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.

Bilateral oophorectomy may have an unfavorable effect on glucose metabolism compared with natural menopause.

The incidence of diabetes mellitus is rising worldwide. The aim of this prospective epidemiological study was to compare the effects of natural and surgical menopause on parameters of glucose metabolism. In a group of 587 repeatedly examined women, with a baseline age of 45-55 years, the following subgroups of women were separated: those after bilateral oophorectomy (BO, n=37) and those in natural menopause (NAT, n=380) including women menopausal already at baseline (POST, n=89). The study parameters including glycemia, insulinemia, HOMA-IR and beta-cell function using HOMA-beta were determined at baseline and 6 years later. Over the study period, there was a marked rise in prediabetic and diabetic values of fasting glycemia; the percentage of women with diabetic values increased in the NAT (from 0.8 % to 3.9 %) and POST (from 2.2 % to 9.0 %) subgroups, with the highest prevalence in the BO subgroup (from 8.1 % to 10.8 %). While, among women with non-diabetic fasting glycemia, an increase in fasting glycemia was observed in all study subgroups, it was more marked in the BO subgroup than in the NAT and POST ones (p=0.02 both). This difference between NAT and BO was also found in the long-term trend of development of glycemia in non-diabetic women (p=0.014). Compared with natural menopause, bilateral oophorectomy may have an adverse effect on glucose metabolism.

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.

Natural postmenopause is associated with an increase in combined cardiovascular risk factors.

Cardiovascular disease, while rare in women of reproductive age, is the main cause of mortality in menopause. The purpose of our study was to determine the association of natural menopause with cardiovascular risk factors, including their clustering into metabolic syndrome (MS). A random 5 % representative population sample of women aged 45-54 years was examined. In 575 women, we were able to determine their natural reproductive aging status. Multiple regression analysis was used to calculate the association between age, menopausal status, and risk factors under study. After adjustment for age, there was an increase in the odds ratio of developing MS, as defined by NCEP (OR=2.0; 95 % CI [1.1; 3.7]), and an increase in plasma lipid ratios (total cholesterol/HDL-C, LDL-C/HDL-C, apolipoprotein-B/apolipoprotein-A1; p<0.05 for all) in postmenopausal women. Age, but not menopausal status, was associated with some single components of MS; only waist circumference significantly increased after menopause, independently of age. Clustering of risk factors in MS and lipid ratios (combined factors) was strongly associated with menopause whereas worsening of single components of MS was strongly associated with age. In conclusion, based on our results, the menopause may pose a risk to women through clustering of cardiovascular risk factors beyond simple aging.

Menopause: clustering of metabolic syndrome components and population changes in insulin resistance.

AIM: The incidence of the metabolic syndrome (MS) in women rises rapidly during the menopause, substantially increasing their cardiovascular risk and mortality. The aim of the study was to analyze menopausal changes in individual MS components and the parameter of insulin resistance (HOMA-IR). METHODS: A random population sample of 909 women aged 45-54 years, resident in Prague 4, was examined in an epidemiological study. After excluding women with gynecological hormone therapy or surgical therapy, the two groups of women were compared: women of reproductive age (REPRO, n = 245) vs. naturally postmenopausal women (POSTm, n = 149). RESULTS: The incidence of MS rose significantly in menopause (REPRO/POSTm 22.9 ± 2.6%/38.3 ± 4.0%; p < 0.001). However, a detailed analysis among the five components defining MS showed that increases were only seen in waist circumference (p < 0.0001) and triglycerides (p < 0.001). There was no increase in the other components or HOMA-IR. A detailed analysis showed an increase in HOMA-IR at levels above the median (REPRO/POSTm: low HOMA-IR 0.9/0.9, not significant; high HOMA-IR 1.8/2.1, p < 0.001) and an increase in the incidence of MS just in these high levels of HOMA-IR and those rising during menopause (REPRO/POSTm: low HOMA-IR 13.8%/18.7%, not significant; high HOMA-IR 30.9%/57.3%, p < 0.0001). In menopause, there was an increase in the clustered incidence (accompanying MS) of each of the five MS components at the expense of isolated incidence (not accompanying MS). CONCLUSION: The acceleration of MS incidence at the onset of menopause may be accompanied by an increase in insulin resistance only in the population at highest risk. Reproductive women entering the menopause with an isolated MS component are at high risk for developing additional risk factors during menopause.

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.

[Pharmacotherapy of pain in rheumatic disease]. / Farmakoterapie bolesti u revmatických onemocnení.

The authors of this article discuss the pharmacotherapy of pain control in patients with rheumatic diseases, and they describe the relevant groups of drugs available, including their adverse events. They focus on non-steroidal antirheumatic drugs, selectice cyclooxygenase-2 inhibitors (coxibs) in particular. They summarise the experience with use of coxibs so far, and also report on drugs soon to be marketed in our country.

[Geriatrization of internal medicine]. / Geriatrizace vnitrního lékarství.

The author draws attention to the need of more profound knowledge of geriatrics in the training of specialists in internal medicine. He draws attention to the ageing population, trends in advanced countries and planned enlistment of general specialists in internal medicine into primary care.

[Corticosteroids in the treatment of rheumatic diseases]. / Pouzití kortikosteroidu v lécbe revmatických onemocnení.

The author describes the use of corticosteroids in the treatment of rheumatic diseases. He mentions different indications, incl. controversial vones, the problem of dosage and undesirable effects of treatment.

[Topical therapy with corticosteroids in rheumatology]. / Lokální lécba kortikosteroidy v revmatologii.

The author summarized when and how to use steroid-injection therapy. He mentions indications, contraindications, complications and the controversial uses of the local treatment.

[Drugs and polypharmacy]. / Léky a polypragmazie.

The author deals with the causes of increasing polypharmacy in the Czech Republic. He discusses all problems concerned with treatment and analyzes attitudes of drug manufacturers, physicians, patients, the state and its health policy. He mentions also possible ways how to reduce polypharmacy. Attention is drawn to the role of the pharmacist in conjunction with extension of the spectrtum of drugs which can be purchased without restriction.

[Minocycline in the treatment of rheumatoid arthritis]. / Minocyklin v lécbe revmatoidní artritidy.

The author presents a review of contemporary knowledge on the treatment of rheumatoid arthritis with minocycline. He analyzes the assumed mechanism of action, dosage and the most frequently encountered undesirable effects of treatment. He informs the reader on the results of the most important studies with minocycline.

[Crouzon's syndrome, arthritis and crural ulcers]. / Crouzonuv syndrom, artritida a bércové vredy.

The author describes a special inflammatory rheumatic disease in a 48-year-old female patient with Crouzon's syndrome which most probably could be included among seronegative spondarthritis. The author discusses the possible ratio of inborn disease in the atypical course of the rheumatic disease.