Not-so-minimal for minimally invasive surgery

Sub?macular hemorrhage poses a potential threat to vision if left untreated. The preferred surgical technique to clear sub?macular hemorrhage includes vitrectomy followed by retinotomy using a 41G needle with subsequent injection of recombinant tissue plasminogen activator (r?tPA) followed by air/SF6 injection into the sub?retinal space. A malleable nature, increased resistance, and the cost of the 41G needle limit its use. We evaluated the safety and efficacy of a 26G needle for retinotomy as a supplement for the 41G needle in a series of six subjects with sub?macular hemorrhage. A slight modification in the procedure was done by injecting air into the sub?retinal space prior to the r?tPA injection. We found that our technique of using the 26G needle for retinotomy is safe and effective due to its stable nature and self?sealing properties. An air injection prior to r?tPA allows for increased bioavailability of the drug by preventing efflux due to its tamponading effect.

Double plating technique for fixing tibial plateau leveling osteotomy and modified cranial closing wedge ostectomy of the tibia in a dog with cranial cruciate ligament disease and excessive plateau angle: case report / [Técnica de placa dupla para fixação concomitante da osteotomia de nivelamento do platô tibial e ostectomia modificada em cunha de fechamento cranial da tíbia em um cão com doença do ligamento cruzado cranial e ângulo de platô tibial excessivo: relato de caso]

Tibial plateau leveling osteotomy (TPLO) associated to cranial wedge closing ostectomy (CCWO) has been one of the best options to manage cranial cruciate ligament (CCL) disease and excessive tibial plateau angle (TPA) in large dogs, however, the complication rate is potentially high. It is believed that a more robust fixation is necessary to stabilize them and decrease the risk of implant failure. A 6-year-old male American Pit Bull, weighing 36kg, with 90-day history of right hind limb lameness, was diagnosed with CCL disease. Due to the excessive tibial plateau angle (42°), TPLO was associated with a modified CCWO using a double plating technique. A final TPA of 12° was accomplished, and a restricted level of exercises and physiotherapy were recommended. The patient was followed monthly until the fifth month postoperatively, when radiographic bone consolidation and no lameness were observed. By the date of this submission, 3 years after the procedure, the owner has reported no complications. The double plating technique for fixing TPLO and modified CCWO proved to be effective for the treatment of CrCL deficiency in a large dog with an excessive TPA.(AU)

A osteotomia de nivelamento do platô tibial (TPLO) associada à ostectomia modificada em cunha de fechamento cranial da tíbia (CCWO) tem sido uma das melhores opções para tratamento de cães grandes com doença do ligamento cruzado cranial (DLCCr) e ângulo excessivo do platô tibial, mas o índice de complicações é alto. Acredita-se haver necessidade de fixação mais robusta para reduzir as chances de falha nos implantes. Um cão macho, seis anos, da raça American Pit Bull, 36kg, com histórico de claudicação em membro pélvico direito há 90 dias, foi diagnosticado com DLCCr. Devido ao ângulo excessivo do platô tibial (42°), a osteotomia de nivelamento do platô tibial foi associada à ostectomia modificada em cunha de fechamento cranial da tíbia (CCWO) por meio da técnica de placa dupla. No pós-operatório imediato, identificou-se TPA de 12°; exercícios controlados e fisioterapia foram recomendados e a evolução do quadro foi analisada mensalmente até o quinto mês pós-cirurgia. Com 150 dias de evolução, não houve alterações de locomoção e havia ocorrido completa consolidação radiográfica das osteotomias. Até o momento da submissão deste artigo, três anos pós-procedimento, o tutor relata ausência de complicações, via contato telefônico. Portanto, a técnica modificada mostrou-se eficaz no tratamento da DLCCr.(AU)

Análise do perfil de textura de apresuntados elaborados com diferentes concentrações de nitrito / Texture profile analysis of restructured cooked ham elaborated with different nitrite contents

O trabalho objetivou estudar os efeitos da adição de diferentes concentrações de nitrito (0 a 300 mg/Kg) nos atributos de textura de apresuntados ao decorrer do tempo de armazenamento a vácuo (0 a 40 dias) utilizando um delineamento composto central rotacional. Maiores perdas de peso por cozimento foram observadas (P0,05) pelos fatores estudados, enquanto que maiores valores de flexibilidade foram observados nos produtos adicionados de maior quantidade de nitrito. Concluiu-se que o perfil de textura de produtos cárneos cozidos é ligeiramente alterado pela adição de nitrito de sódio.

