Fetal outcomes with and without the use of sugammadex in pregnant patients undergoing non-obstetric surgery: a multicenter retrospective study.

BACKGROUND: The influence of sugammadex exposure during pregnancy on progesterone withdrawal and miscarriage is unknown. We aimed to compare the fetal outcomes in pregnant patients who had undergone non-obstetric surgery with and without sugammadex. METHODS: We retrospectively reviewed the medical charts of pregnant women who underwent non-obstetric surgery at three tertiary perinatal care centers in Japan from January 2013 to December 2020. The women were divided into those who received general anesthesia with sugammadex (GA with SGX) and those who received general anesthesia without sugammadex (GA without SGX). We compared miscarriages and preterm births within four weeks after surgery. RESULTS: Among the 124 women, 73 and 51 were included in the GA with SGX and GA without SGX groups, respectively. The two groups showed no differences in the rate of miscarriages or preterm births (3.0 % vs 4.3 %; odds ratio 1.42, 95 % confidence interval 0.19 to 10.47; P = 1.00). The SGX and no SGX groups were missing outcomes for 8.2 % and 7.8 % of cases, respectively. CONCLUSIONS: Having GA with SGX or GA without SGX did not result in different rates of miscarriage or preterm birth within four weeks after the procedure. These findings do not exclude a potential association between sugammadex exposure during pregnancy and adverse pregnancy outcomes. Missing data may have obscured possible adverse outcomes from sugammadex exposure.

Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells.

Objective: To elucidate the roles of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in cell cycle regulation and proliferation of rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). Methods: Under stimulation with IL-6/soluble interleukin-6 receptor (sIL-6R) and TNF-α, we examined the expression of cell cycle regulators [p16INK4a, p21Cip1, p27Kip1, cyclin-dependent kinase-4 (CDK4), CDK6, Cyclin D, Cyclin E, and retinoblastoma protein (pRB)] by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining. The expression of pRB, with or without 10% foetal bovine serum, was examined by Western blotting. DNA synthesis and cell viability were examined by the BrdU assay and WST-8 assay, respectively. After transfection with siRNA/p16INK4a, siRNA/p21Cip1, siRNA/p27Kip1, siRNA/CDK4, or siRNA/CDK6, RA-FLSs were successively stimulated with or without IL-6/sIL-6R or TNF-α to determine cell viability. Results: IL-6/sIL-6R significantly decreased the expression of p16INK4a, and increased p21Cip1, Cyclin E1, CYCLIN D, and pRB. TNF-α decreased the expression of CDK4, and significantly increased p27Kip1, CDK6, Cyclin E1/E2, CYCLIN D, CYCLIN E, pRB, and phosphorylated pRB (phospho-pRB). By immunofluorescence staining, CYCLIN D and phospho-pRB were simultaneously stained in the single cell. In serum-free culture, the expression of pRB was apparently decreased. DNA synthesis and cell viability were significantly increased by IL-6/sIL-6R and TNF-α. Silencing of CDK6 attenuated the cell viability induced by IL-6 and TNF-α. Conclusion: The results indicate that IL-6 and TNF-α interact with each other in regulating the cell cycle and accelerate the proliferation of RA-FLSs.

Peripheral facial palsy after bilateral sagittal split ramus osteotomy: case report.

Bilateral sagittal split ramus osteotomy (BSSRO) is commonly used in orthognathic surgery. Although abnormal sensation in areas that are innervated by the inferior alveolar nerve is a well-known neurological complication of mandibular osteotomy, facial palsy is rare postoperatively. We present a case of peripheral facial palsy that developed the day after BSSRO to correct a mandibular protrusion in a 42-year-old man. Oral prednisolone was begun on the second day postoperatively, and was gradually tapered off over time. One month after operation, he had gradually recovered all movements in his right facial muscle and, after two months, had completely recovered without residual asymmetry. Possible causes of the palsy were compression of the facial nerve as a result of the insertion of a retractor around the posterior border of the ramus, and postoperative oedema. Peripheral facial palsy after BSSRO should be considered a rare, but possible, complication and as such, should be mentioned in consent forms.

