Development and characterization of nanostructured pharmacosomal mesophases: An innovative delivery system for bioactive peptides

Purpose: To potentially enhance the bioavailability and extend the bioactivity effectiveness of Isoleucine-Proline-Proline (IPP, an antihypertensive bioactive peptide of dairy origin), a novel Lyotropic Liquid Crystalline Pharmacosomal Nanoparticle (LLCPNP) was synthesized, and its physicochemical and technological characteristics were studied. Methods: LLCPNPs precursors were developed using IPP and soy phosphatidylcholine via complex formation. Polarized light microscopy, small angle X-ray scattering, differential scanning calorimetry, dynamic light scattering and Fourier transform infrared spectroscopy were employed to characterize the physicochemical properties of the nanoparticles. The in-vitro release and its related mechanisms were also studied. Results: Fourier transform infrared spectroscopy confirmed the complexation between the components of LLCPNPs. Phase behavior evaluation by polarized light microscope showed the characteristic birefringent texture. These findings along with those of small angle X-ray scattering and differential scanning calorimetry proved the formation of lamellar LLCPNPs. These particles represented nanometric size (<100 nm), high incorporation efficiency (93.72%) and proper physicochemical stability during long-term storage. In-vitro studies demonstrated a sustained release behavior fitted to non-Fickian diffusion and Higuchi kinetic models. Conclusion: The present study results emphasized that LLCPNPs could be proposed as an unrivaled carrier to promote the bioavailability, stability and shelf-life of nutraceutical and biopharmaceutical formulations containing bioactive peptides

Antimicrobial susceptibility patterns among bacteria isolated from intensive care units of the largest teaching hospital at the northwest of Iran

This study was conducted to determine the antimicrobial susceptibility patterns among common pathogens in the intensive care units (ICUs) of a university hospital in northwestern Iran. A retrospective study was done on laboratory records of patients with nosocomial infection who were admitted to five ICUs of Imam Reza Hospital during a 21-month period from March 2010 to January, 2012. A total number of 556 isolates from 328 patients were evaluated. The most common sites of infections included respiratory (51.7%), urinary (24.8%), and blood (10.4%). The most frequently isolated microorganisms were Enterobacter aerogenes (50.6%) followed by Escherichia coli (16.7%) and Pseudomonas aeruginosa (7.5%). Staphylococcus aureus was the most frequent pathogen among gram-positives (39.7%). The rate of methicillin-resistant Staphylococcus aureus (MRSA) was 87.5%. Multidrug-resistant (MDR) gram-negative bacteria were documented in 25.8% of Acinetobacter, 20% of Klebsiella, and 16.6% of Pseudomonas. The most active antimicrobials were vancomycin (93.5%) followed by amikacin (71.5%) and gentamicin (46%). The overall antibiotic susceptibility was as follows: 36% ciprofloxacin, 19% imipenem, 20% trimethoprim-sulfamethoxazole, 20.5% ceftazidime, and 12% ceftriaxone. Due to the high rate of antimicrobial resistance in the ICU setting, more surveillance and control of the use of antimicrobials is needed to combat infections

Taurine in Septic Critically Ill Patients: Plasma versus Blood

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body’s antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients’ outcome, and the disease severity, and organ failure

Utilization Evaluation of Antimicrobial Agents in Neutropenic Cancer Patients in a Teaching hospital: Urgent of Drug Utilization Evaluation Studies

