Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome.

BACKGROUND: The evaluation of renal function in patients with decompensated cirrhosis is important for prognosis, dosage assessment of potentially nephrotoxic drugs and recognition of changes in glomerular filtration rate (GFR) to decide paracentesis and diuretic therapy. Patients with many different disorders of hepatic function can present with various abnormalities of renal function in the absence of other known causes of renal failure which has been called hepatorenal syndrome (HRS). Some reports have pointed out that serum creatinine levels frequently failed to rise above normal levels even when glomerular filtration rate (GFR) is very low in cirrhotic patients with hepatorenal syndrome. The aim of this study was to determine if estimation of serum cystatin C could replace creatinine clearance in routine GFR determinations for patients with cirrhosis. METHODS: Serum cystatin C, creatinine clearance (Clcr), and 99mTc-DTPA clearance were determined in 26 patients with cirrhosis. According to Child-Pugh's classification, 21 patients were in group C and 5 were in Group B. RESULTS: Pearson correlation analyses showed that correlation between serum cystatin C and 99mTc-DTPA clearance was r=-0.522, p=0.006, between serum creatinine and 99mTc-DTPA was r=-0.373, p=0.06. The results of our study demonstrated that neither serum creatinine nor creatinine clearance (Clcr) were good indicators of hepatorenal syndrome because the mean value for Clcr was found to be higher than Tc-DTPA clearance, and there was no correlation between these two parameters (r=0.059). Additionally, the mean value of serum creatinine was found to be within the normal range, whereas the mean DTPA clearance level was lower than normal range. CONCLUSIONS: This finding could be explained by the fact that cirrhotic patients with poor nutrition may have decreased protein intake, low muscle mass and lack of converting capacity of creatine to creatinine. Thus, we suggest that serum cystatin C assay, which has good analytical performance, could replace or at least be added to creatinine measurement for GFR assessment in patients with cirrhosis.

Solitary skull metastasis from occult thyroid carcinoma.

Metastatic tumors to the skull, though relatively rare, are most often from lung, breast or prostate. In this report, we describe a case of skull metastasis from occult thyroid carcinoma and discuss the differential diagnosis of these lesions.

Mass flux balance-based model and metabolic flux analysis for collagen synthesis in the fibrogenesis process of human liver.

A mass flux balance-based stoichiometric model for human liver metabolism has been set up. The model considers 125 reaction fluxes, and there are 83 metabolites that are assumed to be in pseudo-steady state. Theoretical metabolic flux distributions in the fibrotic and healthy liver cells were determined by maximizing respectively the collagen and palmitate synthesis in the objective function for the solution of the model. The flux distribution maps of the analysis for the collagen synthesis showed that the glycolysis pathway was active down to fructose-6-phosphate and the gluconeogenesis pathway was active up to glyceraldehyde 3-phosphate synthesis. However, the flux distribution maps for the palmitate synthesis revealed that both the glycolysis pathway and the gluconeogenesis pathway were active towards 3-phospho glycerate. The TCA cycle operated from citrate towards oxalacetate, and the anaplerotic reactions that connect the TCA cycle to the gluconeogenesis pathway were active in both analyses. Metabolic flux analysis shows that the amino acid fluxes are indeed important in the collagen synthesis. The results of the comparative analyses for the occurrence of the collagen synthesis in the fibrotic liver cells reveal that among the non-essential amino acids three, namely glycine, proline and aspartic acid, and among the essential amino acids one, methionine, are respectively the potential metabolic bottlenecks and the limiting amino acid. The diversions in the pathways and certain metabolic reactions are also presented, and potential strategies for controlling the collagen synthesis and consequently the fibrosis are also discussed.

Contribution of adrenomedullin to homeostatic response to cold stress in rat model.

Acute stress known to stimulate sympathetic activity as well as the hypothalamo-pituitary-adrenal (HPA) axis, produces a significant increase in adrenomedullin (ADM) levels in the pituitary gland, plasma and adrenal glands, all of which are key components of HPA axis, suggesting a regulatory or protective role for ADM in countering HPA activation following a variety of physiological and psychological stressors. This study was conducted to assess a rat model for in depth investigation of biochemical mechanisms and consequences of cold stress. Four groups of Sprague-Dawley rats were observed for their serum total protein, glucose, trigliceride and cholesterol levels as well as their blood pressures after housing at room temperature, administration of ADM (1.0 nm/kg), exposing to cold stress (8 degrees C for 48 h) and exposing to ADM injection in addition to cold stress. The results suggest that application of ADM in addition to cold stress may act via receptors on different end-organs and causes altered metabolic regulation taking partial or total occupation of ADM receptors, stimulated in response to cold application induced physiologic ADM release before pharmacological ADM administration.

