Diagnostic Value of D-Dimer and INR in Patients Suspected to Have Prosthetic Valve Dysfunction

ABSTRACT Introduction: Prosthetic valve dysfunction is a potentially critical complication of heart valve replacement. An easy and quickly applicable diagnostic procedure is required for recognizing the prosthetic valve dysfunction. The purpose of this study was to prospectively define the diagnostic value of D-dimer and INR level in predicting prosthetic valve dysfunction. Methods: This cross-sectional study was performed in 70 patients suspected to have prosthetic valve dysfunction admitted to Imam Ali Hospital, affiliated with Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. Cinefluoroscopy, as the gold standard diagnostic test, was used for the diagnosis of prosthetic valve dysfunction in enrolled patients. Two milliliters of blood from each patient were taken into a tube containing sodium citrate anticoagulant. To evaluate D-dimer, the cutoff value was set at 500 ng/ml. Also, to evaluate international normalized ratio (INR), the cutoff value was set at 2. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the serum markers were used to describe predictive properties. Results: Of 70 patients, 27 (38.6%) were male and 43 (61.4%) were female, and the mean age was 54.67±15.11 years (range, 18 to 80 years). Of 70 patients, 27 (38.6%) had prosthetic heart valve malfunction demonstrable by fluoroscopy, and 19 patients (27.1%) had D-dimer levels >500 ng/ml. Elevated D-dimer levels (>500 ng/ml) have been indicated to have sensitivity of 70.4%, and hence an NPV of 84.3%, specificity of 100%, PPV of 100%, NLR of 0.3, and the infinity value of PLR for predicting prosthetic valve dysfunction. There was a significant relationship between fluoroscopy and D-dimer test (P=0.001). A kappa coefficient value of 0.745 indicated a substantial agreement between D-dimer and fluoroscopy testing. Mixing test (combination of D-dimer and INR) showed to have 100% sensitivity, and hence a NPV of 69.8%, specificity of 69.8%, PPV of 51.8%, NLR of 1.41, and PLR of 1.44 for predicting prosthetic valve dysfunction. Conclusion: D-dimer with moderate sensitivity and high specificity is an ideal marker for the diagnosis of prosthetic valve dysfunction in suspected patients. Enhanced plasma D-dimer level is not by itself diagnostic of a prosthetic valve dysfunction but may alert physicians to refer the patient for more detailed examination, preferably by fluoroscopy. Mixing test with 100% sensitivity can apply as a rule-out test.

Protective effect of methanolic extract of Berberis integerrima Bunge. root on carbon tetrachloride-induced testicular injury in Wistar rats

Background: Tissue protective effect of compounds with antioxidant properties has been demonstrated. The alkaloids found in barberry root are considered as antioxidants

Objective:According to barberry protective effects in different tissues, in this study, the protective effect of Berberis integerrima Bge. root [MEBIR] was evaluated against CCl4-induced testicular damages in Wistar rats

Materials and Methods:40 mature male rats were randomly divided into 5 groups: 1: Normal control, 2: Sham: received CCl4 diluted in olive oil [50% v/v; 1ml/kg bw], intraperitoneally, twice a week for 4 weeks, 3 and 4: Sham rats treated with MEBIR [250 and 500 mg/kg bw] for 28 days, 5: Sham rats treated with silymarin [50 mg/kg bw] for 28 days. After 28 days, serum testosterone level, absolute testis weight, catalase activity, malondialdehyde level, and histological parameters were investigated

Results: In the treated rats with MEBIR [250 and 500 mg/kg bw] or silymarin [50 mg/kg bw], there was a significant increase in the absolute testis weight, testosterone level, seminiferous tubules diameter [p<0.001], thickness of the epithelium, tubule differentiation index [p<0.001], spermiogenesis index [p<0.001], the activity of catalase, and a significant decrease in interstitial tissue thickness [p<0.001] and malondialdehyde level in comparison with CCl4-treated group. The effect of the MEBIR at dose of 500 mg/kg bw is more than that of the standard drug, silymarin [50 mg/kg bw]

