The therapeutic effects of Agrimonia eupatoria L.

Agrimonia eupatoria L. is an herb of the Rosaceae family, widely used in traditional (folk) medicine for its beneficial effects. Its water extracts (infusions and decoctions) are used in the treatment of airway and urinary system diseases, digestive tract diseases, and chronic wounds. Phytochemical analyses of Agrimonia eupatoria L. identified a variety of bioactive compounds including tannins, flavonoids, phenolic acids, triterpenoids and volatile oils possessing antioxidant, immunomodulatory and antimicrobial activities. The authors review the available literature sources examining and discussing the therapeutic and pharmacological effects of Agrimonia eupatoria L. at the molecular level in vitro and in vivo.

Metformin: the past, presence, and future.

The authors trace the history of metformin and its clinical use to the present day. Recent insights into its mode of action and latest data from experimental and clinical medicine have unraveled novel properties of metformin, which may be particularly useful in the treatment of conditions other than diabetes. Results of ongoing clinical trials will show whether or not the hypoglycemic effect of metformin will become only one of the many to be employed in clinical practice.

Proopiomelanocortin but not vasopressin or renin-angiotensin system induces resuscitative effects of central 5-HT1A activation in haemorrhagic shock in rats.

The aim of this study was to determine the effectory mechanisms: vasopressin, renin-angiotensin system and proopiomelanocortin-derived peptides (POMC), partaking in the effects of serotonin through central serotonin 1A receptor (5-HT1A) receptors in haemorrhagic shock in rats. The study was conducted on male Wistar rats. All experimental procedures were carried out under full anaesthesia. The principal experiment included a 2 hour observation period in haemorrhagic shock. Drugs used - a selective 5-HT1A agonist 8-OH-DPAT (5 µg/5 µl); V1a receptor antagonist [ß-mercapto-ß, ß-cyclo-pentamethylenepropionyl(1),O-me-Tyr(2),Arg(8)]AVP (10 µg/kg); angiotensin type I receptor antagonist (AT1) ZD7155 (0.5 mg/kg, i.v.); angiotensin-converting-enzyme inhibitor captopril (30 mg/kg, i.v.); melanocortin type 4 (MC4) receptor antagonist HS014 (5 µg, i.c.v.). There was no influence of ZD715, captopril or blocking of the V1a receptors on changes in the heart rate (HR), mean arterial pressure (MAP), peripheral blood flow or resistance caused by the central stimulation of 5-HT1A receptors (P≥0.05). However, selective blocking of central MC4 receptors caused a slight, but significant decrease in HR and MAP (P<0.05). POMC derivatives acting via the central MC4 receptor participate in the resuscitative effects of 8-OH-DPAT. The angiotensin and vasopressin systems do not participate in these actions.

The effect of selected pre-analytical phase variables on plasma thromboxane A2 measurements in humans.

AIMS: Platelet function testing is often affected by the existence of different pre-analytical variables that can cause platelet activation. The aim of this study was to assess the effect of such variables that are present when samples are taken (different anticoagulants, incubation temperature, and storage conditions) to select those which enable to reach optimal range of measured plasma concentrations of the two stable thromboxane A2 metabolites, that is, thromboxane B2 (TxB2) and 11-dehydrothromboxane B2 (11-dTxB2). MATERIALS AND METHODS: For the purpose of this study, whole blood samples obtained from 20 volunteers were screened for TxB2 and 11-dTxB2 concentrations using commercial EIA kits (Cayman Chemicals™; Neogen™) in relation to the effect of different anticoagulants, using different incubation temperatures and storage conditions. RESULTS: Trisodium citrate has been shown not to be affecting the TxB2 and 11-dTxB2 concentrations compared with the values measured in the serum. Incubation of the samples for 1 h at 37 °C and freezing at -20 °C or -80 °C give the most suitable concentration range of both thromboxanes in the used EIA measurement. CONCLUSION: This study describes the setup of such pre-analytical phase conditions that enable the screening of platelet function in terms of the plasma concentrations of TxB2 and 11-dTxB2 in selected EIA measurement.

The inhibitory effect of statins on urinary 11-dehydrothromboxane levels.