Effect of Puerarin Combined with Tanshinone ⅡA on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions / 中国实验方剂学杂志

Objective:To observe the protective effect and mechanism of combination of puerarin combined with tanshinone ⅡA on diabetes mellitus (DM) rats with vascular lesions. Method:The SD rats (fed with high-fat diet) were administrated with streptozotocin(STZ) through intravenous injection to make the model of diabetic vascular lesions. The successfully modeled rats were randomly divided into the model control group, the high-dose group (0.5 g·kg-1+1.0 g·kg-1), the middle-dose group (0.25 g·kg-1+0.5 g·kg-1), the low-dose group (0.05 g·kg-1+0.1 g·kg-1), the puerarin group (0.25 g·kg-1), the tanshinone ⅡA group (0.5 g·kg-1) and the positive control group (Metformin, 0.09 g·kg-1). Each group was administrated with drugs respectively by gavage for 70 days. After intervention in each group, the general conditions and body weight of the rats were observed. The contents of blood grucose and blood lipids were determined by automatic biochemical analyzer. The contents of insulin, advanced glycation end products (AGEs), superoxide dismutase(SOD), glutathione peroxidase (GSH-Px) in serum, the contents of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and thromboxane B2 (TXB2) in plasma, as well as the contents of AGEs and oxidized low-density lipoprotein(ox-LDL) in aorta homogenate were detected by enzyme-linked immunosorbent assay(ELISA). The content of malondialdehyde(MDA) in serum was determined by chemical colorimetry. Pathological changes of coronary tissue were observed by htoxylin eosin(HE) staining. The expression of PAI-1 protein of aorta was observed by immunohistochemistry. Result:Compared with the normal control group, in the model group, the levels of blood grucose and blood lipids (PPPP2 in plasma (PPPPPPPPP2 in plasma (PPPPPPPConclusion:Puerarin combined with Tanshinone ⅡA could relieve vascular lesions of DM rats. The mechanisms may be related to the reduction of oxidative stress and the regulation of coagulation-fibrinolysis system.

The safety and efficacy of tPA intravenous thrombolysis for treating acute ischemic stroke patients with a history of cerebral hemorrhage

Alteplase (tPA) intravenous thrombolysis is an effective treatment for acute ischemic stroke (AIS) when administered within 4.5 h of initial stroke symptoms. Here, its safety and efficacy were evaluated among AIS patients with a previous history of cerebral hemorrhage. Patients who arrived at the hospital within 4.5 h of initial stroke symptoms and who were treated with tPA intravenous thrombolysis or conventional therapies were analyzed. The 90-day modified Rankin scale (90-d mRS) was used alongside mortality and incidence of symptomatic intracerebral hemorrhage (SICH) rates to evaluate the curative effect of these therapies. Among 1,694 AIS patients, 805 patients were treated with intravenous thrombolysis, including patients with (n=793) or without (n=12) a history of cerebral hemorrhage, and the rate of incidence of SICH significantly differed between them (8.3 vs 4.3%, P=0.039). No significant difference was found in 90-d mRS measurements (41.7 vs 43.6%, P=0.530) and 90-d mortality rates (8.3 vs 6.5%, P=0.946). A total of 76 AIS patients with a history of cerebral hemorrhage received tPA thrombolytic therapy (n=12) or conventional therapy (n=64), and a significant difference was noted in the 90-d mRS scores between the two groups (41.7 vs 23.4%, P=0.029), while no significant difference was found in SICH measurements (8.3 vs 4.6%, P=0.610) and 90-d mortality rates (8.3 vs 9.4%, P=0.227). A history of cerebral hemorrhage is not an absolute contraindication for thrombolytic therapy; tPA intravenous thrombolysis does not increase SICH measurements and mortality rates in patients with a history of cerebral hemorrhage, and they may benefit from thrombolytic therapy.

