Facial Scanning and Additive Manufacturing Used in Production Nasal Prosthesis.

Maxillofacial prosthesis is an effective treatment for patients with facial sequelae, but it remains challenging for professionals due to its high esthetic complexity. This study describes a clinical case of successful nasal prosthetic rehabilitation using digital technology and additive manufacturing. Initially, the 76-year-old patient, with a facial defect in the nasal region, had her face scanned with 3-dimensional scanner for laboratory planning of the prototype of a nasal prosthesis. After approving the prototype image, working models in muffle shape were obtained in additive manufacture for the inclusion of the prosthesis. In the final session, the prosthesis was colored extrinsically and installed. The procedures digital in the manufacture of the facial prosthesis was applicable and agile, allowing the professional greater predictability regarding the shape of the rehabilitated organ, esthetic improvement in the mutilated area and patient satisfaction in relation to the speed, of the procedure and the quality of the prosthesis.

Synergistic induction of interleukin-6 expression by endothelin-1 and cyclic AMP in adipocytes.

BACKGROUND: We have demonstrated previously that endothelin-1 (ET-1) may stimulate interleukin-6 (IL-6) release from 3T3-L1 adipocytes. In this study, we further examined the combined effect of ET-1 and cyclic adenosine monophosphate (cAMP) on IL-6 release. METHODS: IL-6 release was measured by enzyme-linked immuosorbent assay. Reverse transcriptase-PCR and real-time PCR analyses were used to determine cellular mRNA levels. A luciferase reporter driven by promoter (-1310/+198) of mouse IL-6 gene was transfected into 3T3-L1 adipocytes to monitor IL-6 transcription. RESULTS: ET-1 and cAMP induced IL-6 release in a synergistic manner that can be attributed to their synergistic induction of IL-6 gene expression, as evidenced by IL-6 mRNA analysis and the IL-6 promoter reporter assay. Both ET(A) and ET(B) receptors seem to be involved. In addition, enhanced IL-6 promoter activity can be similarly induced by ET-1 and catecholamines (epinephrine and norepinephrine). The cooperative interaction between ET-1 and cAMP on IL-6 expression seems distinctive, as no other proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-1ß, are similarly affected. In fact, cAMP inhibited ET-1-stimulated TNF-α and IL-1ß expressions in adipocytes. Furthermore, injection of mice with epinephrine and ET-1 induced a tremendously synergistic increase in serum IL-6 levels. Nevertheless, whereas cAMP induced IL-6 expression in RAW264.7 mouse macrophages, ET-1 had no effect on either the basal or the cAMP-induced IL-6 expression. CONCLUSION: ET-1 and epinephrine may boost plasma IL-6 levels in mice in a synergistic manner, probably through their synergistic induction of IL-6 expression in adipocytes. SIGNIFICANCE: This study should provide a new perspective for treating IL-6-related diseases, especially those accompanied with elevated ET-1 and catecholamine levels.

Liver Surgery for Hepatocellular Carcinoma: Laparoscopic versus Open Approach.

In this study, we try to compare the benefit of laparoscopic versus open operative procedures. Patients and Methods. One hundred and sixteen patients underwent laparoscopic liver resection (LR) and another 208 patients went for open liver resection (OR) for hepatocellular carcinoma (HCC). Patients' selection for open or laparoscopic approach was not randomized. Results. The CLIP score for LR and OR was 0.59 ± 0.75 and 0.86 ± 1.04, respectively, (P = .016). The operation time was 156.3 ± 308.2 and 190.9 ± 79.2 min for LR and OR groups, respectively. The necessity for blood transfusion was found in 8 patients (6.9%) and 106 patients (50.9%) for LR and OR groups. Patients resumed full diet on the 2nd and 3rd postoperative day, and the average length of hospital stay was 6 days and 12 days for LR and OR groups. The complication rate and mortality rate were 0% and 6.0%, 2.9% and 30.2% for LR and OR groups, respectively. The 1-yr, 3-yr, and 5-yr survival rate was 87.0%, 70.4%, 62.2% and 83.2%, 76.0%, 71.8% for LR and OR group, respectively, of non-significant difference. From these results, HCC patients accepted laparoscopic or open approach were of no significant differences between their survival rates.

Insulin sensitivity and resistin expression in nitric oxide-deficient rats.

AIMS/HYPOTHESIS: The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. METHODS: Male Sprague-Dawley rats received [Formula: see text]-nitro-L: -arginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. RESULTS: Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.

