Antibacterial, chemical and physical properties of sealants with polyhexamethylene guanidine hydrochloride

Abstract The aim of this study was to evaluate the influence of polyhexamethylene guanidine hydrochloride (PHMGH) in the physico-chemical properties and antibacterial activity of an experimental resin sealant. An experimental resin sealant was formulated with 60 wt.% of bisphenol A glycol dimethacrylate and 40 wt.% of triethylene glycol dimethacrylate with a photoinitiator/co-initiator system. PHMGH was added at 0.5 (G0.5%), 1 (G1%), and 2 (G2%) wt.% and one group remained without PHMGH, used as control (GCTRL). The resin sealants were analyzed for degree of conversion (DC), Knoop hardness (KHN), and softening in solvent (ΔKHN), ultimate tensile strength (UTS), contact angle (θ) with water or α-bromonaphthalene, surface free energy (SFE), and antibacterial activity against Streptococcus mutans for biofilm formation and planktonic bacteria. There was no significant difference for DC (p > 0.05). The initial Knoop hardness ranged from 17.30 (±0.50) to 19.50 (± 0.45), with lower value for GCTRL (p < 0.05). All groups presented lower KHN after immersion in solvent (p < 0.05). The ΔKHN ranged from 47.22 (± 4.30) to 57.22 (± 5.42)%, without significant difference (p > 0.05). The UTS ranged from 54.72 (± 11.05) MPa to 60.46 (± 6.50) MPa, with lower value for G2% (p < 0.05). PHMGH groups presented no significant difference compared to GCTRL in θ (p > 0.05). G2% showed no difference in SFE compared to GCTRL (p > 0.05). The groups with PHMGH presented antibacterial activity against biofilm and planktonic bacteria, with higher antibacterial activity for higher PHMGH incorporation (p < 0.05). PHMGH provided antibacterial activity for all resin sealant groups and the addition up to 1 wt.% showed reliable physico-chemical properties, maintaining the caries-protective effect of the resin sealant over time.

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins / Em busca de uma melhor compreensão da doença renal crônica: uma atualização em toxinas urêmicas

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

A doença renal crônica (DRC) caracteriza-se pela redução progressiva da filtração glomerular e/ou presença de proteinúria, e subsequente retenção progressiva de compostos orgânicos, denominados toxinas urêmicas. Nas últimas décadas, um grande número destes compostos foi identificado, assim como seus efeitos adversos no organismo, sobretudo no sistema cardiovascular. Nesta revisão, apresentamos a classificação das toxinas urêmicas, proposta pelo grupo europeu de estudo em toxinas urêmicas (EUTox), e discutiremos os efeitos de algumas das principais toxinas, como ADMA, fosfato, FGF-23, PTH, AGEs, indoxil sulfato e para-cresil sulfato. Além disso, abordaremos as principais estratégias terapêuticas para aumentar a remoção das toxinas urêmicas por métodos convectivos e/ou adsortivos; e para diminuir a produção e absorção intestinal dessas toxinas por meio de intervenções dietéticas e farmacológicas, respectivamente. A compreensão de que múltiplas toxinas contribuem para a uremia expõe a necessidade de novos alvos-terapêuticos, com potencial impacto positivo na progressão da DRC e na sobrevida dos pacientes.

Comparison of different methods for total RNA extraction from sclerotia of Rhizoctonia solani

Background Rhizoctonia solani (teleomorph: Thanatephorus cucumeris) is one of the most important pathogens of rice (Oryza sativa L.) that causes severe yield losses in all rice-growing regions. Sclerotia, formed from the aggregation of hyphae, are important structures in the life cycles of R. solani and contain a large quantity of polysaccharides, lipids, proteins and pigments. In order to extract high-quality total RNA from the sclerotia of R. solani, five methods, including E.Z.N.A.™ Fungal RNA Kit, sodium dodecyl sulfate (SDS)-sodium borate, SDS-polyvinylpyrrolidone (PVP), guanidinium thiocyanate (GTC) and modified Trizol, were compared in this study. Results The electrophoresis results showed that it failed to extract total RNA from the sclerotia using modified Trizol method, whereas it could extract total RNA from the sclerotia using other four methods. Further experiments confirmed that the total RNA extracted using SDS-sodium borate, SDS-PVP and E.Z.N.A.™ Fungal RNA Kit methods could be used for RT-PCR of the specific amplification of GAPDH gene fragments, and that extracted using GTC method did not fulfill the requirement for above-mentioned RT-PCR experiment. Conclusion It is concluded that SDS-sodium borate and SDS-PVP methods were the better ones for the extraction of high-quality total RNA that could be used for future gene cloning and expression studies, whereas E.Z.N.A.™ Fungal RNA Kit was not taken into consideration when deal with a large quantity of samples because it is expensive and relatively low yield.

