pilocarpine or kainate, widely used models of temporal lobe epilepsy. Unexpectedly, in addition to endothelial Pgp staining, intense Pgp staining was found in neurons in the CA3c/CA4 sectors and hilus of the hippocampus formation, but not in other brain regions examined. The neuronal Pgp staining was confirmed by two different Pgp antibodies. Double immunolabeling and confocal microscopy showed that Pgp was colocalized with the neuronal marker neuronal nuclear antigen, but not with the glial marker glial fibrillary acidic protein. No neuronal Pgp staining was seen in control rats. The expression of Pgp in neurons after limbic seizures was substantiated by determining Pgp encoding genes (mdr1a, mdr1b) in neurons by real time quantitative RT-PCR. Increased Pgp expression in hippocampal neurons is likely to affect the action of drugs with intraneuronal targets and, in view of recent evidence from other cell types, could be associated with prevention of apoptosis which is involved in neuronal damage developing after seizures such as produced by pilocarpine. [Copyright &y& Elsevier]

The author discusses a report by Harcourt-Brown on the consequences of otitis media with effusion (OME) on hearing in Cavalier King Charles Spaniels (CKCS). It found that CKCS with OME had a hearing loss of 10-33 decibels (dB) although hearing loss was not detected. Just like in humans, treatment with tympanostomy tube placement is not recommended. It was pointed out that OME in CKCS was characterized by thickening of the soft palate and decreased nasopharyngeal dimensions, just as OME in children is associated with Eustachian tube dysfunction.

Abstract: This study of the Jabiru oil field, Timor Sea (Australia), shows how the variability of visual properties of fluid inclusions in palaeo-oil zones can be mapped to identify internal structures that result from fluid interactions in the reservoir. Variability in the attributes of oil inclusion assemblages (OIAs) is greater within an inferred palaeo-gas cap (Zone 1) and current residual zone (Zone 3) and less within the current oil zone (Zone 2). In Zone 3, where water imbibed, a higher proportion of OIAs with visual white fluorescing oil inclusions correlates with less mono-aromatic compounds and a higher abundance of polar compounds determined on a bulk extract of inclusion oil using High Performance Liquid Chromatography (HPLC). The CH2/CH3 ratios and water contents, determined by Fourier Transform-Infrared Spectroscopy (FT-IR), are higher. In Zone 1, where gas drained, there is a higher proportion of OIAs with visual yellow fluorescing oil inclusions, and these correlate with low HPLC mono-aromatic and moderate polar contents, and low FT-IR CH2/CH3 ratios and water contents. Interpretation of the grains with oil inclusions (GOI™) and pressure–volume–temperature-composition (PVTx) fluid inclusion data suggests that a gas-saturated blue fluorescing palaeo-oil was present in the three zones at the same Pressure–Temperature fluid inclusion forming event PT 1. Lighter gas-saturated blue fluorescing oil was present in Zone 2, but was rarer in Zones 1 and 3 at the later fluid inclusion forming event PT 2. The yellow and white inclusion oils, trapped in Zones 1 and 3 respectively, are gas-depleted and interpreted to result from the interaction between non-movable residual oil around grains with the surrounding gas and water, respectively. Comparison between the PVTx data and the published burial curve suggests that most of the fluid inclusions were trapped during two different hot fluid flow events. The full oil column is interpreted to have been present during Early–Mid Tertiary. The palaeo-oil column was reduced during the Late Miocene by imbibition of water in the present residual zone and drainage of gas at the top of the reservoir. [Copyright &y& Elsevier]