Conclusion:From the results, it is suggested that the protective effects of MEBIR is possibly due to antioxidant effects of its bioactive compounds

Cloning and expression of TNF related apoptosis inducing ligand in Nicotiana tabacum

Molecular farming has been considered as a secure and economical approach for production of biopharmaceuticals. Human TNF Related Apoptosis Inducing Ligand [TRAIL] as a promising biopharmaceutical candidate has been produced in different expression hosts. However, little attention has been paid to molecular farming of the TRAIL in spite of numerous advantages of plant expression systems. Therefore, in this study the cytoplasmic production of the TRAIL was tackled in Nicotiana tabacum using Agrobacterium tumefaciens LBA 4404. Initially, the desired coding sequence was obtained using PCR technique on the constructed human cDNA library. Afterward, the necessary requirements for expression of the TRAIL in plant cell system were provided through sub-cloning into 35S-CaMV [Cauliflower Mosaic Virus] helper and final 0179-pGreen expression vectors. Then, the final TRAIL-pGreen expression vector was cloned into A. tumefaciens LBA 4404. Subsequently, the N. tabacum cells were transformed through co-culture method and expression of the TRAIL was confirmed by western blot analysis. Finally, the recombinant TRAIL was extracted through chromatographic technique and biological activity was evaluated through MTT assay [Methylthiazol Tetrazolium Assay]. The result of western blot analysis indicated that only monomer and oxidized dimer forms of the TRAIL can be extracted from the N. tabacum cells. Moreover, the lack of trimeric assembly of the extracted TRAIL diminished its biological activity in sensitive A549 cell line. In conclusion, although N. tabacum cells can successfully produce the TRAIL, proper assembly and functionality of the TRAIL were unfavorable

Antihyperglycemic and antihyperlipidemic effects of fruit aqueous extract of berberis integerrima bge. in streptozotocin-induced diabetic rats

Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids disorder to normal level is clinically very important. The aim of present study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous extract [BIFAE] on blood glucose and lipid profile in streptozotocin [STZ] - induced diabetic rats. The STZ-induced diabetic rats were treated by fruit aqueous extract of Berberis integerrima Bge. at doses [250 and 500 mg/Kg bw] and glibenclamide [0.6 mg/Kg bw] for 42 days by gavage. Blood glucose levels and body weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were determined in normal and STZ-induced diabetic rats after administration of the BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a significant [P<0.001] increases in the levels of blood glucose, triglycerides [TG], total cholesterol [TC], low density lipoprotein LDL-cholesterol [LDL-C] while body weight and high density lipoprotein HDL-cholesterolan [HDL-C] were significantly [P<0.001] decreased compared to normal rats. Daily administration of BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ- diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE in traditional medicine for the treatment of diabetes may need more investigation

Cardiovascular risk factors and nutritional intake are not associated with ultrasound-defined increased carotid intima media thickness in individuals without a history of cardiovascular events

Carotid ultrasound appears to be useful in the assessment of cardiovascular risk. In this study, we have assessed the carotid intima-media thickness [CIMT] in a group of individuals without a history of cardiovascular events. A sample of 431subjects [189 [43.9%] males and 242 [56.1%] females] was obtained from an urban population using a stratified-cluster method in Mashhad stroke and heart atherosclerosis disorder study. None of the subjects had a history of the cardiovascular event. Carotid artery duplex ultrasound was used to determine the CIMT in all subjects, and to identify those with an abnormal value [CIMT [+]; i.e., CIMT >/= 0.8 mm]. Dietary intake of participants was assessed using a questionnaire for 24-h dietary recall. The relationship between anthropometric, biochemical and dietary data and CIMT were assessed. The mean age of subjects was 48.7 +/- 8.0 years. Of the 431 patients, 118 [27.4%] were found to be CIMT [+]. Of the cardiovascular parameters assessed, only age [odds ratio [OR] [95% confidence interval [CI]], 1.11 [0.56-4.34]; P < 0.01] and male gender [OR [95% CI], 1.14 [0.63-2.23]; P < 0.05] were significant independent predictors of ultrasound defined CIMT. Crude and total energy adjusted intake were not associated with the presence of CIMT [+]. It appears that within a relatively young Iranian population of individuals without a history of cardiovascular event, the presence of CIMT [+] defined by duplex ultrasound cut-off value of >/= 0.8 mm, did not associate with several modifiable cardiovascular risk factors or measures of dietary intake