Frequency of stroke patients qualified for recombinant tissue plasminogen activator (r-TPA) injection and limitations in Zahedan 2016

Background: Stroke is one of the common causes of mortality and disability. By introducing r-TPA into the global drug market and its effect on the patients’ prognosis, using this drug is recommended in all patients with ischemic stroke who visited less than 4.5 hours after stroke and do not have contraindications. The aim of this study was to investigate the frequency of stroke patients qualified for recombinant tissue plasminogen activator (r-TPA) and its limtations.Methods: In this descriptive cross-sectional study, 244 patients examined with stroke admitted to the Neurology Department of Zahedan city hospital in 2016. Information form were completed with demographic data, transmission method, referral time, CT scan preparation time, and the response of the patients' trials, and finally the data were inserted in SPSS.16 software and analysed by statistical methods.Results: Out of all patients with ischemic stroke, 28 (11.5%) patients had contraindication to receive drug. Of 216 remain patients, 201 patients (93.1%) had no possibility to receive r-TPA due to the loss of golden time and only 15 patients (6.9%) had possibility to receive drug because of visited 4.5 hours before the beginning of symptoms. Of them, 3 (20%) patients due to delay in CT scan and test results, had no possibility to receive r-TPA. In summary, of all patients with inclusion criteria, only 12 (5.5%) patients could use the r-TPA in this study.Conclusions: The most important barrier to using r-TPA has been the loss of golden time and training to raise awareness of the society can lead to early referral from the onset of stroke symptoms.

Successful development of squamous cell carcinoma and hyperplasia in RGEN-mediated p27 KO mice after the treatment of DMBA and TPA / 한국실험동물학회지

To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months.

Effects of Salvia Miltiorrhiza and Rrhizoma Alismatis on Lipid Metabolism and Fibrinolytic System in Rats with Non-alcoholic Fatty Liver / 中国药师

Objective:To preliminarily discuss the mechanism of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of lipid metabolism through regulating the imbalance of fibrinolytic system in rats with non-alcoholic fatty liver. Methods:The model of non-alcoholic fatty liver in rats was duplicated by high-fat diet feeding. Totally 60 adult Wistar rats were randomly divided into 6 groups (n=10 per group), namely the control group, the model group, Salvia miltiorrhiza group, Rrhizoma alismatis group, Salvia miltiorrhiza and Rrhizoma alismatis group,and Dongbaogantai group. The control group and the model group were given distilled water,and the other group was given Salvia miltiorrhiza,Rrhizoma alismatis,Salvia miltiorrhiza combined with Rrhizoma alismatis and Dongbaogantai,respectively. Rhizoma Alismatis decoction at high dose and low dose as well as Dongbaogantai was respectively adminis-trated in the designed groups,and the corresponding indices were detected 4 weeks later. Results:In the model control group,the con-tents of TC、TG、FFA in serum and the expression of PAI-1 were significantly elevated(P<0.05 or P<0.01),while the expression of t-PA was significantly reduced(P<0.01).After treatment,the contents of TC、TG、FFA in serum and the expression of PAI-1 in every treatment groups were reduced(P<0.01),while the expression of t-PA was elevated(P<0.01).Conclusion: Increasing the expres-sion of t-PA and reducing the expression of PAI-1 might be viewed as the mechanisms of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of non-alcoholic fatty liver disease.

NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tissue plasminogen activator-induced haemorrhagic transformation after cerebral ischaemia / 中国药理学与毒理学杂志

OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.

Impact of sodium butyrate and mild hypothermia on metabolic and physiological behaviour of CHO TF 70R cells

Background: To reduce costs associated with productivity of recombinant proteins in the biopharmaceutical industry, research has been focused on regulatory principals of growth and survival during the production phases of the cell culture. The main strategies involve the regulation of cell proliferation by the modulation of cell cycle control points (G1/S or G2/M) with mild hypothermia and the addition of sodium butyrate (NaBu). In this study, batch culture strategies were evaluated using CHO TF 70R cells producing the recombinant human tissue plasminogen activator (rh-tPA), to observe their individual and combined effect on the cellular physiological state and relevant kinetic parameters. Results: NaBu addition has a negative effect on the mitochondrial membrane potential (ΔΨm), the values of which are remarkably diminished in cultures exposed to this cytotoxic compound. This effect was not reflected in a loss of cell viability. NaBu and mild hypothermic conditions increased the doubling time in the cell cultures, suggesting that these strategies triggered a general slowing of each cell cycle phase in a different way. Finally, the individual and combined effect of NaBu and mild hypothermia produced an increase in the specific rh-tPA productivity in comparison to the control at 37°C without NaBu. Nevertheless, both strategies did not have a synergistic effect on the specific productivity. Conclusions: The combination of NaBu addition and mild hypothermic condition causes an impact on physiological and metabolic state of CHO TF 70R cells, decreasing cell growth rate and improving glucose consumption efficiency. These results therefore provide a promising strategy to increase specific productivity of rh-tPA.