Links between deficits identified on neurological examination, age of seizure onset and the presence of structural forebrain disease have often been postulated in dogs presenting with a history of seizures. The purpose of this study was to assess the influence of such factors on the likelihood of structural or functional brain disease, via a thorough history taking process and interictal neurological examination. Four hundred and four dogs with seizures due to intracranial causes were included. Data including age, sex, neuter status, time until diagnosis, age of seizure onset in years, type of seizure, seizure symmetiy, seizure severity, interictal neurological deficits, MRI changes and side effects associated with antiepileptic drugs were extracted from medical files. Two hundred and fifty-eight dogs were diagnosed with epilepsy of unknown origin (EUO), 11 with symmetrical structural lesions and 135 with asymmetrical structural lesions. Multinomial analysis demonstrated that dogs that were older at seizure onset were significantly more likely to have an asymmetrical structural lesion than EUO (OR 95% Cl: 1.4-1.8). Dogs that had single seizures rather than cluster seizures were less likely to have asymmetrical structural lesions than dogs with EUO (OR 95% Cl: 0.2-0.7). Dogs with abnormal neurological examinations were 16.5 times more likely to have asymmetrical structural lesions (OR 95% Cl: 8.5-32.1) and 12.5 times more likely to have symmetrical structural lesions (OR 95% Cl: 3.0-52.3) than EUO. These findings support the importance of considering interictal neurological deficits and seizure history in clinical reasoning. [ABSTRACT FROM AUTHOR]

Canine Chiari-like malformation (CM) is characterised by herniation of part of the cerebellum through the foramen magnum. In humans with Chiari type I malformation (CM-I), abnormal pulsation of the cerebellum during the cardiac cycle has been documented and is pivotal to theories for the pathogenesis of syringomyelia (SM). In this retrospective study, cardiac-gated cine balanced fast field echo (bFEE) magnetic resonance imaging (MRI) was used to assess pulsation of the brain in dogs and to objectively measure the degree of cerebellar pulsation with the neck in a flexed position. Overall, 17 Cavalier King Charles Spaniels (CKCS) with CM, including eight with SM and nine without SM, were compared with six small breed control dogs. Linear regions of interest were generated for the length of cerebellar herniation from each phase of the cardiac cycle and the degree of cerebellar pulsation was subsequently calculated. Age, bodyweight and angle of neck flexion were also compared. CKCS with CM and SM had significantly greater pulsation of the cerebellum than control dogs (P = 0.003) and CKCS with CM only (P = 0.031). There was no significant difference in age, bodyweight and angle of neck flexion between the three groups. Cardiac-gated cine bFEE MRI permitted the dynamic visualisation of cerebellar pulsation in dogs. These findings support the current theories regarding the pathogenesis of SM secondary to CM and further highlight the similarities between canine CM and human CM-I. [ABSTRACT FROM AUTHOR]

Abstract: Micro-algae are seen as one of the major future fuel sources. Culture and growth of oil rich micro-algae and catalytic process for the conversion of their crude oils or biomass is reviewed here. While there is a significant literature on growth and extraction of oil from the resultant biomass the literature on the problems of refining these oils is diverse and needs collation. It is clear that previous work has been focused on the two green algae Botryococcus braunii and Chlorella protothecoides containing terpenoid hydrocarbons and glyceryl lipids as their major crude oils, respectively, both of which will need different refinery technology for upgrading. Studies show a number of conventional catalysts in the petroleum refining industry including transition metals, zeolites, acid and base catalysts can be used with variable effect. These have been employed for cracking, hydrocracking, liquefaction, pyrolysis and transesterification processes to produce diesel, jet fuel and petrol (gasoline). However there is strong evidence that new nano-scale materials containing a high number of active sites and high surface areas may offer more potential. [Copyright &y& Elsevier]