A Study on Anlaysis of Patch Test Positive Reactivity according to the Reading Time with T.R.U.E. TEST(R) / 대한피부과학회지

BACKGROUND: The patch test is widely used for diagnosis of allergic contact dermatitis. However, nearly half of positive reactions can be observed only on day 2 or day 4 and it is difficult to interpret these reactions. OBJECTIVE: The purpose of this study is to assess the frequency of transient and delayed reactions in TRUE-test and detect common antigens that provoke these reactions. METHODS: A total of 311 patients with allergic contact dermatitis were evaluated by TRUE-test between Jan 2007 and December 2011. Records of patch test results of day 2 and day 4 were reviewed and analyzed. RESULTS: A total 311 cases of T.R.U.E. TEST(R) records (male 79, female 232) were analyzed. Persistent reactions were observed in 80.1% patients tested, transient reactions were observed in 18.3%, and delayed reaction in 5%. Frequent allergens which showed transient reactions were cobalt dichloride (2.9%), nickel sulfate (2.2%), thiomersal (1.9%), and carba mix (1.6%), in order of frequency. Allergens which showed delayed reactions were nickel sulfate (0.3%), fragrance mix (0.3%), p-tert-butylphenol formaldehyde resin (0.43). CONCLUSION: Our results showed a relatively high frequency of transient reaction in T.R.U.E. TEST(R). This suggests that additional reading at day 4 in the patch test would be of value.

Aminoguanidine suppresses methylglyoxal-mediated oxygen-glucose deprivation injury in human brain microvascular endothelial cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the effects of aminoguanidine on methylglyoxal-mediated oxygen-glucose deprivation (OGD) injury in the cultured human brain microvascular endothelial cells (HBMEC).</p><p><b>METHODS</b>Cultured HBMEC cells were pretreated with methylglyoxal before oxygen-glucose deprivation injury. Cell vitality was determined by MTT method, cell mortality was assessed by LDH release method, cell apoptosis was examined by Annexin V/PI formation method, and the advanced glycation end products (AGEs) were detected by Western-blot.</p><p><b>RESULTS</b>Methylglyoxal induced HBMEC injury in a dose-dependent manner. At 2 mmol/L of methylglyoxal, the cell viability was 56.1% when methylglyoxal-pretreated cells exposed to oxygen-glucose deprivation, the cell inhibition rate was 90.0%. Aminoguanidine (1 mmol/L) inhibited methylglyoxal and OGD induced LDH release and Annexin V/PI formation. Furthermore, aminoguanidine (1 mmol/L) also decreased advanced glycation end products (AGEs) formation induced by methylglyoxal and oxygen-glucose deprivation.</p><p><b>CONCLUSION</b>Aminoguanidine protected methylglyoxal mediated-oxygen-glucose deprivation injury in the cultured HBMEC, which may be associated with anti-glycation activity.</p>

Relaxing Effect of Acetylcholine on Phenylephrine-Induced Contraction of Isolated Rabbit Prostate Strips Is Mediated by Neuronal Nitric Oxide Synthase

PURPOSE: The location of acetylcholinesterase-containing nerve fibers suggests a role for acetylcholine in both contractility and secretion in the prostate gland. The colocalization of nitrergic nerves with cholinergic nerves, and the cotransmission of nitric oxide with acetylcholine in cholinergic nerves, has been demonstrated in the prostate glands of various species. Thus, we investigated the effects of acetylcholine on phenylephrine-induced contraction and the correlation between cholinergic transmission and nitric oxide synthase by using isolated prostate strips of rabbits. MATERIALS AND METHODS: Isolated prostate strips were contracted with phenylephrine and then treated with cumulative concentrations of acetylcholine. Changes in acetylcholine-induced relaxation after preincubation with NG-nitroarginine methyl ester, 7-nitroindazole, and aminoguanidine were measured. The effects of selective muscarinic receptor antagonists were also evaluated. RESULTS: In the longitudinal phenylephrine-contracted strip, the cumulative application of acetylcholine (10(-9) to 10(-4) M) elicited a concentration-dependent relaxation effect. Acetylcholine-induced relaxation was inhibited not only by nitric oxide synthase inhibitors (10 microM L-NAME or 10 microM 7-nitroindazole) but also by 10 microM atropine and some selective muscarinic receptor antagonists (10(-6) M 11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one and 10(-6) M 4-diphenylacetoxy-N-methyl-piperidine). In contrast, relaxation was significantly increased by pretreatment of the strips with 10 mM L-arginine. CONCLUSIONS: Acetylcholine relaxed phenylephrine-induced contractions of isolated rabbit prostate strips. This relaxation may be mediated via both cholinergic and constitutive nitric oxide synthase with both the M2 and M3 receptors possibly playing key roles.