The novel G-quadruplex-containing long non-coding RNA GSEC antagonizes DHX36 and modulates colon cancer cell migration.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in a variety of human cancers. However, their biological roles in these cancers remain incompletely understood. In this study, we analyze the gene expression profiles of colon cancer tissues and identify a previously unannotated lncRNA, FLJ39051, that we term GSEC (G-quadruplex-forming sequence containing lncRNA), as a lncRNA that is upregulated in colorectal cancer. We further demonstrate that knockdown of GSEC results in the reduction of colon cancer cell motility. We also show that GSEC binds to the DEAH box polypeptide 36 (DHX36) RNA helicase via its G-quadruplex-forming sequence and inhibits DHX36 G-quadruplex unwinding activity. Moreover, knockdown of DHX36 restores the reduced migratory activity of colon cancer cells caused by GSEC knockdown. These results suggest that GSEC plays an important role in colon cancer cell migration by inhibiting the function of DHX36 via its G-quadruplex structure.

A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.

Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy.

BACKGROUND: Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from renal cell carcinoma (RCC) tissue that has been associated with RCC metastasis. However, in prostate cancer, the expression of DSGb5 has not yet been fully assessed. In this study, we investigated DSGb5 expression in prostate tissues and the relationship between DSGb5 expression and clinicopathological characteristics of prostate cancer patients. METHODS: A total of 130 patients who underwent radical prostatectomy (RP) at our hospital between January 2005 and December 2007 were analyzed in this study. The expression of DSGb5 in prostatectomy specimens was examined by immunohistochemical analysis with monoclonal antibody 5F3 (anti-DSGb5). Associations between 5F3 expression and clinicopathological findings were investigated and the factors that affected PSA failure-free survival were assessed by Kaplan-Meier analysis and a Cox regression model. RESULTS: When immunoreactivities of 5F3 were measured, negative to strong staining was observed in prostate cancer tissue, whereas strong staining was observed in benign prostate glands. These expression patterns suggest that DSGb5 may act as a differentiation antigen in cancerization. The PSA failure-free survival was significantly higher in the 5F3 intact expression group than in the 5F3 reduced expression group (log-rank P=0.0220). On multivariate analysis, 5F3 intact expression showed significantly worse PSA failure-free survival following RP. CONCLUSIONS: 5F3 expression reflects the clinical and pathological features of prostate cancer and is correlated with the outcomes following RP. Further studies are necessary to clarify the functional roles of DSGb5 and establish a novel biomarker for prostate cancer.

The male-specific factor Sry harbors an oncogenic function.

Sgf29, a component of the SPT-ADA-GCN5 acetyltransferase (SAGA) complex, binds H3K4me2/3 marks and leads to histone H3 acetylation. Previously, we found that downregulation of Sgf29 suppresses c-Myc-mediated malignant transformation. Nonetheless, the upstream regulator of the Sgf29 gene is not yet known. Here, we report that Sry (sex-determining region Y), an HMG (high-mobility group) domain containing transcription factor, directly upregulates Sgf29 gene expression. Sry expression was deregulated in two out of the four tested male rodent hepatocellular carcinoma (rHCC) cell lines. Luciferase reporter and chromatin immunoprecipitation assays indicated that Sry could bind HMG-boxes in the proximal promoter region of the Sgf29 gene. Knockdown of Sry robustly lowered anchorage-independent growth, invasiveness and tumorigenicity of rHCC cells, whereas ectopic expression of Sry conferred more malignant properties. Thus, these data show that Sry is involved in male-specific malignant conversion of rHCCs via Sgf29 upregulation.

Primary aldosteronism associated with subclinical Cushing syndrome.

BACKGROUND: Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. AIM: In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). MATERIAL AND METHODS: Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. RESULTS: In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3ßHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo- pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. CONCLUSIONS: The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.

Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma.

