Use of prostaglandin I2 analog in treatment of massive hepatic necrosis associated with endothelial cell injury and diffuse sinusoidal fibrin deposition

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I₂, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin followingCorynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed totert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearning action.     

Interleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis

OBJECTIVE—To investigate changes in cytokine expression in the coronary circulation induced by percutaneous transluminal coronary angioplasty (PTCA).
METHODS—The study involved 32 patients with ischaemic heart disease who underwent elective PTCA for isolated stenotic lesions of the left coronary artery. Ten patients had plain old balloon angioplasty, 10 had percutaneous transluminal rotational atherectomy, and 12 had stent implantation. Blood samples were drawn from the coronary sinus before and immediately after PTCA. Plasma concentrations of interleukin 6 (IL-6), platelet derived growth factor (PDGF), monocyte chemoattractant protein 1 (MCP-1), and macrophage coronary stimulating factor (M-CSF) were measured. The patients were scheduled for follow up angiography six months after PTCA. Late loss index was calculated using quantitative coronary angiography.
RESULTS—IL-6 concentrations in coronary sinus blood increased immediately after PTCA (p < 0.001), but there was no change in PDGF, MCP-1, or M-CSF. There was a positive correlation between changes in IL-6 concentrations immediately after PTCA and late loss index six months after PTCA (r = 0.73, p < 0.001). IL-6 concentrations in coronary sinus blood were higher in patients with late restenosis than in those without restenosis (p < 0.001).
CONCLUSIONS—PTCA induces IL-6 production in the coronary circulation. This may induce subsequent inflammatory responses in injured vessels and play an important role in late restenosis after PTCA.


Keywords: inflammation; cytokine; restenosis     

Early positive biomarker in relation to myocardial necrosis and impaired fatty acid metabolism in patients presenting with acute chest pain at an emergency room.

BACKGROUND: Measurement of circulating biomarkers has enabled early diagnosis and risk assessment of acute coronary syndrome. This study sought diagnostic values of the first single-point data of biomarkers obtained soon after patient arrival by comparing with scintigraphically quantified myocardial injury in patients presenting with acute chest pain at an emergency room. METHODS AND RESULTS: Serial blood samples were taken soon after arrival in an emergency department in 74 patients with suspected acute coronary syndrome to quantify blood levels of troponin-T (TnT), heart-type fatty acid-binding protein (H-FABP), myocardial-bound creatine kinase (CK-MB), and myoglobin. Myocardial perfusion and metabolic defects were scintigraphically quantified. The first single-point data had high positive predictive values for detecting the defects (80-100%) but low negative predictive values (15-41%). CK-MB and TnT had higher specificities (73-100%) but significantly lower positive rates (22-27%) than the others (61-68%), resulting in greater sensitivities of H-FABP and myoglobin (75-80%) than those of CK-MB and TnT (29-35%). Among biomarkers, TnT peak concentrations most closely correlated with scintigraphic abnormalities. CONCLUSION: H-FABP can contribute to early detection of myocardial injury and TnT is most likely to correlate with injured myocardial mass. The differential features of biomarkers are complementary in patients with acute chest pain presenting at an emergency room.     

Appearance of specific mucins recognized by monoclonal antibodies in rat gastric mucosa healing from HCl-induced gastric mucosal damage

Background Mucus is an important factor in the physiological defense mechanism of the gastrointestinal tract. We have reported that two distinct antigenicities reacting with anti-mucin monoclonal antibodies (mAbs), HCM31 and RGM26, emerged in epithelial cells regenerating from acetic acid-induced gastric damage in the rat. Here, we examined whether the expression of specific mucins occurred during the healing stage of acute gastric mucosal lesions, and what was the principal alteration of the mucus in the regenerating process of gastric epithelia from slight mucosal lesions.Methods Eight-week-old male Wistar rats were used. The animals were administered 0.6N hydrochloric acid, or 0.5% carboxymethyl cellulose sodium salt into their stomachs. Twenty-four, 48, and 72h after the HCl administration, their stomachs were removed. Immunohistochemical observation was performed after staining with the mAbs, RGM21, RGM26, HIK1083, or HCM31.Results Twenty-four hours after the administration of HCl, mucous cells stained with RGM26 emerged in the deeper area of the surface epithelial cells in the damaged corpus mucosa. After 48h, HCM31-positive cells were noted in the epithelial cells where the mucosal damage reached more deeply.Conclusions The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing process from acute gastric mucosal damage.     

Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia

OBJECTIVE: Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH. PATIENTS AND MEASUREMENTS: Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I-adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1-AVP receptor, mRNA by RT-PCR. RESULTS: All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I-adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over-expression of V1-AVP receptor mRNA in AIMAH tissue was determined by RT-PCR. CONCLUSION: Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1-AVP receptors.     

Central pontine myelinolysis after living donor liver transplantation

There are few reports of central pontine myelinolysis after living donor liver transplantation. A 59-year-old male received a right liver graft from his daughter for hepatitis B-related liver cirrhosis. Methylprednisolone and tracrolimus were used for immunosuppression. Dysarthria and dysphasia were noted on the second postoperative day. Brain magnetic resonance image taken on the 9th postoperative day revealed a hyperintense area at the center of his pons in T2-weighted images. The symptoms improved spontaneously 1 month after the operation. Central pontine myelinolysis should be included in the differential diagnosis when neurologic manifestations are observed after living donor liver transplantation.     

Non-enhanced magnetic resonance angiography can evaluate restenosis after carotid artery stenting with the Carotid Wallstent

Background

Carotid artery stenting (CAS) requires follow-up imaging to assess in-stent restenosis (ISR). This study aimed to determine whether non-enhanced magnetic resonance angiography (NE-MRA) is useful for evaluating ISR.

Method

Between 2009 and 2013, we performed 118 consecutive CAS procedures using the Precise stent (n?=?78) and the Carotid Wallstent (n?=?40). We reviewed 1.5 T NE-MRA and examined visualization of the stent lumen and the degree of ISR if present. Other imaging modalities were used as references.

Results

NE-MRA performed just after CAS was not able to visualize the stent lumen in all patients because of metal artifacts. In the Carotid Wallstent group, follow-up NE-MRA was available in 22 patients. The stent lumen was visible more than three months after CAS in all patients. Among them, >40 % ISR was observed by other modalities in eight lesions. The degree of restenosis measured by NE-MRA (y%) had a linear relationship with that measured by conventional angiography (x%) (y?=?0.97x-0.4, r?=?0.79, P?=?0.021). In one case among 17 without ISR (6 %), NE-MRA showed false ISR. In the Precise stent group, NE-MRA did not visualize the stent lumen in the follow-up period.

Conclusions

NE-MRA can visualize the stent lumen in the Carotid Wallstent more than three months after CAS, but not in the Precise stent at follow-up. This delayed visualization might depend on endothelialization of the stent lumen. The degree of ISR measured by NE-MRA is comparable to that by conventional angiography. NE-MRA can evaluate ISR after CAS with the Carotid Wallstent (100 % sensitivity and 94 % specificity).     

Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients

Background

The FIB-4 index is a simple formula to predict liver fibrosis. This study aimed to evaluate the utility of the FIB-4 index and associated time-course changes as a predictor of hepatocellular carcinoma (HCC) development.

Methods

A total of 171 chronic hepatitis C patients who underwent paired liver biopsies and 875 patients who underwent a single liver biopsy (validation group) were investigated during mean follow-up periods of 6.4 and 5.9 years, respectively. All patients had received interferon therapy and had not achieved a sustained virological response. Factors associated with HCC development were analyzed in these patients.

Results

HCC developed in 30 patients in the paired biopsy group and 89 patients in the validation group. Univariate analysis demonstrated that the FIB-4 index >3.25 and change in the FIB-4 index per year (ΔFIB-4/year) ≥0.3 were predictive factors for HCC development in both groups. Multivariate analysis in the combined population revealed that these two factors were independent. The hazard ratio (HR) for the FIB-4 index >3.25 was 2.7 (p < 0.001) and ΔFIB-4/year ≥0.3 was 1.8 (p = 0.003). Patients with a FIB-4 index >3.25 and a ΔFIB-4/year ≥0.3 were defined as high risk, and those with a FIB-4 index ≤3.25 and a ΔFIB-4/year <0.3 were defined as low risk. The HR of HCC development in patients at high risk was 7.3 (95 % confidence interval 4.3–12.5, p < 0.001).

Conclusions

It was possible to define a group at high risk of developing HCC by intermittently measuring the FIB-4 index and considering time-course changes in this index.