Patch Test (T.R.U.E. Test) Results in Patients with Allergic Contact Dermatitis: 2007~2011, Chungcheongnamdo / 대한피부과학회지

BACKGROUND: A number of skin manifestations in patients with allergic contact dermatitis result from sensitization with specific allergens, and patch testing is used as a diagnostic means of identifying theses allergens. In Korea, the commercial patch test panel, the TRUE-test, has been available since 2005. However, there have been few reports regarding the results of the TRUE-test. OBJECTIVE: The purpose of this study was to analyze the type, frequency, and changes in common contact allergens in Korea using the TRUE test. METHODS: A total of 311 patients with allergic contact dermatitis were evaluated by the TRUE test between January 2007 and December 2011 at Soonchunhyang hospital. Patch test reading was performed on day 2 and day 4. RESULTS: A total of 311 cases of TRUE test records (male 79, female 232) were compiled and analyzed. The highest age distribution was the 4th decade in females. The face, with exception of the lips, was the most frequently affected site (40.2%). Overall, 58.8% of patients had at least on positive reaction, and the most common allergens were nickel sulfate (31.8%), p-phenylenediamine (13.5%), cobalt chloride (10.0%), thiomersal (7.4%), and carba mix (5.5%). Nickel allergen displayed higher positive rates than the rates in other countries. CONCLUSION: There was no significant difference in the overall positive rate of patch test results compared with recent studies. However, we confirmed that metal-related allergens remain the most common, and that the results provide the basis for the use of the TRUE test in patients with contact dermatitis in Korea.

Modified TRIzol method for RNA and DNA co-extraction from blood / 法医学杂志

OBJECTIVE@#To establish a new method for RNA and DNA co-extraction from the same sample by TRIzol reagent.@*METHODS@#After the aqueous phase which contained total RNA was removed by traditional TRIzol method, the values of pH of the interphase phase and organic phase were adjusted. The DNA was precipitated with ethanol and purified with DNA IQ system. The purified DNA was measured in quality and quantity. As the template, it was amplified and typed by PCR-STR. The data was compared with that extracted by traditional TRIzol method.@*RESULTS@#The DNA extracted by this modified method showed a better result of quality and quantity than that by traditional TRIzol method and a good STR typing.@*CONCLUSION@#The modified TRIzol method is advisable and reliable to simultaneously extract both DNA and RNA from the same sample. It could be used for individual identification and paternity testing to satisfy the need of forensic science.

Nafamostat Mesilate: Can It Be Used as a Conduit Preserving Agent in Coronary Artery Bypass Surgery?

BACKGROUND: Graft vessel preservation solution in coronary artery bypass surgery is used to maintain the graft conduit in optimal condition during the perioperative period. Nafamostat mesilate (NM) has anticoagulation and anti-inflammatory properties. Therefore, we investigated NM as a conduit preservative agent and compared it to papaverine. METHODS: Sprague-Dawley (SD) rat thoracic aortas were examined for their contraction-relaxation ability using phenylephrine (PE) and acetylcholine (ACh) following preincubation with papaverine and NM in standard classical organ baths. Human umbilical vein endothelial cells (HUVECs) were cultured to check for the endothelial cell viability. Histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were performed on the thoracic aortas of SD rats. RESULTS: The anti-contraction effects of papaverine were superior to those of NM at PE (p90% in various concentrations of both NM and papaverine. A histopathological study showed a protective effect against necrosis and apoptosis (p<0.05) in the NM group. CONCLUSION: NM exhibited good vascular relaxation and a reasonable anti-vasocontraction effect with a better cell protecting effect than papaverine; therefore, we concluded that NM is a good potential conduit preserving agent.