Replication-competent retrovirus (RCR) vectors have been shown to achieve significantly enhanced tumor transduction efficiency and therapeutic efficacy in various cancer models. In the present study, we investigated RCR vector-mediated prodrug activator gene therapy for the treatment of malignant mesothelioma, a highly aggressive tumor with poor prognosis. RCR-GFP vector expressing the green fluorescent protein marker gene successfully infected and efficiently replicated in human malignant mesothelioma cell lines, as compared with non-malignant mesothelial cells in vitro. In mice with pre-established subcutaneous tumor xenografts, RCR-GFP vector showed robust spread throughout entire tumor masses after intratumoral administration. Next, RCR-cytosine deaminase (RCR-CD), expressing the yeast CD prodrug activator gene, showed efficient transmission of the prodrug activator gene associated with replicative spread of the virus, resulting in efficient killing of malignant mesothelioma cells in a prodrug 5-fluorocytosine (5FC)-dose dependent manner in vitro. After a single intratumoral injection of RCR-CD followed by intraperitoneal administration of 5FC, RCR vector-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous tumor growth, and significantly prolonged survival in the disseminated peritoneal model of malignant mesothelioma. These data indicate the potential utility of RCR vector-mediated prodrug activator gene therapy in the treatment of malignant mesothelioma.

An 8-month-old boy with congenital fibromuscular dysplasia presenting with shock caused by sudden renal hemorrhage.

Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, multifocal segmental angiopathy. FMD is the most common cause of pediatric renovascular hypertension. Aneurysmal formation of the main renal artery and distal branches is a rare complication of FMD in infancy. We report an 8-month-old boy with FMD presenting with shock caused by sudden renal hemorrhage that necessitated removal of one kidney. A diagnosis of renovascular hypertension resulting from intimal type FMD with aneurysmal formation was made on the basis of the presence of hypertension, elevation of PRA and aldosterone activity, pathological findings and the results of renal angiography. Our findings suggest that it is therefore necessary to consider FMD with aneurysmal formation as a possible cause of hypertension and renal hemorrhage in infants.

Exendin-4 protects pancreatic beta cells from the cytotoxic effect of rapamycin by inhibiting JNK and p38 phosphorylation.

It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.

Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration.

The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC interacts with the Rac1- and Cdc42-specific guanine-nucleotide exchange factors (GEF), Asef and Asef2, which contain an APC-binding region (ABR) in addition to Dbl homology, Pleckstrin homology (PH) and Src homology 3 (SH3) domains. APC stimulates the GEF activity of Asef and Asef2, and thereby regulates cell adhesion and migration. Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). In response to hepatocyte growth factor (HGF) treatment of HeLa cells, Asef2, Neurabin2 and APC were induced to accumulate and colocalize in lamellipodia and membrane ruffles. Neurabin2 did not affect the GEF activity of Asef2. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation. These results suggest that Asef2, Neurabin2 and APC cooperatively regulate actin cytoskeletal organization and are required for HGF-induced cell migration.

Truncation mutations abolish chromatin-associated activities of adenomatous polyposis coli.

The adenomatous polyposis coli (APC) is a tumor suppressor whose loss of function leads to colon cancer. APC shuttles between the nucleus and cytoplasm, however its role in the nucleus remains elusive. We have found that nuclear APC specifically associates with transcriptionally active chromatin through structural elements located downstream to the region of frequent truncation mutations found in colorectal tumors. We show that a recombinant APC fragment comprising such elements associates in vivo with euchromatin and preferentially binds in vitro to acetylated histone H3. Induction of DNA double-strand breaks (DSB) stimulates accumulation of APC at the damaged DNA chromatin marked by histone H2AX and S139-phosphorylated histone H2AX. A nuclear complex containing the DNA-dependent protein kinase catalytic subunit (DNAPKcs) and APC associates with chromatin in response to DNA DSB. APC knockdown with siRNA decreased the rate of DNA DSB-induced S139 histone H2AX phosphorylation in cells expressing endogenous full-length APC, but not in colon cancer cells with its truncation mutants, whereas ectopic APC expression stimulated the H2AX phosphorylation regardless of the type of endogenous APC. Our data suggest that APC involves in the DSB DNA repair and that truncation mutations impair chromatin-associated functions of APC.

[Pseudomesotheliomatous carcinoma of the lung].

