Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Variant Wasserstein Generative Adversarial Network Applied on Low Dose CT Image Denoising

Computed Tomography(CT)images have been extensively employed in disease diagnosis and treatment,causing a huge concern over the dose of radiation to which patients are exposed.Increasing the radiation dose to get a better image may lead to the development of genetic disorders and cancer in the patients;on the other hand,decreasing it by using a Low-Dose CT(LDCT)image may cause more noise and increased artifacts,which can compromise the diagnosis.So,image reconstruction from LDCT image data is necessary to improve radiologists’judgment and confidence.This study proposed three novel models for denoising LDCT images based on Wasserstein Generative Adversarial Network(WGAN).They were incorporated with different loss functions,including Visual Geometry Group(VGG),Structural Similarity Loss(SSIM),and Structurally Sensitive Loss(SSL),to reduce noise and preserve important information on LDCT images and investigate the effect of different types of loss functions.Furthermore,experiments have been conducted on the Graphical Processing Unit(GPU)and Central Processing Unit(CPU)to compare the performance of the proposed models.The results demonstrated that images from the proposed WGAN-SSIM,WGAN-VGG-SSIM,and WGAN-VGG-SSL were denoised better than those from state-of-the-art models(WGAN,WGAN-VGG,and SMGAN)and converged to a stable equilibrium compared with WGAN and WGAN-VGG.The proposed models are effective in reducing noise,suppressing artifacts,and maintaining informative structure and texture details,especially WGAN-VGG-SSL which achieved a high peak-signalto-noise ratio(PNSR)on both GPU(26.1336)and CPU(25.8270).The average accuracy of WGAN-VGG-SSL outperformed that of the state-ofthe-art methods by 1 percent.Experiments prove that theWGAN-VGG-SSL is more stable than the other models on both GPU and CPU.

Effect of low dose laser cycloplasty on deepening anterior chamber in chronic angle-closure glaucoma

AIM:To describe the outcome of using low-dose laser cycloplasty(LCP)in chronic angle-closure glaucoma(CACG).METHODS:A retrospective case series.Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed.The main outcomes included intraocular pressure(IOP),the number of glaucoma medication,anterior segment parameters and surgery-related complications.RESULTS:A total of 7 eyes of 7 CACG patients(age 38.9±11.0y)underwent LCP with a mean follow-up of 27.1±13.7mo(range 16-48mo).Following LCP,mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg(P=0.027)with 0.4±1.1 glaucoma medications(P=0.001)at final follow-up.The anterior chamber depth(ACD),angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm,0.05 mm(range 0-0.30 mm)and 5.1°(range,0-31.97°)at baseline to 1.98±0.43 mm(P=0.073),0.53 mm(range 0.42-0.91 mm,P=0.015),45.9°(range,40.2°-59.4°),(P=0.015)in the long-term follow-up,respectively.The deepening of ACD and reopening of anterior chamber angle(ACA)was observed in 6 eyes(85.7%).CONCLUSION:LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications.In addition,LCP can bring a significant deepening in ACD and reopening of ACA.

Efficacy of Low Dose Naltrexone on Pain Reduction in Chronic Pain Syndromes: A Meta Analysis

Chronic pain is a multifaceted debilitating experience often associated with significant physical and emotional burden. Low dose naltrexone (LDN) has gained attention in recent years for its potential utility in the management of fibromyalgia, irritable bowel syndrome, multiple sclerosis, and painful diabetic neuropathy. LDN’s analgesic effects have been associated with its ability to increase the production of endorphins while reducing the production of tumor necrosis factor-alpha, interleukin-6, reactive oxygen species and nitric oxide. This meta-analysis aims to systematically review and synthesize the available evidence on efficacy of LDN as an analgesic in pain syndromes, with a focus on chronic (neuro) inflammatory diseases. The goal is to provide clinicians with a more comprehensive estimate of the effectiveness of LDN as a non-opioid option for managing chronic pain and guide future research in the area. Thirteen randomized control trials, published from 1990 to 2022, were selected for the analysis that satisfied inclusion criteria. The overall effects in these studies were calculated using the standardized mean difference (SMD) between the LDN and placebo groups. We found an overall SMD of -10.77 (95% CI: -13.96 to -7.58) with a p-value of 0.002. This indicated that the LDN group experienced a statistically significant reduction in pain compared to placebo. This meta-analysis provides evidence for the potential efficacy of low dose naltrexone in reducing pain and enhancing analgesia in various pain syndromes. LDN may be a useful treatment option for patients suffering from chronic pain, particularly with fibromyalgia, multiple sclerosis, or diabetic neuropathy. However, further research is needed to confirm the efficacy and safety of low dose naltrexone for chronic pain conditions, especially with larger sample sizes, standardized dosing regimens and treatment durations.