Inhibition of NHE1 down-regulates IL-8 expression and enhances p38 phosphorylation / 中国实验血液学杂志

This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.

possible protective role of aminoguanidine in gentamicin-induced ototoxicity in guinea pig: a histological and immunohistochemical study

Introduction: Gentamicin is an ototoxic drug affecting both auditory and vestibular cells. Reactive oxygen species might play important role in the molecular pathway of this ototoxicity. Aminoguanidine is one of the guanidine derivatives and is considered as an antioxidant therapy

Aim of the work: to investigate the possible protective effect of aminoguanidine on ototoxicity induced by gentamicin in guinea pig

Materials and methods: Twenty one adult male guinea pigs were used. They were divided into three groups, seven animals each. Group I: served as a control group. Group II: I.M. injection of gentamicin [80 mg/kg/day] was used for 14 days. Group III: animals received gentamicin in the same way as group II and then followed by aminoguanidine [100 mg/kg/ day] administration using a gastric tube for 14 days. At the end of experiment, the cochlea was excised and prepared for light [LM] and scanning electron microscope [SME] examination. Immunohistochemichal technique was done to detect iNOS. Morphometric and statistical studies were also done

Results: By LM and SME examination, the present study showed that aminoguanidine protected the structure of organ of Corti in the cochlea by decreasing the degeneration of hair cells and other supporting cells. It also showed a significant decrease in the iNOS immune-reactivity in organ of Corti, stria vascularis and bipolar cells in spiral ganglia compared to group II

Conclusion: Aminoguanidine is a promising and successful antioxidant therapy for ototoxicity

Could Nafamostat or Gabexate Prevent the Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis? / 대한소화기학회지

BACKGROUND/AIMS: ERCP is the most common procedure for the diagnosis and treatment of bile duct and pancreatic disease, but Post-ERCP pancreatitis makes poor outcome in some cases. The protease inhibitors, nafamostat and gabexate, have been used to prevent pancreatitis related to ERCP, but there is some debate. We tried to evaluate the efficacy of gabexate and nafamostat for the prevention of post-ERCP pancreatitis. METHODS: Two hundred forty two patients (73 patients in the gabexate group, 88 patients in the nafamostat group and 81 patients in the placebo group) were included in the study after selective exclusion. The incidence of pancreatitis after ERCP was compared among groups. RESULTS: The incidence of pancreatitis were 6.8% in the gabexate group, 5.7% in the nafamostat group and 6.2% in the placebo group (p=0.954). CONCLUSIONS: There was no meaningful difference among the gabexate, nafamostat and placebo group.

Protease Inhibitor Treatment of Disseminated Intravascular Coagulation Associated with Aortic Dissection / 대한내과학회지

Disseminated intravascular coagulation (DIC) is a rare complication of aortic dissection. We report an unusual case of a 64-year-old woman with DIC associated with chronic aortic dissection who developed catastrophic intracranial hemorrhage. Computed tomography (CT) revealed partially thrombosed false lumen in the chronic dissected aneurysm of the thoracoabdominal aorta, which remained after surgery for acute type A aortic dissection. The laboratory profile showed features of DIC, including thrombocytopenia, hypofibrinogenemia, and increased D-dimer levels. Bleeding diathesis, including ecchymosis and coagulopathy, showed improvement following treatment with protease inhibitors (nafamostat and camostat).

Comparison of different methods for isolating total RNA from bulblet of Fritillaria anhuiensis / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize a simple and effective method for total RNA extraction from bulblet of Fritillaria anhuiensis.</p><p><b>METHOD</b>Four methods, i. e. guanidine isothiocyanate, bentonite, modified SDS/phenol and the RNAiso plus, were used to extract total RNA from bulblet of F. anhuiensis. Then the results of the extraction were compared and analyzed by electrophoresis detection and RT-PCR verification.</p><p><b>RESULT</b>The total RNA extracted by bentonite method were clear and no dispersion, the integrity of the RNA was well, and there was no obvious contamination with DNA and other impurities, was suitable for RT-PCR test.</p><p><b>CONCLUSION</b>The bentonite method is quick, economic, and efficient for total RNA extraction from bulblet of F. anhuiensis.</p>

Immunoresuscitation Effect on Hemorrhagic Shock-Induced Acute Lung Injury in Rats