Hierarchical cluster analysis as an approach for systematic grouping of diet constituents on basis of fatty acid, energy and cholesterol content: application on consumable lamb products.

The role of dietary fat in the etiology of chronic diseases is both a qualitative and a quantitative issue. The dietary fat intake is largely influenced by behavioral and social influences on food choice. Ongoing scientific research has led to dietary recommendations with main concerns being the percentage of saturated, essential fatty acids and cholesterol with respect to total energy intake. However, the compositional complexity of food choice constituting the diet is a critical concept complicating the interpretation of epidemiologic, clinical and laboratory evidence to define the role of dietary fat in the etiology of diseases. This study was conducted on the observation of the need to better systematically classify consumable food based on complex composition and lamb meat is randomly selected as a non-specific subset for application of hierarchical cluster analysis method to obtain the dendogram using average linkage. Data on fat composition of consumable lamb prepared by different methods was obtained from USDA Nutrient Database for Standart Reference. Using agglomerative hierarchical cluster analysis lamb meat was grouped into two main clusters among which one divided into two families of which each was subdivided into two subfamilies based on fatty acids, cholesterol and energy composition. Present work may be considered as a leading study to systematically classify larger food sets. As high fat foods are rich in flavor and overall palatability, the outcome of this study may lead to behaviorally more acceptable but healthier dietary replacements. Besides future use of the results obtained may reveal the effect of complex compositional dietary influences on health and disease and may have superiority to studies questioning individual dietary items. Furthermore, hieararchial cluster analysis may be used to cluster food including other compositional data in food items like amino acids, vitamins, carbohydrates, as well.

Correlation between tissue levels of carboxy-terminal propeptide of type I procollagen and clinicopathological characteristics in human colorectal cancer.

BACKGROUND/AIMS: Type 1 collagen is the most abundant protein in the human body and a major constituent of the interstitial connective tissue. However, little is known about carboxy-terminal propeptide of type I procollagen (PICP) expression in human colorectal tumor tissues. We therefore evaluated the concentrations of PICP in colorectal tumor tissue as well as surrounding normal tissues and examined the relationship between its level and clinicopathological variables. METHODOLOGY: Tumor and normal tissues from 40 patients with colorectal carcinoma who had been operated on were stored at -80 degrees C until assays. PICP was assayed by sandwich immunoassay. RESULTS: It was found that the PICP level was significantly higher in the tumor extracts than in the normal tissue extracts (P < 0.0001). The ANOVA test showed that the level of PICP in tumor tissue was higher in the patients with advanced colorectal tumor than those with early stage disease (P < 0.0001). There were statistically significant differences with regard to the depth of tumor invasion, presence of lymph node metastasis, and hepatic metastasis (P < 0.05). There were also quantitative differences with respect to the PICP levels between obstructing tumors and non-obstructing carcinoma (P < 0.05), but the elevated PICP levels in tumor tissues were not associated with the type of histologic differentiation (P > 0.05). CONCLUSIONS: Although these findings suggest that PICP value in tumor tissue is most likely related to the some histomorphological architecture of the tumor, the authors believe that the prognostic significance of PICP expression in primary colorectal tumor and normal tissues requires further evaluation.

Serum cytotoxin and oxidant stress markers in N-acetylcysteine treated thioacetamide hepatotoxicity of rats.

