Chronic restraint stress aggravated arthritic joint swell of rats through regulating nitric oxide production.

Stress-related hormone norepinephrine (NE) displayed diverse effects on immune system including macrophages, which influenced many kinds of inflammatory diseases. Nitric oxide (NO) from activated macrophages played an important role in inflammatory diseases. In this study, we investigated under chronic restraint stress how NE influenced the joint swell of Complete Freund's Adjuvant (CFA)-induced arthritis of rats and whether NE regulated macrophage's production of NO through influencing phosphorylation of protein kinases C (PKC). The results showed chronic restraint stress exacerbated paw swell of rats with arthritis. Inhibitor of inducible nitric oxide synthase, S-methylisothiourea (SMT), and 6-hydroxydopamine (6-OHDA) could counteract the effect of restraint stress on arthritis. NE, NO and endotoxin in plasma of rats underwent restraint were improved significantly. In vitro experiments, NE could promote macrophage to produce more NO and iNOS when macrophage was activated by lipopolysaccharide (LPS). This effect could be inhibited by α adrenergic antagonist phentolamine. Nevertheless, through α receptor NE could promote the phosphorylation of PKC and PKC inhibitor staurosporine could counteract NE's enhancive effect on production of NO and iNOS of macrophages. This study revealed that NE could exacerbate arthritic joint swell through promoting NO production, which was in α receptor dependent way through enhancing phosphorylation of PKC for NE to enhance the iNOS expression of activated macrophage.

Enhanced phosphorylation of MAPKs by NE promotes TNF-α production by macrophage through α adrenergic receptor.

The aim of this study was to investigate whether norepinephrine (NE) could regulate macrophage production of tumor necrosis factor alpha (TNF-α) by influencing the phosphorylation of mitogen-activated protein kinases (MAPKs). Primary macrophages from male BALB/c mice were applied to explore the mechanism by which NE influences the the secretion of TNF-α when macrophages were activated by lipopolysaccharides (LPS). We found that NE could increase crophage production of TNF-α when macrophages were activated by LPS, and this effect could be inhibited by α adrenergic antagonist phentolamine. Also, NE could increase the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), and p38, through α receptor. Furthermore, JNK inhibitor SP600125, ERK inhibitor U0126, and p38 inhibitor SB203580 could all partially counteract NE's effect on the phosphorylation of MAPKs, as well as TNF-α production by macrophages. This study revealed that as macrophages were activated by LPS, NE promoted the secretion of inflammatory factors by increasing the phosphorylation of MAPKs through an α receptor-dependent pathway. Our results provide the evidence of a relationship between stress and diseases, as well as the mechanism by which stress induces or affects the inflammation-related diseases.

Diagnosis and surgical treatment of primary hepatic lymphoma.

AIM: To assess the benefits and limits of surgery for primary hepatic lymphoma (PHL), and probability of survival after postoperative chemotherapy. METHODS: A retrospective analysis was undertaken to determine the results of surgical treatment of PHL over the past 8 years. Only nine patients underwent such treatment. The detailed data of diagnosis, treatment, and prognosis were carefully studied. RESULTS: All patients were mistaken as having α-fetoprotein-negative hepatic cancer before pathological diagnosis. The mean delay time between initial symptoms and final diagnosis was 26.8 d (range: 14-47 d). Hepatitis B virus infection was noted in 33.3% of these patients. Most of the lesions were found to be restricted to a solitary hepatic mass. The surgical procedure performed was left hepatectomy in five cases, including left lateral segmentectomy in three. Right hepatectomy was performed in three cases and combined procedures in one. One patient died on the eighth day after surgery, secondary to hepatic insufficiency. The cumulative 6-mo, 1-year, and 2-year survival rates after hepatic surgery were, respectively, 85.7%, 71.4%, and 47.6%. One patient survived for > 5 years after surgery without any signs of recurrence until latest follow-up, who received routine postoperative chemotherapy every month for 2 years and then regular follow-up. By univariate analysis, postoperative chemotherapy was a significant prognostic factor that influenced survival (P = 0.006). CONCLUSION: PHL is a rare entity that is often misdiagnosed, and has a potential association with chronic hepatitis B infection. The prognosis is variable, with good response to early surgery combined with postoperative chemotherapy in strictly selected patients.

Bidirectional influences of acetazolamide on central nervous system oxygen toxicity of rats.