PURPOSE: Recent studies have indicated that cytokines and inflammatory responses are related to hemorrhagic shock-(HS) induced acute lung injury. Novel, synthetic, broad-acting serine protease inhibitors that protect a wide range of animals from lethal shock have been evaluated as potential immunoresuscitation modulators. The aim of this study was to test the hypothesis that a test modulator could decrease serum and tissue pro-inflammatory mediator levels, prevent HS-induced acute lung injury, and suppress activation of the inflammatory cascade. METHODS: This HS model consisted of four phases: Phase I, initiation of HS (from 15~30 min) with a volume-controlled hemorrhage of 2.7 mL/100 g over 15 min; Phase II, maintenance of HS (HS Phase, from 30~90 min), with maintenance of shock without resuscitation; Phase III, resuscitation (RT phase, from 90~150 min), with reinfusion of 1.5 mL/100 g of blood and Ringer's lactate fluid; and Phase IV, observation and post-resuscitation (OB phase, from 150~270 min). The test rats were randomized into two groups of 15: group 1 with fluid resuscitation (control group) and group 2 with fluid and 0.5mg/kg nafamostat mesilateinfusion (treated group). RESULTS: The mean arterial pressure (MAP) of the treated group increased significantly during the observation and post-resuscitation period (Phase IV, OB 90 min). The heart rate of the control group increased significantly during the maintenance of shock (Phase II, HS 60 min), resuscitation (Phase III, RT 30 and 60 min), and observation periods (Phase IV, OB 120 min). The serum concentrations for IL-6 and IL-10 did not differ significantly between the treated and control groups. The TNF-alpha levels for the treated group were significantly lower than those of the control group (p<0.05). At the end of the observation period (OB 120 min), the treated group had significantly lower concentrations of IL-8 in the bronchoalveolar lavage fluid (BALF) than the control group (676.7+/-791.9 vs. 1062.5+/-609.9, p=0.013). CONCLUSION: We conclude that the tested serine protease inhibitor improves hemodynamic parameters, prevents acute lung injury after HS, and attenuates a robust proinflammatory cytokine response in rats.

The different roles of the spinal protein nNOS and iNOS in morphine naloxone-precipitated withdrawal response / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of intrathecal injection of neuronal nitric oxide synthase (nNOS) inhibitors 7-Nitroindazole (7-Ni) and inducible nitric oxide synthase(iNOS) inhibitors aminoguanidine (AG) on the behavioral changes of morphine-induced dependent and withdrawal rats; the expression of Fos, nNOS and iNOS in spinal cord.</p><p><b>METHODS</b>To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/ kg every day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg ip). 7-Ni, an nNOS inhibitor or iNOS inhibitors AG were intrathecally injected 30 min before the administration of naloxone respectively. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed. One hour after naloxone-precipitated withdrawal, Fos protein expression was assessed by immunohistochemical analysis and Western blot was used to detect the expression of nNOS and iNOS in the rat spinal cord.</p><p><b>RESULTS</b>Intrathecal administration of nNOS inhibitor 7-Ni and iNOS inhibitors AG decreased the scores of morphine withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited the increase of Fos protein expression in the spinal cord of morphine withdrawal rats. nNOS and iNOS positive neurons in dorsal horn in nNOS group and iNOS group were significantly lower than that in withdrawal group. Compared with withdrawal group, level of nNOS and iNOS protein in spinal cord in nNOS group and iNOS group were significantly lower.</p><p><b>CONCLUSION</b>It is suggested that nNOS and iNOS in the spinal cord may contribute to naloxone-precipitated withdrawal in rats and may play different roles in the above-mentioned effect.</p>

Aging impairs vasodilatory responses in rats / 대한마취과학회지

BACKGROUND: Aging causes profound changes of stiffness and compliance in the cardiovascular system, which contributes to decreased cardiovascular reserve. Mechanisms of the underlying endothelial vasodilator dysfunction in vasodilator signaling pathways may occur at multiple sites within any of these pathways. METHODS: Age-related changes in the vasculature were investigated in adult young (3-6 months, Y) and old (26-29 month, O) Wistar rats (n = 6). The aortas were carefully dissected from the rat and cut into rings 1.5-2.0 mm in length to measure in vitro isometric tension. Vasorelaxant responses of aortic rings to acetylcholine (ACh), sodium nitroprusside (SNP) and P1075 were examined using Dose Response software (AD Instruments, Mountain View, CA). RESULTS: Endothelium-dependent vasodilator function was impaired. The endothelium of aging rats impaired endothelial NO dependent vasodilation, but the machinery for vasodilation was not impaired. CONCLUSIONS: Age-related NO-mediated vasorelaxation in the aging endothelium was inhibited and appears to be major mechanism of vascular change and impaired vascular regulation.

Inducible nitric oxide synthase is involved in neuronal death induced by trimethyltin in the rat hippocampus / 대한수의학회지

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.