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The ω3 polyunsaturated fatty acids (PUFAs) are known to have beneficial effects on health and diseases, and hence their intake is encouraged. However, it remains unknown as to how ω3 PUFAs affect female reproduction processes, in which ω6 PUFA-derived prostaglandin (PG) E

Background Alginates have a wide variety of potential clinical applications, including use in cell encapsulation, drug delivery, and tissue engineering. Although the compounds are typically used in the form of a calcium hydrogel, alginates in this form possess several disadvantages, including low biodegradability, induction of foreign body reactions, and cytotoxicity secondary to Ca2+ efflux and contamination with bioincompatible substances. Thus, the goal of the present study was to develop a new method of obtaining sterilized, pure, highly viscous alginate sol from seaweed alginates and to determine its utility as an injectable antiadhesion drug. Methods Viscous injectable pure alginate sol was produced from a commercially available sodium alginate, and its molecular and physical characteristics were analyzed. The biological properties of the viscous injectable pure alginate sol were analyzed using cultured fibroblasts prepared from the dorsal skin of neonatal rats to determine its biocompatibility and its effects on cell proliferation, cell migration, and collagen lattice contraction. Results The mannuronic acid-to-glucuronic acid ratio of viscous injectable pure alginate sol, as determined by nuclear magnetic resonance studies, was 1.2, and its viscosity at 5 percent was 17,800 mPa. Purification used to produce viscous injectable pure alginate sol decreased contamination by insoluble particles by 20 percent and decreased polyphenol concentration by 17 percent. In vitro analyses with cultured fibroblasts demonstrated that viscous injectable pure alginate sol had excellent biodegradability and biocompatibility and that viscous injectable pure alginate sol inhibited fibroblast proliferation and migration. Furthermore, assessment of collagen contraction with floating fibroblast-loaded collagen lattices indicated that viscous injectable pure alginate sol enhanced wound healing in surrounding connective tissues. Conclusions The authors conclude that viscous injectable pure alginate sol can inhibit scar formation by presenting a physical barrier to invading fibroblasts and by enhancing wound healing of surrounding tissues.

The patient was a 48-year-old man in whom a slow progression in walking difficulty occurred over a year. Magnetic resonance imaging (MRI) and computed tomography myelography (CTM) revealed duplicated dura mater from T1 to T12 and spinal cord herniation in the inner layer of the dura at the T4-T5 level. Idiopathic spinal cord herniation with duplicated dura mater was diagnosed, and surgery was performed. Intraoperative findings were of an elliptical defect of about 1 cm in the inner layer of the dura at the T4-T5 level, into which the spinal cord was herniated. A 1.5-cm cephalocaudal incision was created in the inner layer of the dura, and the incarcerated spinal cord was released, resulting in resolution of gait disturbance and an excellent postoperative clinical course. We reviewed the reports of 11 cases of idiopathic spinal cord herniation with duplicated dura mater and summarized the clinical and imaging characteristics as follows: 1) A hernial orifice was found at the T4-T6 level, 2) cross-sectional MRI or CTM showed a "snowman-like" deformation of the spinal cord, and 3) symptoms were often improved by widening the hernia orifice.

This study describes the pharmacologic profile of a new Na+/H(+)-exchange inhibitor, FR183998, in anesthetized rats. FR183998 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes with median inhibitory (IC50) value of 0.3 nM. Treatment with FR183998 (0.01-0.32 mg/kg, i.v.) reduced or completely abolished ventricular fibrillation and mortality induced by 5-min ischemia followed by reperfusion, when it was administered not only 5 min before ischemia but also 1 min before reperfusion. Myocardial infarct size induced by 30-min ischemia and 60-min reperfusion was reduced significantly in a dose-dependent manner by FR183998 (0.1-1.0 mg/kg, i.v.) when the drug was administered preischemically or at an early phase of ischemia. The ventricular tachycardia and the ventricular fibrillation observed during the ischemic period also were suppressed significantly. These results indicate that FR183998 has a strong inhibitory effect on Na+/H+ exchange and suggest that treatment with FR183998 either before or immediately after the onset of ischemia can prevent the occurrence of arrhythmias and myocardial cell necrosis in situations of ischemia and reperfusion.