Central nervous system oxygen toxicity, which occurs during diving and hyperbaric oxygen treatment, can lead to very dangerous situations, and it is of great importance to explore its mechanisms. We have speculated that cerebral blood flow plays a pivotal role in its occurrence. Except for acting as an anticonvulsant in clinical applications, acetazolamide is also a vasodilator used in both clinical and laboratory settings. In this study, when acetazolamide from 5 to 500 ug/kg body weight was administered by intracerebroventricular injection, the latency of central nervous system oxygen toxicity detected by electroencephalogram recording in rats subjected to hyperbaric oxygen at 6 atmospheres absolute was prolonged significantly. On the contrary, when the dose of intracerebroventricular injection achieved 5,000 ug/kg body weight, acetazolamide shortened the latency significantly. Intraperitoneal injection of acetazolamide more than 7.5 mg/kg body weight also shortened the latency significantly. Results also showed both intracerebroventricular injection of acetazolamide at a dose of 5,000 ug/kg body weight and intraperitoneal injection at dose of 7.5 mg/kg body weight inhibited the activity of carbonic anhydrase and increased the cerebral blood flow significantly, which helped aggravate oxidation damage and resulted in increased MDA and impaired glutathione peroxidase in brain tissue. But intracerebroventricular injection of acetazolamide at 5 ug/kg body weight had no effect on MDA and glutathione peroxidase, though it inhibited the activity of carbonic anhydrase. These observations indicated acetazolamide covers bidirectional influences on central nervous system oxygen toxicity. Within local brain tissue, especially neurons, it could exert its anticonvulsive effect on the central nervous system at low doses. On the other hand, under high doses, it would display its convulsive-hastening effect through increasing cerebral blood flow to aggravate the oxidation state of brain tissues and exacerbate central nervous system oxygen toxicity when subjected to hyperbaric oxygen. Blood flow of brain plays a pivotal role in central nervous system oxygen toxicity.

Hemorrhagic hepatic cysts mimicking biliary cystadenoma.

The hemorrhagic simple hepatic cyst is extremely rare and can sometimes be confused with biliary cystadenoma or cystadenocarcinoma. Here we present two cases of huge hemorrhagic simple hepatic cysts. Case 1 was a 43-year-old man with a cystic lesion measuring 13 cm x 12 cm in the right hepatic lobe. Ultrasound and computed tomography showed several mural nodules on the irregularly thickened wall and high-density straps inside the cyst. Case 2 was a 60-year-old woman with a huge cyst measuring 15 cm x 14 cm in the central liver. Ultrasound and magnetic resonance imaging showed the cystic wall was unevenly thickened and there were some flame-like prominences on the wall. The iconographic representations of the two cases mimicked biliary cystadenoma. Cystectomy and left hepatectomy were performed for the two patients, respectively. Both patients recovered quickly after their operations and showed no recurrence.

2-(3-Oxo-1,3-dihydro-isobenzofuran-1-yl)-phthalazin-1(2H)-one.

The reaction of 2-carboxy-benzaldehyde and hydrazine hydrate unexpectedly yielded the title compound, C(16)H(10)N(2)O(3), which comprises one phthalide ring, one phthalazine system and a chiral centre. The phthalide unit is almost perpendicular to the phthalazine system, forming a dihedral angle of 87.1 (3)°. The packing is governed by weak C-H⋯O hydrogen-bonding inter-actions, forming layers parallel to the ab plane.

[Extended hepatic pedicle occlusion in major hepatectomy for primary liver cancer].

OBJECTIVE: To evaluate the influence of extended hepatic pedicle occlusion (HPO) on hepatic ischemic/reperfusion (I/R) injury and intraoperative blood loss in major hepatectomy for primary liver cancer (PLC). METHODS: Between June 2001 and December 2005, a total number of 843 patients with PLC had been operated on. Those whose hepatic pedicle were occluded continuously for or longer than 30 min during hepatectomy were retrospectively reviewed (continuous HPO group) and compared to the patients whose hepatic pedicle were occluded for the same length of time but intermittently (intermittent HPO group). The amount of intraoperative blood loss, the percentage of the patients who needed blood transfusion and postoperative liver biochemical tests were compared between the two groups. RESULTS: There were 35 cases in continuous HPO group and 38 cases in intermittent HPO group with occlusion time between 30 min and 45 min. The two groups were matched for underlying liver disease ,preoperative liver function, tumor size and location, major intrahepatic vessel involvements and the types and extensions of the hepatectomies. The mean intraoperative blood loss in continuous HPO group was significantly less than that in intermittent HPO group (660 ml vs. 1054 ml, P < 0.05); accordingly, the percentage of patients who need blood transfusion in continuous HPO group was significantly lower than that in intermittent HPO group (48.6% vs. 78.9%, P < 0.01). Patients in both of the groups were recovered smoothly after operation, with no occurrence of liver failure. CONCLUSIONS: The hepatic pedicle can be continuously occluded for 3045 min in cirrhotic patients with well compensated liver function, and when compared to routine intermittent HPO, continuous HPO significantly decreases the intraoperative blood loss and reduces the need for transfusion. Meanwhile it does not increase the hepatic I/R injury.