Acute rejection (AR) is a dominant risk factor for developing chronic allograft nephropathy (CAN) after kidney transplantation. CAN is characterized by progressive interstitial fibrosis. It has been associated with increased transforming growth factor (TGF)-β1 expression, however, kinetic studies are absent. We investigated whether intragraft TGF-β1 expression in various causes of early graft dysfunction may influence late renal allograft dysfunction. A total of 174 human renal biopsies were quantified for TGF-β1 mRNA expression using real-time reverse transcriptase-polymerase chain reaction. Expression levels were correlated with the Banff histopathological grades, TGF-β1 immunohistology, and clinical follow-up. TGF-β1 was most markedly upregulated in AR, CAN, and acute tubular necrosis – delayed graft function compared to non-rejecting controls (P<0.001). TGF-β1 expression was heightened in borderline changes (P<0.01), recurrence of glomerulonephritis, and cyclosporine toxicity (P<0.05). There was no correlation between intragraft TGF-β1 expression during AR and short-term outcome of a rejection episode. TGF-β1 gene overexpression during CAN has been shown to be associated with the increased risk for renal allograft dysfunction 18 months after biopsy (odds ratios 9.9 vs 3.2, respectively). Intragraft TGF-β1 mRNA expression is significantly upregulated in both AR and CAN. Thus, our results support the hypothesis that TGF-β1 might play a key role in chronic allograft dysfunction.Kidney International (2006) 69, 1872–1879. doi:10.1038/sj.ki.5000328; published online 12 April 2006 [ABSTRACT FROM AUTHOR]

The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymerase chain reaction-based analyses of candidate markers in urine open the opportunity to closely monitor kidney-transplanted patients non-invasively. The chemokine interferon-inducible protein 10 (IP-10; CXCL10) might be an interesting candidate to uncover ongoing immune processes within the graft. Urine samples from kidney-transplanted recipients were retrospectively analyzed for IP-10 mRNA and protein expression. IP-10 levels were correlated with the incidence of acute rejection episodes proven by histology and long-term graft function assessed by the glomerular filtration rate 6 months post transplantation. IP-10 expression in urine identified patients with ongoing acute rejection episodes several days before a biopsy was indicated by rising serum creatinine levels. Most importantly, elevated levels of urinary IP-10 protein within the first four postoperative weeks were predictive of graft function at 6 months even in the absence of acute rejection. These data reveal a correlation between elevated IP-10 expression in urine at early time points post-transplantation and intragraft immune activation that leads to acute rejection and compromised long-term graft function.Kidney International (2006) 69, 1683–1690. doi:10.1038/sj.ki.5000343; published online 29 March 2006 [ABSTRACT FROM AUTHOR]

Abstract: Despite advances in immunosuppression in past decades, allograft rejection remains the main reason for kidney graft failure. Recently, despite great improvements in understanding of molecular basis of allograft rejections, renal histology remains the primary method to monitor the onset of graft rejection. The aim of the present study was to ascertain whether cytokine and chemokine expression profiles in kidney allografts contributed to the diagnosis of graft dysfunction. We analyzed mRNA expression in 174 kidney graft biopsies for the following cytokines: TGF-ß1, TNF-a, IL-10, and chemokine RANTES. Based on the expression levels obtained by real-time RT-PCR, we correlated data with the results of morphologic examinations. All tested cytokines and chemokines were upregulated (P < .001) during acute rejection compared to nonrejecting controls. Upregulation was also found in chronic allograft nephropathy (CAN) group for TGF-ß1, IL-10 (P < .001), TNF-a, and RANTES (P < .01). Upregulated expression of IL-10 (P < .001), TGF-ß1, (P < .01) and RANTES (P < .05) showed borderline changes. Higher expression levels (P < .001) of TGF-ß1 and IL-10 were also found during ATN. IL-10 was upregulated (P < .01) in specimens with recurrent glomerulonephritis. Weakly increased (P < .05) expressions of TGF-ß1 were found during CsA toxicity. Distinctive expression levels between acute rejection and CAN were only found for IL-10 (P < .01). TNF-a showed a different expression profile in acute rejection versus ATN (P < .001). These findings suggest that distinct cytokine and chemokine expression profiles in grafts may contribute to the diagnosis for and elucidation of the immunopathologic process during graft dysfunction. [Copyright &y& Elsevier]

Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a common phenomenon in kidney transplant patients that might be a prestage of posttransplant lymphoproliferative disease (PTLD). Because the role of Epstein-Barr virus (EBV) for PTLD development is well established, we wondered about the association between EBV and MGUS. Thus, B-cells from kidney transplant patients (25 with and 100 without MGUS) and from 100 healthy controls were analyzed for EBV latent (EBER1) and lytic (EA, VCA) gene expression by RT-nested PCR. The EBV load was measured by real-time PCR. A significantly higher EBV load and expression of the nonimmunogenic latency associated EBER 1 gene was observed in patients with MGUS compared to both control groups (P < .001). In addition, a rare detection of the highly immunogenic lytic transcripts demonstrated a linkage between latency-associated EBV infection and MGUS in transplant patients. This pattern was similar to EBV-associated B-cell lymphomas in nonimmunosuppressed patients. It contrasted with PTLD patients who express higher EBV loads and both lytic and latent EBV transcripts. These data suggest that transplant patients with MGUS demonstrate a more sufficient control of EBV-infected B-cells. Nevertheless, EBV monitoring should be performed in patients with EBV-associated MGUS for early detection of later PTLD. [Copyright &y& Elsevier]

Chronic heart failure is a state of immune activation, and endotoxin is a potential trigger for cytokine production. Our aim was to study whether immune activation and endotoxemia occur in adults with congenital heart disease. We prospectively measured tumor necrosis factor (TNF)-alpha, soluble TNF receptors (sTNFR-1, sTNFR-2), interleukin-6, interleukin-10, endotoxin, and soluble CD14 levels in 52 consecutive adults with congenital heart disease (age 34 +/- 2 years [mean +/- SEM]) and 18 healthy controls (age 31 +/- 1 years). A variety of congenital heart lesions were studied: single ventricle physiology (n = 15), systemic right ventricle (n = 7), tetralogy of Fallot (n = 20), and "other" congenital heart disease (n = 10). Patients were subgrouped into asymptomatic (New York Heart Association [NYHA] class I, n = 11), mild (NYHA class II, n = 30), and moderate/severe (NYHA class III/IV, n = 11) categories. Patients had elevated TNF and interleukin-6 levels compared with controls (TNF 2.8 vs 2.1 pg/ml, p <0.05; interleukin-6 8.5 vs 5.7 pg/ml, p <0.001). TNF levels were higher in patients with moderate/severe symptoms compared with patients who were asymptomatic or had mild symptoms (p <0.05). Soluble TNFR-1 levels related directly to the degree of systemic ventricular impairment (p <0.05). There were no significant differences in sTNFR-1, sTNFR-2, interleukin-10, or sCD14 levels between patients and controls. Endotoxin levels were greater in patients with congenital heart disease versus controls (0.40 vs 0.26 endotoxin units/ml, p <0.0001). Thus, adults with congenital heart disease have elevated levels of inflammatory cytokines and bacterial endotoxin, which relate to functional status. Congenital heart disease in adults may be amenable to novel anti-inflammatory therapies in selected patients. [ABSTRACT FROM AUTHOR]

Immunodeficiencies can be divided into innate and acquired forms. Usually, innate immunodeficiency is persistent whereas acquired immunodeficiency is of temporary nature. Clinical consequences of immunodeficiency are infectious complications, malignancies, but also decreased alloreactivity. Temporary immunodeficiency can be seen in different patient groups for instance in septic patients, in patients with stress due to severe trauma/surgical operations, and in transplant patients. The mechanisms leading to temporary immunodeficiency in these patient groups include inflammation-induced anti-inflammation, stress-induced anti-inflammation and high dose immunosuppressive therapy. Monocytic HLA-DR expression allows to assess the severity of temporary immunodepression, and depending on its cause different therapeutic strategies like immunostimulation, plasmapheresis or temporary reduction of immunosuppressive therapy are discussed. [Copyright &y& Elsevier]

Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P = 0.10 and 0.71, respectively). Seizures were classified as having partial onset in 61% of individuals in the study population (95% CI 42.41-76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported. [ABSTRACT FROM AUTHOR]

Abstract: Posttransplantation alloantigen¿dependent and alloantigen-independent processes are both mediated by cytokines and chemokines. Recently cytokines and chemokines, as well as their receptors, have been shown to be highly polymorphic. The cytokine and chemokine gene polymorphisms are associated with variable production, activity, expression, or ligand-receptor affinity. The aim of our study was to analyze the relation between selected cytokine and chemokine gene polymorphisms in kidney donors and recipients as a function of donor-recipient match and posttransplantation outcome. Polymorphisms transforming growth factor-ß (TGF-ß); tumor necrosis factor-¿ (TNF-¿); interleukin (IL)¿6, and IL-10; monocyte chemoattractant protein-1 (MCP-1); and RANTES (regulated upon activation, normal T-cell expressed and secreted) genes were determined using DNA polymerase chain reaction technology in 268 healthy volunteers, 345 kidney transplant recipients (1997 to 1999), and 298 cadaveric donors. Patients were followed up for 4 to 6 years. The distribution of alleles of selected genes was identical in control subjects, cadaveric donors, and recipients. Low TGF-ß production in both the donor and recipient genotypes was associated with risk for early rejection (6 months) and worse graft function at 4 years. The only tendency for worse graft outcome was observed among donor-recipient combinations mismatched for TGF-ß genotype. Genetic determination of TNF-¿ and IL-10 production was associated with delayed graft function and rejection. IL-6 gene polymorphisms had no effect on the incidence of early acute rejections, but was associated with worse 5-year outcomes. Determinations of MCP-1 overproduction and RANTES¿109 TT allele were associated with significant deterioration of graft function. Our data support the hypothesis that the strength of the alloimmune response after transplantation is in part genetically determined. Donor-recipient matching of cytokine gene polymorphisms has a marginal effect. [Copyright &y& Elsevier]

Abstract: Chronic allograft dysfunction remains the major obstacle for long-term successful transplantation. To date there is no effective treatment. Overexpression of protective genes has provided increased graft function and survival. This mechanism has been implicated in the process of graft accommodation. One of these genes that has been shown to mediate protective effects decodes the enzyme heme oxygenase-1 (HO-1), and an HO-1 downstream product, carbon monoxide (CO). Using an established model of kidney chronic allograft rejection in the rat, we investigated the impact of methylene chloride (MC), a CO donor, as a therapeutic tool to reduce chronic graft deterioration. We showed that donor and long-term recipient treatment with MC improved graft function and reduced histological signs of chronic rejection. Carbon monoxide may be a promising agent to improve graft quality and long-term graft function. [Copyright &y& Elsevier]

Abstract: Clinical and laboratory findings of acute rejection (AR) are often late and misleading. Core needle biopsy, the most reliable diagnostic method, is usually performed late in the course of AR and is associated with several complications. Therefore noninvasive approaches to monitor the immune system for detection of early AR is one of the major aims in transplant medicine. In a fully MHC-mismatched renal allograft model in the rat, we quantified donor-derived DNA (ddDNA) in the recipient serum using real-time RT-PCR as an alternative screening procedure for the early diagnosis of acute rejection. We also investigated the influence of different immunosuppressive protocols on the levels of ddDNA. Our results show that donor-derived DNA is present in the serum of kidney allograft recipients prior to acute rejection. Animals that received a syngeneic graft and animals that received a mismatched allograft but were treated with immunosuppressive drugs did not show significant elevations of ddDNA. When steroid therapy failed to avoid acute rejection, the animals showed a delayed peak of ddDNA. In summary, the detection of ddDNA in recipient serum offers a noninvasive diagnostic approach to uncover ongoing rejection processes in the graft. [Copyright &y& Elsevier]