Selection of statin considering the HDL cholesterol level

Low HDL cholesterol level is an independent risk factor in the cardivascular diseases and the therapeutic aim is to increase this. In high risk patients (cardiovascular disease-, diabetic- or metabolic syndrome patients), the target value of HDL cholesterol is more than 1,0 mmol/l in males and 1,3 mmol/l in females. The PPARalpha receptor activity has an expressed impact on the HDL cholesterol metabolism. It has been proved that in addition to fibrates, statins also influence its functioning. Simvastatin, as compared to atorvastatin, increases the HDL cholesterol level in a better way which positive effect has also been proved by the clinical trials. On choosing a therapy the optimisation of the HDL cholesterol level is also important in addition to achieving an LDL cholesterol target value.     

New strategy in the treatment of hypertension: inhibition of renin-angiotensin-aldosterone system with renin inhibitor

In the Hungarian population, there is also a growing number of patients with hypertension. In order to prevent the target organ's damage or in order to slow down the process, it is indispensable to reach the therapeutic target blood pressure. An opportunity for reducing the cardiovascular morbidity and mortality is the inhibition of the renin-angiotensin-aldosterone system. So far, we have had three large families, the angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, to our disposal. The above are the key molecules for the hypertension treatment, but their application is accompanied by plasma renin level elevations, and thus, increase of plasma renin activation. The protection against increased plasma renin activation is helped by the renin inhibitors. Several decades were needed for their clinical introduction, till a non-peptide, safety medicament was successfully produced, which can be administered orally in small once-per-day doses. Their most promising representative is aliskiren. Still an open question is the mapping of the advantage of the angiotensin-converting enzyme inhibitor and angiotensin receptor blockers combination with aliskiren. The morbidity and mortality investigations are still missing and we curiously await them.     

Trisomies and other chromosome abnormalities detected after positive sonographic findings

OBJECTIVE: To evaluate the rate of trisomies and other chromosome abnormalities after positive ultrasound findings in thefirst and second trimester of pregnancy. STUDY DESIGN: The study investigated chromosome abnormalities detected in cases with prior abnormal ultrasoundfindings. During a 10-year period there were 1907 invasive interventions carried out with the purpose of chromosome analysis. The intervention was genetic amniocentesis in 1619 cases and chorionic villus sampling in 288. RESULTS: Karyotyping revealed 103 cases (5.4%) of chromosome abnormalities. Abnormalities with subcutaneous edema were examined: abnormal karyotype was found in 20% of cases with nonimmune hydrops, 48.1% of cases with cystic hygroma and 53.8% of cases with nonimmune hydrops and cystic hygroma together, 8.3% of cases with nuchal edema in the first trimester and 5.5% in the second trimester. The incidence of chromosome abnormalities in cases of cerebral anomalies was 6.3% of cases with ventricular dilatation, 3.6% of cases with choroid plexus cysts and 15.9% of cases with other cranial anomalies. Regarding abnormalities of the heart, isolated echogenic intracardiac focus and ventricular septal defects were not associated with chromosome abnormality, but, in conjunction with other positive ultrasound findings, the incidence of chromosome abnormalities was 7.9% and 26.7%, respectively. Other anomalies of the heart and large blood vessels showed an abnormal karyotype incidence of 18.2%. In cases of unilateral pyelectasis unassociated with other anomalies, the incidence of chromosome abnormalities was 1%. In cases of bilateral pyelectasis or pyelectasis associated with other anomalies, the incidence was 3%. In terms of anomalies of the abdominal wall and abdomen, the incidence of association with chromosome abnormalities was 9.5% in cases of omphalocele, 11.8% in cases of duodenal atresia and 5.7% in cases of echogenic bowel. In cases of short femur and humerus the rate of abnormal karyotypes was 16%. CONCLUSION: Ultrasound plays an important role in prenatal diagnosis. In cases of positive ultrasound findings, karyotyping is reasonable.     

Structure-activity relationship studies optimizing the antiproliferative activity of novel cyclic somatostatin analogues containing a restrained cyclic beta-amino acid

The cyclic somatostatin analogue cyclo[Pro(1)-Phe(2)-D-Trp(3)-Lys(4)-Thr(5)-Phe(6)] (L-363,301) displays high biological activity in inhibiting the release of growth hormone, insulin, and glucagon. According to the sequence of L-363,301, we synthesized a number of cyclic hexa- and pentapeptides containing nonnatural alpha- and beta-amino acids. The N- fluorenylmethoxycarbonyl protected cyclic beta-amino acid [1S, 2S, 5R]-2-amino-3,5-dimethyl-2-cyclohex-3-enecarboxylic acid (cbetaAA), for the replacement of the Phe(6)-Pro(1) moiety of L-363,301, was synthesized in two steps by an enantioselective multicomponent reaction using (-)-8-phenylmenthol as a chiral auxiliary. The resulting peptide cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] (Trt = triphenylmethyl) shows high antiproliferative effects in an in vitro assay with A431 cancer cells. The same peptide without the Trt group does not reveal any biological activity, whereas L-363,301 and closely related hexapeptides show only minor activity. By comparison of the solution structure of cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] with the structure of l-363,301, a nearly perfect match of the betaII'-turn region with d-Trp in the i + 1 position was observed. The cyclic beta-amino acid cbetaAA is likely needed for the bioactive conformation of the peptide.     

Pharmaceutical and formulation aspects of Petroselinum crispum extract

Parsley (Petroselinum crispum L.) is a very popular spice and vegetable in Europe, it is widely spread and easy to grow. It's herb and fruits are known to be diuretic, smooth muscle relaxant and hepatoprotective. The most important identified active ingredients are flavonoids, cumarins and vitamin C. Apigenin and its glycosides are the main flavonoids in parsley, it can be found relatively large amounts in the leaves. The bioactive flavonoid apigenin has antiinflammatory, antioxidant and anticancer activities. The objectives of this study were the preparation and detemination of the apigenin content of the parsley extract and the formulation using inert pellets by layering the apigenin in fluid-bed process.     

X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns

Historically X-linked sideroblastic anemia, with rare exceptions, was thought to be manifested only in males. Since the discovery of the erythroid-specific isoform of 5-aminolevulinate synthase (ALAS2) and the cloning of its gene (ALAS2) 15 years ago, mutation analysis has revealed that clinical expression of this X-linked disorder is prevalent in females as well. However, presence of the disease in both genders within affected kindreds appears to be very uncommon. We report a unique family with the disorder in three women who have had widely disparate clinical courses. The anemia is associated with a previously unrecognized ALAS2 mutation (Arg436Trp) and is unresponsive to pyridoxine. To clarify the varied clinical courses of the patients, X-chromosome inactivation patterns were examined in hematopoietic and non-hematopoietic cells. We observed inactivation patterns supporting the conclusions that one daughter has a mild phenotype at age 31 because of moderate constitutive skewed X-chromosome inactivation, another daughter with clinical onset at age 16 is severely affected due to extreme constitutive X-skewing, whereas the mother developed progressive anemia in the fifth decade as she acquired an age-related non-random X-inactivation in hematopoietic cells. In addition, we observed random X-inactivation in reticulocytes of all three women that contrasted with a markedly skewed inactivation pattern in bone marrow erythroid cells. This discordance is attributable to apoptosis of erythroid precursors derived from progenitor cells with an active X-chromosome bearing the ALAS2 mutation. The features of the disorder in this family are also instructive in regard to the differential diagnosis of sideroblastic anemias in women.