Effect of Xiang-Qi-Tang on coagulation factors in mice with endotoxemia / 中国兽医学报

To study the anticoagulant effect of Xiang-Qi-Tang (XQT),the mice model of endotoxemia was established to detect the expression of coagulation factors and their regulatory proteins in serum and aorta.The results showed that XQT could decrease the expression of TF and increase the expression of tPA in the aorta of mice with endotoxemia,and also decrease the expression of sEPCR in the serum.We further found that XQT caused the decrease of sEPCR through the regulation of PKC δ and ADAM17 to contribute the anticoagulation in mice.This study may provide a new strategy for treating endotoxin-induced disease and provide evidences for further researching the pharmacological action of XQT.

Optimization of the establishment protocol of a mouse model of MBA/TPA-induced skin cancer / 中国实验动物学报

Objective To induce skin cancer in BALB/c mice using DMBA as initiator and TPA as tumor promot-er. Through optimizing the doses and frequencies of DMBA administration to establish a stable skin cancer model with less time and causing less skin damage. Methods Shaving the back of mice to expose a piece of skin around 2 cm × 2 cm. The mice were divided into a blank control group and four treatment groups randomly. These four groups were given 1, 2, 4, 7 times 100μg/100μL DMBA/acetone, respectively, in the first week, and twice 4μg/100μL TPA/acetone per week in the next 11 weeks. The body weight changes, time of tumor formation and number of tumors formed were recorded during the experiment. The mice were sacrificed at 12th week and samples of tumor tissue and adjacent normal skin tissue were taken for pathological examination using HE staining. Results Tumors were observed at the 7th week in the group with once DMBA administration in the first week and at the 4th week in the group with twice DMBA administration in the first week. Skin cancers were formed also in the group with 4?time DMBA administration in the first week, however, with signif?icantly more severe skin damages. The mice receiving DMBA everyday in the first week died at the 3th week. Conclusions The best induction protocol for skin cancer in BALB/c mice should be twice DMBA in the first week followed by twice TPA

Establishment and evaluation of a rat model of endometriosis with pelvic adhesions / 中国比较医学杂志

Objective To establish and evaluate a rat model of endometriosis with pelvic adhesions. Methods To establish a rat model of endometriosis and pelvic adhesions by autologous transplantation of endometrial tissue to the mesenterium. After modeled, eight rats were randomly selected for examination at 1, 3, 5, 7, 14, 21 and 28 days after op-eration. The American Society for Reproductive Medicine Classification of Endometriosis and Haber Adhesion Score were used to evaluate the pelvic adhesions. At the same time, the lesions and surrounding peritoneal adhesions were taken for pathological examination using HE staining. The tissue-type plasminogen activator (tPA) content was detected at 5, 7, 14, 21 and 28 days after operation. Results The two adhesion scoring methods showed that typical pelvic adhesions were formed 5 days after modeling. Compared with the blank control group and the sham operation group, the tPA content in the pelvic adhesions of the model group was significantly decreased after 5 days ( P< 0. 01 ) , and increased at 28 days after model establishment, but still significantly lower than that of the blank control group and sham operation group ( P <0. 01). Conclusions The autologous transplantation method is successfully used to establish a rat model of pelvic adhe-sions of endometriosis in the mesenterium. The model is matured at 5 days after surgery. The tPA is correlated with the formation of pelvic adhesions of endometriosis.