We have studied the effects of FR168888 (5-hydroxymethyl-3-(pyrrol-1-yl)benzoylguanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in anesthetized rats and compared them with those of other cardioprotective compounds. FR168888 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes acidified with Na+-propionate with a Ki value of 6.4 nM. Pretreatment with FR168888 (0.032-0.32 mg/kg, i.v.) reduced or completely abolished the ventricular fibrillation (VF) induced by reperfusion after 5 min of regional ischemia, while lidocaine, a class I antiarrhythmic agent, showed less effect against VF as compared with FR168888. The size of myocardial infarction induced by 60-min ischemia and 60-min reperfusion was attenuated by FR168888 dose-dependently (1.0-10 mg/kg, i.v.), and ventricular tachycardia and VF were significantly reduced during the ischemic period. In contrast, propranolol and diltiazem did not show such protective effects on myocardial infarct size. In addition, FR168888 did not change hemodynamic parameters in rats. These results indicate that FR168888 has a strong inhibitory effect on Na+/H+ exchange and that treatment with FR168888 can protect the heart from arrhythmia and myocardial cell death in ischemic and reperfused situations.

The transcriptional factor nuclear factor-kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes that might be involved in myocardial damage after ischemia and reperfusion. Therefore, we hypothesized that synthetic double-stranded DNA with high affinity for NFkappaB could be introduced in vivo as "decoy" cis elements to bind the transcriptional factor and to block the activation of genes mediating myocardial infarction, thus providing effective therapy for myocardial infarction. Treatment before and after infarction by transfection of NFkappaB decoy, but not scrambled decoy, oligodeoxynucleotides before coronary artery occlusion or immediately after reperfusion had a significant inhibitory effect on the area of infarction. Here, we report the first successful in vivo transfer of NFkappaB decoy oligodeoxynucleotides to reduce the extent of myocardial infarction following reperfusion, providing a new therapeutic strategy for myocardial infarction.

The lack of efficient treatment for myocardial infarction remains an unresolved problem in the field of cardiovascular disease. Gene therapy may be a potential therapeutic strategy for the treatment of myocardial infarction. However, current methods of in vivo gene transfer into the heart are limited by their low efficiency and/or potential toxicity. In the present study, we developed an efficient technique of gene transfer into the intact heart in vivo using the Sendai virus (HVJ: Hemagglutinating Virus of Japan)--liposome method. We used the beta-galactosidase gene, luciferase gene and human angiotensin converting enzyme (ACE) gene as markers. In vivo gene transfer into the rat heart was performed as follows: (1) direct injection into the rat heart, (2) incubation within the pericardium, and (3) infusion into a coronary artery. Direct injection of the HVJ-liposome complex containing the beta-galactosidase vector into the rat heart resulted in limited staining of beta-galactosidase 3 days after transfection. To compare transfection efficiency between "naked" plasmid DNA transfection and the HVJ-liposome method, we also transfected the luciferase reporter gene into the heart. Luciferase activity was significantly higher in hearts transfected by the HVJ-liposome method than that in hearts transfected by direct "naked" plasmid transfection (P0.01). To confirm the successful gene in the protein level, we measured ACE activity in the hearts. Cardiac ACE activity was significantly increased in hearts transfected with human ACE gene as compared to hearts transfected with control vector (P0.01). On the other hand, incubation of HVJ-liposome complex, containing beta-galactosidase vector, within the pericardium resulted in widespread staining of cardiac myocytes and fibroblasts, mainly located in several surface layers beneath the pericardium. More importantly, widespread stained areas of beta-galactosidase were also observed in the middle of the myocardium around the vasa vasorum. We also examined the efficiency of gene transfer by the HVJ-liposome method in a rat myocardial infarction model. In the infarction model, using the pericardium incubation approach, staining for beta-galactosidase was observed in the viable cells around the infarction area. Finally, direct infusion of the HVJ complex, containing the beta-galactosidase vector, into coronary artery also resulted in widespread staining of beta-galactosidase in cardiac myocytes around the microvasculature. Using direct injection, we found significant injury to the myocardium and severe fibrosis at the injection site, whereas no apparent injury was observed using pericardium incubation and coronary infusion. There was no evidence of cytotoxicity or inflammation caused by the HVJ-liposome complex itself. Overall, we have established an efficient in vivo gene transfer method into the heart using the HVJ-liposome method. Direct infusion into the coronary artery resulted in widespread transfection without damaging the myocytes; incubation within the pericardium demonstrated the usefulness of the HVJ-liposome method for studying cardiac function and as a means of gene therapy for cardiovascular diseases.