Infective endocarditis in patients receiving chronic hemodialysis: clinical features and outcome.

BACKGROUND AND AIM OF THE STUDY: Patients undergoing chronic hemodialysis are at increased risk of infective endocarditis (IE), and mortality is high in this group. The study aim was to determine clinical features and outcome of IE in patients with chronic renal failure and receiving hemodialysis. METHODS: Between 1987 and 2002, all consecutive patients with infective endocarditis treated at the authors' institution who were not intravenous drug abusers were selected prospectively. A comparative analysis was performed of patients undergoing hemodialysis and other patients in the series. RESULTS: A total of 241 cases of IE was diagnosed, and 14 patients (6%) were receiving hemodialysis. A lower frequency of known predisposing heart disease (14% versus 74%, p <0.01) and prosthetic valve endocarditis (0% versus 35%, p <0.05) and a higher rate of negative blood cultures (21% versus 12%, p <0.05) were detected in hemodialysis patients. Early surgery was performed in 50% of patients in both groups. The frequency of complications was similar in both groups, but early (43% versus 16%, p = 0.03) and late (22% versus 9%, p <0.05) mortality were higher in hemodialysis patients. CONCLUSION: Patients with IE who are undergoing hemodialysis have a lower frequency of predisposing heart disease and higher rates of negative blood cultures. Although patient groups were similarly treated, early and late mortality was significantly higher among those receiving dialysis.

Clinical significance of cell differentiation in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is commonly found in Asian countries and prognosis still remains unsatisfactory due to recurrence after surgical tumor resection. METHODOLOGY: We try to demonstrate the recurrence and survival time in 99 surgical patients grading by tumor cellular differentiation from surgical specimen. RESULTS: The rates of well, moderate, and poor differentiation were encountered in 21 cases (21.2%), 61 cases (61.6%) and 17 cases (17.7%), respectively. Small tumor (< 3 cm) was found in only one (5.9%) in the poor differentiation group and 38.1% and 37.7% in the well and moderate differentiation groups. Capsular invasion was found in 13 (61.9%), 39 (63.9%) and 7 (41.1%) in the well, moderate and poor differentiation group, respectively. We found 41.9% (18/43) and 22.4% (13/58) to be tumor free in capsule invasion (-) and (+) after a period of 18.1 and 29.9 months, respectively. However, the recurrent time was 10.6 and 11.3 months, respectively with no significant difference (p > 0.05). Vascular invasion was more frequent in the poor differentiation group (76.5%) than the well (23.8%) and moderate (60.7%) differentiation groups (P < 0.05). We found 23.5% (4/17) and 35% (21/60) to be tumor free but the recurrence time was 6.5 and 14.1 months for the vascular invasion (-) and (+), respectively. The residual median survival times were 6.5 and 14 months after recurrence, respectively. The tumor recurrence rates were 52.7% (11/21), 52.4% (32/61), and 35.5% (6/17) and recurrence times were 11.7, 11.9, and 4.5 months for the well, moderate and poor differentiation group respectively totally. The recurrence time of young age group (< 39 years old) was shorter than the others and there was no patient of well differentiation less than 40 years old. The recurrence time was shorter in the poor differentiation group but there was no significant difference according to age group. The median survival times were 22.2, 22.9, and 9.5 months for each group, respectively. CONCLUSIONS: Differentiation of hepatocellular carcinoma cell had a clinical significance and was found to be positively correlated with the invasive proclivity. The median survival time was longer in both the well and moderate differentiation group, but not in the poor differentiation group. The clinical data revealed that the extended operations performed upon the patients with poor differentiation effected the recurrence time but not the survival time.

Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids.

Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.

The stimulatory effect of vasoactive intestinal peptides on the cortisol production of guinea pig Zona fasciculata cells: an extra-ACTH regulatory model of the adrenocortical function.