N-acetylcysteine (NAC) is a glutathione precursor used to treat several clinical conditions where intracellular oxidant-antioxidant balance is disturbed, among which, acetaminophen induced hepatotoxicity may be counted. In this study, administering thioacetamide (TAA) as a hepatotoxic agent, a rat model of hepatotoxicity has been established, to investigate some of the immune mediated basic oxidant-antioxidant homeostatic mechanisms involved, and potential serum markers for follow-up of disease and treatment. To do this, four experimental groups receiving saline/saline, saline/NAC, saline/TAA and NAC/TAA as intraperitoneal injections, have been formed. Rat serum tumor necrosis factor-alpha (TNF-alpha), Interleukin1-beta (IL1-beta), malondialdehyde (MDA) as a measure of final oxidant damage and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) have been assayed. Hepatocellular damage has been measured via the biochemical estimates ALT, AST and LDH as well as histopathological grading. It was found that both TNF-alpha and IL1-beta were significantly elevated in saline/TAA receivers (P<0.01) when compared to NAC/TAA receivers. Serum MDA was also increased in TAA receivers in addition to SOD (P<0.05) and GSH-Px (P<0.05). Serum nitrite levels have also been assayed to give an estimate of nitric oxide that is suggested as a counter-balancer of oxidant stress. NAC/saline receivers had the highest levels of nitrites in the serum (P<0.05). Our results indicate that part of the hepatocellular injury to rat liver, induced by TAA is mediated by oxidative stress caused by the action of cytokines imparted by the enzymatic SOD and GSH-Px and non-enzymatic gaseous nitric oxide mechanisms causing an alleviation on administration of NAC. In addition, TNF-alpha, IL1-beta, MDA, SOD, GSH-Px and nitrites are potential candidates of serum indicators for monitorization of pathophysiological stage of liver disease.

Histological assessment of root cementum at periodontally healthy and diseased human teeth.

This study aimed to investigate and compare the lipid and polysaccharide content of the cemental surfaces of healthy and periodontally-involved teeth. Thirty periodontally-involved single-rooted teeth from fifteen patients with localized juvenile, adult and rapidly progressive periodontitis were included in the experimental group and 5 healthy teeth were assessed in the control group. Frozen serial sections were obtained and stained with hematoxylin-eosin for morphological assessment. Oil-Red-O and Alcian Blue-Periodic Acid Schiff stains were used to evaluate the presence of lipids, neutral and acidic polysaccharides using light microscopy. It was found that with hematoxylin-eosin staining in the experimental group, both the involved and uninvolved cementum surfaces of teeth, which belong to all periodontitis groups, showed generally irregular surfaces that contain some resorption areas. Alcian Blue-Periodic Acid Schiff positive staining was observed only superficially and at the areas associated with microbial dental plaque. However, Oil-Red-O staining was positive only superficially at 5 teeth that belonged to localized juvenile and rapidly progressive periodontitis groups. Apparent lipopolysaccharide staining into cementum was not seen in any of the diseased teeth. The results presented here suggest that endotoxin was only localized in superficial layers and associated with only microbial colonization.

Cauda-filar paraganglioma with 'silk cocoon' appearance on spinal angiography.

'Silk cocoon' appearance on spinal angiography is pathognomonic to differentiate paragangliomas from several vascular tumors and malformations of cauda-filar region.

Giant-cell tumour of the lumbar spine. Case report.

Giant-cell tumours of the spine are very rare. They occur mainly in long bones. We report a patient with a giant-cell tumour of the lumbar spine which had been operated on at another hospital 5 months previously as a protruded lumbar intervertebral disc.

Lumbar disc herniation and tight hamstrings syndrome in adolescence.

BACKGROUND: Lumbar intervertebral disc herniation is infrequently encountered in children and adolescents. Additional signs and symptoms such as postural deformities and abnormal gait accompany the classical findings of lumbar root irritation. These unusual signs have been described in the literature as "tight hamstrings syndrome". Waddling gait with flexed knees is considered as pathognomonic for this condition and may be masked by the signs of root irritation due to prolapsed intervertebral disc material. CASE REPORT AND DISCUSSION: We report an adolescent patient with lumbar disc herniation in whom gait abnormality and limitation of lumbar movements persisted after surgical intervention. A review of the literature on tight hamstrings is presented.

Prevention of intra-abdominal adhesions by using Seprafilm in rats undergoing bowel resection and radiation therapy.