The aim of this study was to compare the antianginal effects of two compounds that release nitric oxide (NO) spontaneously, i.e. (+/-)-N-[(E)-4-ethyl-3-[(Z-hydroxyimino]-5-nitro-3-hexenyl] -3-pyridinecarboxamide (FR144420) and (+/-)-(E)-ethyl-2-[(E)-hydroxyimino] -5-nitro-3-hexenamide (FK409), in two different rat models of coronary vasospasm. In the rat methacholine-induced coronary vasospasm model, FR144420 suppressed the elevation of the ST segment dose dependently and significantly at 1.0 mg/kg, i.d. 185 min after its administration. FK409 suppressed the ST elevation only 5 min after its administration at 1.0 mg/kg, i.d. FR144420 and FK409 significantly decreased mean blood pressure at all doses tested only 5 min after their intraduodenal administration, but did not change heart rate at any time. Although the suppression of the ST elevation by FK409 had the same duration as its hypotensive effect, the FR144420-induced suppression of the ST elevation lasted longer than its hypotensive effect. In the rat vasopressin-induced coronary vasospasm model, FR144420 (32 mg/kg) significantly inhibited the depression of the ST segment both 60 min and 120 min after oral administration, whereas FK409 (32 mg/kg) significantly inhibited this ST depression only 60 min after oral administration. These data suggest that FR144420 inhibits coronary vasospasm for longer than FK409 does and particularly shows more prolonged antianginal effects than hypotensive effects in the methacholine-induced coronary vasospasm model. Thus FR144420 is expected to be a useful NO releaser for investigating the in vivo actions of NO.

Clinical treatment of recurrent symptoms following peripheral nerve decompression is problematic. Removal of scar tissue can produce an inappropriately pronounced healing response and thereby lead to more serious tethering or compression of the nerve. The goal of the present study was to test the ability of viscous injectable pure alginate sol to prevent perineurial adhesion using a rat neurolysis model.The antiadhesive effect of viscous injectable pure alginate sol after neurolysis was evaluated histologically and biomechanically. A total of 40 rats were used in this study. The viscous injectable pure alginate sol was applied topically on the right side after external (six rats) or extensive internal (six rats) neurolysis, whereas the left side received no treatment. The nerves were harvested over 6 weeks, and histologic analysis was performed with hematoxylin and eosin staining and Masson trichrome staining. Functional analysis of the blood and perineurial barriers was also evaluated with Evans blue albumin (four rats). Sixteen rats were used for biomechanical analysis, and eight rats were used as a control group. The results were analyzed statistically using a post hoc test.Histologic examination showed that the use of viscous injectable pure alginate sol was associated with excellent biocompatibility and strong inhibition of perineurial granulation. Viscous injectable pure alginate sol was absorbed completely within 6 weeks without inducing inflammation. In addition, viscous injectable pure alginate sol enhanced repair of the perineurium associated with regeneration of epithelial-like cell layers, a key structure necessary for barrier function of the inner layer of the perineurium. Functional analysis with Evans blue albumin clearly demonstrated that, although blood nerve barrier function recovered by 6 weeks postoperatively in all nerves, the perineurial barrier function recovered only in the sol-treated nerves. Biomechanical study showed a significant antiadhesive effect of viscous injectable pure alginate sol.Viscous injectable pure alginate sol inhibited adhesion formation around nerves and enhanced regeneration of the perineurium with barrier function. Because excessive perineurial fibrosis and tethering at the neurolysis or neurorrhaphy site is a common postoperative problem in peripheral nerve surgery, viscous injectable pure alginate sol appears to have potentially broad clinical applications.