Pseudomesotheliomatous carcinoma is the lung cancer with marked pleural extension resembling malignant pleural mesothelioma on diagnostic imaging. We report a rare case of pseudomesotheliomatous carcinoma of the lung in a 72-year-old man. The patient had complained of dyspnea and a chest roentgenogram showed right pleural effusion. Computed tomography (CT) of the chest revealed diffuse irregular pleural thickening, which mimicked pleural malignant mesothelioma. Pleural tissue sampling was performed to obtain definitive diagnosis by video-assisted thoracoscopic surgery. At the operation. the tumor was found to have a spread along the pleural surface and primary lesion was not detected in the right lung parenchyma. Immunohistochemically, the tumor was positive for carcinoembryonic antigen (CEA), but negative for calretinin, thrombomodulin, and pulmonary surfactant apoprotein. Final diagnosis was adenocarcinoma of the lung.

Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42.

The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC interacts with the Rac1-specific guanine-nucleotide exchange factor (GEF) Asef, which contains an APC-binding region (ABR) in addition to Dbl homology (DH), Pleckstrin (PH) and Src homology 3 (SH3) domains. APC stimulates the GEF activity of Asef, and thereby regulates cell adhesion and migration. Here, we have identified a second Asef, termed Asef2, that shows significant structural and functional similarities to Asef. We found that both the N-terminal ABR and SH3 domains of Asef2 are responsible for its interaction with APC. When expressed in HeLa cells, a mutant Asef2 lacking the ABR and SH3 domains, Asef2-DeltaABR/SH3, induced increases in the levels of the active forms of Rac1 and Cdc42. Full-length Asef2 also showed this activity when co-transfected with truncated mutant APC expressed in colorectal tumor cells. Consistent with this, either Asef2-DeltaABR/SH3 or Asef2 plus truncated mutant APC stimulated lamellipodia formation in MDCK cells and filopodia formation in HeLa cells. Furthermore, RNA interference experiments showed that Asef2 is required for migration of colorectal tumor cells expressing truncated APC. These results suggest that similar to Asef, Asef2 plays an important role in cell migration, and that Asef2 activated by truncated mutant APC is required for aberrant migration of colorectal tumor cells.

Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc.

c-Myc N-terminal conserved domains, MbI and MbII, are essential for c-Myc-mediated transformation and transactivation. These domains recruit the STAGA (SPT3-TAF9-GCN5-acetyltransferase) coactivator complex, but not TFTC (TATA-binding protein-free TAF-containing) to the target gene promoter. Although components of this complex are well conserved between yeast and mammals, four mammalian orthologs of yeast SPT8, SPT20, SGF11 and SGF29 remain to be identified. Here, we isolated a rat ortholog of yeast SGF29, a component of yeast SAGA (SPT-ADA-GCN5-acetyltransferase) complex. Both rat (r) SGF29 and c-myc mRNAs were overexpressed in five out of the eight tested rodent tumor cells. rSGF29 directly interacted with rADA3 and co-immunoprecipitated with two other TFTC/STAGA components, rGCN5 and rSPT3. rSGF29 was recruited to the c-Myc target gene promoters together with c-Myc, and it activated c-Myc target gene expressions. Downregulation of rSGF29 suppressed the expression of c-Myc target genes and inhibited anchorage-independent growth and tumorigenicity and lung metastasis of rat hepatoma K2 cells when injected into nude mice. These results show that rSGF29 is a novel component of TFTC/STAGA complexes and could be involved in the c-Myc-mediated malignant transformation.

Wnt signalling and the actin cytoskeleton.

The tumour suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC binds to beta-catenin, a key component of the Wnt signalling pathway, and induces its degradation. In addition to this role, there is increasing evidence for additional roles of APC, including the organization of cytoskeletal networks. APC interacts with microtubules and accumulates at their plus ends in membrane protrusions. Also, it has been reported that APC is associated with the plasma membrane in an actin-dependent manner. Moreover, APC interacts with IQGAP1, an effector of Rac1 and Cdc42, and APC-stimulated guanine nucleotide exchange factor (Asef), a Rac1-specific guanine nucleotide exchange factor (GEF). IQGAP1 mediates association of APC with cortical actin in the leading edge of migrating cell and both proteins are required for cell polarization and directional migration. APC interacts with Asef and stimulates its activity, thereby regulating the actin cytoskeletal network, cell morphology, adhesion and migration. Truncated mutant APCs present in colorectal tumour cells activate Asef constitutively and contribute to their aberrant migratory properties, which may be important for adenoma formation as well as tumour progression to invasive malignancy.