3,5,6-trichloro-2-pyridinyloxyacetic acid as effective thinning agent for fruit of 'Montenegrina' mandarin / Ácido 3,5,6-tricloro-2-piridiniloxiacético como raleante químico efetivo de frutos da tangerineira 'Montenegrina'

ABSTRACT: The 'Montenegrina' mandarin ( Citrus deliciosa Tenore) is widely cultivated in southern Brazil. This cultivar has a great tendency for alternate bearing, requiring thining of the fruit. However, the chemical thinners studied until now in this cultivar have not been successful. The objective of this research was to evaluate the effect of 3,5,6-trichloro-2-pyridinyloxyacetic acid (3,5,6-TPA) on the production and fruit quality of the 'Montenegrina' mandarin, in comparison with hand thinning and the options of chemical thinning previously studied. Hand thinning and no thinning were used as controls. Ethephon was applied in three doses: 200mg L-1, 300mg L-1 or 200mg L-1 + 3% urea; or 3,5,6-TPA, in four doses: 10, 20, 30 or 40mg L-1. Fruits of the hand thinned trees and those treated with 40mg L-1 showed greater average size, greater distribution of commercial caliber and more orange colors. No treatment reduced alternate bearing. Applications of 40mg L-1 of 3,5,6-TPA as a chemical thinner, during the physiological drop of young fruit, had a similar effect that of hand thinning over yield and quality of fruits of 'Montenegrina' mandarin.

RESUMO: A tangerineira 'Montenegrina' ( Citrus deliciosa Tenore) é amplamente cultivada no sul do Brasil. Possui grande tendência à alternância de produção, necessitando de raleio de frutos. Contudo, os raleantes químicos estudados até hoje nesta cultivar não se demonstraram eficientes. Este trabalho teve como objetivo avaliar o efeito do ácido 3,5,6-tricloro-2-piridiniloxiacético (3,5,6-TPA) sobre a produção e qualidade de frutos da tangerineira 'Montenegrina', em relação às opções de raleio químico previamente estudadas. Foram utilizados, como padrão, raleio manual e plantas sem raleio (controle). Realizaram-se aplicações de ethephon em três doses: 200mg L-1, 300mg L-1 e 200mg L-1 + 3% de ureia; e aplicações de 3,5,6-TPA, em quatro doses: 10, 20, 30 e 40mg L-1. Os frutos de árvores raleadas manualmente e de tratadas com 3,5,6-TPA a 40mg L-1 apresentaram maior tamanho médio, melhor distribuição de calibres comerciais e cores mais alaranjadas. Nenhum tratamento reduziu a alternância de produção. Aplicações de 40mg L-1 de 3,5,6-TPA como raleante químico, durante a queda fisiológica de frutos jovens, propiciaram efeito similar ao raleio manual sobre a produção e qualidade dos frutos de tangerineira 'Montenegrina'.

Comparative study of anti-inflammatory activity and qualitative-quantitative composition of triterpenoids from ten genotypes of Ugni molinae / Estudio comparativo de la actividad antiinflamatoria y composición química cualitativa y cuantitativa de triterpenoides de diez genotipos de Ugni molinae

The aim of this study was to assess the differences in qualitative-quantitative composition of triterpenoids and total phenolic contents, together with anti-inflammatory activity of Ugni molinae leaves obtained from ten genotypes. The ethyl acetate (EAE) and ethanol extracts (ETE) were obtained and analyzed. The plant genotypes were grown under same soil and climate conditions and under same agronomic management; the leaves were also harvested under the same conditions. Anti-inflammatory activity was evaluated by mice ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) at a single dose of 200 mg/kg BW of each extract. Composition of triterpenoids and total phenolic contents was determined by HPLC-DAD and Folin-Ciocalteu method, respectively. Ugni molinae leaves of different plant genotypes exhibited significant differences in regard to their anti-inflammatory activity, as well as in qualitative-quantitative composition of triterpenoids and total phenolic content.

El objetivo de este estudio fue establecer las diferencias en la composición cualitativa y cuantitativa de triterpenoides y en los contenidos totales de fenoles, junto con la actividad antiinflamatoria de las hojas de Ugni molinae provenientes de diez genotipos. Los extractos de acetato de etilo (EAE) y etanólicos (ETE) fueron obtenidos y analizados. Los genotipos fueron cultivados bajo las mismas condiciones edafo-climáticas y con el mismo manejo agronómico; las hojas fueron cosechadas bajo las mismas condiciones. La actividad antiinflamatoria fue evaluada en ratones a los que se les indujo un edema en la oreja mediante la aplicación del 12-O-tetradecanoilforbol-13 acetato (TPA) y los extractos fueron evaluados a una dosis única de 200 mg/kg de peso corporal. La composición en triterpenoides y los contenidos de fenoles totales fueron determinados por CLAE-DAD y por el método de Folin-Ciocalteu, respectivamente. Las hojas provenientes de los diferentes genotipos de U. molinae, exhibieron significativas diferencias en sus actividades antiinflamatorias, así como, en el contenido cualitativo y cuantitativo de triterpenoides y en el contenido de fenoles totales.

