Characterization and microbiological evaluation of chitosan-alginate microspheres for cefixime vaginal administration.

Chitosan-alginate microspheres (MS) were developed for cefixime vaginal administration, to overcome problems associated with its oral administration. The effect of increasing drug-loading amount, by keeping the chitosan-alginate content constant, was investigated. Mucoadhesion studies indicated that all formulations assured in situ permanence longer than 2 h. Entrapment efficiency increased with drug loading concentration in the starting solution, reaching a plateau at 30 mg/mL indicative of the achievement of an optimal drug-to-polymer ratio. MS swelling properties increased with the entrapped drug amount, and, interestingly, water-uptake reached its maximum value at the same drug loading concentration of 30 mg/mL. The relationship found between MS water-uptake and drug release rate confirmed MS prepared with 30 mg/mL cefixime as the best formulation. Microbiological studies showed a relation between cefixime release rate from MS and Escherichia coli viability reduction, definitely indicating the selected MS formulation as the best for an effective local treatment of urogenital infections.

Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol.

BACKGROUND: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. AIM: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. METHOD: Interaction between atenolol and randomly methylated beta-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. RESULTS: The formation of a stabile inclusion complex (K(s) = 783.4 +/- 21.6 M(-1)) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. CONCLUSION: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.

Hydroxypropyl methylcellulose microspheres with piroxicam and piroxicam-hydroxypropyl-beta-cyclodextrin inclusion complex.

Inclusion complexation between piroxicam (PX) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) in the presence of hydroxypropyl methylcellulose (HPMC) was studied in aqueous solution and in the solid state. Phase solubility studies were used to evaluate the HPbetaCD complexation in the presence of HPMC. Stability constants, Ks, of the complexes were determined. The stability of the inclusion complex was improved in the presence of HPMC. Solid microspheres were obtained by spray drying, and were characterized by differential scanning calorimetry (DSC), regarding drug content, and particle size distribution. Scanning electron microscopy (SEM) was also used to characterize the systems prepared. In the solid system HPMC facilitated to some extent the drug dissolution due to increased solubility. The presence of HPMC and HPbetaCD in the microspheres promoted dissolution rate. Cyclodextrin complexation increased PX flux through a semipermeable membrane. Presence of HPMC in the system additionally increased the drug flux more than 80%, by increasing the drug solubility and consequently the affinity of the ternary complex for the aqueous diffusion layer in the donor compartment.

Clinical value of biochemical markers in the diagnosis of acute myocardial infarction.

Current strategy for the use of biochemical markers in the diagnosis of acute myocardial infarction is not yet uniform. New markers of myocardial damage have significantly altered the former viewpoints. The study included 41 patients with confirmed acute myocardial infarction (25 males and 16 females, age range 42-85 years). Control group comprised of 25 patients with chronic renal failure without signs of acute coronary event (n = 11) and patients with confirmed coronary artery disease (n = 14). The level and activity of CKMB (microgram/L and U/L), and the level of myoglobin and cTnl were determined. The results showed the sensitivity of CKMB (microgram/L) in the first six hours from the onset of pain to be statistically significantly higher than the sensitivity of cTnl, while myoglobin was confirmed to be the earliest marker. Determination of CKMB (U/L) activity should be abandoned since it was found to have the lowest sensitivity and specificity. Also, a combination of myoglobin and CKMB (microgram/L) showed a statistically significantly higher sensitivity and diagnostic efficacy but lower diagnostic specificity compared to the combination of myoglobin and cTnl.

[Presence of Chlamydia pneumoniae antibodies in patients with ischemic heart disease and acute myocardial infarct]. / Nazocnost protutijela protiv Chlamydia pneumoniae u bolesnika s ishemicnom bolesti srca i akutnim infarktom miokarda.

Numerous seroepidemiological studies that suggest an association of C. pneumoniae infection and atherosclerosis have been published in last decade. The aim of this study was to assess a prevalence of C. pneumoniae antibodies in population of Zagreb area, and to investigate possible differences in prevalence of antibodies in patients with atherosclerosis and healthy controls. Forty-seven patients with coronary artery disease or myocardial infarction and 54 controls without any previous history of atherosclerosis were enrolled in the study. Sera were examined by microimmunofluorescence test. Persons with IgA antibody titers > or = 1:32, and/or IgG antibody titers > or = 1:64 were considered as seropositive. We found 75% seropositive in a total number of subjects, although number of seropositive and higher titers of antibodies were found more often in patients with atherosclerosis compared to control group: 74.5% of IgA seropositive patients versus 33.3% seropositive in control group, and 89.4% of IgG seropositive patients compared to 63% seropositive controls. Chronic (persistent) infections with C. pneumoniae were noted in 74.5% of patients and 33.3% controls.