AIM: Elevated urinary 11-dehydrothromboxane levels place patients at an increased risk for experiencing cardiovascular events. Statins exert an inhibitory effect on platelets. The aim of our study was to determine the effect of 3-month statin therapy on 11-dehydrothromboxane elimination in two groups of patients, one not receiving antiplatelet therapy with acetylsalicylic acid and the other receiving 100 mg acetylsalicylic acid per day. METHODS: We examined the urinary levels of 11-dehydrothromboxane in a total of 58 patients before and after 3-month therapy with a statin at standard doses (simvastatin, fluvastatin, atorvastatin). We also examined the plasma levels of total cholesterol, triglycerides, LDL- and HDL-cholesterol, C-reactive protein, and blood glucose. RESULTS: After 3-month statin therapy, both groups of patients (with and without antiplatelet therapy) showed a significant decrease in urinary 11-dehydrothromboxane levels. Significant decreases were also seen in LDL- and total cholesterol, and C-reactive protein. Changes in the other parameters were not significant. CONCLUSION: Three-month statin therapy significant reduces the rate of 11-dehydrothromboxane elimination, even in patients on acetylsalicylic acid. In addition to its usual lipid-lowering effect, it significantly decreases the plasma levels of C-reactive protein. Combination therapy with a statin plus acetylsalicylic acid may be effective even in patients with incomplete thromboxane inhibition on antiplatelet therapy with acetylsalicylic acid.

Plasma levels of nitrite/nitrate and inflammation markers in elderly individuals.

INTRODUCTION: Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing itself is associated with a mild degree of chronic inflammation. Besides, asymptomatic infectious and non-infectious inflammation is frequent in old age. All this may lead to an increased formation of nitric oxide via inducible nitric oxide synthase. The plasma levels of nitric oxide metabolites in older age groups are not known. The aim of our study was to determine the plasma levels of metabolites of nitric oxide (nitrite and nitrate) and to correlate them with the levels of inflammation markers in clinically healthy individuals aged over 80. METHODS: The plasma levels of nitrite/nitrate as well as erythrocyte sedimentation rate, and the levels of C-reactive protein and tumor necrosis factor alpha were determined in a group of 30 clinically healthy individuals aged over 80 years. Results were compared with those obtained in a control group. RESULTS: Nitrate levels were increased and the levels of inflammation markers were significantly higher compared with those in a control group. CONCLUSIONS: The levels of nitric oxide metabolites in elderly, clinically healthy individuals may be increased due to inflammation (Tab. 2, Fig. 1, Ref. 32). F

Aspirin resistance.

Acetylsalicylic acid, is one of the most effective antiplatelet agents. It effectively reduces the risk of thrombotic events across wide spectrum of patients with cardiovascular disease. However, the treatment failures are relatively common and significant number of patients don't benefit from aspirin therapy. In the last decade the term "aspirin resistance" has been used to describe several different phenomena. This article exposes the difficulties in defining aspirin resistance, discusses the mechanisms by which resistance may occur and deals with its clinical impact. It is necessary to standardize a definition of aspirin resistance, to develop reliable tests for it, and to assess the clinical utility of testing on patients outcomes (Tab. 3, Ref. 60).

The effectiveness of antiplatelet treatment with aspirin in polymorbid patients.

AIM: The ineffectiveness of antiplatelet treatment with aspirin is a widely discussed problem today. It is usually described with individual diseases. In old age, the patient is polymorbid and uses numerous treatments. This work enquires into how polymorbidity and polymedication can have an influence on the anti-aggregation effect of aspirin. METHODS: A group of 508 patients, who used 100 mg aspirin daily, was examined. Clinical and laboratory tests were carried out on all, and pharmacotherapy analysis was conducted. Selected, concurrently used medicines were divided into 12 groups. Levels of 11-dehydrothromboxane B2 (11-dTxB2) in the first morning urine sample were examined in all cases. RESULTS: Of the 508 patients, 233 patients (46%) showed insufficient suppression of urinary thromboxanes. In the resistant group, a statistically significant negative correlation was found with a higher concentration of C-reactive protein and smoking, from co-morbidity with atrial fibrillation and ischemic cerebral stroke in the case history. The risk of ineffective anti-aggregation therapy is increased 1.8 times by smoking and 1.6 times by ischemic cerebral stroke. Every increase in C-reactive protein by one unit increases the ineffectiveness of anti-aggregation therapy by 1.3 times. From the field of pharmacotherapy, a significant positive statistical effect on treatment with statins and nitrates occurred, and a negative effect with digoxin. The possible effectiveness and ineffectiveness of anti-aggregation treatment were not, in this study, influenced to a statistically significant degree by the presence of ischemic coronary disease, ischemic diseases of the lower limbs, arterial hypertension, diabetes and heart failure. CONCLUSION: Anti-aggregation treatment with aspirin in doses of 100 mg per day is, for a major part of polymorbid patients, insufficient. The risk of ineffectiveness of the treatment is increased by smoking, increased levels of C-reactive protein, and from comorbidities of atrial fibrillation and ischemic cerebral stroke. From the point of view of concurrently used medicines, the risk is increased by treatment with digoxin and on the other hand, reduced by treatment with statins and nitrates.