Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with ß-thalassemia.

Pregnant patients with ß-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with ß- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that ß CD 41-42(-TTCT)/ßA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype ß CD 41-42(-TTCT)/ßA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with ß-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.

A randomized, double-blind, placebo-controlled trial on the efficacy of tranexamic acid combined with rivaroxaban thromboprophylaxis in reducing blood loss after primary cementless total hip arthroplasty.

AIMS: Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. PATIENTS AND METHODS: A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. RESULTS: TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). CONCLUSION: In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis.

Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease.

AIMS: Erythropoiesis-stimulating agents used to treat anaemia in patients with chronic kidney disease (CKD) have been associated with cardiovascular adverse events. Hepcidin production, controlled by bone morphogenic protein 6 (BMP6), regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anaemia in CKD patients. To investigate alternative therapies to erythropoiesis-stimulating agents for CKD patients, monoclonal antibodies, LY3113593 and LY2928057, targeting BMP6 and ferroportin respectively, were tested in CKD patients. METHODS: Preclinical in vitro/vivo data and clinical data in healthy subjects and CKD patients were used to illustrate the translation of pharmacological properties of LY3113593 and LY2928057, highlighting the novelty of targeting these nodes within the hepcidin-ferroportin pathway. RESULTS: LY2928057 bound ferroportin and blocked interactions with hepcidin, allowing iron efflux, leading to increased serum iron and transferrin saturation levels and increased hepcidin in monkeys and humans. In CKD patients, LY2928057 led to slower haemoglobin decline and reduction in ferritin (compared to placebo). Serum iron increase was (mean [90% confidence interval]) 1.98 [1.46-2.68] and 1.36 [1.22-1.51] fold-relative to baseline following LY2928057 600 mg and LY311593 150 mg respectively in CKD patients. LY3113593 specifically blocked BMP6 binding to its receptor and produced increases in iron and transferrin saturation and decreases in hepcidin preclinically and clinically. In CKD patients, LY3113593 produced an increase in haemoglobin and reduction in ferritin (compared to placebo). CONCLUSION: LY3113593 and LY2928057 pharmacological effects (serum iron and ferritin) were translated from preclinical-to-clinical development. Such interventions may lead to new CKD anaemia treatments.

Functional and Biochemical Parameters of Erythrocytes during Mexicor Treatment in Posttraumatic Period after Experimental Blood Loss and Combined Traumatic Brain Injury.

Mexicor treatment (8 mg/kg body weight per day) during the posttraumatic period after concomitant traumatic brain injury and acute blood loss in rats increased electrophoretic mobility and concentration of 2,3-diphosphoglycerate, and reduced malondialdehyde content in erythrocytes. These changes improved hemodynamics and oxygen-transporting function of the blood. The most pronounced effects of Mexicor were observed at the early stages of posttraumatic period.

High-Dose Filgrastim Treatment of Nonregenerative Pancytopenia Associated With Chronic Canine Ehrlichiosis.

OBJECTIVE: To report the management and outcome of a dog with canine monocytic ehrlichiosis and nonregenerative pancytopenia, with high doses of filgrastim. CASE DESCRIPTION: An 8-year-old male, mixed-breed dog, weighing 5.6kg, presented with a 1-month history of hyporexia, adynamia, and a weight loss of approximately 1kg. The general condition of the dog was observed to be poor as follows: lethargy, tachycardia, marked pallor of the mucous membranes, petechiae on the abdomen, hepatosplenomegaly, and cervical lymphadenopathy. A complete blood count analysis revealed severe leukopenia, thrombocytopenia, and anemia. A direct immunofluorescence assay using anti-Ehrlichia canis-immunoglobin G (1:400) yielded positive result. The dog was diagnosed with nonregenerative pancytopenia associated with canine monocytic ehrlichiosis. The dog presented poor prognostic signs (neutropenia, thrombocytopenia, and severe anemia). The dog was treated with antibiotics and a short course of high-dose filgrastim (50µg/kg, SC, q 48h for 4 days) to stimulate bone marrow response, prednisone to decrease peripheral platelet destruction, and an iron supplement to compensate for the iron deficiency in the bone deposits. Although temporary side effects associated with filgrastim use, such as bone pain, bleeding, and the worsening of thrombocytopenia, were observed, the treatment improved the clinical course and the cell counts in less than a month. CLINICAL RELEVANCE: The treatment protocol used in this case might be an alternative for treating cases of severe myelosuppression. This treatment plan can substantially change the clinical course of the disease for the better, compared to conventional treatment.