OBJECTIVE: Intra-abdominal adhesions are an important surgical problem. Colorectal operations are a major cause of adhesive obstruction. Radiation therapy (RT) is frequently used as an adjuvant therapy to surgery for rectal cancer, though its value for colon carcinoma remains unclear. Peritoneal injuries including the surgical trauma, tissue ischaemia as well as RT are associated with peritoneal fibrinolytic activity. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (Seprafilm) has been used to reduce intra-abdominal adhesion formation. We have investigated the effect of Seprafilm on intra-abdominal adhesion in rats receiving RT after the resection of the left colon. MATERIALS AND METHODS: Thirty-two male Wistar rats were divided into two groups: group 1 (n=16), control (colon resection, no Seprafilm); group 2 (n=16), study group (colon resection and Seprafilm). All the rats received 50 Gy RT after left colon resection. Intra-abdominal adhesions were evaluated by grading and measurement of tissue-type plasminogen activator (tPA) as a tissue adhesion marker in peritoneal samples from the rats. tPA was determined using a commercially available ELISA kit. RESULTS: The levels of tPA were significantly increased in group 2 rats compared with those in the control group (P=0.0276). It was also seen that adhesions in the rats receiving Seprafilm were significantly less severe than those in the control group. CONCLUSION: Our findings suggest that the intraperitoneal administration of Seprafilm reduced the frequency and strength of adhesions.

The comparison of adenosine deaminase activity values with polymerase chain reaction results in patients with tuberculosis.

Three methods in the diagnosis and treatment of tuberculosis have been compared in this study. Serum adenosine deaminase activities of patients with tuberculosis was compared with those of control groups with (+) and (-) PPD (purified protein derivative) results and were found to be higher than the controls. Within the controls the PPD (+) group displayed higher adenosine deaminase activities in comparison to the PPD (-) group. All patients had growth of B. Tuberculosis in the culture medium and all but one had positive polymerase chain reaction (PCR) results. Control patients were negative for culture and PCR. The sensitivity of ADA (adenosine deaminase) assay was 91.7% and specificity was 94.5%, whereas PCR had a sensitivity of 95.8% and a specificity of 100%. The ADA assay may be used in adjunction with other methods in the follow-up of tuberculosis with high sensitivity, specificity, and ease in applicability and specimen collection.

Ossified adamantinous type craniopharyngiomas. A series of 13 patients.

Thirteen patients admitted to hospital mainly with visual disturbances (100%), retarded growth (39%) and diabetes insipidus (23%) were all diagnosed as ossified adamantinous craniopharyngioma. Tumour size was found to be large in all patients. Localization displayed a heterogenous dissemination; 8% intra-suprasellar, 69% suprasellar-extraventricular, 15% extra-intraventricular, and 8% in the suprasellar region extending bilaterally to the frontal and temporal lobes. During the early postoperative period, four patients died with hypothalamic deterioration. Three patients underwent a second operation in view of recurrence, and one died from an infection. Thus, the postoperative survival rate was 62%. All the patients who survived continued to have visual disturbances, but only one deteriorated. Five patients exhibited diabetes insipidus during the postoperative period, among them 4 after surgical intervention and 5 patients displayed panhypothyroidism, three of them after surgery. Consequently, it is confirmed by the present review that craniopharyngiomas still offer a potential dilemma in their management. Difficulties caused by adhesion or invasion of ossified craniopharyngiomas and thus the increase in morbidity and mortality during surgical intervention and in the postoperative period are discussed.

Differential regulation of Pyk2 and focal adhesion kinase (FAK). The C-terminal domain of FAK confers response to cell adhesion.

Pyk2 is a recently described cytoplasmic tyrosine kinase that is related to focal adhesion kinase (FAK) and can be activated by a variety of stimuli that elevate intracellular calcium. In this report, we showed that Pyk2 and FAK tyrosine phosphorylation are regulated differentially by integrin-mediated cell adhesion and soluble factors both in rat aortic smooth muscle cells, which express endogenous Pyk2 and FAK, and in transfected Chinese hamster ovary cells. We also found that Pyk2 is diffusely present throughout the cytoplasm, while FAK is localized in focal contacts as expected, suggesting that the different localization may account for their differential regulation. By analyzing a chimeric protein contain N-terminal and kinase domains of Pyk2 and C-terminal domain of FAK, we provided evidence that the distinctive C-terminal domains of Pyk2 and FAK were responsible for their differential regulation by integrins and soluble stimuli as well as their subcellular localization. Finally, we correlated FAK, Pyk2, and the chimeric protein binding to talin, but not paxillin, with their regulation by integrins and focal contact localization. These results demonstrate that the distinctive C-terminal domain of Pyk2 and FAK confer their differential regulation by different subcellular localization and association with the cytoskeletal protein talin.