Postoperative host responses in elderly patients after gastrointestinal surgery.

BACKGROUND/AIMS: The age-associated dysregulation of hemodynamic, metabolic and immune responses contributes to the high incidence of complications after major abdominal surgery. METHODOLOGY: Ninety-five patients who underwent gastric resection (n=51) and colorectal resection (n=44) were divided according to age into Groups A (n=45, less than 70 years old), B (n=30, 70-79 years) and C (n=20, over 80 years). Flow cytometric analysis of CD4+ lymphocytes for interferon (IFN)-gamma and interleukin (IL)-4 production determined the Th1/2 balance. Energy expenditure was measured by indirect calorimetry, and hemodynamics were studied using pulse dye densitometry. RESULTS: Surgical procedures, operating time, blood loss and morbidity did not significantly differ among the three groups. The cardiac index (CI) in group A and B increased significantly over preoperative levels until POD 3, but there were no significant perioperative changes in the CI levels of group C. Resting energy expenditure levels changed similarly to those of CI. The postoperative Th1/2 ratio decreased from young to elderly to very elderly patients, although no differences were significant before surgery. The postoperative percentage of CD4+IFN-gamma +T cells (Th1) in group C decreased significantly despite of no significant changes in that of group A and B. In contrast, the ratio of CD4+IL-4+T cells (Th2) in the all groups significantly increased after surgery. CONCLUSIONS: Host responses in elderly patients after major abdominal surgery were more hyperdynamic and hypermetabolic than those of young patients. Postoperative dysregulation of the Th1/2 balance was also associated with aging. However, host responses appear to significantly differ between elderly and very elderly patients.

Primary erythrocytosis in a Japanese black calf: a case report.

An 8-month-old Japanese Black heifer with severe erythropoietic symptoms was subjected to clinical, histological and cytological examinations. During the 1 month clinical observation period, severe increases in RBC count, packed cell volume and haemoglobin concentration were observed. The plasma erythropoietin (Epo) concentration of the heifer (20.7 mIU/ml) was similar to that observed in normal control heifers. Blood gas examinations of the arterial and venous blood revealed low levels of partial pressure O(2) (PaO(2)), partial pressure CO(2) (PaCO(2)) and O(2) saturation (SaO(2)), while the blood pH was within the normal range. Gross lesions could not be detected. However, microscopic observation revealed severe proliferation of erythroblasts in the bone marrow and in the spleen without evidence of neoplastic changes. Based on these clinical and pathological examinations, we diagnosed the heifer as being the first case of primary erythrocytosis in Japanese Black cattle.

Prognostic predictive values of serum cytochrome c, cytokines, and other laboratory measurements in acute encephalopathy with multiple organ failure.

AIMS: To evaluate the prognostic predictive values of cytochrome c, cytokines, and other laboratory measurements in serum collected during neurological onset in acute encephalopathy with multiple organ failure. METHODS: In addition to general laboratory examinations, the concentrations of cytochrome c (apoptosis marker) and cytokines (inflammatory markers) were measured in serum samples collected at the initial phase in 29 patients with acute encephalopathy. The obtained values were evaluated as predictors for the development of severe encephalopathy. RESULTS: Cytochrome c, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF-receptor 1 (sTNF-R1), and aspartate aminotransferase (AST) concentrations at the initial phase were high and correlated well with patient outcome. High concentrations of serum cytochrome c (>45 ng/ml), sTNF-R1 (>2000 pg/ml), AST (>58 IU/dl), IL-6 (>60 pg/ml), and TNF-alpha (>15 pg/ml) predicted an unfavourable prognosis (sequelae and death) at 93%, 79%, 82%, 77%, and 60%, respectively. The specificity of those markers was 100%, 89%, 83%, 100%, and 100%, respectively. CONCLUSIONS: Serum cytochrome c is the most sensitive and specific predictor for the development of severe encephalopathy at the initial phase. Results suggest that this marker might be used to guide decisions regarding the start of the initial treatment and further intensive care.