[Cost Price Estimation of Clinical Laboratory Services in Shafa Hospital based on Activity-based Costing, Kerman, 2011]

Background: Activity-based costing is one of the main methods for operational budgeting which provides the ability to manage and control costs for managers. This study was conducted to estimate the cost price of Shafa hospital laboratory services in Kerman using activity-based costing technique and compared with services tariff.

Materials and Methods: This study is a cross-sectional and applied study was conducted in the clinical Laboratory of Shafa Hospital at Kerman University of Medical Sciences in 2011. The cost price of FBS, CPK and Cr tests calculated which had the highest frequency in the year as well as HBS, HIV and three times blood culture which had the higher tariffs than other tests. Initially, data were manually collected through interview with hospital officials and review of relevant documents. Then, in order to achieve the targets of the study, the cost price results were analyzed using Excel software.

Results: The results showed that the total annual costs of the departments were the sum of 5, 002, 917, 493 Rails that 94.9 percent and 5.1 percent of it were related to the direct and indirect costs respectively. Laboratory personnel cost by 74.2 percent and consumables cost by 21.1 percent had the largest share of the costing. The cost price of Cr and CPK tests calculated the sum of 10.019 and 21.517 Rails respectively that according to the public tariffs, had a suitable profit.

Conclusion: This study showed that there is a difference between the actual cost of the laboratory services and public tariffs that has led a loss to the laboratory. Therefore, by improving the performance management in the field of human resource and standardizing, can reduce the cost price of services and optimize resources consumption.

Factors affecting drug-induced liver injury: antithyroid drugs as instances

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

Effects of aqueous extract of Berberis integerrima root on some physiological parameters in streptozotocin-induced diabetic rats

Diabetes mellitus is a common endocrine disorder. Anti-diabetic agents from natural and synthetic sources are available for the treatment of this disease. Berberis integerrima is a medicinal shrub used in conventional therapy for a number of diseases. The aim of the present study was to investigate the effects of aqueous extract of Berberis integerrima root [AEBI] on some physiological parameters in normal and streptozotocin-induced [STZ-induced] diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides [TG], total cholesterol [TC], low density lipoprotein LDL-cholesterol [LDL-C], creatinine [Cr], urea, alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], total bilirubin while body weight, high density lipoprotein HDL-cholesterol [HDL-C] and total protein levels were significantly decreased compared to normal rats. Treatment of diabetic rats with different doses of aqueous extract of Berberis integerrima root [250 and 500 mg/Kg bw] resulted in a significant decrease in blood glucose, triglycerides, cholesterol, LDL-cholesterol, ALT, AST, ALP, total bilirubin, creatinine and urea while HDL-cholesterol and total protein levels were markedly increased after six weeks compared to untreated diabetic rats. The effects of the AEBI at dose of 500 mg/Kg in all parameters except blood glucose [similar] is more than to the standard drug, glibenclamide [0.6 mg/Kg, p.o.]. The results of this study indicate that the tested aqueous extract of Berberis integerrima root possesses hypoglycemic, hypolipidemic and antioxidant effects in STZ-induced diabetic rats

[Cost-effectiveness of methadone maintenance centers to prevent HIV among intravenous drug users]

Objective [s]: The rising of risky injections has caused HIV infections epidemics among Intravenous Drug Users [IDUs]. So, high costs of HIV/AIDS care and low financial resources necessitate economic evaluation to choose the best decision to control HIV/AIDS. This study was conducted to determine cost-effectiveness of Methadone Maintenance Treatment [MMT] centers to prevent HIV infections among IDUs