Background: More than 80% of patients with hematologic  malignancies will develop fever during more than one chemotherapy cycle combined with neutropenia. We aim to evaluate empiric antibiotic strategies in Febrile Neutropenic (FN) cancer patients. Methods: This is a concurrent study performed in the “Shahid Ghazi” teaching hospital, hematology-oncology center of Tabriz, Iran during the period of December 2011 to September2012. During this period, patients with FN were evaluated in view of antibiotics utilization based on Infectious Disease Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) instructions. Results: Seventy patients had a total of 91 episodes of FN in the duration of this study. Among them 63 (90%) patients were the cases of acute leukemia. For 88 (96.7 %) patients, imipenem was used as the initial empirical antibiotic regimen. It was changed to piperacillin/tazobactam in 8 (8.8%) of them without indication. Cultures didn’t obtain before the initiation of empirical therapy in 19 (20.9%) episodes. Empiric vancomycin didn’t discontinue after 3 days even if it was not warranted in 23 episodes. In 16 cases vancomycin was switched to teicoplanin. The fluconazole dosages generally given to patients were all suboptimal. Adjusting the dosages of vancomycin or imipenem was not done correctly in 13 (14.29%) episodes. Conclusion: The results of this study showed that choosing antimicrobial agents and their dosing for prophylaxis and treatment of FN patients and discharge antimicrobial planning of FN patients do not follow the evaluated guidelines. Drug Usage Evaluation studies need to be done regularly in such a center

Pharmacy Students' Self-Identified Interests in a Hospital Pharmacy Internship Course in Iran

Introduction: After revision of pharmacy curriculum by, Iranian Health and Education Ministry reviewed in 2005, it was decided that pharmacy students need extra internship courses such as hospital internship course. Hospital internship course could provide students with the opportunity to acquire the knowledge and master the skills required for current pharmacy practices in community and hospital setting. The aim of this study was to identify and analyze pharmacy students’ experiences during hospital internship. Methods: Each student attended in 3 wards and provided a logbook for each ward. Students were asked to document at least one topic interesting for them on each day. The collected information was divided into sections and analyzed using SPSS ver 14. Results: Seventeen students enrolled in the course. Endocrinology and nephrology wards had the highest and neurology the lowest number of attended students. Seven hundred and one reported learning subjects were divided into 24 areas. The highest numbers of reported topics were the drugs indications, adverse drug reactions and diagnosis of diseases while the lowest number was pretreatment laboratory tests, pharmacoeconomy, counseling medical staffs and off label use of medications. Gastroenterology and endocrinology wards with 210 reports had the highest and neurology ward with 12 had the lowest number of reports. Conclusion: Completing the logbooks was an encouragement for students to seek and document and learn new topics and also a major feature of the clinical assessment scheme of the course. The majority of the reported topics were learning objectives but not the interventional ones. The present study showed us some areas of pharmacy education which need further attention

Medication errors in oral dosage form preparation for neonates: The importance of preparation technique

Objective: Considering the inability of neonates to swallow oral drugs in the form of solid tablets, the lack of appropriate dosage forms for infants, and the necessity to prepare some pills for neonates, the current study investigated dosage accuracy in drugs for neonates prepared from tablets by analyzing the concentrations of final products. Methods: Captopril and spironolactone, oral dosage forms that are not suitable for infants, were chosen as the drug model for this study. Demographic characteristics of nurses providing medications and tablet preparation methods were documented in a random observational method. To determine concentrations of final solutions, 120 drug samples (60 captopril and 60 spironolactone samples) prepared by Neonatal Intensive Care Unit nurses of the Children Cure and Health Hospital of Tabriz University of Medical Sciences were analyzed using high performance liquid chromatography (HPLC) and spectrophotometry. Findings: There was a significant error rate in the concentration of captopril in prepared solutions compared with the ordered dosage. No differences were observed in the demographic characteristics of the nurses and the method of preparation between the two drugs. The only difference related to the preparation technique was that in most cases (70.8%), one whole spironolactone tablet was used, whereas in around 50% of samples in captopril group, half or a quarter of one captopril tablet was utilized for the intended dosage (P = 0.009). Conclusion: This research suggests that the use of a whole tablet instead of a divided tablet in the manual preparation of medication dosage forms for neonates is the most appropriate approach