[Surgical resection of hepatic tumor in segment IXb by anterior transhepatic approach].

OBJECTIVE: To evaluate the feasibility and the effect of surgical resection of hepatic tumor originated from segment IXb. METHODS: The cases with hepatic tumors in segment IXb who had been operated on between March 2003 and January 2007 were retrospectively reviewed. RESULTS: A total of 15 tumors in segment IXb, including 13 primary liver cancers and 2 benign tumors with a mean diameter of (4.3 +/- 1.6) cm, were successfully resected by anterior transhepatic approach under sequential occlusions of portal tride and total hepatic vascularity or portal tride clamping only. There was no operative mortality,with a mean operative time of (190.3 +/- 37.6) min and a mean operative blood lose of (376.7 +/- 252.7) ml. All the patients had uneventful postoperative course except one who suffered from ascites and edema of the low body, which was successfully managed medically. The mean postoperative hospital stay was (13.3 +/- 6.0) d. During the follow-up of 1-47 months, two patients with benign tumor enjoyed a normal life. Among the 13 patients with primary live cancers, 1 patient died of recurrence, 2 patients remained alive with intrahepatic recurrence and 10 patients survived without any sign of relapse, with a median tumor-free survival time of 23.5 months. CONCLUSIONS: Surgical resection of hepatic tumor in segment IXb, despite their sophisticated anatomic position, is feasible in technique with high safety. The local resection can provide the patients with potential to cure.

[Expression of heparanase mRNA and its clinical significance in primary hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of heparanase mRNA and its relation with the clinicopathological features and angiogenesis in primary hepatocellular carcinoma (HCC). METHODS: Expression of heparanase mRNA was detected by RT-PCR in 51 HCC lesions, and microvessel density (MVD) was detected by immunohistochemical stain with a factor VIII-related monoclonal antibody. RESULTS: Expression of heparanase mRNA was shown in 49.0% (25/51) HCC lesions. The positive rate of heparanase expression in tumors larger than 3 cm (63.6%, 21/33) was significantly higher than those in smaller tumors (22.2%, 4/18; P < 0.01). Heparanase expression was more frequent in highly invasive tumors (70.0%, 14/20) compared with moderately invasive tumors (46.7%, 7/15) and low invasive ones (25.0%, 4/16; P < 0.05). Moreover, heparanase expression in tumors with high MVD (62.5%, 20/32) was significantly higher than those in tumors with low MVD (26.3%, 5/19; P < 0.05). CONCLUSION: Heparanase mRNA expression may be important for the growth, invasion and angiogenesis of hepatocellular carcinoma.

[Inhibition of invasiveness of human mammary carcinoma cell line MDA435 by heparanase antisense oligodeoxynucleotide].

OBJECTIVE: To evaluate the inhibitory effect of heparanase antisense oligodeoxynucleotide (AS-ODN) on the invasiveness of human mammary carcinoma cell line MDA435. METHODS: The AS-ODN complementary to the start codon region of heparanase mRNA and its control, scrambled nonsense oligodeoxynucleotide (NS-ODN) were designed and synthesized and phosphorothioated. The ODNs were embedded in cationic liposome Lipofectin and transfected into MDA435 cells. The total RNAs and proteins were extracted from the cells 48 hours after transfection and then semi-quantitative RT-PCR and Western blotting were performed to evaluate the heparanase gene and protein expression levels respectively. The invasiveness of transfected MDA435 cells were measured quantitatively by Matrigel invasion assays. RESULTS: The heparanase gene and protein expression and invasiveness of MDA435 cells treated with AS-ODN of different final concentrations were significantly decreased compared with that of the controls (P < 0.01). Besides, the inhibitory effects were significantly different between the cells treated with AS-ODN of different concentrations (P < 0.01). The invasiveness inhibition rates were 34.0%, 57.8% and 79.7% at the cells treated with AS-DON of the final concentrations of 0.1 micro mol/L, 0.2 micro mol/L, and 0.4 micro mol/L, respectively. CONCLUSION: Heparanase AS-DON complementary to the start codon region of heparanase mRNA has a significant inhibitory effect on the invasiveness of human mammary carcinoma cell line in a dose-dependent manner.