Toxicity of PBBs with Special Reference to Porphyrinogenic Action and Spectral Interaction with

Some of the polyhalogenated aromatic compounds (PHAs) which are able to produce porphyria are presently known as environmental contaminants. Chronic exposure to PHAs causes hepatic porphyria in different species. Qualitatively PBBs act comparable to PHAs. An increase in accumulation of porphyrins caused by PHAs is not simply related to an increase of 8-ALAS activity in liver. Heme cannot exert a feedback when porphyria develops. Induction of P450 mediated drug enzymes is needed. The PHAs interact with P-450 in vitro. The PHAs are converted into a reactive intermediate, not a known metabolite, which depletes liver GSH and then becomes reactive to tissue structures. Mitochondria are damaged; fluorescence of porphyrins is detected in the region of central veins where degenerative change in hepatocytes is most marked. A possible pathological change in the cell membrane permeability is assumed too. In this porphyric stage uroporphyrinogen decarboxylase (urogen decarboxylase) is inhibited. The proportion of steroid hormones product by ovaries and testes compared to each other are possibly involved in sensitivity to porphyrinogenic compounds

DMD Fast Forward. Published on June 18, 2007 as doi:10.1124/dmd.107.016295 DMD #16295 CHARACTERIZATION OF DIURON N-DEMETHYLATION BY MAMMALIAN

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Resistance

Background: The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF). Methodology/Principal Findings: Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IkBa and NF-kBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3b phosphorylation. Conclusions/Significance: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance

Effect of Intensive Insulin Therapy Using a Closed-Loop Glycemic Control System in

OBJECTIVE — Intensive insulin therapy (IIT) reduces morbidity and mortality in patients in surgical intensive care units. The aim of this study is to assess the effect of IIT using a closed-loop system in hepatectomized patients. RESEARCH DESIGN AND METHODS — Patients were randomly assigned to receive IIT using a closed-loop system: an artificial pancreas (AP group) or conventional insulin therapy using the sliding-scale method (SS group). RESULTS — The incidence of surgical-site infection in the AP group was significantly lower than that in the SS group. The length of hospitalization required for patients in the AP group was significantly shorter than that in the SS group. CONCLUSIONS — Total hospital costs for patients in the AP group were significantly lower than for patients in the SS group. IIT using a closed-loop system maintained nearnormoglycemia and contributed to a reduction in the incidence of SSI and total hospital costs due to shortened hospitalization. Large randomized trials in which the use of tight blood glucose control with intensive insulin therapy (IIT) was compared with standard blood glucose control in surgical intensive care unit (ICU) patients have demonstrated that strict control of postoperative blood glucose levels not only significantly reduced patient mortality but also reduced morbidity (1,2). These results helped initiate several short-lived multicenter randomized control studies designed to evaluate the benefit of tight glycemic control with IIT (3,4). Unfortunately, however, these clinical trials were stopped early, mainly because of the high incidence of hypoglycemia (10–17%) induced by IIT (5). Considering the frequency of the use Diabetes Care 32:1425–1427, 2009 of IIT in patients undergoing surgical treatment in the ICU, we conducted a prospective randomized controlled trial to evaluate the postoperative condition of the patients and the effect of a closed-loop artificial pancreas (6–9) on tight glycemic control during IIT in hepatectomized patients

Letters to the Editor Annals of Oncology 16: 331–335, 2005

obstruction and oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer: a real entity? We have read with interest the study of Rubbia-Brandt et al. [1] entitled ‘Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer’. In this study, the investigators identified in the specimens from liver resection for colorectal metastases, some histological lesions of the non-tumoral liver parenchyma attributed to oxaliplatin-based chemotherapy. The results of this study raise some comments. First, it is well known that a variability in the assessment of the lesions and their severity may exist when examination is performed by multiple observers. In this study, the review o

SCIENTIFIC PAPER Laparoscopic Management of

Background: Hydatid disease is an endemic condition in several parts of the world. Owing to ease of travel, even surgeons in nonendemic areas encounter the disease and should be aware of its optimum treatment. A safe, new method of laparoscopic management of hepatic hydatid disease is described along with a review of the relevant literature. Methods: Sixty-six cases of hepatic hydatid disease were operated on laparoscopically using the Palanivelu Hydatid System. The special trocar-cannula system used and the technique of operation are described. Results: The majority of the patients presented with pain. Most of the patients had only a single cyst. The right lobe of the liver was most commonly involved. Cysts wer

CASE REPORT Laparoscopic Debridement of Hepatic Necrosis After

Background and Objectives: Hepatic artery chemoembolization (HACE) used to treat neuroendocrine tumors metastatic to the liver has shown both survival benefit and improvement in symptoms. The development of hepatic necrosis after HACE is rare, but the consequences can be devastating. We report the first case of laparoscopic management of extensive hepatic necrosis occurring after HACE. Case Report: A 58-year-old man with neuroendocrine tumor metastatic to the liver underwent HACE in addition to medical management. He had undergone previous biliary stenting for biliary obstruction. After HACE was performed via the right hepatic artery, the patient developed sepsis due to right hepatic lobe infarction. Percutaneous drainage and antibiotics were attempted for 2 months, but hepatic debridement was ultimately required due to repeated drain malfunction and septic complications. Laparoscopic necrosectomy was performed with ease and with little blood loss. The patient quickly recovered without any further infectious complications. Conclusion: Infected hepatic necrosis resulting from HACE that fails percutaneous management can be successfully managed with laparoscopic necrosectomy. This report adds to the growing evidence that minimally invasive techniques can be used to manage complicated hepatic conditions

Summary

The migration pathways for dendritic cells (DC) from the blood are not yet completely resolved. In our previous study, a selective recruitment of DC progenitors from the blood to the liver was suggested. To clarify the role of the hepatic sinusoids in the migration of blood DC, relatively immature DC and mature DC were isolated from hepatic and intestinal lymph, and intravenously transferred to allogeneic hosts. It was then possible to detect small numbers of DC within secondary lymphoid tissues either by immunostaining for donor type major histocompatibility complex class I antigen or, at much higher sensitivity, for bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes), which responded to the alloantigen presented by the administered DC. The intravenously injected DC accumulated in the paracortex of regional lymph nodes of the liver via a lymph-borne pathway. Intravenously injected fluorochrome-labeled syngeneic DC behaved similarly. In contrast, very few DC were found in spleen sections and were hardly detectable in other lymph nodes or in other tissues. An in situ cell binding assay revealed a significant and selective binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC can undergo a blood–lymph translocation via the hepatic sinusoids, but not via the high endothelial venules of lymph nodes. Hence the hepatic sinusoid

Edita Prima Oy

To be publicly discussed, with the permission of the Faculty of Biosciences of th