The Evaluation of Albumin Use in an Iranian University Hospital

Background: Albumin is an expensive protein colloidal solution with various indications, especially in critically ill patients. The vast use of albumin in health care centers (particularly ICUs), the theoretical danger of contaminant transmission (as with any blood derivative), and the existence of more economical alternatives of equal efficacy evidence the importance of conducting a drug-utilization evaluation. The objective of this study was to assess the usage of albumin in patients at a hospital in Iran. Methods: Albumin administration was evaluated in 210 patients from different wards on randomly selected days during one year. Reasons for the prescription, the consumed dose, length of administration, and related laboratory tests were recorded. Results: Albumin was prescribed inappropriately in 76.2% and appropriately in 23.8% of inpatients. The most frequent inappropriate prescribing motives were hypoalbuminemia (35.6%), nutritional support (32.5%), and edema (24.4%), while the most appropriate prescriptions were edema (46%), nephrotic syndrome (18%), and plasmapheresis (16%). The total amount of albumin used for 210 patients was 68930 g, from which 51290 g costing $274607.1429 was administered for inappropriate indications. Conclusion: Despite the many valid guidelines defining the appropriate indications of albumin, this study demonstrated the extensive inappropriate use of this expensive preparation in one of the largest university-affiliated hospitals in northwestern Iran. It seems advisable to have the consumption of albumin continuously monitored

Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs) have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed

Education alone is not enough in ventilator associated pneumonia care bundle compliance

Objective: Ventilator-associated pneumonia (VAP) described as a secondary and preventable consequence in mechanically ventilated patients, emerges 48 h or more after patients intubation. Considering the high morbidity and mortality rate of VAP and the fact that VAP is preventable, it seemed necessary to evaluate care bundle compliance rate and effect of education on its improvement. Methods: This observational study was conducted on 10 Intensive Care Units (ICUs) of four university affiliated hospitals in three steps. In the first step, VAP care bundle compliance including head of bed (HOB) elevation, endotracheal cuff pressure (ETCP), mouthwash time, utilizing close suction systems, subglottic secretion drainage, type of suction package, and hand wash before suctioning was evaluated. In the second and third steps, ICU staffs were trained and its effect on VAP care bundle compliance was investigated. Finally, an inquiry from nurses was conducted to evaluate the obtained results. Findings: A total of 552 checklists consisting of 294 observations in the pre-education group and 258 observations in the posteducation group were filled. Mean VAP care bundle compliance in pre-education and posteducation stages was 36.5% and 41.2%, respectively (P > 0.05). Except for patients′ mouth washing, there were no improvement in HOB elevation (>30΀), hand washing and ETCP after education. Based on the results of questionnaire received from nurses at the end of study, more than 90% of nurses believed that lack of rigid monitoring of VAP care bundle is a main reason of low adherence for VAP care bundle compliance. Conclusion: The adherence to VAP care bundle was inappropriate. Education seems to be ineffective on improving VAP care bundle compliance. Frequent recall of the necessity of the VAP care bundle and the continuous supervision of ICU staffs is highly recommended

Inhibition of P-glycoprotein expression and function by anti-diabetic drugs gliclazide, metformin, and pioglitazone in vitro and in situ

P-glycoprotein (P-gp) is a trans-membrane drug efflux pump. Several drugs are P-gp substrates. Some drugs may affect the activity of P-gp by inhibiting its function, resulting in significant drug-drug interactions (DDIs). It is critical to understand which drugs are inhibitors of P-gp so that adverse DDIs can be minimized or avoided. This study investigated the effects of gliclazide, metformin, and pioglitazone on the function and expression of P-gp. Rhodamine 123 (Rh 123) efflux assays in Caco-2 cells and western blot testing were used to study in vitro the effect of the drugs on P-gp function and expression. The in situ rat single-pass intestinal permeability model was developed to study the effect of the drugs on P-gp function. Digoxin and verapamil were used as a known substrate and inhibitor of P-gp, respectively. Digoxin levels in intestinal perfusion samples were analyzed by high-performance liquid chromatography. Intestinal effective permeability (Peff) of digoxin in the presence of 0.1, 10, and 500 μM gliclazide, 100 and 7000 μM metformin, and 50 and 300 μM pioglitazone was significantly increased relative to the digoxin treated cells (P 0.05). It was found that gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ and down-regulated P-gp expression in vitro. Further investigations are necessary to confirm the obtained results and to define the mechanism underlying P-gp inhibition by the drugs