Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro

PURPOSE: We investigated the cavernosal relaxant effect of osthole, a coumarin isolated from Cnidium monnier (L.) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were precontracted with phenylephrine. Corporal relaxation evoked by osthole was then determined in the absence and presence of nitric oxide synthase inhibitor (L-NAME), soluble guanylate cyclase inhibitor (ODQ), cyclooxygenase inhibitor (indomethacin), tetradotoxin, and after endothelium deprivation. RESULTS: Corpus cavernosal strips showed relaxation in response to osthole (0.1 approximately 30 microM) in a dose-dependent manner. These effects were reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption. However, they were not affected by indomethacin and tetradotoxin treatment. Osthole pretreatment (from 1 to 30 microM) enhanced the sodium nitroprusside (0.3 microM)-induced relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 microM osthole. However, this effect was abolished in the presence of zaprinast. Additionally, a higher concentration of osthole (30 microM) also enhanced forskolin-induced relaxation. CONCLUSION: The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase.     

Association between paternal age and risk of schizophrenia: a nationwide population–based study

PurposeTo study the association between paternal age and schizophrenia in offspring.MethodsThis report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan’s National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596).ResultsThe median age at first presentation with schizophrenia was 20 years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father’s age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32 years), mother’s age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29 years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father’s age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father’s age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01).ConclusionThis study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.     

柚皮素对ARPE-19和HUVEC细胞的抗氧化作用

目的：研究柚皮素对人视网膜色素上皮细胞（ARPE-19）和人脐静脉内皮细胞（HUVEC）的抗氧化作用。 方法：采用MTT的方法检测ARPE-19和HUVEC细胞的生存率及增殖率。 结果：3，10mg／L柚皮素能显著增加ARPE-19细胞的增殖率达10．8％和11．4％。10mg／L柚皮素能提高ARPE-19细胞在缺氧，0．3mmol／LNaN，及200μmol／L，H2O2条件下的生存率分别为55．2％，69．2％及50．3％。1mg／L柚皮素能提高ARPE-19细胞在50μmol／L t-BHP和30mg／LNaIO3条件下的生存率达20．2％和30．4％。30mg／L柚皮素能够促进ARPE-19细胞在50μmol／L t-BHP条件下的增殖率达32．2％，而1mg／L柚皮素可以提高30，100，300mg／LNaIO3处理的ARPE-19细胞的增殖率达30．3％，10．3％及18．5％。3，10及30mg／L柚皮素抑制HUVEC的增殖率分别为23．9％，70．4％及77．9％。1，3mg／L柚皮素能提高HUVEC细胞在缺氧条件下的生存率达10．7％和13．1％，以及提高在300mg／LNaIO3条件下的生存率达41．2％和37．7％。3mg／L柚皮素能提高HUVEC细胞在200，400μmol／L H2O2条件下的生存率达20．1％和21．5％． 结论：柚皮素能够促进ARPE-19细胞的增殖率，抑制HU-VEC生长，同时对这两种细胞均有抗氧化作用。因此，柚臾素是治疗老年黄斑变性的很有前景的候选药物。     

Elucidation of Anti-Hypertensive Mechanism by a Novel Lactobacillus rhamnosus AC1 Fermented Soymilk in the Deoxycorticosterone Acetate-Salt Hypertensive Rats

Dietary intake of fermented soymilk is associated with hypotensive effects, but the mechanisms involved have not been fully elucidated. We investigated the anti-hypertensive effects of soymilk fermented by L. rhamnosus AC1 on DOCA-salt hypertension from the point of view of oxidative stress, inflammatory response and alteration of the gut microbiome. The antioxidant assays in vitro indicated the ethanol extract (EE) of L. rhamnosus AC1 fermented soymilk showed better antioxidative effects than the water extract (WE). Those extracts displayed a hypotensive effect using a tail-cuff approach to measuring blood pressure and improved nitric oxide (NO), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α) and interleukin factor-6 (IL-6) on DOCA-salt hypertensive rats. Furthermore, cardiac and renal fibrosis were attenuated by those extracts. The gut microbiota analysis revealed that they significantly reduced the abundance of phylum Proteobacteria, its family Enterobacteriaceae and genus Escherichia-Shigella. Moreover, metabolomic profiling revealed several potential gut microbiota-related metabolites which appeared to involve in the development and recovery of hypertension. In conclusion, fermented soymilk is a promising nutritional intervention strategy to improve hypertension via reducing inflammation and reverting dysbiotic microbiota.     