Increased Levels of p53 and PARP-1 in EL-4 Cells Probably Related with the Immune Adaptive Response Induced by Low Dose Ionizing Radiation in vitro

Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.

A retrospective analysis of the safety and efficacy of low dose tacrolimus (FK506) for living donor liver transplant recipients

We sought to evaluate the efficacy and effects of low-dose tacrolimus （FK506） to recipients with living donor liver transplantation （LDLT）. A total of 66 patients who underwent LDLT between 2001 and 2007 were enrolled in this study. According to different doses of tacrolimus, the recipients were randomly divided into two groups： the low-dose tacrolimus group （group A） and the normal-dose tacrolimus group （group B）. The blood concentration of tacrolimus and its side effects including infection, hyperglycemia, hypertension, high blood creatinine and jaundice were monitored once a week at the perioperative period, and once a month thereafter. Besides, the survival rates of the recipients were analyzed at the 1and 3-year time point after operation. Among these patients, no significant acute rejection was detected after LDLT. The incidences of infection, hyperglycemia, liver dysfunction and renal impairment in group A were markedly lower than those in group B. However, no significant differences were detected in the incidence of hypertension between the two groups. Moreover, the recipients in each group had a similar survival rate according to the results of 1and 3-year follow-up. The incidence of side effects that associated with tacrolimus positively correlated with tacrolimus blood concentration. In conclusion, long-term and low-dose administration of tacrolimus is a safe and effective treatment for LDLT recipients.

Low Dose Hyper-radiosensitivity in Human Lung Cancer Cell Line A549 and Its Possible Mechanisms

The low dose hyper-radiosensitivity （HRS） in human lung cancer cell line A549 was investigated, the changes of ATM kinase, cell cycle and apoptosis of cells at different doses of radiation were observed, and the possible mechanisms were discussed. A549 cells in logarithmic growth phase were irradiated with ^60Co y-rays at doses of 0-2 Gy. Together with flow cytometry for precise cell sorting, cell survival fraction was measured by means of conventional colony-formation assay. The expression of ATM1981 Ser-P protein was examined by Western blot 1 h after radiation. Apoptosis was detected by Hoechst 33258 fluorescent staining, and Annexin V-FITC/PI staining flow cytometry 24 h after radiation. Cell cycle distribution was observed by flow cytometry 6, 12 and 24 h after radiation. The results showed that the expression of ATM1981Ser-P protein was observed at 0.2 Gy, followed by an increase at 〉0.2 Gy, and reached the peak at 0.5 Gy, with little further increase as the dose exceeded 0.5 Gy. Twenty-four h after radiation, partial cells presented the characteristic morphological changes of apoptosis, and the cell apoptosis curve was coincident with the survival curve. As compared with control group, the cell cycle almost had no changes after exposure to 0.1 and 0.2 Gy radiation （P〉0.05）. After exposure to 0.3, 0.4 and 0.5 Gy radiation, G2/M phase arrest occurred 6 and 12 h after radiation （P〈0.05）, and the ratio of G2/M phase cells was decreased 24 h after radiation （P〈0.05）. It was concluded that A549 cells displayed the phenomenon of HRS/IRR. The mode of cell death was mainly apoptosis. The activity of ATM and cell cycle change may take an important role in HRS/IRR.

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.

Effect of Low Dose Radiation on Intracellular Calcium and Protein Kinase C in Lymphocytes

It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming micc With 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+], mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBl with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic（LC） method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature（40 1C） using a mobile phase of acetonitrile：methanol：0.03 M ammonium acetate（p H 3.8）（30：15：55, v/v/v）, run at a flow rate of 1.5 m L/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2（paddle） at 100 rpm and 900 m L of phosphate buffer at p H 6.8 as the dissolution medium.Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Estimation of enhanced low dose rate sensitivity mechanisms using temperature switching irradiation on gate-controlled lateral PNP transistor

The mechanisms occurring when the switched temperature technique is applied, as an accelerated enhanced low dose rate sensitivity （ELDRS） test technique, are investigated in terms of a specially designed gate-controlled lateral PNP transistor （GLPNP） that used to extract the interface traps （Nit） and oxide trapped charges （Not）. Electrical characteristics in GLPNP transistors induced by 60Co gamma irradiation are measured in situ as a function of total dose, showing that generation of Nit in the oxide is the primary cause of base current variations for the GLPNP. Based on the analysis of the variations of Nit and Not, with switching the temperature, the properties of accelerated protons release and suppressed protons loss play critical roles in determining the increased Nit formation leading to the base current degradation with dose accumulation. Simultaneously the hydrogen cracking mechanisms responsible for additional protons release are related to the neutralization of Not extending enhanced Nit buildup. In this study the switched temperature irradiation has been employed to conservatively estimate the ELDRS of GLPNP, which provides us with a new insight into the test technique for ELDRS.