The effect of vasoactive intestinal peptide (VIP) on cortisol production was studied in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells. In ZF cells, VIP stimulates cortisol secretion and enhances the steroidogenic action of ACTH. Compared to ACTH on an equal molar basis, the cortisol-stimulatory effect of VIP is at least 10-fold less potent. As VIP exhibits a wide range of biological actions with widespread distribution in the body, the steroidogenic action of VIP on the adrenal glands is not tissue-specific. There are VIP receptors in ZF cells. With the aid of a VIP receptor antagonist, we found that ACTH and VIP mutually bind each other's receptors with an affinity-ranking order of ACTH > VIP receptor antagonist > VIP. VIP stimulates cortisol production most likely through the cyclic AMP (cAMP) signaling pathway. Both ACTH receptors and the VIP receptors bind VIP receptor antagonist more avidly than VIP, but the bindings do not lead to a consequential effect on cAMP production and cortisol secretion. However, the VIP receptor antagonist counteracted ACTH and VIP to lower both cAMP and cortisol production. In addition, ASIF and BNP-32, which are the proven ACTH receptor antagonists, reduced the cortisol-stimulatory effect of ACTH and VIP. These results suggest that besides ACTH, VIP be an important factor in regulating the cortisol secretion from the adrenal cortex at the site of ACTH receptors. In cases with hypercortisolemia being detected concomitantly with normal or low ACTH levels, we may need to investigate the influential role of VIP.

Laparoscopic subsegmentectomy for hepatocellular carcinoma with cirrhosis.

BACKGROUND/AIMS: Laparoscopic liver resection is feasible for both benign and malignant disease with today's laparoscopic techniques and technology. Location of the tumor at the edge of segment 3, 4, 5, or 6 of our patients makes them an ideal candidate for laparoscopic resection. METHODOLOGY: There were 9 patients who underwent laparoscopic subsegmentectomy for hepatocellular carcinoma with cirrhosis. They were classified as Child A in 6 and B in 3 patients. Hepatitis B was found in 5 and Hepatitis C in 4 cases. Preoperative diagnosis of hepatocellular carcinoma was completed in 7 and definitive histologic diagnosis from frozen section in 2 cases. All 9 patients underwent subsegmentectomy and removal of the tumor with non-tumor cirrhotic liver with a distance of 10 mm at the least margin. Laparoscopic ultrasound allows exact localization of lesions and achievement of adequate resection margin. RESULTS: Those patients resumed a full diet on the 2nd-3rd day after the operation and were discharged home on day 4-7 with no complications but one had prolonging discharge due to ascitis from a drainage tube. Finally, the ascitis was controlled by medications for 1 week. All patients had high postoperative satisfaction. CONCLUSIONS: Laparoscopic liver resection is a procedure of significant risk and technically demanding. Therefore, it should be performed only by experienced liver surgeons with a high level of laparoscopic skill and in the carefully selected patient.

Further study of aldosterone secretion-inhibitory factor and brain natriuretic peptide on cortisol production of guinea pig zona fasciculata cells.

The suppressive effect of aldosterone secretion-inhibitory factor (ASIF) and brain natriuretic peptide (BNP-32) on the basal and ACTH-stimulated cortisol production in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells was further studied. The binding of 125I-labeled ACTH(1-24) and ASIF to ZF cells was found to be displaced by ACTH(1-24), [Phe2, Nle4 and Ala24]-ACTH(1-24), ASIF, and BNP in a concentration-dependent manner. The binding of 125I-labeled [Phe2, Nle4 and Ala24]-ACTH(1-24) to two transformed clones of mammalian cells expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF and BNP. ASIF and BNP significantly suppressed ACTH-stimulated cAMP production in ZF cells. The 10- and 30-min cellular changes in cAMP induced by ASIF and BNP did not correlate in the rank order with the ultimate magnitude of cortisol suppression observed in ZF cells after a 24-hour treatment with these peptides. Nevertheless, the results did conform to the signaling mechanism of their action. Overall, the findings clearly demonstrated that ASIF and BNP suppressed the adrenocortical function and inhibited ACTH for their antagonistic action against ACTH primarily at the ACTH receptor site. These results support the notion that a physiological role of adrenal medulla in regulating the adrenocortical function may be mediated by the neuropeptides through a paracrine pathway.

Laparoscopic subsegmentectomy for hepatocellular carcinoma with cirrhosis: a case report.

Laparoscopic liver resection is feasible for both benign and malignant disease with present laparoscopic techniques and technology. Laparoscopic liver tumor resection is indicated instead of the conventional hepatectomy if the tumor is located in the peripheral part of the liver. Here, we reported a case of a 73-year-old woman who accepted laparoscopic subsegmentectomy for hepatocellular carcinoma of segment 6. After traditional laparoscopic trocar was settled down under the low pneumoperitoneal pressure of 8 mm Hg, laparoscopic ultrasound allowed exact localization of lesions first and then transection line was marked. Then, dissection the liver parenchyma was carried out with laparoscopic microwave coagulator and ultrasonic aspirator gradually. After operation, she resumed full diet on the second day and was discharged on the 5th post-operative day with no complications and high patient satisfaction. She had follow-up study regularly in our clinic and was disease free at nine months. With the improvement of laparoscopic techniques and the development of new and dedicated technologies, laparoscopic hepatectomy has become feasible.