Methods: In this study, we selected all seven MMT centers and their IDUs [n = 259]. We calculated all costs from government perspective. Mathematical models were used to estimate number of HIV cases averted from risky injecting behaviors changes

Results: Total cost of MMT centers was 204297.7 dollar and cost of HIV/AIDS care in no intervention scenario, was estimated 13942756.8 dollar. ICER was 109035.3 dollar per HIV case averted based on an estimated 126 HIV case averted. The results of the sensitivity analysis indicated that MMT intervention is cost-effective even in worst scenario and ICER varies from 39149.42 dollar to 290004.1 dollar per HIV case averted

Conclusion: Considering to high effectiveness and cost-effectiveness of MMT centers, it is necessary to develop these centers in regional and national levels to cover the high risk people more

Comparison of gastric ulcerogenicity of percolated extract of Anacardium occidentale [Cashew Nut] with indomethacin in rats

In traditional Iranian medicine, the core of the fruit of Anacardium occidentale [cashew nut] has been used in the management of the pain. In this study gastric ulcerogenicity effect of the percolated extract of A. occidentale was investigated in rats. The extract or indomethacin [200, 300, 400 and 800 mg/kg] was administrated orally. In the control group normal saline [5 ml/kg] was used. After getting extract, indomethacin or normal saline, animals were slaughtered. The stomachs were detached and 10 ml of 2% formalin injected in to the stomach for fixing the internal coat of the gastric wall. The stomachs were then slitted open near the bigger curvature and lacerations in the glandular part were evaluated. The ulcer index was determined using j-score. Data demonstrated that the oral dose of 200 mg/kg of the extract did not provoke any ulcerogenic consequence in the rat's stomach. Gastric ulcerginicity of the extract at the doses of 300, 400 and 800 mg/kg was less than the similar doses of indomethacin [p<0.01]. Therefore, A. occidentale is an appropriate plant for ongoing search for establishing an analgesic agent with low gastrointestinal side effects for clinical use

Effect of natural honey from Ilam and metformin for improving glycemic control in streptozotocin-induced diabetic rats

Diabetes mellitus is a public health problem and one of the five leading causes of death globally. In the present study, the effect of Metformin with natural honey was investigated on glycemia in the Streptozotocin-induced diabetic rats. Thirty Wistar male rats were randomly divided into six groups including C: non diabetic rats received distilled water, CH: non diabetic rats received honey, CD: diabetic rats administered with distilled water, DM: Metformin treated diabetic rats, DH: honey treated diabetic rats, and DMH: diabetic rats treated with a combination of Metformin and natural honey. Diabetes was induced by a single dose of Streptozotocin [65 mg/kg; i.p.]. The animals were treated by oral gavage once daily for four weeks. At the end of the treatment period, the animals were sacrificed and their blood samples collected. Amount of glucose, triglyceride [TG], total cholesterol [TC], HDL cholesterol, LDL cholesterol, VLDL cholesterol, total bilirubin, and albumin were determined in serum. Group CD: showed hyperglycemia [252.2 +/- 4.1 mg/dl], while level of blood glucose was significantly [p<0.01] reduced in groups DH [124.2 +/- 2.7 mg/dl], DM [108.0 +/- 3.4 mg/dl], and DMH [115.4 +/- 2.1 mg/dl]. Honey in combination with Metformin significantly [p<0.01] reduced level of bilirubin but Metformin alone did not reduce bilirubin. Honey alone and in combination with Metformin also significantly reduced triglycerides, total cholesterol, LDL, VLDL and increased HDL, but Metformin did not reduced triglycerides and increased HDL. The results of the present study demonstrated that consuming natural honey with Metformin improves glycemic control and is more useful than consuming Metformin alone. The higher therapeutic effect of Ilam honey on lipid abnormalities than Tualang honey was also evident

Effects of melatonin and vitamin E on peripheral neuropathic pain in streptozotocin-induced diabetic rats