Evaluation of hepatic glycogen content, some haematological and biochemical parameters of alloxan-induced diabetic rats treated with combinations of glibenclamide and G. latifolium extract.

Background Diabetes is associated with both biochemical and haematological complications. Combination therapy has been advocated to mitigate some of these complications. Aim This study was designed to investigate the effects of glibenclamide and Gongronema latifolium (GL) on hepatic glycogen content and haemato-biochemical parameters. Methods Thirty male Wistar rats were assigned into five groups of six rats each. Groups 2-5 rats received intraperitoneally, 160 mg/kg of alloxan monohydrate while group 1 rats served as normal control. Groups 2-5 rats were respectively treated with 10 mL/kg distilled water (DW), 2 mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL, while group 1 rats received 10 mL/kg DW. All treatments were per os daily for 21 days. Blood samples for investigation of haemato-biochemical (red blood cell [RBC], packed cell volume [PCV], haemoglobin concentration [Hb], blood urea nitrogen [BUN] and creatinine) parameters were collected on days 7, 14 and 21 post-treatment (PT), while the liver sample for hepatic glycogen determination was obtained on day 21 PT. Results Creatinine and BUN values of groups 3 and 4 rats were comparable to that of group 1 but were significantly (p<0.05) lower when compared with those of groups 2 and 5. There were significant (p<0.05) increases in the mean hepatic glycogen content, RBC, PCV, and Hb of group 4 rats when compared to those of group 2. Conclusions It was concluded that a combination of glibenclamide and G. latifolium in treatment of diabetic rats improved glycogen storage and demonstrated beneficial effects on haematology and kidney marker parameters.

Management of the Jehovah's Witness in Obstetrics and Gynecology: A Comprehensive Medical, Ethical, and Legal Approach.

IMPORTANCE: Obstetricians and gynecologists frequently deal with hemorrhage so they should be familiar with management of patients who refuse blood transfusion. Although there are some reports in the literature about management of Jehovah's Witness patients in obstetrics and gynecology, most of them are case reports, and a comprehensive review about these patients including ethicolegal perspective is lacking. OBJECTIVE: This review outlines the medical, ethical, and legal implications of management of Jehovah's Witness patients in obstetrical and gynecological settings. EVIDENCE ACQUISITION: A search of published literature using PubMed, Ovid Medline, EMBASE, and Cochrane databases was conducted about physiology of oxygen delivery and response to tissue hypoxia, mortality rates at certain hemoglobin levels, medical management options for anemic patients who refuse blood transfusion, and ethical/legal considerations in Jehovah's Witness patients. RESULTS: Early diagnosis of anemia and immediate initiation of therapy are essential in patients who refuse blood transfusion. Medical management options include iron supplementation and erythropoietin. There are also some promising therapies that are in development such as antihepcidin antibodies and hemoglobin-based oxygen carriers. Options to decrease blood loss include antifibrinolytics, desmopressin, recombinant factor VII, and factor concentrates. When surgery is the only option, every effort should be made to pursue minimally invasive approaches. CONCLUSION AND RELEVANCE: All obstetricians and gynecologists should be familiar with alternatives and "less invasive" options for patients who refuse blood transfusions.

Medical Adjuvant Treatment to Improve the Patency of Arteriovenous Fistulae and Grafts: A Systematic Review and Meta-analysis.

BACKGROUND: Many patients using haemodialysis for end-stage renal disease (ESRD) require arteriovenous fistulae (AVF) or grafts. Patency can be variable, and this systematic review aimed to determine the effects of adjuvant drug treatment on the patency of AVFs and grafts. METHODS: The Cochrane Peripheral Vascular Diseases Group searched the Specialised Register and CENTRAL for all randomised controlled trials (RCTs) investigating the effect of active drug versus placebo on patency. The primary outcome was fistula or graft patency rate. The odds ratio (OR) was used as the measure of effect for each outcome. If several trials assessed the same adjuvant therapy then a meta-analysis was conducted using a Mantel-Haenszel model. RESULTS: Fifteen trials were deemed suitable for inclusion, investigating nine drug treatments in 2,230 participants. Overall, the quality of evidence was low. Three trials compared ticlopidine (a platelet aggregation inhibitor) versus placebo and favoured active treatment (OR 0.45, 95% CI 0.25 to 0.82; p = .009). Three RCTs assessed aspirin versus placebo and did not show a statistical benefit (OR 0.40, 95% CI 0.07-2.25; p = .30). Two trials compared clopidogrel with placebo. The overall result did not favour treatment (OR 0.40, 95% CI 0.13 to 1.19; p = .10). Three trials evaluated human type-I pancreatic elastase but did not provide evidence of improved patency (OR 0.75, 95% CI 0.42-1.32; p = .31). Finally, two RCTs assessed fish oil and did not favour treatment (OR 0.24, 95% CI 0.03-1.95; p = .18). Single trials comparing dipyridamole alone, dipyridamole plus aspirin, and sulfinpyrazone against placebo favoured active treatment but a meta-analysis could not be undertaken. Finally, a single trial of warfarin versus placebo found warfarin resulted in increased complications and worse patency rates. CONCLUSION: This systematic review has not demonstrated a beneficial effect for any adjuvant treatment to increase the patency of AVF or grafts in the short term, except ticlopidine which has been taken off the market.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) Stapf extracts.