Due to the lack of correlation between symptom severity and electrophysiology or nerve function, the 'container hypothesis' has emerged as a new concept in carpal tunnel syndrome (CTS). This proposes that symptoms relate to connective tissue alteration rather than to nerve fibre pathology. This study was conducted to investigate the pathology of the flexor tenosynovium and its relationship with symptomatology. The subjects comprised 40 patients with electrophysiologically proven CTS who underwent open carpal tunnel release (age range: 31-79 years). In all patients, subjective symptom severity was assessed with a Likert scale and symptom duration was recorded preoperatively. Flexor tenosynovium biopsied during surgery was analysed for arterial and connective tissue alteration. Proliferative arteriosclerosis was graded using the modified Banff score. Gelatin zymography and immunohistochemistry were also performed to investigate the role of gelatinase in CTS. Relationships were evaluated using Spearman rank correlation coefficients. Proliferative arteriosclerosis occurred with disease progression in the flexor tenosynovium, in the absence of inflammation. This event did not correlate with patient age but correlated closely with symptom duration. Immunohistochemistry with antibodies against MMP-2 and elastic van Gieson staining revealed that arterioles express high levels of MMP-2 within 3 months of symptom onset and that intimal hyperplasia proceeded rapidly between 4 and 7 months, resulting in severe vascular narrowing. Gelatin zymography showed that MMP-2 activity correlated negatively with symptom duration and positively with pain severity.

1. The aim of this study was to compare antianginal effects of (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), a new spontaneous nitric oxide releaser, with those of isosorbide dinitrate (ISDN). We used two types of rat angina model; methacholine- and arginine vasopressin (AVP)-induced coronary vasospasm models. 2. In the in vitro study, FK409 showed 80 times more potent vasorelaxant effect in dog isolated coronary artery than ISDN (EC50 = 16.7 +/- 4.8 and 1340 +/- 320 nM, respectively). 3. In the rat methacholine-induced coronary vasospasm model, FK409 suppressed the elevation of ST segment dose-dependently and significantly at 0.1 mg kg-1, i.d. On the other hand, ISDN suppressed it significantly at 3.2 mg kg-1, i.d. In addition, the efficacy of 3.2 mg kg-1 ISDN in the model was almost the same as that of 0.1 mg kg-1 FK409. 4. In the above experiments, FK409 and ISDN decreased mean blood pressure significantly at the maximum dose tested (1.0 mg kg-1, i.d. and 3.2 mg kg-1, i.d., respectively) but did not change heart rate at these doses. Therefore, the hypotensive effect of FK409 was 10 times weaker than the antianginal effect of the compound, while those of ISDN were almost the same. 5. In the rat AVP-induced coronary vasospasm model, 32 mg kg-1 FK409 significantly inhibited the depression of ST segment 60 min after oral administration. On the other hand, 32 mg kg-1 ISDN did not inhibit it at 60 and 120 min after oral administration. 6. In conclusion, FK409 inhibits coronary vasospasm more potently in two types of rat angina models than ISDN. In addition, FK409 shows an antianginal effect more selectively that a hypotensive effect,compared with ISDN.