Oxidative stress is insignificant in N1S1-transplanted hepatoma despite markedly declined activities of the antioxidant enzymes.

It has been proposed that persistent oxidative stress accounts for the increased levels of DNA damage in cancer tissues. We have examined the profile of anti-oxidant enzymes in a transplanted hepatic tumor model by injecting N1S1 rat hepatoma cells into the liver of Sprague-Dawley rats. The transplanted N1S1 tumors displayed characteristics resembling human hepatocellular carcinoma. The immunoreactivities of catalase (CAT), manganese-superoxide dismutase (Mn SOD), copper/zinc-SOD (Cu/Zn SOD), and glutathione peroxidase (GPx) were found to decrease significantly. The enzyme activity in tumors decreased 26.2-, 4.2-, 4.5-, and 5.4-fold for CAT, Mn SOD, Cu/Zn SOD, and GPx, respectively, relative to those in normal liver tissue from the same animals. In contrast, the mRNA levels of CAT and GPx in tumors decreased only 5- and 2-fold, respectively, and the mRNA levels of Cu/Zn SOD and Mn SOD showed either no change or an increase as compared to those of normal liver tissue. The contents of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and thiobarbituric acid-reactive substances (TBARS) were comparable to those of normal controls. Furthermore, mitochondrial production of superoxide in tumors was 4 times lower than that in normal tissues. In conclusion, the data indicate that the reduced activities of anti-oxidant enzymes in the N1S1 tumor did not cause significant oxidative stress.

Role of angiogenesis in hepatitis and hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is usually a hypervascular tumor. Factor VIII-related antigens, including von Willebrand factor, are known to be expressed in HCC, which cause capillarization of the sinusoids of HCC. Capillarization of hepatic sinusoids may play a role in hepatocarcinogenesis and its metastasis. The aim of this study is to clarify the expression of Factor VIII in patients with hepatitis B or C (n = 18) and HCC (n = 16). METHODOLOGY: All specimens were sufficient for immunohistochemical study of the neo-angiogenesis with regard to clinical results. Microvessel count per square millimeter (MVC) and hot spot of microvessel per square millimeter (HSV) were measured from the histochemical study. RESULTS: In the patients with hepatitis group, the positive staining on the vessels of the portal triad was 11.1% (2/18) but in the non-neoplastic tissue of HCC patients the positive rate was 68.7% (11/16) showing a significant difference from the hepatitis group. The amount of vasculatures was easily found in the surrounding capsule of resected HCC. The MVC of the capsule was 10.17 +/- 2.78 and 13.66 +/- 5.42 for the HCC with non-direct invasion and direct invasion during operation, respectively. The HSV of capsules were 7.51 +/- 2.09 and 9.14 +/- 4.02 for the non-invasion and invasion, respectively. Therefore, in our study, it is clear that the high MVC or HSV scores were found in patients of direct invasion. However, there was no relation between hepatitis B or hepatitis C to the tumor invasiveness. The median survival times were 21.5 months for the non-invasive group and 14.5 months for the invasive group (p < 0.05). The positive rate of Factor VIII in the vessels of the portal triad were 60% and 83.3% for the non-invasive and invasive groups, respectively. However, the lower values of MVC and HSV showed a trend toward a longer recurrence time. CONCLUSIONS: It is pertinent to prove that the high score of neo-angiogenesis has a high risk of recurrence. In addition, it is wise to pay more attention to the interval of the follow-up study to detect the recurrent lesion earlier, where possible, in the patient with a high score of microvascularity.

Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and subsequent hypertension in rats.

In many clinical and animal studies, hypertension and insulin resistance coexist, but their mechanistic relationship is unclear. We explored the causal link between these two parameters in a rat model with chronic hyperinsulinemia induced with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats with saline minipumps served as a control. During the first experiment, plasma levels of insulin and glucose and the systolic blood pressure of the two groups were continuously monitored for 17 days. In the subsequent four experiments, rats were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and the glucose transport into and insulin and ET-1 binding of isolated adipocytes. In one experiment, rats were tested for oral glucose tolerance on days 10 and 13. In another experiment, ET-1 binding to the aortic plasma membrane was also determined. The results showed that rats became hyperinsulinemic throughout the experimental period by the instillation of exogenous insulin. Hyperinsulinemic rats were consistently hypoglycemic during the first day, but they became euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance was obvious by day 10, but significant hypertension was not detected until the 11th day on insulin infusion. Compared with the saline controls, insulin-infused rats had an increase of plasma ET-1 levels but a decrease of both basal and insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes of the insulin-infused group was elevated significantly from day 10 through day 13. ET-1 binding to the aortic membranes, supposedly downregulated by the increased plasma ET-1 and hypertension, was similar to that found in the controls on day 13. These results imply that hyperinsulinemia in rats could lead to hypertension via the elevation of plasma ET-1 levels together with an unaltered vascular binding of ET-1, which was probably unrelated to the insulin resistance.