Cymbopogon citratus is a widely distributed perennial herb belonging to the Poaceae family and has been extensively consumed for its medicinal, cosmetic, and nutritional effects for centuries. A large number of reports have been published describing the pharmacological, biological, and therapeutic actions of this herb. In this review, we summarized the literatures on related studies (up to January, 2014) that highlighted the pharmacologic and biological effects of the major phytochemicals isolated from C. citratus extracts and its essential oil. The components of the essential oils found in C. citratus have a similar pharmacokinetic properties, including absorption, distribution, metabolism, and excretion. They are quickly absorbed following oral, pulmonary, and dermal administration. Based on the published reports, it can also be inferred that, after absorption from the small intestine, some phytochemicals in C. citratus can undergo oxidation, glucuronidation, sulfation, and/or O-methylation. Excretion is through urine, feces and/or expired volatiles. The biotransformation reactions of C. citratus bioactive constituents are essential for its relatively safe consumption and therapeutic applications. The data available so far warrant further studies evaluating C. citratus pharmacokinetics. Reliable pharmacokinetic data in humans would be critical for a better understanding of the the systemic handling of C. citratus.

Bioactive components from the tea polyphenols influence on endogenous antioxidant defense system and modulate inflammatory cytokines after total-body irradiation in mice.

The present study aimed to evaluate the radioprotective efficacy of green tea polyphenols and the component ingredients against irradiated-induced damage in mice and elucidate the underlying mechanisms. Green tea polyphenols (GTP 50, 50 and 100 mg/kg, p.o. daily) and its four individual components (25 and 50 mg/kg, p.o. daily) were administrated to the irradiated-injured mice for 21 days. The radioprotective effect on the hematopoietic system, serum cytokines, and endogenous antioxidant enzymes was studied. GTP 50 significant revert the irradiated-induced decline in hematological parameters (RBCs, WBCs, Hb), meanwhile, protected antioxidant defense system, as evidenced by decreased of serum lipid peroxidation (malonyldialdehyde) and elevation the antioxidant enzyme superoxide dismutase (SOD). Among the GTP components, catechin showed the best effect on elevation of hematological parameters, and epigallocatechin gallate showed the best antioxidant activity. Moreover GTP and its bioactive components (catechin, epigallocatechin and epigallocatechin-3-gallate) assisted in decreasing the leukocytopenia seen after whole mice irradiation and significantly reduced the elevated serum inflammatory cytokines (TNF-α, IL-1ß, and IL-6). Green tea polyphenols have a potential to be developed as radioprotective agents against irradiated-induced toxicity. Furthermore the antioxidant and anti-inflammatory activities of GTP can be attributed to the interaction of the different components through multiple and synergistic mechanisms.

Garlic in health and disease.

The present article reviews the historical and popular uses of garlic, its antioxidant, haematological, antimicrobial, hepatoprotective and antineoplastic properties and its potential toxicity (from sulfoxide). Garlic has been suggested to affect several cardiovascular risk factors. It has also been shown that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. Since garlic and its constituents can suppress carcinogen formation, bioactivation and tumour proliferation, it is imperative that biomarkers be established to identify which individuals might benefit most. Garlic powder, aged garlic and garlic oil have demonstrated antiplatelet and anticoagulant effects by interfering with cyclo-oxygenase-mediated thromboxane synthesis. Garlic has also been found to have synergistic effects against Helicobacter pylori with a proton pump inhibitor. The active compound allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages. Freshly prepared garlic homogenate protects against isoniazid+rifampicin-induced liver injury in experimental animal models. Several mechanisms are likely to account for this protection.

Emerging drugs for acute myocardial infarction.