A Successful Case of Thrombolytic Therapy for Tricuspid Mechanical Valve Thrombosis with Tissue Plasminogen Activator / 日本心臓血管外科学会雑誌

<p>A 41-year-old man had undergone mitral valve replacement (On-X 27/29 mm) and tricuspid valve replacement (TVR) (On-X 31/33 mm) for infectious endocarditis of the mitral valve and severe tricuspid regurgitation 6 years ago. Postoperative echocardiography showed aortic regurgitation and perivalvular leakage of the prosthetic mitral valve and left ventricular (LV) septal perforation. He therefore underwent aortic valve replacement (On-X 25 mm), patch closure of a leak around the prosthetic mitral valve, direct closure of the LV septal perforation, and re-TVR (On-X 31/33 mm). After discharge, he was placed on anticoagulant therapy with warfarin (international normalized ratio of prothrombin time target : 2.0-2.5). Transthoracic echocardiography three and -a half years after the operation revealed an increased mean tricuspid valvular pressure gradient (14 mmHg) compared with that seen on an echocardiograph of previous year. Cine-fluoroscopy showed almost no movement of the leaflets of the mechanical tricuspid valve. Tricuspid valve thrombosis or pannus formation was suspected. He was placed on thrombolytic therapy using tissue plasminogen activator (monteplase 1.6 million units). Five days later, cine-fluoroscopy showed movement of the mechanical tricuspid valve leaflets, and echocardiography revealed recovery of the mean tricuspid valve pressure gradient (4 mmHg). Valvular thrombosis was diagnosed as the cause of the non-moving valve. Hemorrhagic and embolic complications were not observed. Thrombolytic therapy was extremely useful.</p>

Screening and Identification of Fibrinolytic Bacteria from Malaysian Fermented Seafood Products.

Natural fibrinolytic enzymes have been focused recently when compared to chemically synthesize thrombolytic drugs as they are more economical and believe to have less adverse reaction. Belacan (shrimp paste), Budu (fish sauce) and Cencaluk (shrimp sauce) were traditional fermented Malay seafood products used as sources for this study. The isolation and screening resulted in the discovery of 43 potential isolates with the ability as an extracellular fibrin degrader. Each isolate were unique due to differences in morphology characteristics and the amounts of fibrinolytic enzyme secretes under standard growth condition. Furthermore, it has been demonstrated that some strains posses the ability to act as tissue plasminogen activator (t-PA) which in deed has beneficial to many medicinal and therapeutic purposes. Of these 43 strains investigated for the fibrinolytic enzyme production, three species, mainly the best producer from each food sample were chosen for further molecular identification. This lead to the discovery of B. cereus 13BN, B. subtilis 2CN and B. subtilis 9BD strains, which posses both high fibrinolytic and t-PA activities, making it extremely valuable and promising producer.

Modulation of p21, DAPK1 and COX-2 during the DMBA/TPA-induced mouse skin tumorigenesis and its prevention by phytic acid.

Chemoprevention by naturally occurring agents is gaining much attention as a newer dimension in the management of cancer. Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models, having relevance to human disease. Phytic acid or Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of Phytic acid against the 7, 12-dimethylbenz [a] anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13- acetate (TPA) induced mouse skin tumorigenesis at 4 and 16 weeks, the time before and after the tumor development. At molecular level we studied expression and promoter CpG methylation status of p21, DAPK1 and COX-2. Our data suggests exposure of DMBA/TPA methylated the promoter region of p21 and DAPK1 genes in time dependent manner that could be the cause of down regulation of their expression with time, which were reversed by administration of phytic acid. But we did not observe methylation in COX-2 whereas upregulation of COX-2 was observed at protein level in mice treated with DMBA followed by TPA in time dependent manner. Administration of phytic acid prevented theses DMBA/TPA induced molecular changes. Study provides a rationale for cancer chemoprevention by natural occurring compounds like Phytic acid.

Neuropathic changes in young type 2 diabetes mellitus related to high serum t-PA.