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors.

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETC receptors, to displace [125I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 >> ET-3, indicating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 micromol/L, BQ-610, a selective ETA antagonist, displaced [125I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETB antagonist, did not. Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes.

Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.

OBJECTIVE: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. DESIGN: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. MATERIALS AND METHODS: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. RESULTS: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Menadione (vitamin K3) enhances the mitogenic signal of epidermal growth factor via extracellular signal-regulated kinases.

The effects of vitamin K3 (VK3) on DNA synthesis, cell proliferation and mitogen-activated protein kinase pathway were investigated in G0-arrested NIH 3T3 fibroblasts. VK3 (5 microM) alone stimulates DNA synthesis by 40% and moderately increases the mitogenic effects of EGF, which is preceded by a rapid phosphorylation of the extracellular signal-regulated kinases (ERKs). At 20 microM, VK3 had an antiproliferative effect. VK3 alone (5 and 50 microM) or in concert with EGF increases the activity of ERK2 (by 2.5 and 5 fold, respectively). Our studies demonstrate that the activation of ERKs by VK3 alone, or VK3 plus EGF can promote either stimulatory or inhibitory effects on the mitogenic signal.

Up-regulation of beta-actin, cyclophilin and GAPDH in N1S1 rat hepatoma.

Beta-actin, cyclophilin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are all constantly expressed proteins that regulate cellular structures and endogenous cytoarchitectural functions. In this study, we used an in vivo N1S1 rat hepatoma model to examine changes in the expression levels of these housekeeping genes in normal and tumor liver samples. The beta-actin, cyclophilin and GAPDH genes were all up-regulated in tumor groups as compared to the controls. Our results suggest that up-regulation of beta-actin, cyclophilin and GAPDH genes may be essential for oncogenesis in hepatoma.

Eccrine porocarcinoma. Report of nine cases.

BACKGROUND: Eccrine porocarcinoma is a rare malignancy of the eccrine sweat gland and usually has a long-standing growth on a lower extremity. OBJECTIVE: The aim of this review was to analyze clinical and histopathological findings of eccrine porocarcinoma. METHODS: We report nine cases of eccrine porocarcinoma that we have seen during last 10 years. RESULTS: Eccrine porocarcinoma affects elderly patients in both sexes and is usually found on the lower extremities, but in our review it is similar on the head. The mean size was 1.9 cm in our cases. Elective primary treatment was excision and we did not perform elective lymph node dissection. We have not found evidence of metastases in any of our cases.

Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation.

In type II diabetic patients, one can detect several pathologic changes including insulin resistance and hypertension. Sprague-Dawley rats fed a fructose-rich diet (group F) exhibited these characteristic abnormalities within 2 weeks and were an excellent laboratory animal model for research on insulin action and development of hypertension. Since fish oils containing omega-3 fatty acids have a beneficial effect in preventing atherosclerotic diseases, we performed repeated experiments to test the effects of fish oil supplementation in group F rats. Compared with control rats on a normal diet (group C), group F consistently developed hypertriglyceridemia without elevated plasma free fatty acid (FFA), fasting hyperinsulinemia together with fasting hyperglycemia (insulin resistance syndrome), and systolic hypertension within 3 weeks. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced. Rats fed the same high-fructose diet but supplemented with fish oil (group O) had alleviation of all of these metabolic defects and a normalized insulin sensitivity and blood pressure. beta-Cell function as shown by plasma glucose and insulin responses to oral glucose remained intact in group F and group O. The plasma endothelin-1 (ET-1) level and ET-1 binding to adipocytes were not different among the three groups. Based on these results, we suggest that dietary high fructose induced hypertriglyceridemia and insulin resistance with normal islet function, and that the induced hypertension was not associated with plasma ET-1 abnormalities and was probably caused by other undefined pathologic changes that can be prevented by dietary omega-3 fatty acids.