IMPORTANCE OF THE FIELD: The present review is aimed at going over the pharmacological profile (and the clinical impact) of the emerging drugs involved in the management of patients with ST-elevation myocardial infarction (STEMI) in order to provide the cardiologists who deal with these patients in the early phase with the most recent evidence on this topic. AREAS COVERED IN THIS REVIEW: Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the treatment of STEMI patients undergoing primary percutaneous coronary intervention (PCI). The main issues that clinicians have to deal with are represented by balancing thrombotic and bleeding risks. In tailoring therapy, variables such as age, sex and previous disease should be taken into account, as well as ongoing complications (such as acute renal failure) that could affect hemostasis. Despite the well-established clinical benefits of antiplatelet agents, questions remain, mainly surrounding potential for variable platelet response, which are strictly related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such as obesity, diabetes mellitus, and inflammation) and genetic determinants. WHAT THE READER WILL GAIN: In their daily practice, cardiologists cannot abstract from the knowledge and updating on the ongoing research fields as well as the newly developed drugs, which they should frame in the very patient in the attempt to the develop a personalized medical strategy. These include also the pharmacological option(s) in the treatment of the reperfusion injury, the metabolic aspects and the stem cell therapy. TAKE HOME MASSAGE: In our opinion, the goal of ongoing research on the pharmacological approach to STEMI patients is a personalized medical strategy that relies on critical clinicians who merge newly developed acquisitions on this topic and a more complete, systemic and critical approach to the patient.

Multi-modality blood conservation strategy in open-heart surgery: an audit.

The objective of this study was to perform an audit of the use of homologous blood and blood products in patients undergoing open-heart surgery by a single surgical team that follows an in-house protocol for blood conservation. The hospital records of 310 consecutive patients (age >15 years) undergoing open-heart surgery over a period of 8 months were retrospectively reviewed to assess the comprehensive blood conservation protocol. Homologous blood and blood product usage during and after surgery, in the intensive care unit and up to hospital discharge was analyzed. Two hundred and fifty-six patients (82.6%) did not receive any blood or blood products. Only 54 patients (17.4%) received one or more units of allogenic transfusion either intraoperatively or postoperatively until discharge. Mean hemoglobin at discharge was 9.8 Grams% (8.9-12 Grams%). A standardized multidisciplinary approach to blood conservation in cardiac surgery decreases bleeding and transfusion requirements in a safe and cost effective manner.

Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis.

OBJECTIVES: The aim of the study was to perform a meta-analysis of randomized trials (RTs) comparing abciximab versus small molecules (eptifibatide and tirofiban) in primary angioplasty (PPCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Abciximab has been shown to provide significant benefits in PPCI for STEMI. However, small molecules represent an attractive strategy due to the reversibility of the inhibition of platelet aggregation and the lower costs. METHODS: We obtained results from RTs comparing abciximab versus small molecules in PPCI. The literature was scanned by searches of electronic databases (MEDLINE and CENTRAL) up to October 2008. The following key words were used: RT, myocardial infarction, reperfusion, primary angioplasty, glycoprotein IIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Concerning tirofiban, we only included trials or groups of patients with high-dose bolus and infusion. The primary end point was 30-day mortality. Secondary end points were 30-day reinfarction, post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, and ST-segment resolution. RESULTS: A total of 6 RTs were included in the meta-analysis, involving 2,197 patients (1,082 randomized to abciximab and 1,115 to small molecules [high-dose tirofiban in 5 trials and eptifibatide in 1 trial]). Abciximab did not improve post-procedural TIMI flow grade 3 (89.8% vs. 89.1%, p = 0.72) or ST-segment resolution (67.8% vs. 68.2%, p = 0.66). Abciximab did not reduce 30-day mortality (2.2% vs. 2.0%, p = 0.66) or reinfarction (1.2% vs. 1.2%, p = 0.88), nor was there any difference in major bleeding complications (1.3% vs. 1.9%, p = 0.27). CONCLUSIONS: This meta-analysis shows among STEMI patients undergoing PPCI similar results between abciximab and small molecules in terms of angiographic, electrocardiographic, and clinical outcome.

[Exploration on effect and mechanism of activating blood circulation to remove stasis method on angiogenesis].

Activating blood circulation to remove stasis method is an important therapy of TCM, which can be matched with various methods, as qi-supplementing, qi-regulating, heat-clearing with detoxication, meridian warming, wind-dispelling to remove dampness, yin-nourishing, phlegm-dissolving to alleviate depression and visceral dredging by purgation, to produce various effects on angiogenesis. Its positive or negative impacts on quality or quantity of angio-genetic regulatory factor play a crucial part for the effects. This article explores the effect and mechanism of activating blood circulation to remove stasis method on angiogenesis bi-directionally.