Time and Dose-related Effects of the Pyrethroid Fluvalinate on Haemolymph Carbohydrates and Gut Lipids of Honeybees,Following in vivo Injection of very Low Doses

The injection to emerging adult workerbees with fluvalinate doses ranging from 1 femtomol to 1 nanomol per individual resulted in a reduction of haemolymph carbohydrate concentrations, particularly at the lowest dose 1 hour after injections. At the same time, a large increase was observed for triacylglycerols and to a much lesser extent for steroids and phospholipids with 0.1 picomol per bee. By contrast, fatty acids, steroids and triacylglycerols exhibited a depress at the higher dose. Most responses were thus biphasic, showing that much attention should be paid to the effects of very low doses of pesticide.

Rotational Angiography for 3D Roadmapping of Catheter Interventions in Congenital Heart Disease: Comparison of a Diagnostic and a Low Dose Program

Objectives: To compare the image quality, accuracy and effective dose of the default diagnostic pro-gram with the low dose program. Methods: The diagnostic and low dose programs of three-dimen-sional rotational angiography were compared considering their signal to noise ratio, their carrier to noise ratio and their actual radiation dose in μGy⋅m2/kg. An anthropomorphic phantom underwent both types of scans to evaluate the effective dose. Comparative measurements of vessel diameters were taken in the diagnostic and the low dose program and compared to the angiography as exact basis. The image quality of the scans using the different programs was rated by a specialist physician. Results: The low dose scan does use significantly less radiation and still provides images, which are adequate for 3D navigation of catheter-based interventions. Conclusion: Three-dimensional rotational angiography can be applied with the low dose program and is sufficient for 3D navigation.

Effect of long-term low dose of aspirin on severity of disease following onset of acute cerebral infarction

BACKGROUND： Aspirin can decrease the incidence risk of high-risk crowdgroup of cerebral infarction, but there are still controversy if it might decrease the degree of disease in degree of patients with acute cerebral infarction. OBJECTIVE： To observe the effect of lower dose of aspirin during taking for a long time on disease degree of disease following onset of acute cerebral infarction. DESIGN： Grouping according to the admission time and 1：1 paired observation.SETTING ： Department of Neurology, Qilu Hospital of Shandong University.PARTICIPANTS ： The participants in present study were 321 patients with acute cerebral infarction who received treatments in the Department of Neurology, Qilu Hospital of Shandong University from January 1999 to June 2000. There were 190 male and 131 female ,with mean （65±11 ）years of age. Inclusive criteria： ① A focal neurological disturbance occurred suddenly and had lasted for more than 24 hours, patients were admitted within 3 days after onset of disease; ② A computed tomography of the brain was performed and excluded hemorrhage in all patients; ③ The patients were proved internal carotid occlusions by clinical features and image findings; ④ The functions of limbs were normal （before the first stroke） or almost normal （before the second stroke）. Exclusive criteria：①The patients who had have cardiogenic cerebral embolism; ②The patients who had taken warfarin orally and other platelet agglutination drugs. METHODS ：①All the patients were divided into 2 groups according to whether they had taken aspirin before： aspirin-treated group （n=110） and blank control group （n=211）. there were 70 male and 40 female in aspirin-treated group, with average（65±10） years of age.All patients had taken 50-100 mg/d aspirin for 6 months to 10 years before onset. There were 120 male and 91 female in blank control group, with average （65±13） years of age. Patients received a clinical scoring within 3 days and similar therapeutic measures （such as anti-platelet agglutination, improving cerebral circulation and metabolism-promoting reagent）. Two groups of patients had the same basic conditions except for taking aspirin or not before. ②The matched pairs were made between 50 cases selected from aspirin-treated group and 50 cases from non-aspirin-treated groups according to age, gender, and other stroke risk factors. ③ Evaluation： Degree of disease after onset was evaluated by means of Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. MAIN OUTCOME MEASURES： Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. RESULTS ： All 321 patients entered the stage of analysis with no loss in the midway. ① The symptom following onset of acute cerebral infarction was evaluated with clinical neurologic impairment scoring criteria, there were no significant differences between aspirin group and blank control group [（17.39±9.90） vs （16.22 ± 9.98） （t=1.025, P〉 0.05）]. ② No significant differences were found in 1：1 matched pairs of 100 cases from aspirin group and blank control group （t=1.74, P 〉 0.05）. CONCLUSION ： Taking a lower dose of aspirin during long time may not decrease the degree of disease following onset of acute cerebral infarction.

