Normal-phase thin-layer chromatography of some angiotensin converting enzyme (ACE) inhibitors and their metabolites

The separation and chromatographic behaviour of five ACE (angiotensin converting enzyme) inhibitors and their four active metabolites were investigated by normal-phase thin-layer chromatography on silica using several mono- and binary non-aqueous solvent systems. The linear relationship between the RM values and the composition of employed mobile phase was obtained. The hydrophobicity parameters RM0 and C0 were determined from the regression data of the plots, analogous to reversed-phase chromatography. The chromatographically obtained hydrophobicity parameters were correlated with the calculated log P values. The current results were correlated with the lipophilicity of the studied ACE inhibitors and their metabolites, previously estimated by reversed-phase chromatography

Kinetics of C-reactive protein, interleukin-6 and -10, and phospholipase A2-II in severely traumatized septic patients

Background/Aim. Injury-induced anergy is one of the key factors contributing to trauma victims' high susceptibility to sepsis. This group of patients is mostly of young age and it is therefore essential to be able to predict as accurately as possible the development of septic complications, so appropriate treatment could be provided. The aim of this study was to assess kinetics of interleukin (IL) -6 and -10, phospholipase A2- II and C-reactive protein (CRP) in severely traumatized patients and explore the possibilities for early detection of potentially septic patients. Methods. This prospective study included 65 traumatized patients with injury severity score (ISS) > 18, requiring treatment at surgical intensive care units, divided into two groups: 24 patients without sepsis and 41 patients with sepsis. C-reactive protein, IL-6 and -10 and phospholipase A2 group II, were determined within the first 24 hours, and on the second, third and seventh day of hospitalization. Results. Mean values of IL-6 and phospholipase A2-II in the patients with and without sepsis did not show a statistically significant difference on any assessed time points. In the septic patients with ISS 29-35 and > 35 on the days two and seven a statistically significantly lower level of IL-10 was found, compared with those without sepsis and with the same ISS. C-reactive protein levels were significantly higher in septic patients with ISS 18-28 on the first day. On the second, third and seventh day CRP levels were significantly lower in the groups of septic patients with ISS 29-35 and > 35, than in those with the same ISS but without sepsis. Conclusion. Mean levels of CRP on the first day after the injury may be useful predictor of sepsis development in traumatized patients with ISS score 18-28. Mean levels of CRP on the days two, three and seven after the injury may be a useful predictor of sepsis development in traumatized patients with ISS score more than 28. Mean levels of IL-10 on the second and seventh day after the injury may be a useful predictor of sepsis development in traumatized patients with ISS score > 28

Procena renalne eliminacije inhibitora enzima koji konvertuje angiotensin sa odabranim molekulskim deskriptorima

Angiotensin-converting enzyme (ACE) inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril) and their renal elimination data, from relevant literature, were investigated. The 'molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS); an electronic descriptor, polar surface area (PSA);, a constitutional parameter, molecular mass (Mr); and a geometric descriptor, volume value (Vol), as well as lipophilicity descriptors (logP values), were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742). In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors' renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425)) or the geometric descriptor (volume value (R2 = 0.7224)) as an independent variable. the application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.Inhibitori enzima koji konvertuje angiotenzin (ACE) modifikuju funkciju renin-angiotenzin-aldosteron sistema i predstavljaju često propisane lekova za sniženje pritiska, posebno kod pacijenata sa insuficijencijom bubrega. U ovom radu, za osam odabranih ACE inhibitora (enalapril, kvinapril, fosinopril, ramipril, benazepril, perindopril, moeksipril, trandolapril) ispitan je odnos između osobina njihovih molekula i njihove eliminacije putem bubrega. Za ispitivane inhibitore ACE korišć enjem različitih softverskih paketa izračunate su vrednosti nekoliko molekulskih deskriptora: rastvorljivost u vodi (logS), elektronski deskriptor - polarna površina molekula (PSA), molekulska masa (Mw), geometrijski deskriptor - volumen molekula (Vol) kao i deskriptor lipofilnosti (logP vrednosti). Primenom proste linearne regresione analize najbolja zavisnost dobijena je između podataka o eliminaciji inhibitora ACE putem bubrega i deskriptora lipofilnosti, AClogP vrednosti (R2 = 0.5742). U sledećoj fazi istraživanja primenjena je metoda višestruke regresione analize (MLR) kako bi se dobila bolja zavisnost između podataka o eliminaciji ACE inhibitora putem bubrega i njihove lipofilnosti (AClogP vrednosti) uz primenu dodatnog molekulskog deskriptora kao nezavisno promenljive. Dobre korelacije su dobijene između podataka o eliminaciji putem bubrega i deskriptora lipofilnosti AClogP, uz primenu molekulske mase (R2 = 0.7425) ili zapremine molekula (R2 = 0.7224) kao nezavisno promenljive. Mogućnost primene izračunatih molekulskih deskriptora u proceni eliminacije lekova je od velikog značaja u njihovom istraživanju

The effect of the molecular properties of calcium channel blockers on their elimination route