[Parameters of thyroid gland function in acute myocardial infarct]. / Pracenje parametara funkcije stitne zlijezde tijekom akutnog infarkta miokarda.

In 31 patients with acute myocardial infarction triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxine (FT4), thyrotropin (TSH) and TBG were measured and T3-test was performed on the 1st and the 10th day of hospitalization. The 1st day values for T3, FT3 and TBG were significantly lower, and T4 and TSH were significantly higher than in the control group. The same differences were noted on the 10th day for T3, FT3 i T4. TBG was significantly higher than the 1st day. TSH was lower and it was not significantly different from control values. These results are compatible with clinical observations described in severe nonthyroidal illnesses.

[Ventricular extrasystole in comparison with manifestations of ventricular tachycardia and ventricular fibrillation in acute myocardial infarct]]. / Ventrikulska ekstrasistolija u usporedbi s pojavom ventrikulske tahikardije i fibrilacije ventrikula u akutnom infarktu miokarda.

We studied 76 patients with first recent myocardial infarction being not older than 12 hours. The patients included 58 men and 18 women. Their mean age was 62 years. We recorded continuously during the first three days following infarction the heart rate, all forms of ventricular premature beats, ventricular tachycardia, ventricular fibrillation, clinical status and activity of creatinine-phosphokinase and its isoenzyme MB. The results showed that ventricular premature beats (coupled and multiform) as well as ventricular tachycardia were more frequent in the first day of illness, while ventricular premature beats (except bigeminy, for which there is no explanation) were infrequent in the second and the third day after development of an infarct. The incidence of ventricular tachycardia during the follow-up period did not differ significantly. Ventricular fibrillation developed in 7 patients (9.2%). A comparison of the relation between ventricular premature beats and malignant ventricular tachycardia, i.e. ventricular tachycardia and ventricular fibrillation, revealed that the patients with more frequent ventricular tachycardia usually had frequent ventricular premature beats, particularly more often bigeminy, trigeminy, polymorphous ventricular premature and coupled ventricular premature beats, but not ventricular premature beats with R-on-T phenomenon. Ventricular tachycardia, however, was also found in patients with an evidence of more rare ventricular premature beats. This suggests that the occurrence of aforementioned forms of ventricular premature beats denotes only a somewhat greater probability that ventricular tachycardia will occur. The fact that there is a lack of correlation between ventricular tachycardia and R-on-T phenomenon indicates that this probability is not so significant. In conclusion, the authors believe that the patients with recent myocardial infarction and ventricular premature beats should be adequately followed up, and that prophylactic antiarrhythmic therapy is not required in most cases, as it was previously widely accepted concept. It should be administered only when ventricular tachycardia develops. Patients with ventricular fibrillation had more frequent ventricular premature beats, although ventricular premature beats in these patients were not statistically more frequent from those found in the patients in whom ventricular fibrillation was not verified. The presence or absence of ventricular tachycardia and ventricular fibrillation, respectively, had no influence on the other followed up parameters.

Concanavalin A as a probe for studying the mechanism of metabolic stimulation of leukocytes.

The disruption of the molecular organization of the plasma membrane of leukocytes by phagocytosable particles, or by agents such as surfactants, antibodies, phospholipase C, fatty acids and chemotactic factors, leads to a stimulation of the phagocyte oxidative metabolism. Concanavalin A (Con A) has been used as a tool to study the mechanism of this metabolic regulation. The binding of Con A to the surface of polymorphonuclear leukocytes (PMNL) or macrophages produces a rapid enhancement of oxygen uptake and glucose oxidation through the hexose monophosphate pathway (HMP). This is explained by an activation of the granular NADPH oxidase, the key enzyme in the metabolic stimulation. The effect of Con A is not due to endocytosed lectin, since Con A covalently coupled to large sepharose beads still acts as stimulant. The metabolic changes caused by Con A are reversible. If, after the onset of stimulation, sugars with high affinity for Con A are added to the leukocyte suspension, the activity of granular NADPH oxidase and the rate of respiration and glucose oxidation return to their resting values. The metabolic burst, while partially supressed by treatment of PMNL with iodoacetate, sodium flouride and cytochalasin B, is slightly increased by colchicine. Con A induces a selective release of granular enzymes (beta-glucuronidase, peroxidase, alkaline phosphatase) from PMNL, whereas no leakage of cytoplasmic enzymes is observed. The enzyme release is inhibited by iodoacetate and by drugs known to increase cell levels of cyclic AMP. Based on a current view of the mode of interaction between Con A and cell surfaces, a model of the metabolic disruption of leukocytes is presented.