Combination therapy using low dose radiation,plasma exchange,and a robust antiviral may induce synergic beneficial interactions for mitigating severe COVID‐19

Recent studies confirm that current antiviral drugs are not fully effective on coronaviruses.Our research team introduced the idea of radiotherapy at low doses for coronavirus disease 2019(COVID-19)in March 2020.This issue later received much attention from many scientists around the world.Low dose radiation therapy exerts modulatory effects in acute inflammation,potentiate the anti-viral immune responses,and can be localized to the organ affected by inflammatory reactions,such as lungs.The findings of the first clinical trial show that low dose radiation therapy is safe,and reveal early promise of efficacy.Moreover,plasma exchange therapy may be a rescue therapy in severe COVID-19 patients,as it can quickly eliminate the cytokines and chemokines from the circulation.Remdesivir was introduced as an anti-virus agent that prevents viral RNA synthesis and coronavirus replication and reduces the viral load.If antiviral therapy is poor,the virus has ample opportunity to mutate and increase its fitness through adaptive mutations.Given this consideration,instead a single treatment,we preferentially recommend a combination therapy using low dose radiation therapy plasma exchange and a robust antiviral agent(not yet available).This review provides a viewpoint concerning the potential synergistic effects of low dose radiation therapy,plasma exchange therapy and robust antiviral agent in severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)-infected patients as a more effective strategy for possible treatment of severe COVID-19 patients.

Effects of low dose Glibenclamide on secondary damage after acute spinal cord injury in rats

Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated

Usefulness of anti-ulcer drugs for the prevention and treatment of peptic ulcers induced by low doses of aspirin

AIM:To investigate the usefulness of anti-ulcer drugs for the prevention and treatment of low-dose aspirin- induced peptic ulcer. METHODS:Upper gastrointestinal endoscopy was performed in 68 patients receiving daily low-dose aspirin(81 or 100 mg/day).The endoscopic findings were classified according to the Lanza score,and the scores were compared between groups categorized according to the concomitant use of anti-ulcer drugs and the types of drugs used.In another study,31 hemorrhagic peptic ulcer patients who had been receiving low-dose aspirin were enrolled.The patients were randomly classified into the proton pump inhibitor (PPI)-treated group and the H2 receptor antagonist (H2RA)-treated group.The administration of low-dose aspirin was continued concomitantly,and endoscopic examinations were performed 8 wk later. RESULTS:The Lanza scores(mean±SD)of the gastro-mucosal lesions were 1.0±1.9 and 1.9±2.3 in 8 and 16 patients receiving prevention therapy with a PPI and an H2RA,respectively.Both scores were significantly smaller than the scores in 34 patients who were not receiving prevention therapy(4.7±1.0)and in 10 patients receiving cytoprotective anti-ulcer drugs (4.3±1.6).In the prospective study,18 and 13 patients received a PPI and an H2RA,respectively.Endoscopic examinations revealed that the tissue in the region of the gastro-mucosal lesions had reverted to normal in all patients in the PPI-treated group and in 12 patients (92%)in the H2RA-treated group;no significant differences were observed between the groups. CONCLUSION:H2RA therapy was effective for both the prevention and treatment of low-dose aspirin- induced peptic ulcer,similar to the effects of PPIs, while cytoprotective anti-ulcer drugs were ineffective in preventing ulceration.

Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy

AIM To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin(LDA)therapy.METHODS A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used,and these groups were compared in several factors.These groups were compared in terms of length of hospital stay,presence/absence of hemoglobin(Hb)decrease,presence/absence of blood transfusion,Forrest Ⅰ,percentage of Helicobacter pylori infection,presence/absence of underlying disease,and percentage of severe cases.RESULTS The percentage of blood transfusion(62.6%vs 47.7%,P<0.001),Hb decrease(53.8% vs 40.8%,P<0.001),and the length of hospital stay(23.5 d vs 16.7 d,P<0.001)were significantly greater in those on drug therapy.The percentage of blood transfusion(65.3%vs 47.8%,P<0.001),Hb decrease(54.2%vs 42.1%,P<0.001),and length of hospital stay(23.3 d vs 17.5 d,P<0.001)were significantly greater in the elderly.In comparison with the LDA monotherapy group,the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned(16.1%vs34.0%,P=0.030).Meanwhile,among those on LDA monotherapy,there was no significant difference between elderly and non-elderly(16.1%vs 16.0%,P=0.985).CONCLUSION A combination of LDA with antithrombotic drugs or nonsteroidal anti-inflammatory drugs(NSAIDs)contributes to aggravation.And advanced age is not an aggravating factor when LDA monotherapy is used.

Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension

AIM: To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo. METHODS: Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1α, TXB2, PGE2 and LTB4 were also performed. RESULTS: The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1α was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged. CONCLUSION: These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats, could act through a COX 2 pathway more than the COX 1, predominant for aspirin at higher doses.