Calcium channel blockers (CCBs) are among the most widely used drugs in cardiovascular medicine. In this study, nine CCBs (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to assess the relationship between their molecular properties and elimination data obtained from literature. The descriptors of the molecular properties of CCBs were calculated using three software packages. The relationship between computed molecular properties and elimination data collected from relevant literature, initially investigated with simple linear regression analysis, showed poor correlation (R-2 lt 0.25). Application of molecular weight or volume data as additional independent variable, multiple linear regression (MLR) revealed better correlations (R-2 similar to 0.38) between CCB renal and fecal elimination data and their lipophilicity. Excluding nimodipine from the calculations resulted in more acceptable correlations. The best correlations were established after computed lipophilicity descriptor and molecular weight were applied (R-2 = 0.66 with acceptable probability value)

The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists

Angiotensin II receptor antagonists (ARBs) modulate the function of the renin-angiotensin-aldosterone system and are commonly prescribed antihypertensive drugs, especially in patients with renal failure. In this study, the relationship between several molecular properties of seven ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan) and their fecal elimination data obtained from the literature were investigated. The ARB molecular descriptors were calculated using three software packages. Simple linear regression analysis showed the best correlation between fecal elimination data and lipophilicity descriptor, ClogP values (R-2 = 0.725). Multiple linear regression was applied to examine the correlation of ARBs' fecal elimination data with their lipophilicity and one additional, calculated descriptor. The best correlation (R-2 = 0.909 with an acceptable probability value, P lt 0.05) was established between the ARB fecal elimination data and their lipophilicity and aqueous solubility data. Applying computed molecular descriptors for evaluating drug elimination is of great importance in drug research

Surfactant mediated particle aggregation in nonpolar solvents

The aggregation behavior of particles in nonpolar media is studied with time-resolved light scattering. At low surfactant concentrations particles are weakly charged and suspensions are not stable. The suspensions become progressively more stable with increasing surfactant concentration as particles become more highly charged. At high concentrations the particles become neutralized and aggregation is again fast. The theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO) is able to predict the stability ratios quantitatively by using the experimentally measured surface charges, screening lengths and van der Waals forces

Determination of the delivered hemodialysis dose using standard methods and on-line clearance monitoring

Background/aim: Delivered dialysis dose has a cumulative effect and significant influence upon the adequacy of dialysis, quality of life and development of co-morbidity at patients on dialysis. Thus, a great attention is given to the optimization of dialysis treatment. On-line Clearance Monitoring (OCM) allows a precise and continuous measurement of the delivered dialysis dose. Kt/V index (K = dialyzer clearance of urea; t = dialysis time; V = patient's total body water), measured in real time is used as a unit for expressing the dialysis dose. The aim of this research was to perform a comparative assessment of the delivered dialysis dose by the application of the standard measurement methods and a module for continuous clearance monitoring. Methods. The study encompassed 105 patients who had been on the chronic hemodialysis program for more than three months, three times a week. By random choice, one treatment per each controlled patient was taken. All the treatments understood bicarbonate dialysis. The delivered dialysis dose was determined by the calculation of mathematical models: Urea Reduction Ratio (URR) singlepool index Kt/V (spKt/V) and by the application of OCM. Results. Urea Reduction Ratio was the most sensitive parameter for the assessment and, at the same time, it was in the strongest correlation with the other two, spKt/V indexes and OCM. The values pointed out an adequate dialysis dose. The URR values were significantly higher in women than in men, p < 0.05. The other applied model for the delivered dialysis dose measurement was Kt/V index. The obtained values showed that the dialysis dose was adequate, and that, according to this parameter, the women had significantly better dialysis, then the men p < 0.05. According to the OCM, the average value was slightly lower than the adequate one. The women had a satisfactory dialysis according to this index as well, while the delivered dialysis dose was insufficient in men. The difference between the women and the men was significant. Conclusion. The application of OCM has shown that it is the most rigorous parameter for the assessment of adequacy and that its regular use would contribute to increasing of the delivered dialysis dose and improvement of the treatment quality

Cardiovascular morbidity and mortality in patients treated with hemodialysis: Epidemiological analysis

Background/Aim. Cardiovascular diseases are the leading cause of death in patients treated with hemodialysis (HD). The annual cardiovascular mortality rate in these patients is 9%. Left ventricular (LV) hypertrophy, ischemic heart disease and heart failure are the most prevalent cardiovascular causes of death. The aim of this study was to assess the prevalence of traditional and nontraditional risk factors for cardiovascular complications, to assess the prevalence of cardiovascular complications and overall and cardiovascular mortality rate in patients on HD. Methods. We investigated a total of 115 patients undergoing HD for at least 6 months. First, a cross-sectional study was performed, followed by a two-year follow-up study. Beside standard biochemical parameters, we also determined cardiac troponins and echocardiographic parameters of LV morphology and function (LV mass index, LV fractional shortening, LV ejection fraction). The results were analyzed using the Student's t test and Mann-Whitney U test. Results. The patients with adverse outcome had significantly lower serum albumin (p < 0.01) and higher serum homocystein, troponin I and T, and LV mass index (p < 0.01). Hyperhomocysteinemia, anemia, hypertriglyceridemia and uncontrolled hypertension had the highest prevalence (86.09%, 76.52%, 43.48% and 36.52%, respectively) among all investigated cardiovascular risk factors. Hypertrophy of the LV was presented in 71.31% of the patients and congestive heart failure in 8.70%. Heart valve calcification was found in 48.70% of the patients, pericardial effusion in 25.22% and disrrhythmia in 20.87% of the investigated patients. The average annual overall mortality rate was 13.74%, while average cardiovascular mortality rate was 8.51%. Conclusion. Patients on HD have high risk for cardiovascular morbidity and mortality