Background and Aims: A substantial number of diabetic patients, diagnosed at relatively younger age, who don’t fit to typical type 2 and type 1 class of diabetes. These patients usually present with very high level of glycemia. The uniqueness of this group of patient provide the opportunity to explore the pathophysiology of nerve functional status at an early stage of diabetes. The present study was aimed to determine markers of endothelial dysfunction and evaluate nerve functional status of a group of newly diagnosed clinically uncomplicated young diabetic patients. Material and Methods: A total number of 32 (male-13 and female-19) newly diagnosed young (diabetes diagnosed under 30 yrs) were consecutively recruited from BIRDEM Out-patient department and 30 age-, BMI-matched healthy subjects with no family history of diabetes up to second generation served as controls. Serum fructosamine was measured by reduction test with NBT method. Serum C-peptide, endothelin-1 and tissue plasminogen activator (t-PA) by ELISA and von Willibrand factor (vWF) by Radial Immunodiffusion (RID) methods. Urinary albumin measured by immunoturbidimetry method. Nerve functional status was evaluated by nerve conduction velocities (NCV), distal latencies (DL), compound muscle action potential (CAMP), F wave latencies (FWL), nerve action potential (SNAP) for motor and sensory nerve as appropriate following the standard protocol. Results: Severe hyperglycemia in the diabetic group was reflected in their mean (SD) fasting C-peptide and fructosamine level. Altered endothelial dysfunction, as evidenced by significantly high tissue plasminogen activator (t-PA) (p<0.001) in the diabetic group. Albumin creatinine ratio (ACR) was almost similar in the two groups. Ulnar distal latency was similar in both the groups. But its CAMP and NCV were significantly lower in the diabetic group (p<0.02-0.001). Ulnar F wave latency were significantly higher (p=0.016) in the diabetic group. Ulnar sensory conduction parameters did not show any difference between two groups. Peroneal motor and sural sensory functional status of the diabetic subjects showed similar trend like that of ulnar motor and sensory status. Peroneal nerve motor NCV was significantly negtively correlated with fasting glucose [r=- 0.456, p=0.001]. Peroneal motor distal latency was significantly correlated with fasting fractosamine [r=0.439, p=0.012]. Fasting fructosamine showed significant negative correlation with motor peroneal NCV [r=-0.572, p=0.001], motor ulnar NCV [r=-0.468, p=0.007], both ulnar and sural sensory NAP (p=0.02 for both]. On the basis of F wave latency 53% of diabetic subjects had diabetic neuropathy and markedly higher t-PA compared to nonneuropathy groups (p=0.001). Conclusions: The data suggest that (i) Young type 2 diabetic subjects had endothelial dysfunction at the time of diagnosis even in the presence of normoalbuminuria state; (ii) Motor nerve conduction parameters are affected more than the sensory component; (iii) F wave latencies are more frequently and early to be involved in these subjects and linked to high serum t-PA.

Impact study of curcumin on ASO and IL-8 level changes in serum of psoriatic mice model induced by TPA / 中国生化药物杂志

Objective To explore the impact of curcumin on antistreptolysin“O”(ASO)and interleukin 8 (IL-8)level changes in serum of psoriatic mice model induced by phorbol ester(TPA).Methods 132 SCID mice were selected and divided into three groups.43 mice in normal group, 46 mice in model group,and 43 mice in intervention group.The mice of model group and intervention group were set up psoriasis model induced by TPA. Mice of the three groups were bred in the same environment,curcumin was injected in the intervention group mice,0.02 g/100 g,once a day,two weeks for a period of treatment.ASO and IL-8 level were compared amorg the three groups of mice after treatment.Results Before the treatment,compared with the normal group,positive rate of ASO in model group and intervention group increased significantly,and the difference was statistically significant (P<0.05 );after treatment,the level of intervention group was significantly lower than model group,and the difference was statistically significant (P<0.05 );before the treatment,compared with the normal group,IL-8 level in intervention group and model group increased significantly,and the difference was statistically significant (P<0.05 );after treatment,level of the intervention group was significantly lower than model group,and the difference was statistically significant (P<0.05).Conclusion Curcumin could effectively reduce ASO and IL-8 level in serum of psoriatic mice model, improve the clinical symptoms of psoriasis mice,it is an effective drug for treatment of psoriasis.