Co-encapsulation of a drug with a protein in erythrocytes for improved drug loading and release: phenytoin and bovine serum albumin (BSA).

The aim of the present study was to use a novel protein co-encapsulation method to prepare phenytoin-loaded human erythrocytes with improved loading parameters and release profiles. Carrier erythrocytes were prepared using the hypotonic pre-swelling method. A series of in vitro characterization tests were carried out on the carrier cells, including loading parameters, drug and hemoglobin release, hematological indices, particle size analysis, osmotic fragility, turbulence fragility, and scanning electron microscopy (SEM). Co-encapsulation with bovine serum albumin (BSA) resulted in about 8-times higher drug loading in erythrocytes, with biphasic release trend instead of triphasic in the case of drug alone loading. In comparison to the normal unloaded cells, MCH and MCHC indices were decreased in the case of both drug and drug/protein loading, apparent cell sizes were unchanged, cell shapes were changed to spherical rather than biconcave discoid, and the osmotic as well as turbulence fragilities were higher in the case of drug/protein but were unchanged in the case of drug alone loading. The most profound finding of this study was the possibility of achieving remarkably higher drug loading and more controllable drug release profile in the case of drug/protein loading, with no unwanted in vitro characteristics change.

Bioequivalence evaluation of a triamterene-hydrochlorothiazide generic product: a new bioequivalence index for fixed-dose combinations.

In this study, an open, double-blind, randomized, two-period, two-group crossover design was conducted in 14 healthy volunteers to study the bioequivalence of a fixed-dose generic product. After administration of test or reference products to each volunteer, both active ingredients were determined simultaneously in plasma samples using a developed and validated HPLC-UV method, and pharmacokinetic parameters, including C(max), T(max), AUC(0-t) , AUC(0∞), terminal elimination rate constant (λz), volume of distribution in steady state (Vd(ss)), mean residence time (MRT), clearance (Cl), terminal elimination rate constant (Kel) were determined in each subject using the standard non-compartmental approach. Statistical comparison showed that the test and reference products were bioequivalent in terms of both the rate and extent of bioavailability of both active ingredients. Finally, a new parameter named range overlap index (ROI) was introduced for the first time in this study in order to judge about the overall bioequivalence of the combination products. This parameter indicates the extent in which the two CI90% ranges of each parameter for two active ingredients overlap with each other. The ROI is suggested to be equal or more than 50% for two combination products in order to be known as bioequivalent. The ROI values of the bioequivalence-indicating parameters were 61.90%, 84.6%, and 76.0% for C(max), AUC(0--->12), and AUC(0--->∞), respectively, which are indicative for bioequivalence in all the cases.

Topography of gastritis and its severity in 864 first degree relatives of gastric cancer patients.

OBJECTIVES: Studies on gastric mucosal histological findings among first degree relatives (FDR) of gastric cancer (GC) patients are scarce. The aim is to evaluate the topography and the severity of gastritis among FDR of GC patients. DESIGN: A total of 989 subjects who were FDR of GC patients, ages 40-65 years underwent gastroscopies. When no gross lesion was found, five specimens were evaluated according to the Sydney Classification and one for urease testing in order to determine the type of gastritis and its severity. RESULTS: Of the 989 subjects, 107 had significant lesions, including two with GC and one with esophageal cancer. The 864 subjects who had complete morphological data taken from five gastric areas (two from the antrum and three from the corpus) comprised 419 males (mean age 48.5±7 years) and 445 females (mean age 47±6.4 years). The H. pylori rate was 76.6%. Normal mucosa was seen in 6.9%, antrum-restricted gastritis in 7.4%, antrum-predominant gastritis in 63.5% and corpus-predominant gastritis in 20% (both had >80% H. pylori infection) and corpus-restricted gastritis in 2%. More atrophy was seen in the antrum and corpus of FDR females than males. The severity did not differ between those with one or more GC patients' relatives. Forty-nine percent of FDR had atrophy and 9.4% intestinal metaplasia (IM) in the corpus. After the age of 40, there was progression of intestinal metaplasia from 12.2 to 27.3% in the antrum and from 6.7% to 26.2% in the corpus during two decades. No high grade dysplasia was found in this mid-age population. CONCLUSION: Only one-fifth of FDR have H. pylori-induced corpus-predominant gastritis who are at risk for cancer and suitable for eradication. Corpus-restricted gastritis is a rare disease in this area.

Lower esophagus in dyspeptic Iranian patients: a prospective study.

BACKGROUND: Gastroesophageal junction cancer has increased over time in Western countries. Gastroesophageal reflux disease (GERD) is considered to be a major risk factor. We prospectively studied the prevalence of clinical, histological and endoscopic GERD, and premalignant changes among dyspeptic Iranian patients referred for upper gastrointestinal endoscopy (UGIE). METHODS: Consenting patients referred for UGIE to our clinic were enrolled. Their symptoms were recorded, UGIE was conducted, and biopsies from all suspicious lesions and across the Z-line were taken. RESULTS: Of the 344 enrolled patients, 269 (135 women, 134 men; mean age: 41.6 years) were evaluated. One major GERD symptom (heart burn, acid regurgitation, dysphagia and chest pain) was seen in 209 (77.6%) patients, and 207 patients (76.1%) had endoscopic esophagitis. Thirteen patients (5%) had specialized intestinal metaplasia at the gastrointestinal junction (SIM-GEJ), and three had glandular dysplasia (two low-grade, one high-grade). No symptom could predict the presence of histological or endoscopic findings. Patients with dysplasia had more advanced degrees of endoscopic esophagitis. CONCLUSION: Gastroesophageal reflux disease is common among Iranian patients referred for diagnostic endoscopy. The prevalence of SIM-GEJ among this population was comparable to that reported in Western countries.