Previous studies have indicated that diabetes mellitus might be accompanied by neuropathic pain. Oxidative stress is implicated as a final common pathway in development of diabetic neuropathy. Pharmacological interventions targeted at inhibiting free radical production have shown beneficial effects in diabetic neuropathy. The aim of this study was to investigate and compare the possible analgesic effects of melatonin and vitamin E in diabetic rats. This study was performed on 32 male Wistar rats divided into 4 groups: control, diabetic, melatonin-treated diabetic and vitamin E-treated diabetic. Experimental diabetes was induced by intraperitoneal streptozotocin [50 mg/kg] injection. Melatonin [10 mg/kg, i.p.] and vitamin E [100 mg/kg, i.p.] were injected for 2 weeks after 21 st day of diabetes induction. At the end of administration period, pain-related behavior was assessed using 0.5% formalin test according to two spontaneous flinching and licking responses. The levels of lipid peroxidation as well as glutathione-peroxidase and catalase activities were evaluated in lumbosacral dorsal root ganglia. Formalin-evoked flinching and total time of licking were increased in both acute and chronic phases of pain in diabetic rats as compared to control rats, whereas treatment with melatonin or vitamin E significantly reduced the pain indices. Furthermore, lipid peroxidation levels increased and glutathione-peroxidase and catalase activities decreased in diabetic rats. Both antioxidants reversed the biochemical parameters toward their control values. These results suggest that oxidative stress may contribute to induction of pain in diabetes and further suggest that antioxidants, melatonin and vitamin E, can reduce peripheral neuropathic pain in streptozotocin-induced diabetic rats

Study of the anti-inflammatory and analgesic effects of novel rigid benzofuran-3, 4-dihydroxy chalcone by formalin, hot-plate and carrageenan tests in mice

It is reported that dihydroxy chalcones have analgesic and anti-inflammatory effects. Study of the structure activity relationship [SAR] shows that benzofuran-3-one derivatives may be more effective in this respect. In this study, a new [Z]-2-[3,4-dihydroxybenzylidene]-5-methoxybenzofuran-3[2H]-one [compound 5] was synthesized and its analgesic and anti-inflammatory effects were evaluated by formalin, carrageenan and hot-Plate methods in mice. The results showed that, compound 5 induced significant antinociceptive and anti-inflammatory effect [P< 0.01]. Maximum analgesia [42.6%] was obtained at dose of 25 mg/kg in the first phase of formalin test. The effect of compound 5 was higher [87.7%] in chronic phase of inflammation induced by formalin [P< 0.01]. Administration of 25 mg/kg of compound 5 inhibited the inflammation induced by carrageenan, 32.8% and 41.7%, 1 and 3 hour after carrageenan injection, respectively. In addition, this dose of compound 5, induces significant analgesia [20.2%] in hot plate test 45 minutes after injection [P<0.01]. Therefore it seems that compound 5 has potential for discovery of a compound with potent anti-inflammatory and analgesic effects and its scaffold could be use for further structural modifications

Antinociceptive and anti-inflammatory activity of the seed and root extracts of ferula gummosa boiss in mice and rats

Ferula gummosa Boiss [Apiaceae] has been used in Iranian traditional medicine for the relief of stomach pain. In this study, effects of aqueous, methanolic and acetone extracts of the seed and root of this plant in experimental models of acute pain [Tail-flick=TF], chronic pain [Formalin test=FT] and inflammation [Cotton pellet granuloma=CPG] was investigated. The results showed that the highest non-sedative dose of each of these three extracts had no effect in TF. Among the extracts, only the acetone extract of the root could reduce licking and biting time in the late phase of FT, although this effect might be to some extent due to the solvent [Tween 80]. None of the extracts had anti-inflammatory effect in CPG. Preliminary phytochemical analysis of methanol and acetone extracts showed presence of terpenoids and alkaloids and small amounts of cardenolids. The results of our study suggest further evaluation of antinociceptive and anti-inflammatory effects of other kinds of extracts in order to determine the best extract with highest efficacy and lowest side effects