Spontaneous Achilles tendon rupture in a patient with systemic lupus erythematosus due to ischemic necrosis after methyl prednisolone pulse therapy

Spontaneous tendon rupture in a patient with systemic lupus erythematosus (SLE) is a rare but potentially disabling complication. Minor trauma, local inflammation and long term corticosteroid therapy are regarded as possible causes. However, ischemic necrosis of the tendon resulting from hypercoagulability and methyl prednisolone (MTP) pulse therapy has not been reported. We present a 20-year old female, newly diagnosed with lupus, who has high titer antiphospholipid antibodies, hyperhomocysteinemia and protein S deficiency. Her severe clinical symptoms of lupus were improved after MTP pulse therapy. Several days later, cold sensation over the right lower leg developed. On day 15 after pulse therapy, acute onset of right heel pain occurred when she was ascending stairs. Rupture of the right Achilles tendon was demonstrated by sonography and MRI. A Doppler sonography revealed narrowing and abrupt cessation of blood flow in the right popliteal artery. Heparin treatment was started. The angiography performed two days after heparinization revealed narrow caliber and decreased flow of the right tibial artery below the right ankle. Surgical repair of the tendon was successful and the pathology of the resected tendon revealed focal necrosis, degeneration and capillary proliferation. MTP pulse therapy in a lupus patient with hypercoaguable state with hyperhomocysteinemia, protein S deficiency and high titer antiphospholipid antibodies may cause spontaneous tendon rupture.     

An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production

Phospholipase C and several inositol polyphosphate kinase (IPK) activities generate a branched ensemble of inositol polyphosphate second messengers that regulate cellular signaling pathways in the nucleus and cytoplasm. Here, we report that mice deficient for Ipk2 (also known as inositol polyphosphate multikinase), an inositol trisphosphate and tetrakisphosphate 6/5/3-kinase active at several places in the inositol metabolic pathways, die around embryonic day 9.5 with multiple morphological defects, including abnormal folding of the neural tube. Metabolic analysis of Ipk2-deficient cells demonstrates that synthesis of the majority of inositol pentakisphosphate, hexakisphosphate and pyrophosphate species are disrupted, although the presence of 10% residual inositol hexakisphosphate indicates the existence of a minor alternative pathway. Agonist induced inositol tris- and bis-phosphate production and calcium release responses are present in homozygous mutant cells, indicating that the observed mouse phenotypes are a result of failure to produce higher inositol polyphosphates. Our data demonstrate that Ipk2 plays a major role in the synthesis of inositol polyphosphate messengers derived from inositol 1,4,5-trisphosphate and uncovers a role for their production in embryogenesis and normal development.     

Cardiac beriberi among illegal mainland Chinese immigrants

The most common symptoms of chronic beriberi due to thiamine deficiency include dyspnoea, fatigue, leg oedema, lower extremity weakness and numbness. When collapsed peripheral circulation, metabolic acidosis, or shock are present, the disease has advanced from chronic beriberi to pernicious or fulminating beriberi heart failure (Shoshin beriberi). We report two patients with fulminating beriberi; both of whom had been incarcerated at a detention centre for 5 months before hospitalization. A prolonged monotonous diet, low in thiamine, was a major risk factor in both patients. Thiamine deficiency should be considered for any patient with symptoms and signs compatible with beriberi.